The Cannabis plant (Cannabis sativa L.) produces an estimated 545 chemical compounds of different biogenetic classes. In addition to economic value, many of these phytochemicals have medicinal and physiological activity. The plant is most popularly known for its two most prominent and most studied secondary metabolites— Δ9-Tetrahydrocannabinol (Δ9-THC) and Cannabidiol (CBD). Both Δ9-THC and CBD have a wide therapeutic window across many ailments and form part of a class of secondary metabolites called cannabinoids—of which approximately over 104 exist. This review will focus on non-cannabinoid metabolites of Cannabis sativa that also have therapeutic potential, some of which share medicinal properties similar to those of cannabinoids. The most notable of these non-cannabinoid phytochemicals are flavonoids and terpenes. We will also discuss future directions in cannabis research and development of cannabis-based pharmaceuticals. Caflanone, a flavonoid molecule with selective activity against the human viruses including the coronavirus SARS-COV2, and certain cancers, is one of the most promising non-cannabinoid molecules that is being advanced into clinical trials. As validated by thousands of years of the use of cannabis for medicinal purposes, vast anecdotal evidence abounds on the medicinal benefits of the plant. These benefits are attributed to the many phytochemicals in this plant, including non-cannabinoids. The most promising non-cannabinoids with potential to alleviate global disease burdens are discussed.

Industrial hemp (Cannabis sativa L.), due to its bioactive compounds (terpenes and cannabinoids), has gained an increasing interest in different fields, including medical purposes. The evaluation of the safety profile of hemp essential oil (EO) and its encapsulated form (nanoemulsion, NE) is a relevant aspect for potential therapeutic applications. This study aimed to evaluate the toxicolog-ical effect of hemp EOs and NEs from cultivars Carmagnola CS and Uso 31, on three cell lines se-lected as models for topical and inhalant administration, by evaluating the cytotoxicity and the cytokine expression profiles. Results show that EOs and their NEs have comparable cytotoxicity, if considering the quantity of EO present in the NE. Moreover, cells treated with EOs and NEs showed, in most of the cases, lower levels of pro-inflammatory cytokines compared to Etoposide used as positive control, and the basal level of inflammatory cytokines was not altered, suggest-ing a safety profile of hemp EOs and their NEs to support their use for medical applications.

The increased cultivation of high THC-containing Cannabis sativa L. (cannabis), particularly in greenhouses, has resulted in a greater incidence of diseases and molds that can negatively affect the growth and quality of the crop. Among them, the most important diseases are root rots (Fusarium and Pythium spp.), Botrytis bud rot (Botrytis cinerea), powdery mildew (Golovinomyces ambrosiae), cannabis stunt disease (caused by Hop latent viroid), and a range of microbes that reduce post-harvest quality. An integrated management approach to reduce the impact of these diseases/microbes requires combining different approaches that target the reproduction, spread and survival of the associated pathogens, many of which can occur on the same plant simultaneously. These approaches will be discussed in the context of developing an integrated plan to manage the important pathogens of greenhouse-grown cannabis at different stages of plant development. These stages include maintenance of stock plants, propagation through cuttings, vegetative growth of plants, and flowering. The cultivation of cannabis genotypes with tolerance or resistance to various pathogens is a very important approach, followed by the maintenance of pathogen-free stock plants. When combined with cultural approaches (sanitation, management of irrigation, and monitoring for diseases) and environmental approaches (greenhouse climate modification), a significant reduction in pathogen development and spread can be achieved. The use of preventive applications of microbial biological control agents and reduced risk biorational products can also reduce disease development at all stages of production in jurisdictions where they are registered for use. The combined use of promising strategies for integrated disease management on cannabis plants during greenhouse production will be reviewed. Future areas for research are identified.

Psychosis can be defined as a combination of psychopathological symptoms including delusions and/or hallucinations without insight. Psychotic disorders may configure a primary psychiatric illness or represent the result of a functional/structural brain damage induced by substance use, neurological diseases or other medical conditions. They are multifactorial disorders in which genetic, environmental and gene-environment interaction factors contribute to the expressiveness of the symptoms. Among the environmental factors, psychotropic substances represent the most important removable facilitators of psychosis. In our study, we compared the prevalence of substance induced psychosis between a sample of patients affected by cannabis use disorder and a sample of patients affected by cocaine use disorder analyzing retrospectively the data of outpatients with no personal or family history of psychiatric illnesses.

Introduction: Substance-induced psychotic disorder (SIPD) is a mental health condition linked to the use of a psychotropic substance whose pathogenesis has not been totally clarified. The present retrospective observational study has the objective to identify differences in clinical features and peripheral biomarkers in SIPD patients according to the main substance of abuse.Methods: A total sample of 218 patients was divided in 3 groups according to the type of consumed substance: alcohol, cannabis and psychostimulants. The 3 groups were compared for continuous variables by one-way analyses of variance (ANOVAs) and for qualitative variables by χ² tests. After removing alcohol-induced psychotic disorder group, the same analyses were repeated. Statistically significant variables from these latter analyses were included in a binary logistic regression model to confirm their reliability as predictors for cannabis- or psychostimulants-induced psychotic disorders. Results: Psychotic cannabis abusers were younger (p<0.01) and had an earlier age at onset (p<0.01). On the contrary, alcohol consumers resulted to have a longer duration of illness (p<0.01), more previous hospitalizations (p=0.04), more frequent medical comorbidity (p<0.01), higher mean Modified Sad Person Scale scores (p<0.01). Finally, psychostimulant abusers had more frequently a lifetime history of poly-substance use disorders (p<0.01). Binary logistic regression revealed that higher mean Brief Psychiatric Rating Scale scores (p<0.01) higher sodium (p=0.012) and haemoglobin(p=0.040) plasma levels were predictors of cannabis misuse in SIPD patients.Conclusions: Different clinical factors and biochemical parameters con be associated to SIPD according to the main substance of abuse, thus requiring a specific management by clinicians.

Fever control is essential in patients with severe traumatic brain injury (TBI). The efficacy of therapeutic hypothermia (TH) in severe TBI has been investigated over the last few decades; however, in contrast to experimental studies showing benefits, no evidence of efficacy has been demonstrated in clinical practice. In this review, the mechanisms and history of hypothermia were briefly outlined, while the results of major randomized controlled trials (RCTs) and meta-analyses investigating TH for adult TBI are introduced and discussed. The retrieved meta-analyses showed conflicting results, with a limited number of studies indicating benefits of TH. Some studies have shown benefits of long-term TH compared with short-term TH. Although TH is effective at lowering elevated intracranial pressure (ICP), reduced ICP does not lead to favorable outcomes. Low-quality RCTs overestimated the benefits of TH, while high-quality RCTs showed no difference or worse outcomes with TH. RCTs assessing standardized TH quality demonstrated the benefits of TH. As TBI has heterogeneous and complicated pathologies, applying a uniform treatment may not be ideal. A meta-analysis of young patients who underwent early cooling and hematoma removal showed better TH results. TH should not be abandoned, and its optimal should be advocated on an individual basis.

Worldwide, approximately 15 million people per year suffer from stroke. With about 5 million deaths, stroke is the second most common cause of death and a major cause of long-term disability. It is estimated that about 25% of people older than 85 years will develop stroke. Cannabis sativa and derived cannabinoids are used for recreational and medical purposes for many centuries. However, due to past legal status, research faced restrictions and cannabis use was stigmatized for potential negative impacts on health. With the legalization of cannabis in many countries of the world, cannabis and cannabis-derived substances such as cannabinoids and terpenes have gained more interest in medical research. Several medical effects of cannabis have been scientifically proven and potential risks were identified. In the context of stroke, the role of cannabis is controversial. Negative impact of cannabis use on stroke has been reported through anecdotal case reports and some population-based studies. However, potential beneficial effects of specific cannabinoids are described in animal studies under certain conditions. In this review, the existing body of evidence regarding the negative and positive impacts of cannabis use prior to stroke will be critically appraised.

Despite the surge in the research of cannabis chemistry and its biological and medical activity, only a few cannabis-based pharmaceutical-grade drugs have been developed and marketed to date. Not many of these drugs are Food and Drug Administration (FDA)-approved and some are still going through regulation processes. Active compounds including cannabinergic compounds (i.e., molecules targeted to modulate the endocannabinoid system) or analogs of phytocannabinoids (cannabinoids produced by the plant) may be developed into single-molecule drugs. However, since in many cases treatment with whole plant extract is preferred over treatment with a single purified molecule, some more recently developed cannabis-derived drugs contain several molecules. Different combinations of active plant ingredients (API) from cannabis with proven synergy may be identified and developed as drugs to treat different medical conditions. However, possible negative effects between cannabis compounds should also be considered, as well as the effect of the cannabis treatment on the endocannabinoid system. FDA registration of single, few or multiple molecules as drugs is a challenging process and certain considerations that should be reviewed in this process, including issues of drug-drug interactions, are also discussed here.

Glycosphingolipids (GSLs), a subtype of glycolipids containing sphingosine, are critical components of vertebrate plasma membranes, playing a pivotal role in cellular signaling and interactions. In human articular cartilage in osteoarthritis (OA), GSL expression is known notably to decrease. This review focuses on the roles of gangliosides, a specific type of GSL, in cartilage degeneration and regeneration, emphasizing their regulatory function in signal transduction. The expression of gangliosides, whether endogenous or augmented exogenously, is regulated at the enzymatic level, targeting specific glycosyltransferases. This regulation has significant implications for the composition of cell surface gangliosides and their impact on signal transduction in chondrocytes and progenitor cells. Different levels of ganglioside expression can influence signaling pathways in various ways, potentially affecting cell properties, including malignancy. Moreover, gene manipulations against gangliosides have been shown to regulate cartilage metabolism and chondrocyte differentiation in vivo and in vitro. This review highlights the potential of targeting gangliosides in the development of therapeutic strategies for osteoarthritis and cartilage injury and addresses promising directions for future research and treatment.

The developmental phase of adolescence is characterized by a multitude of neurocognitive and psychosocial changes and is therefore considered one of the most critical developmental periods of life. Experimentation on the use of substances often begins in adolescence and so does the addiction process. Most research in human subjects shows that chronic cannabis abuse is the cause of the impairment of some cognitive functions, affecting the performance on divided attention, verbal memory and working memory. In this study, we wanted to investigate how the abuse of cannabis (chronic, occasional and absence use) can influence global cognitive functioning, also through executive functions. From the statistical analyzes of our study, it emerges that the group of subjects who use chronic cannabis (group 1) has a significant drop in working memory tasks compared to the group that does not use it (group 3). In addition, the goal of future studies by our group is to verify the permanent alteration of cognitive processes affected through revaluations with calendar follow-up (controlled).

A detailed review of the scientific literature was undertaken to examine the most recent developments in plasma processing in the field of medicine. The first part of the review includes a detailed breakdown of the different types of coatings that can be applied onto medical devices using plasma, with a specific focus on antimicrobial surfaces. The developments during 2023 in plasma deposited biocompatible, drug delivery and adhesive coatings are described and specific applications in additive manufacturing are highlighted. The use of plasma and plasma activated liquids as standalone therapeutics continues to evolve and pertinent advances in this field are described. In addition, the combination of plasma medicine with conventional pharmaceutical interventions was reviewed and key emerging trends were highlighted, including the use of plasma to enhance drug delivery directly into tissue. The potential synergies between plasma medicine and chemotherapeutics for oncology and infection treatment is a growing area and recent advancements are noted. Finally, the use of plasma to control excess antibiotics and to intentionally degrade such materials in waste streams is described.

Cannabis has been used as an herbal remedy for thousands of years and recent research indicates promising new uses in medicine. Researchers have been particularly interested in the potential uses of cannabinoids in treating cancer due their ability to regulate cancer-related cell cycle pathways, leading to many beneficial effects such as tumor growth prevention, cell cycle obstruction, and cell death. The aim of this review is to summarize current knowledge on mechanisms of cannabinoids and their role in treating chemotherapy-induced nausea and vomiting, relieving cancer-associated pain, and obstructing tumor cell growth.

The cannabis plant has been known for millennia for its properties such as textile fiber, food, recreational and medicinal use. Since the origin of its domestication in Asia, cannabis has been transported to the rest of the continents by merchants, nomads, settlers, and slaves, who have also carried with them valuable knowledge about its uses. Its medical use was one of the major contributions of this plant in the various civilizations through which it passed. This article aims to understand its origins, dissemination, and medical use over the years to the present day.

Endocannbinoids system (ECS) engrossed a considerable interest as potential therapeutic targets in various carcinomas and cancer related conditions alongside with neurodegenerative diseases. Cannabinoids are implemented in several physiological processes such as appetite stimulation, energy balance, pain modulation and the control of chemotherapy induced nausea and vomiting (CINV). However, pharmacokinetics and pharmacodynamics interactions could be perceived in drug combinations, so in this short review we tried to shed the light over the potential drug interactions of medicinal cannabis. Hitherto, few data have been provided to the healthcare practitioners about the drug-drug interactions of cannabinoids with other prescription medications. In general, cannabinoids are usually well tolerated, but the bidirectional effects may be expected with concomitant administered agents via affected membrane transporters (glycoprotein p, breast cancer resistance proteins) and metabolizing enzymes (Cytochrome P450 and UDP- glucuronosyltransferases). The caveats should be undertaken to closely monitor the responses of cannabis users with certain drugs to guard their safety, especially for the elderly and people with chronic diseases or kidney and liver conditions.

Background: Peritoneal sclerosis (PS) and its most severe form, encapsulating PS (EPS), are rare entities that can occur in various procedures (liver transplantation, intraperitoneal chemotherapy), secondary to medications ( beta-blockers); however, PS or EPS typically occur in patients undergoing peritoneal dialysis as a form of renal function substitution. Medical or surgical treatments can be applied, but morbidity and mortality have high rates . This condition typically presents clinically as an intestinal obstruction caused by the inclusion of the intestinal loops in the peritoneal fibrous membrane. Methods: Herein we present data from a single tertiary surgery center that has dedicated teams for patients receiving dialysis. In 12 years we analyzed a group of 63 patients admitted for catheter replacement/removal or for acute surgical pathology. In 5 cases (7,9%) we diagnosed EPS . Two patients with EPS presented with atypical abdominal pathologies requiring emergency surgery: one case of hemoperitoneum caused by a ruptured ovarian cyst and one case of uterine fibroids and metrorrhagia. Results: The definitive diagnoses were established intraoperatively and by analyzing the morpho-pathological changes of the peritoneum. The possible intraoperative challenges included laborious dissection, difficulties in restoring the correct anatomical landmarks, increased duration of the surgical intervention and a high rate of incidents and accidents Conclusions: The aim of the present study was to emphasize the possibility of other surgical pathologies overlapping with EPS, increasing the complexity of the surgical intervention. Also, we sought to determine whether there is a correlation between the morpho-pathological results of these patients who underwent emergency surgery and the common EPS morpho-pathological changes.

The gastrointestinal tract is colonized by trillions of different microorganisms, named the gut microbiota, which is key to degrade undigested food such as dietary fibers. The fermentation of these food components leads to the production of short-chain fatty acids (SCFA) acetate, propionate, and butyrate, which exploit several beneficial roles for the host’s health. Their production and absorption happen in different ways in the human intestine and depend on the type of dietary fiber reaching the gut and the microorganisms involved in the fermentation. The supplementation of SCFAs, mostly butyrate, in treating gastrointestinal, metabolic, cardiovascular, and gut-brain-related diseases has been reported in the medical literature. This review aims to give an overview of the production and absorption dynamics of acetate, propionate, and butyrate in the human gut, with a final focus on the role played by these SCFAs on gastrointestinal and metabolic health and the present therapeutic implications.

Fibrodysplasia Ossificans Progressiva (FOP) is an enigmatic, ultra-rare genetic disorder characterized by progressive heterotopic ossification, wherein soft connective tissues undergo pathological transformation into bone structures. This incapacitating process severely limits patient mobility and poses formidable challenges for therapeutic intervention. Predominantly caused by missense mutations in the ACVR1 gene, the disorder has hitherto defied comprehensive mechanistic understanding and effective treatment paradigms. This write-up offers a comprehensive overview of the contemporary understanding of FOP's complex pathobiology, underscored by advances in molecular genetics and proteomic studies. We shed light on targeted therapy, spanning genetic therapeutics, enzymatic and transcriptional modulation, stem cell therapies, and innovative immunotherapies. We also focused on the intricate complexities surrounding clinical trial design for ultra-rare disorders like FOP, addressing fundamental statistical limitations, ethical conundrums, and methodological advancements essential for the success of interventional studies. We advocate for the adoption of a multi-disciplinary approach that converges bench-to-bedside research, clinical expertise, and ethical considerations to tackle the challenges of ultra-rare diseases like FOP and comparable ultra-rare diseases. Overall, this article serves a dual role: as a definitive scientific resource for ongoing and future FOP research and as a call to action for innovative solutions to address methodological and ethical challenges that impede progress in the broader field of medical research for ultra-rare conditions.

Introduction: Increasing cannabis legalization raises concerns that tobacco use, frequently used with cannabis, will also increase. This study investigated the association between legal status of cannabis in place of residence and prevalence of cannabis and tobacco co-use, simultaneous use, and mixing by comparing the prevalence among adults in Canada (prior to cannabis legalization) vs. adults in US states that had legalized recreational cannabis vs. US states that had not as of September 2018. Methods: Data were drawn from the 2018 International Cannabis Policy Study, conducted with respondents aged 16-65 in Canada and the US recruited from non-probability consumer panels. Differences in the prevalence of co-use, simultaneous use, and mixing between tobacco and different cannabis products were examined using logistic regression models by legal status of place of residence among past 12-month cannabis consumers (N=6744). Results: Co-use and simultaneous use in the past 12 months were most common among respondents in US legal states. Among cannabis consumers, co-use and simultaneous use were less common in US legal states, while mixing was less frequent in US states with both legal and illegal cannabis compared to Canada. Use of edibles was associated with lower odds of all three outcomes, while smoking dried herb or hash was associated with higher odds. Conclusions: The proportion of cannabis consumers who used tobacco was lower in legal jurisdictions despite higher prevalence of cannabis use. Edible use was inversely associated with co-use suggesting that edible use does not appear to be associated with increased tobacco use.

Recently we have seen a relaxation of the historic restrictions on the use and subsequent research on the Cannabis plants, generally classified as Cannabis sativa and Cannabis indica. What research has been performed to date has centered on chemical analysis of plant flower products, namely cannabinoids and various terpenes that directly contribute to phenotypic characteristics of the female flowers. In addition, we have seen many groups recently completing genetic profiles of various plants of commercial value. To date, no comprehensive attempt has been made to profile the proteomes of these plants. We report herein our progress on constructing a comprehensive draft map of the Cannabis proteome. To date we have identified over 17,000 potential protein sequences. Unfortunately, no annotated genome of Cannabis plants currently exists. We present a method by which “next generation” DNA sequencing output and shotgun proteomics data can be combined to produce annotated FASTA files, bypassing the need for annotated genetic information altogether in traditional proteomics workflows. The resulting material represents the first comprehensive annotated protein FASTA for any Cannabis plant. Using this annotated database as reference we can refine our protein identifications, resulting in the confident identification of 13,000 proteins with putative function. Furthermore, we demonstrate that post-translational modifications play an important role in the proteomes of Cannabis flower, particularly lysine acetylation and protein glycosylation. To facilitate the evolution of analytical investigations into these plant materials, we have created a portal to host resources we have developed from proteomic and metabolomic analysis of Cannabis plant material as well as our results integrating these resources. All data for this project is available to view or download at www.CannabisDraftMap.Org

This article analyzes laws, normative reforms and regulations surrounding the practices and mechanisms of control over the consumption, cultivation and commercialization of cannabis. On the one hand, I investigate regulatory practices that deny rights for the consumption of cannabis classified as recreational. On the other hand, I study regulatory practices that extend rights for the production, consumption and commercialization of cannabis classified as medicinal and industrial. The empirical moment is composed of four stages and methodological tools. First, I conduct an analysis of state policies. Then, I analyze nine laws and codes on cannabis regulation from 1970 to the present. Next, I perform five semi-structured interviews. Finally, I develop two life stories of former people deprived of their liberty for cannabis cultivation and trade. In this way, I trace forms of regulation on multiple demands, knowledge, interests and beliefs. This research focuses on state regulation. Cannabis regulatory regimes are conceived as constructions of political, social and economic truths, meanings and rights. In sum, the answer to the question of how collective demands around cannabis are regulated in Ecuador stipulates that state action reinforces stigmatization and criminalization. In addition, it legitimizes moral entrepreneurs and counter-movements around cannabis.

Rationale:First discovered in 1990, the endocannabinoid system (ECS) was initially shown to have an intimate relationship with central areas of the nervous system associated with pain, reward, and motivation. Recently, however, the ECS has been extensively implicated in the cardiovascular system with contractility, heart rate, blood pressure, and vasodilation. Emerging data demonstrates modulation of the ECS plays an essential role in cardio metabolic risk, atherosclerosis, and can even limit damage to cardiomyocytes during ischemic events.Patient Concerns:This case describes a 63-year-old male who presented to a primary care physician for a medical cannabis (MC) consult due to unstable angina (UA) not relieved by morphine or cardiac medications; having failed all first- and second-line poly-pharmaceutical therapies. The patient reported frequent, unprovoked, angina and exertional dyspnea.Diagnosis:Having a complex cardiac history, the patient first presented 22 years ago after a suspected myocardial infarction (MI). He re-presented in 2010 and underwent stent placement at that time for inoperable triple-vessel coronary artery disease (CAD) which was identified via percutaneous transluminal coronary angioplasty. UA developed on follow up and, despite medical management over the past 6 years, his UA became progressively debilitating.Interventions and Outcomes:In conjunction with his standard cardiac care, patient had a gradual lessening of UA related pain, including frequency and character, after using an edible form of medical cannabis (MC) (1:1 CBD:THC). Following continued treatment, he ceased long term morphine treatment and describes the pain as no longer crippling. As demonstrated by his exercise tolerance tests, the patient experienced an improved functional capacity and reported an increase in his daily functioning, and overall activity.Lessons:This case uniquely highlights MC in possibly reducing the character, quality, and frequency of UA; while concordantly improving functional cardiac capacity in a patient with CAD. Additional case reports are necessary to verify this.

The many strains of Cannabis spp. are associated with many effects on users and contain many different potentially psychoactive metabolites, but the links between metabolite profiles and user effects are unclear. Here we take a statistical approach to linking cause (i.e. metabolites) to effects in Cannabis spp. through the prism of strains, using quantitative data for metabolite composition and user effects. We find that species (indica vs. sativa) explains <2% of the variability in metabolite profiles, while strain explains 1/3 of variability, indicating species is nonindicative of metabolite composition, while strain is approximately indicative. Using random forests we generate a table of potential metabolite-effect links. We also find that effect-weighted metabolite composition can effectively be described in terms of four values representing the concentrations of pairs or triplets of particular compounds.

Osteoporosis (OP), a prevalent skeletal disorder characterized by compromised bone strength and increased susceptibility to fractures, poses a significant public health concern. This review aims to provide a comprehensive analysis of the current state of research in the field, focusing on the application of proteomic techniques to elucidate diagnostic markers and therapeutic targets for OP. The integration of cutting-edge proteomic technologies has enabled the identification and quantification of proteins associated with bone metabolism, leading to a deeper understanding of the molecular mechanisms underlying OP. In this review, we systematically examine recent advancements in proteomic studies related to OP, emphasizing the identification of potential biomarkers for OP diagnosis and the discovery of novel therapeutic targets. Additionally, we discuss the challenges and future directions in the field, highlighting the potential impact of proteomic research in transforming the landscape of OP diagnosis and treatment.

The retinoblastoma (RB) transcriptional corepressor 1 (RB1) is a critical tumor suppressor gene, governing diverse cellular processes implicated in cancer biology. Dysregulation or deletion in RB1 contributes to the development and progression of various cancers, making it a prime target for therapeutic intervention. RB1's canonical function in cell cycle control and DNA repair mechanisms underscores its significance in restraining aberrant cell growth and maintaining genomic stability. Understanding the complex interplay between RB1 and cellular pathways is beneficial to fully elucidate its tumor-suppressive role across different cancer types and for therapeutic development. As a result, investigating vulnerabilities arising from RB1 deletion-associated mechanisms offers promising avenues for targeted therapy. Recently, several findings highlighted multiple methods as a promising strategy for combating tumor growth driven by RB1 loss, offering potential clinical benefits in various cancer types. This review summarizes the multifaceted role of RB1 in cancer biology and its implications for targeted therapy.

Industrial hemp (Cannabis sativa L.) is an attractive candidate for sustainable pest management due to its abundance of bioactive compounds with potential pesticidal properties. Solvent choice has a significant impact on the extraction efficiency of bioactive compounds. Deep Eutectic Solvents (DESs) are gaining popularity in extraction because they are safe and environmentally friendly, making them viable alternatives to organic solvents (OSs). This research first compared the extraction efficiency of OSs on the extraction of phytochemicals from the infloresences of two hemp varieties, Citrus and Cherry Dwarf. Inflorescences were extracted using three OSs, ethanol, ethyl acetate, and hexane. The highest level of cannabidiol (CBD; 0.69%) was extracted from Cherry Dwarf using ethanol while the level of delta-9 tetrahydrocannabinol THC (0.19%) was essentially the same in both. Therefore, Cherry Dwarf was selected to compare the extraction efficiency of DESs to the OSs. The DESs were choline chloride/ethylene glycol, citric acid/ethylene glycol, menthol/lauric acid, choline chloride/urea and choline chloride/glycerol. In the targeted analysis, choline chloride/ethylene glycol extracted the highest amount of CBD (0.87%) followed by choline chloride/urea (0.78%). As some DESs outperformed ethanol, the popular solvent for extracting cannabinoids, DESs are viable candidates to replace organic solvents.

The recent legalization of Cannabis sativa L. in many regions has revealed a need for effective propagation and biotechnologies for the species. Micropropagation affords researchers and producers methods to rapidly propagate insect/disease/virus free clonal plants, store germplasm, and forms the basis for other biotechnologies. Despite this need, research in the area is limited due to the long history or prohibitions and restrictions. Existing literature has multiple limitation: many publications use hemp as a proxy for drug-type Cannabis when it is well established that there is significant genotype specificity, studies using drug-type cultivars are predominantly op-timized using a single cultivar, most protocols have not been replicated by independent groups, and some attempts demonstrate a lack of reproducibility across genotypes. Due to culture decline and other problems the multiplication phase of micropropagation (stage 2) has not been fully developed in many reports. This review will provide a brief background on the history and botany of Cannabis as well as a comprehensive and critical summary of Cannabis tissue culture. Special attention will be paid to current challenges faced by researchers, the limitations of existing Cannabis micropropagation studies, and recent developments and future directions of Cannabis tissue culture technologies.

Cannabis is among the oldest human domesticates and has been subjected to intensive artificial (human-mediated) selection throughout history to create a wide array of varieties and biotypes for diverse uses, including fibre, food, biofuel, medicine and drugs. This paper briefly reviews the available literature on the taxonomy, evolutionary origin and domestication of this plant, as well as its worldwide dispersal, in both its wild and cultivated forms. Emphasis is placed on Europe and especially on the Iberian Peninsula. Today, it is accepted that Cannabis is a monospecific genus with two subspecies, C. sativa subsp. sativa and C. sativa subsp. indica, originating in Europe and Asia, respectively, by allopatric differentiation after geographic isolation fostered by Pleistocene glacial-interglacial cycles. Palynological and phylogeographic evidence situates the Cannabis ancestor on the NE Tibetan Plateau during the mid-Oligocene. The timing and place of domestication is still a matter of debate between contrasting views that defend single or multiple Neolithic domestication centres situated in different parts of the Eurasian supercontinent, notably central/southeastern China and the Caucasus region. Recent meta-analyses have suggested that wild Cannabis may have already been spread across Europe in the Pleistocene, and its domestication could have occurred during the European Copper/Bronze ages. According to the available reviews and meta-analyses, pre-anthropic dispersal of Cannabis into the Iberian Peninsula seems to have occurred only in postglacial times, and the earlier signs of cultivation date to the Early Medieval Ages. However, the palynological and archaeological evidence used to date is insufficient for a sound assessment, and the development of thorough Iberian databases to address further meta-analysis is essential for more robust conclusions. Some clues are provided for these achievements to be fulfilled.

Emerging autologous cellular therapies that utilize platelet-rich plasma (PRP) applications have the potential to play adjunctive roles in a variety of regenerative medicine treatment plans. There is a global unmet need for tissue repair strategies to treat musculoskeletal (MSK) and spinal disorders, osteoarthritis (OA), and patients with chronic complex and recalcitrant wounds. PRP therapy is based on the fact that platelet growth factors (PGFs) support the three phases of wound healing and repair cascade (inflammation, proliferation, remodeling). Many different PRP formulations have been evaluated, originating from human, in vitro, and animal studies. However, recommendations from in vitro and animal research often lead to different clinical outcomes because it is difficult to translate non-clinical study outcomes and methodology recommendations to human clinical treatment protocols. In recent years, progress has been made in understanding PRP technology and the concepts for bioformulation, and new research directives and new indications have been suggested. In this review, we will discuss recent developments regarding PRP preparation and composition regarding platelet dosing, leukocyte activities concerning innate and adaptive immunomodulation, serotonin (5-HT) effects and pain killing. Furthermore, we discuss PRP mechanisms related to inflammation and angiogenesis in tissue repair and regenerative processes. Lastly, we will review the effect of certain drugs on PRP activity, and the combination of PRP and rehabilitation protocols.

Gastric cancer is an aggressive disease with increasing global incidence in recent years. Human epidermal growth receptor 2 (HER2) is overexpressed in approximately 10-20% of gastric cancers. The implementation of targeted therapy against HER2 as part of the standard of care treatment in metastatic disease has improved the prognosis of this subset of patients. However, gastric cancer still has high mortality rates and urgently requires new treatment strategies. The combination of immunotherapy with HER2-targeted therapies has shown synergistic effects in preclinical models, being the rationale behind exploring this combination in clinical trials in locally advanced and metastatic settings. Additionally, the irruption of antibody-drug conjugates and other novel HER2-targeted agents has led to the development of numerous clinical trials showing promising results. This review presents the molecular mechanisms supporting the use of HER2-targeted drugs in combination with immunotherapy and provides an overview of the therapeutic scenario of HER2-positive disease. We focus on the role of immunotherapy but also summarize emerging therapies and combinations under clinical research that may change the standard treatment in HER-2 positive disease in the future.

Background: The Liver Imaging Reporting and Data System (LI-RADS) combines standardized terminology with a classification system for imaging findings in patients with HCC, therefore rendering diagnostic biopsy unnecessary in many cases. This retrospective study included 23 patients with a biopsy diagnosis of HCC, performed either before or after local interventional procedures, in order to evaluate the histopathologic changes induced by previous procedures and their potential influence on the response to immune therapy. Material and Methods: The study encompassed a cohort of patients diagnosed with Hepatocellular Carcinoma (HCC). Diagnosis was established through contrast-enhanced computer tomography or magnetic resonance imaging that identified LI-RADS-5 nodules in conjunction with historical liver disease and elevated alpha-fetoprotein (AFP) levels, or through histological examination confirming positivity for glypican3, heat shock protein70, and glutamine synthetase. The study detailed the liver disease etiology, LI-RADS scores, characteristics and dimensions of HCC nodules, serum AFP concentrations, Edmondson-Steiner grading, and the expression of programmed cell death ligand 1 (PD-L1) in the tumor cells. Results: Among the study's cohort of Hepatocellular Carcinoma (HCC) patients, a portion had not received any prior treatments, while the remainder experienced local HCC recurrence following trans-arterial chemoembolization or radiofrequency ablation. Observations indicated elevated alpha-fetoprotein (AFP) levels in those who had not undergone any previous interventions, showing statistical significance. The Edmondson-Steiner classification predominantly identified grade III differentiation across patients, irrespective of their treatment history. Furthermore, an increase in intra-tumoral programmed cell death ligand 1 (PD-L1) expression was noted in patients who had not been subjected to previous therapies. Conclusion: Liver biopsy offers valuable insights for patients with Hepatocellular Carcinoma (HCC), assisting in the tailoring of immune therapy strategies, particularly in cases of recurrence following prior local interventions.

Clusterin (CLU) protein is involved in various pathophysiological processes including carcinogenesis and tumor progression. In recent years, the role of the secretory isoform has been demonstrated in tumor cells, where it inhibits apoptosis and favors the acquisition of resistance to conventional treatments used to treat cancer. To determine the possible therapeutic potential of inhibiting this protein, numerous studies have been carried out in this field. In this paper, we show the existing knowledge on the inhibition of this protein in different types of cancer and discuss the importance it could have in the development of new therapies directed against this pathology.

Sarcopenia is an age-related condition that involves a progressive decline in muscle mass and function, leading to increased risks of falls, frailty, and mortality. Although the exact mechanisms are not fully understood, aging-related processes like inflammation, oxidative stress, reduced mitochondrial capacity, and cell apoptosis contribute to this decline. Disruption of the circadian system with age may initiate these pathways in skeletal muscle, preceding the onset of sarcopenia. At present, there is no pharmacological treatment for sarcopenia, only resistance exercise and proper nutrition may delay its onset. Melatonin, derived from tryptophan, emerges as an exceptional candidate for treating sarcopenia due to its chronobiotic, antioxidant, and anti-inflammatory properties. Its impact on mitochondria, organelle where it is synthesized and crucial in aging skeletal muscle, further highlights its potential. In this review, we discuss the influence of clock genes in muscular aging, with special reference to peripheral clock genes in the skeletal muscle, as well as their relationship with melatonin, which is proposed as a potential therapy against sarcopenia.

Extracellular vesicle (EV) release, which occurs in most eukaryotic cells, has recently been associated with peptidylarginine deiminase (PAD)-driven protein deimination. Evidence points to the involvement of deiminated cytoskeletal proteins and changes in histone deimination. Both PADs and EVs are associated with various pathologies including cancers, autoimmune and neurodegenerative diseases. The elevated PAD expression observed in cancers may contribute to increase in EV shedding observed from cancer cells, contributing to cancer progression. Similarly, elevated PAD expression observed in neurodegenerative diseases may cause increased EV shedding and spread of neurodegenerative EV cargo, contributing to disease progression and pathologies. Pharmacological inhibition of PAD-mediated deimination using pan-PAD inhibitor Cl-amidine, reduced cellular EV release in prostate cancer cells, rendering them significantly more susceptible to chemotherapeutic drugs. Studies on models of central nervous system damage have demonstrated critical functional roles for PADs and neuroprotective effects using PAD inhibitors in vivo, while human neurodegenerative iPSC in vitro models showed evidence of increased protein deimination. Besides using refined PAD inhibitors to selectively manipulate EV biogenesis for novel combination therapies in cancer treatment, we also speculate how EV biogenesis could be targeted via the newly identified PAD-pathway to ameliorate neurodegenerative disease progression.

Melatonin is a ubiquitous molecule found in living organisms, ranging from bacteria to plants and mammals. It possesses various properties, partly due to its robust antioxidant nature and partly owed to its specific interaction with melatonin receptors present in almost all tissues. Melatonin regulates different physiological functions and contributes to the homeostasis of the entire organism. In the human eye, a small amount of melatonin is also present, produced by cells in the anterior segment and the posterior pole, including the retina. In the eye, melatonin may provide antioxidant protection along with regulating physiological functions of ocular tissues, including intraocular pressure (IOP). Therefore, it is conceivable that the exogenous administration of sufficiently high amounts of melatonin to the eye could be beneficial in several instances: for the treatment of eye pathologies like glaucoma, due to the IOP-lowering and neuroprotection effects of melatonin; for the prevention of other dysfunctions, such as dry eye and refractive defects (cataract and myopia) mainly due to its antioxidant properties; for diabetic retinopathy due to its metabolic influence and neuroprotective effects; for macular degeneration due to the antioxidant and neuroprotective properties; and for uveitis, mostly owing to anti-inflammatory and immunomodulatory properties. This paper reviews the scientific evidence supporting the use of melatonin in different ocular districts and provides data suggesting that the topical administration of melatonin as eye drops is a real possibility. This way, its distribution and concentration in different ocular tissues may support its pleiotropic therapeutic effects.

Most commercial Cannabis sativa L. (cannabis) genotypes are short-day plants and cultivators typically use a 12.0 h uninterrupted dark period to induce flowering; however, scientific information is lacking to prove this is the optimal dark period for all genotypes, and cultivar specific photoperiods may increase productivity. Tissue culture can be used for research requiring multiple treatments, proper replication, and in a controlled environment on a smaller scale compared to greenhouse and indoor facilities. To determine whether cannabis explants can flower under varied photoperiods in vitro, explants were grown under one of six photoperiod treatments: 12.0, 13.2, 13.8, 14.4, 15.0, and 16.0 h for four weeks. The percentage of flowering explants was highest under 12.0 and 13.2 h treatments. There were no treatment effects on the fresh weight, final height, or growth index of the explants. The results suggest an uninterrupted dark period of at least 10.8 h (i.e. 13.2 h photoperiod) is needed to induce the flowering of this genotype. In vitro flowering could provide a unique and high throughput approach to study floral/seed development and secondary metabolism in cannabis under highly controlled conditions. Further research should determine if this response is the same on a whole plant level.

Myocardial hypertrophy is the most common condition that accompanies heart changings in children. Transcriptional pathways regulating gene expression playing a critical role both in cardiac embryogenesis and in the pathogenesis of congenital hypertrophic cardiomyopathy, neonatal posthypoxic myocardial hypertrophy and congenital heart diseases. This paper describes the state of cardiac gene expression and potential pharmacological modulators at different transcriptional levels. An experimental model of perinatal cardiac hypoxia showed downregulated expression of genes responsible for cardiac muscle integrity and overexpressed genes associated with energy metabolism and apoptosis, which may provide a basis for a therapeutic approach. Current evidence suggests that RNA drugs, theaflavin, neuraminidase, proton pump and histone deacetylase inhibitors are promising pharmacological agents in progressive cardiac hypertrophy. The different points of application of the above drugs makes combined use possible, potentiating the effects of inhibition in specific signaling pathways. The special role of N-acetyl cysteine in both the inhibition of several signaling pathways and the reduction of oxidative stress was emphasized.

There is a growing interest in the endocannabinoid system and the gut microbiota. Both areas have been suggested to play a role in endometriosis, however this is yet to be studied comprehensively. The purpose of this narrative review is to identify the gaps in endometriosis research in the context of these two areas. It underscores the limited knowledge regarding the involvement of the endocannabinoid system and gut microbiota in endometriosis. Further research in these areas is essential to unlock the therapeutic potential of cannabis and enhance the understanding of endometriosis pathogenesis.

Cannabis is the most widely cultivated, trafficked and abused illicit drug (“WHO | Cannabis,” n.d.; “World Drug Report 2020,” n.d.). In 2018, an estimated 192 million people aged 15-64 years used cannabis for nonmedical purposes globally (Degenhardt et al., 2013). The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 estimated that, across the globe, there were more than 22·1 million people with cannabis dependence (Degenhardt et al., 2018). Moreover, the same study calculated that cannabis dependence could be accounted for 646 thousand Disability Adjusted Life Years, globally. Importantly, cannabis dependence mostly affects young adults (20-24 years), and thus has significant negative impact on the growth and productivity of not only these individuals but also to the societies and nations (Degenhardt et al., 2013). In addition to the dependence syndrome, cannabis use is associated with increased risk of psychosis, cognitive dysfunction, academic problems, and road side accidents (Volkow et al., 2014). A review showed a fairly consistent associations between cannabis use and both lower educational attainment and increased reported use of other illicit drugs (Macleod et al., 2004). In the United States, Cannabis Use Disorder (CUD) is an escalating problem in young adults by legalization (Cerdá et al., 2020) where National Survey on Drug Use and Health reported increased prevalence from 5.1% in 2015 to 5.9% in 2018 in 18-25 year olds (“2019 NSDUH Detailed Tables | CBHSQ Data,” n.d.). The psychoactive effects are due to type 1 cannabinoid receptor (CB1), the cannabinoid binding protein, that are highly expressed in the cerebellar cortex (Marcaggi, 2015). CB1 is primarily found in the molecular layer at the most abundant synapse type in the cerebellum (Marcaggi, 2015) that can shape the spike activity of cerebellar Purkinje cell (Brown et al., 2019). Moreover, granule cell to Purkinje cell synaptic transmission can trigger endocannabinoid release (Alger and Kim, 2011), which may be important for information processing by cerebellar molecular layer interneurons (Dorgans et al., 2019). This suggests that endocannabinoids could be essential to neurocognitive aspects of cerebellar function (Di Marzo et al., 2015)^,(Marcaggi, 2015)^,(Alger and Kim, 2011). Accumulating evidence also suggests cerebellar modulation of the reward circuitry and social behaviour, via direct cerebellar innervation of the ventral tegmental area (VTA) including dopamine cell bodies (A1) in the VTA (Carta et al., 2019). The VTA-dopamine (DA) signalling in the nucleus accumbens (NAc) and the medial prefrontal cortex (mPFC) (Lohani et al., 2019) play a key role in motivatedbehaviours and cognition. Cerebellar neuropathological changes can result in aberrant dopaminergic activity in the NAc and mPFC (ROGERS et al., 2011)^,(Lohani et al., 2019). Therefore, there is a critical need to determine how cerebellum modulate limbic VTA-DA signalling. Cerebellar Non-Invasive Brain Stimulation (NIBS) is postulated to be most relevant in CUD since endocannabinoids are essential to cerebellar function that includes reward-related behaviours, information processing, and cognitive control. (Di Marzo et al., 2015)^,(Marcaggi, 2015)^,(Alger and Kim, 2011). Furthermore, cerebellar NIBS can facilitate training of cognitive control in CUD during a during visual cue reactivity paradigm using a mobile virtual reality (VR) interface that can also allow remote delivery of cerebellar NIBS in conjunction with VR-based cognitive training for home-based intervention. Specifically, transcranial electrical stimulation (tES) can be translatable to low-cost (<$150) mobile devices that can be used in a low resource home-based setting (Carvalho et al., 2018).

Gold nanoparticles have been increasingly used in several electronic, material fabrication, and biomedical applications. Several methods have been reported to prepare gold nanoparticles of various shapes and sizes with different photophysical properties. Although useful to prepare gold nanoparticles, most of the methods are not stable enough and undergo degradation, if stored at room temperatures (up to 30 °C) for a few days. In this paper, we report a novel environmentally friendly method to synthesize self-assembled gold nanoparticles in cruciform shapes by using leaf extract of Cannabis indica as a reducing agent without the aid of any polymers or additional chemicals. The nanoparticles are found to be stable for more than a month when stored at room temperature (30 °C). They were able to form stable conjugates with bovine α-lactalbumin protein that may possess anti-cancerous properties.

Understanding how cannabis affects our heart is like navigating through a maze of conflicting findings. While it's known for its diverse uses, from medicinal to industrial, cannabis also raises red flags regarding its impact on heart health. This review dives into the intricate relationship between cannabis use and cardiovascular well-being, particularly focusing on changes seen in electrocardiogram (ECG) readings, which serve as vital indicators of heart function and rhythm. When someone tokes up, their heart might race temporarily, but chronic cannabis use paints a darker picture, with potential risks of heart attacks and strokes looming on the horizon. The ECG alterations observed in cannabis users, such as irregular heartbeats and unusual wave patterns, hint at disruptions in the heart's normal workings. Furthermore, cannabis has been linked to prolonging the QT interval in the heart's electrical cycle, potentially setting the stage for dangerous arrhythmias. Amidst this mixed bag of effects, some studies even suggest that tiny amounts of THC, the main psychoactive component of cannabis, might lend a helping hand to the heart. However, caution flags are raised, especially for vulnerable groups. While researchers strive to unravel the mysteries of cannabis and the heart, limitations in current studies remind us that we're still far from having all the answers. Moving forward, future investigations should delve deeper into understanding how cannabis tinkers with our heart's inner workings, especially across different demographics. Armed with this knowledge, we can better tailor interventions to safeguard the heart health of cannabis users.

Obesity is treatment-resistant, and is linked with a number of serious, chronic diseases. Adult obesity rates in the United States have tripled since the early 1960s. Recent reviews show that an increased ratio of omega-6 to omega-3 fatty acids contributes to obesity rates by increasing levels of the endocannabinoid signals AEA and 2-AG, overstimulating CB₁R and leading to increased caloric intake, reduced metabolic rates, and weight gain. Cannabis, or THC, also stimulates CB₁R and increases caloric intake during acute exposures. The present meta-analysis reveals significantly reduced body mass index and rates of obesity in Cannabis users, in conjunction with increased caloric intake. We provide for the first time a causative explanation for this paradox, in which rapid and long-lasting downregulation of CB₁R following acute Cannabis consumption reduces energy intake and storage and increases metabolic rates, thus reversing the impact on body mass index of elevated dietary omega-6/omega-3 ratios.

Abstract: Background: With the growing trends in recreational marijuana use, our study aims at analyzing the association between Acute coronary syndromes (ACS) and Ventricular Fibrillation (Vfib) and cannabis use disorder in young adults (18 – 45) Methods: National In-patient Sample was used for population analysis. Probit logistic regression was used for analyzing the associations between diagnosis of ACS/ Vfib and documented cannabis use disorder. Propensity Score matched samples were made from the ACS/Vfib admissions with Cannabis use disorder to analyze the in-hospital outcomes. Results: Statistically significant association was found between admission diagnosis of ACS/ vfib, and documented cannabis use disorder in the study population. The association remained sig-nificant after accounting for potential confounders. Documented race as black, documented di-agnosis of uncontrolled hypertension and diabetes were found to have significant association with admissions for ACS among the population with documented Cannabis use disorder. No difference in mortality were found between ACS admissions with and without documented cannabis use disorder in the propensity matched cohorts. Conclusions: Documented diagnosis of Cannabis use disorder has statistically significant associ-ation with admission diagnosis of ACS/Vfib even after accounting for confounders. Documented race as black, and co existing diagnosis of uncontrolled hypertension and diabetes had significant association with admission diagnosis of ACS in population with documented cannabis use dis-order. Keywords: Cannabis use disorder; ACS; Ventricular fibrillation

The rise in cannabis use has caused significant concerns pharmacy students’ abilities to counsel patients over cannabis. This study aims to understand pharmacy students’ preparedness to counsel patients with cannabis use disorder (CUD) and evaluate the relationship between knowledge, attitudes towards medical cannabis (MC) and recreational cannabis (RC), and behavior intention (BI) to counsel over CUD. A cross-sectional survey was administered to pharmacy students. Descriptive analysis of sample characteristics were assessed with T-test and one-way ANOVA test. Pearson correlation and linear regression were conducted measuring the strength and direction of relationships. The average scores for knowledge, attitudes towards MC use and RC, and BI were 81% (SD 16%), 4.13 (SD 0.75), 3.28 (0.80), and 2.74 (1.00). Significant correlations were observed between knowledge-attitudes toward MC, knowledge-attitudes towards RC, and attitudes towards RC-BIs. Linear regression indicated attitudes towards MC use and RC, academic year, awareness of MC use legality, obtained knowledge, and past patient interaction were significantly associated with BI on confidence in counseling over CUD. There is a gap in students’ BI to counsel. These findings emphasize the importance of a comprehensive curriculum and state policy and practice changes, enabling future pharmacists to address patient needs related to cannabis use confidently.

Cannabis is a flowering plant that has long been used for medicinal, therapeutic, and recreational purposes. Cannabis contains more than 500 different compounds, including a unique class of terpeno-phenolic compounds known as cannabinoids; Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most prevalent cannabinoids and have been associated with the therapeutic and medicinal properties of the cannabis plant. In this paper, continuous flow microwave assisted extraction (MAE) is presented and compared with other methods for commercial cannabis extraction. The practical issues of each extraction method are discussed. The main advantages of MAE are: continuous-flow method which allows for higher volumes of biomass to be processed in less time than existing extraction methods, improved extraction efficiency leading to increased final product yields, improved extract consistency and quality because the process does not require stopping and restarting material flows, and ease of scale-up to industrial scale without the use of pressurised batch vessels. Moreover, due to the flexibility of changing the operation conditions, MAE eliminates additional steps required in most extraction methods, such as biomass decarboxylation, winterisation, which typically adds at least a half day to the extraction process. Another factor that sets MAE apart is the ability to achieve high extraction efficiency even at the industrial scale. Whereas the typical recovery of active compounds using supercritical CO¬2 remains around 70-80%, via MAE up to 95% of the active compounds from cannabis biomass can be recovered at the industrial scale.

Several recent studies have indicated that miR-30a plays critical roles in various biological processes and diseases. However, the mechanism of miR-30a participation in the regulation of idiopathic pulmonary fibrosis (IPF) is ambiguous. Our previous study demonstrated that miR-30a may function as a novel therapeutic target for lung fibrosis by blocking mitochondrial fission, which is dependent on dynamin-related protein-1 (Drp-1). However, the regulatory mechanism between miR-30a and Drp-1 has yet to be investigated. In addition, whether miR-30a can act as a potential therapeutic has not been verified in vivo. In this study, the miR-30a expression in IPF patients was evaluated. Computational analysis and a dual luciferase reporter system assay were used to identify the target gene of miR-30a, and cell transfection was used to confirm this relationship. Ten-eleven translocation 1 (TET1) was validated as a direct target of miR-30a, and the transfection of miR-30a mimic/inhibitor significantly reduced/increased the expression of TET1 protein. Further experiment verified that the interference on TET1(siRNA) could inhibit the hydroxymethlation of the Drp-1 promoter. Finally, miR-30a agomir was designed and applied to identify and validate the therapeutic effect of miR-30a in vivo. Our study demonstrated that miR-30a could inhibit the TET1 expression by base pairing with complementary sites in the 3′ untranslated region to regulate the hydroxymethlation of the Drp-1 promoter. Furthermore, miR-30a could act as a potential therapeutic target for IPF.

Metabolic-associated fatty liver disease (MASLD) is not only associated with traditional cardiovascular risk factors such as T2DM and obesity, but it is also an independent risk factor for the development of cardiovascular disease. MASLD has been shown to be independently related to endothelial dysfunction and atherosclerosis. MASLD is characterized by a chronic proinflammatory response that, in turn, may induce a prothrombotic state. Several mechanisms such as endothelial and platelet dysfunction, changes in the coagulation cascade, decreased fibrinolytic activity can contribute to induce the prothrombotic state. Platelets are players and addresses of metabolic dysregulation; obesity and insulin resistance are related to platelet hyperactivation. Furthermore, platelets can exert a direct effect on liver cells, particularly through the release of mediators from granules. Growing data in literature support the use of antiplatelet agent as a treatment for MASLD. The use of antiplatelets drugs seems to have potential clinical implication for the prevention of HCC patients with MASLD, since platelets contribute to fibrosis progression and cancer development. This review aims to summarize the main data on the role of platelets in the pathogenesis of MAFLD and its main complications such as cardiovascular events and the development of liver fibrosis. Furthermore, we will examine the role of antiplatelet therapy not only in the prevention and treatment of cardiovascular events but also as a possible anti-fibrotic and anti-tumor agent.

Migraine and neuropathic pain (NP) are evocative of painful, disabling, chronic conditions which exhibit resembling symptoms and thus considered to share a common etiology. Calcitonin gene-related peptide (CGRP) has gained credit as a target for migraine management; nevertheless, the efficacy and the applicability of CGRP modifiers warrant search for more effective therapeutic targets for pain management. This scoping review overviews human studies of common pathogenic factors in migraine and NP to explore potential novel therapeutic targets. CGRP causes inflammation in the meninges; monoclonal antibodies and inhibitors target CGRP. Gluta-mate-induced hyperexcitability and subsequent sensitization are closely linked to an alteration of the tryptophan (Trp)-kynurenine (KYN) metabolic system; the Trp-KYN system may serve as a potential target. Microglial overaction is observed in migraine and NP; modifying the microglial activity may be a possible approach. Cytokine-induced inflammation is a leading hypothesis of the pathogenesis of the conditions; alleviating neuroinflammation may complement a pain-relieving armamentarium. Transient receptor potential (TRP) ion channels evoke the release of several substances; TRP ion channels may potentially emerge as new targets. The endocannabinoid system plays a major role in the pain trafficking pathway; modification of the system may open a new path toward discovery of new analgesics. Here we highlight the mechanism of those common pathogenic factors to explore therapeutic targets for innovative pain management in migraine and NP.

Public perception contrasts scientific findings on the depression-related effects of cannabis. However, earlier studies were performed when cannabis was predominantly illegal, its production was mostly uncontrolled, and the idea of medical cannabis was incipient only. We hypothesized that recent changes in attitudes and legislations may have favorably affected research. In addition, publication bias against cannabis may have also decreased. To investigate this hypothesis, we conducted a systematic review of research studies published over the last three years. We found 156 relevant studies. In most cross-sectional studies, depression was higher in those who consumed cannabis than in those who did not. An increase in cannabis consumption was typically followed by an increase in depression, whereas withdrawal from cannabis ameliorated depression in most cases. Albeit medical cannabis reduced depression in most studies, none of these were placebo controlled. In clinical studies published in the same period, placebo also ameliorated depression and in addition, the average effect size of placebo was larger than the average effect size of medical cannabis. We also investigated the plausibility of the antidepressant effects of cannabis by reviewing molecular and pharmacological studies. Taken together, the reviewed findings do not support the antidepressant effects of herbal cannabis.

Products derived from Cannabis sativa have gained increased interest and popularity. As these products become common amongst the public, the heath and potential therapeutic values associated with hemp have become a premier focus of research. While the psychoactive and medicinal properties of Cannabis products have been extensively highlighted in literature, the antibacterial properties of CBD have not been explored in depth. This research serves to examine the antibacterial potential of CBD against Salmonella newington and Salmonella typhimurium. In this study we observed bacterial response to CBD exposure through biological assays, bacterial kinetics, and fluorescence microscopy. Additionally, comparative studies between CBD and ampicillin were conducted against Salmonella typhimurium and Salmonella newington to determine comparative efficacy. Furthermore, we observed potential resistance development of our Salmonella spp. against CBD treatment.

Cannabis Sativa L. has been used for a long time to obtain food, fiber and as a medicinal and psychoactive plant. Today the nutraceutical potential of C. Sativa is being increasingly reappraised; however, C. Sativa roots remain poorly studied, despite citations in the scientific literature. In this direction, we identified and quantified the presence of valuable bioactives (namely β-sitosterol, stigmasterol, campesterol, friedelin and epi-friedelanol) in the root extracts of C. Sativa, a finding which might pave the way to the exploitation of the therapeutic potential of C. Sativa in all its parts. To facilitate roots harvesting and processing, aeroponic (AP) and aeroponic elicited cultures (AEP), have been set up and compared to soil-cultivated plant (SP): interestingly a considerable overgrowth of the plants - particularly of roots - and a significant increase (up to 20 fold in the case of β-sitosterol) in the total content of the above roots’ bioactive molecules have been observed in AP and AEP. In conclusion aeroponics, an easy, standardised, free of contaminant cultivation tecchnique, allows an ease harvesting/processing of roots along with a greater production of their secondary bioactive metabolites which could be utilized in the formulation of health promoting and health care products.

Cannabis use disorder (CUD) is a growing public health concern, with rising prevalence and significant impact on individuals across age groups. This systematic review examined pharmacological and psychosocial interventions for CUD among adolescents, young adults, transitioning adults, and older adults. Database searches were conducted for randomized controlled trials of CUD interventions reporting outcomes such as cannabis use, abstinence, withdrawal symptoms, and treatment retention. In total, 53 studies were included. Pharmacological treatments such as cannabinoid agonists, gabapentin, and N-acetylcysteine demonstrated modest benefits predominantly in alleviating withdrawal and craving. Psychosocial approaches including motivational interviewing, cognitive behavioral therapy, and contingency management conferred greater abstinence and retention, either alone or combined with pharmacotherapy. However, age-specific efficacy remains unclear. Technology-based interventions represent promising alternatives to expand access and improve cost-effectiveness. In conclusion, cannabis disorders require expanded, affordable treatment tailored to individuals’ developmental stage. Further research should clarify the utility of harm reduction outcomes and establish age-specific best practices.

Cannabis, renowned for its historical medicinal use, harbours various bioactive compounds—cannabinoids, terpenes, and flavonoids. While major cannabinoids like THC and CBD have received extensive scrutiny for their pharmacological properties, emerging evidence underscores the collaborative interactions among these constituents, suggesting a collective therapeutic potential. This comprehensive review explores the intricate relationships and synergies between cannabinoids, terpenes, and flavonoids in cannabis. Cannabinoids, pivotal in cannabis's bioactivity, exhibit well-documented analgesic, anti-inflammatory, and neuroprotective effects. Terpenes, aromatic compounds imbuing distinct flavours, not only contribute to cannabis's sensory profile but also modulate cannabinoid effects through diverse molecular mechanisms. Flavonoids, another cannabis component, demonstrate anti-inflammatory, antioxidant, and neuroprotective properties, particularly relevant to neuroinflammation. The entourage hypothesis posits that combined cannabinoid, terpene, and flavonoid action yields synergistic or additive effects, surpassing individual compound efficacy. Recognizing the nuanced interactions is crucial for unravelling cannabis's complete therapeutic potential. Tailoring treatments based on the holistic composition of cannabis strains allows optimization of therapeutic outcomes while minimizing potential side effects. This review underscores the imperative to delve into the intricate roles of cannabinoids, terpenes, and flavonoids, offering promising prospects for innovative therapeutic interventions and advocating continued research to unlock cannabis's full therapeutic potential within the realm of natural plant-based medicine.

Emerging research has revealed a complex bidirectional interaction between the gut microbiome and cannabis. Preclinical studies have demonstrated that the gut microbiota can significantly influence the pharmacological effects of cannabinoids. One notable finding is the ability of the gut microbiota to metabolise cannabinoids, including Δ^9-tetrahydrocannabinol (THC). This metabolic transformation can alter the potency and duration of cannabinoid effects, potentially impacting their efficacy in cancer treatment. Additionally, the capacity of gut microbiota to activate cannabinoid receptors through the production of secondary bile acids underscores its role in directly influencing the pharmacological activity of cannabinoids. While the literature reveals promising avenues for leveraging the gut microbiome-cannabis axis in cancer therapy, several critical considerations must be accounted for. Firstly, the variability in gut microbiota composition among individuals presents a challenge in developing universal treatment strategies. The diversity in gut microbiota may lead to variations in cannabinoid metabolism and treatment responses, emphasising the need for personalised medicine approaches. The growing interest in understanding how the gut microbiome and cannabis may impact cancer has created a demand for up-to-date, comprehensive reviews to inform researchers and healthcare practitioners. This review provides a timely and invaluable resource by synthesizing the most recent research findings and spotlighting emerging trends. A thorough examination of the literature on the interplay between the gut microbiome and cannabis, specifically focusing on their potential implications for cancer, is presented in this review to devise innovative and effective therapeutic strategies for managing cancer.

The increased cultivation of Cannabis sativa L. in North America, represented by high Δ9-tetrahydrocannabinol-containing (high-THC) cannabis genotypes and low THC-containing hemp genotypes, has been impacted by an increasing number of plant pathogens. These include fungi which destroy roots, stems and leaves, in some cases causing a build-up of populations and mycotoxins in the inflorescences that can negatively impact quality. Viroids and viruses have also increased in prevalence and severity and can reduce plant growth and product quality. Rapid diagnosis of the occurrence and spread of these pathogens is critical. Techniques in the area of molecular diagnostics have been applied to study these pathogens in both cannabis and hemp. These include polymerase chain reaction (PCR)-based technologies, including RT-PCR, multiplex RT-PCR, RT-qPCR, and ddPCR, as well as whole genome sequencing (NGS) and bioinformatics. In this study, examples of how these technologies have enhanced the rapidity and sensitivity of pathogen diagnosis on cannabis and hemp will be illustrated. These molecular tools have also enabled studies on the diversity and origins of specific pathogens, specifically viruses and viroids, and these will be illustrated. Comparative studies on the genomics and metabolomics of healthy and diseased plants are urgently needed to provide insight into their impact on quality and composition of cannabis and hemp-derived products. Management of these pathogens will require monitoring of their spread and survival using the appropriate technologies to allow accurate detection, followed by appropriate implementation of disease control measures.

Terpenes and terpenoids content in cannabis plant was already studied in the past with three used methods. Since these works did not compare the content of these substances under the same conditions, we tried to make this comparison exactly. Three different gas chromatography/mass spectrometry (GS/MS) methods - hexane based liquid extraction (Liq), static head-space extraction (HS), and head-space solid phase microextraction (SPME) – were compared to identify volatile compounds in four different cannabis chemotypes - Green fields, Titan chemotype, Black Domina chemotype, and Neptune chemotype. The main compounds focused on were monoterpenes/monoterpenoids and sesquiterpenes/sesquiterpenoids. Extraction with hexane gave comparable results, however the other two methods allowed for the identification of more substances. For the final evaluation of the comparison of the three methods of analysis, extraction with hexane gives comparable results (which is advantageous for quantitative analysis), although the other two methods allowed for the identification of more substances. This means that the same method should be used everywhere for the quantitative evaluation of constituents in cannabis.

De novo regeneration of Cannabis sativa L. (cannabis) using tissue culture techniques remains unreliable and infrequent. Conventional methods for the regeneration and transformation of cannabis have not achieved the reliability and replicability needed to be integrated into research and breeding programs. Protoplast systems are effective for gene expression studies, transformation and genome editing technologies, and opens the possibility of somatic hybridization to create interspecific hybrids. To date, leaf-derived protoplast have been isolated for transient gene expression studies, but attempts at protoplast-to-plant regeneration have not been reported. The present study aims to test the efficacy of using a callus culture system, as an abundant source for protoplast isolation and lays the groundwork for a protoplast-to-plant regeneration system. Using hypocotyl-derived callus cultures, which are known to have relatively greater regenerative potential, the efficacy of protoplast isolation and initial cell division were assessed. In this study, the effect of 2-aminoindane-2-phosphonic acid (AIP) in callus culture media and the effect of subculture frequency on protoplast yield were assessed. This study found that inclusion of AIP at 1 mM resulted in a 334% increase in protoplast yield compared with AIP-free medium, representing the first known use of AIP in cannabis tissue culture. Inclusion of AIP led to a 28% decrease in total soluble phenolics and 52% decrease in tissue browning compared to the control medium. Lastly, a two-phase culture system for protoplast regeneration was tested. At a concentration of 2.0×10^5 protoplasts per mL, division was observed, providing the first know report of cell division from cannabis protoplasts and setting the stage for future development of a protoplast-to-plant regeneration system.

Cannabis (Cannabis sativa L.) stands as a historically significant and culturally important plant, embodying economic, social, and medicinal relevance for human societies. However, years of prohibition and stigmatization have hindered the cannabis research community, which is hugely undersized and suffers from a scarcity of understanding of cannabis genetics and how key traits are expressed or inherited. In this study, we conducted a comprehensive phenotypic characteriza-tion of 176 drug-type cannabis accessions, representative of Canada's legal market. We assessed germination methods, evaluated various traits including agronomic, morphological, and canna-binoid profiles, and uncovered significant variation within this population. Notably, yield dis-played a negative correlations with maturity-related traits but positive correlation with fresh biomass. Additionally, the potential THC content showed positive correlation with maturi-ty-related traits but negative correlation with yield. Significant different were observed between plants derived from regular female seeds and feminized seeds, as well as between plants derived from cuttings and seeds for different traits. This study advances our understanding of cannabis cultivation, offering insights into germination practices, agronomic traits, morphological charac-teristics, and biochemical diversity. These findings establish a foundation for precise breeding and cultivar development, enhancing cannabis's potential in the legal market.

The literature on substance use usually extracts conclusions from data with correlational methods. Our study shows the usefulness of complementing ordered logistic regression (OLR) and fuzzy set qualitative comparative analysis (fsQCA) to assess factors inducing cannabis consumption in a sample of 1,935 teenagers. OLR showed a significant influence of gender (odd ratio (OR) =0.383, p<0.0001), parental monitoring (OR=0.587, p=0.0201); religiousness (OR=0.476, p=0.006); parental tolerance to substance use (OR=42.01, p<0.0001) and having close peers that consume substances (OR=5.60, p<0.0001). FsQCA has allowed fitting linkages between factors from a complementary perspective. (1) Coverage (cov) and consistency (cons) attained by solutions explaining use (cons=0.808, cov=0.357) are clearly lower than by recipes of non-use (cons=0.952, cov=0.869) (2) The interaction of gender, a tolerant family to use and the attitude toward substances by peers is very consistent to explain cannabis use. (3) The most important recipe explaining resistance to cannabis is simply parental disagreement with substance consumption (cons=0.956, cov=0.861) (4) Factors as gender, religiosity, parental monitoring and age show also a relevant impact on attitude toward cannabis use. However, whereas some of them impact symmetrically on use and non-use this does not follow in factors such as parental monitoring or age.

Acute exposure to cannabis has been associated with an array of cognitive alterations, increased risk for neuropsychiatric illness, and other neuropsychiatric sequelae including the emergence of acute psychotic symptoms. However, the brain alterations associating cannabis use and these behavioral and clinical phenotypes remains disputed. To this end, neuroimaging can be a powerful technique to non-invasively study the impact of cannabis exposure on brain structure and function in both humans and animal models. While chronic exposure studies provide insight into how use may be related to long-term outcomes, acute exposure may reveal interesting information regarding the immediate impact of use and abuse on brain circuits. Understanding these alterations could reveal the connection with symptom dimensions in neuropsychiatric disorders and, more specifically with psychosis. The purpose of the present review is to: 1) provide an update on the findings of pharmacological neuroimaging studies examining the effects of administered cannabinoids and 2) focus the discussion on studies that examine the sensitive window for the emergence of psychosis. Current literature indicates that cannabis exposure has varied effects on the brain, with the principal compounds in cannabis (delta-9-tetrahydrocannabinol and cannabidiol) altering activity across different brain regions. Importantly, we also discorvered critical gaps in the literature, particularly regarding sex-dependent responses and long-term effects of chronic exposure. Certain networks often characterized as dysregulated in psychosis, like the default mode network and limbic system, were also impacted by THC exposure, identifying areas of particular interest for future work investigating the potential relationship between the two.

Hypertensive disorders of pregnancy (HDP), including preeclampsia (PE) and gestational hypertension (GH), are major causes of maternal and fetal morbidity and mortality. This review elucidates the role of regulatory T cells (Tregs) in the immunological aspects of HDP and explores their therapeutic potential. Tregs, known for maintaining immune tolerance, are crucial in pregnancy to prevent immune-mediated rejection of the fetus. In HDP, Treg numbers and function imbalance are observed, correlating with disease severity. The review highlights that Tregs contribute to immunological adaptation in normal pregnancy, ensuring fetal acceptance and placental development. In contrast, HDP is associated with Treg dysfunction, marked by decreased numbers and impaired regulatory capacity, leading to inadequate immune tolerance and abnormal placental development. This dysfunction is particularly evident in PE, where Tregs fail to adequately modulate the maternal immune response against fetal antigens, contributing to the pathophysiology of the disorder. Therapeutic interventions aiming to modulate Treg activity represent a promising avenue for HDP management. Studies in animal models and limited clinical trials suggest that enhancing Treg functionality could mitigate HDP symptoms and improve pregnancy outcomes. However, the review acknowledges the complexity of translating these findings into effective clinical therapies, given the multifactorial nature of HDP and the intricate regulatory mechanisms of Tregs. In conclusion, while the precise role of Tregs in HDP is still being unravelled, their central role in immune regulation during pregnancy is indisputable. Further research is needed to fully understand the mechanisms by which Tregs contribute to HDP and to develop targeted therapies that can safely and effectively harness their regulatory potential for treating hypertensive diseases of pregnancy.

Proprotein convertase subtilisin/Kexin type 9 (PCSK9) is a proteolytic enzyme that indirectly regulates serum LDL cholesterol by destroying LDL receptors. In clinical studies, the main role of the proprotein convertase subtilisin/Kexin type9 (PCSK9) inhibitor in cholesterol regulation was elucidated. It is produced in the liver but is also present in the kidney and intestine. It prevents HMGCo from synthesizing cholesterol. SREBP-2 is a reductase that is induced by statins. In a dose-dependent manner, increasing SREBP-2 levels enhanced LDL-R and PCSK9 gene expression. At the minimum, two procedures have been developed to overcome the plasma level of PCSK9. This is the LDLR test, polyclonal antibodies, and sentience oligonucleotide. Lower dosage statin treatment with a proprotein convertase subtilisin/Kexin type9 inhibitor will be most efficient in lowering LDL and avoiding statin adverse effects. In multiple long-term trials, statins have been found to reduce cardiovascular mortality by 30% and stroke incidence by 20%. In this way, we conclude the role of PCSK9 in hypercholesterolemia.

Cannabis has developed into a multi-billion dollar industry that relies on clonal propagation of elite genetics with desirable agronomic and chemical phenotypes. While the goal of clonal propagation is to produce genetically uniform plants, somatic mutations can accumulate during growth and compromise long-term genetic fidelity. Cryopreservation is a process in which tissues are stored at cryogenic temperatures, halting cell division and metabolic processes to facilitate high fidelity germplasm preservation. In this study, a series of experiments were conducted to optimize various stages of cryopreservation and develop a protocol for long-term germplasm storage of Cannabis sativa. The resulting protocol uses a standard vitrification procedure to cryopreserve nodal explants from in vitro shoots as follows: Nodes were cultured for 17 hours in a pre-culture solution (PCS), followed by a 20 minute treatment in a loading solution (LS), and a 60 minute incubation in plant vitrification solution 2 (PVS2). The nodes were then flash frozen in liquid nitrogen, re-warmed in an unloading solution at 40°C, and cultured on basal MS culture medium in the dark for 5 days followed by transfer to standard culture conditions. This protocol was tested across 13 genotypes to assess the genotypic variability. The protocol was successful across all 13 genotypes, but significant variation was observed in tissue survival (43.3-80%) and regrowth of shoots (26.7-66.7%). Plants grown from cryopreserved samples were morphologically and chemically similar to control plants for most major traits, but some differences were observed in the minor cannabinoid and terpene profiles. While further improvements are likely possible, this study provides a functional cryopreservation system that works across multiple commercial genotypes for long-term germplasm preservation.

Since the recent legalization of medical and recreational use of cannabis (Cannabis sativa L.) in many regions worldwide, there has been high demand for research to improve yield and quality. With the paucity of scientific literature on the topic, this study investigated the relationships between light intensity (LI) and photosynthesis, inflorescence yield, and inflorescence quality of cannabis grown in an indoor environment. After growing vegetatively for 2 weeks under a canopy-level photosynthetic photon flux density (PPFD) of ≈ 425 μmol·m-2·s-1 and an 18-h light/6-h dark photoperiod, plants were grown for 12 weeks in a 12-h light/12-h dark ‘flowering’ photoperiod under canopy-level PPFDs ranging from 120 to 1800 μmol·m-2·s-1 provided by light emitting diodes. Leaf light response curves varied both with localized (i.e., leaf-level) PPFD and temporally, throughout the flowering cycle. Therefore, it was concluded that the leaf light response is not a reliable predictor of whole- plant responses to LI, particularly crop yield. This may be especially evident given that dry inflorescence yield increased linearly with increasing canopy-level PPFD up to 1800 μmol·m-2·s-1, while leaf-level photosynthesis saturated well below 1800 μmol·m-2·s-1. The density of the apical inflorescence and harvest index also increased linearly with increasing LI, resulting in higher-quality marketable tissues and less superfluous tissue to dispose of. There were no LI treatment effects on cannabinoid potency, while there were minor LI treatment effects on terpene potency. Commercial cannabis growers can use these light response models to determine the optimum LI for their production environment to achieve the best economic return; balancing input costs with the commercial value of their cannabis products.

Plants, including Cannabis (Cannabis sativa subsp. sativa) host distinct beneficial microbial communities on and inside their tissues, designated the plant microbiota from the moment that they are planted into the soil as seed. They contribute to plant growth promotion, facilitating mineral nutrient uptake, inducing defense resistance against pathogens, higher yield and modulating plant secondary metabolites. Understanding the microbial partnerships with Cannabis has the potential to affect agricultural practices by improving plant fitness and the production yield of cannabinoids. Much less is known about this beneficial Cannabis-microbe partnership, and the complex relationship between the endogenous microbes associated with various tissues of the plant, particularly, the role that cannabis may play in supporting or enhancing them. This review will focus on Cannabis microbiota studies and the effect of endophytes on the elicitation of secondary metabolites production in Cannabis plants. The aim of this review is to shed light on the importance of Cannabis microbiome and how cannabinoid compounds concentration can be stimulated through symbiotic and or mutualistic relationships with endophytes.

Indole is a versatile pharmacophore widely distributed in bioactive natural products. This privileged scaffold has been found in a variety of molecules isolated from marine organisms such as algae and sponges. Among these, indole alkaloids represent one of the biggest, most promising family of compounds, having shown a wide range of pharmacological properties, including anti-inflammatory, antiviral and anticancer activities. The aim of this review is to show the current scenario of marine indole alkaloid derivatives, covering not only the most common chemical structures, but also new synthetic routes developed during the last years as well as promising therapeutic applications.

In the recent years, Cannabis and hemp-based products have become increasingly popular for various applications ranging from recreational use, edibles, beverages to health care products and medicines. The rapid detection and differentiation of phytocannabinoids is, therefore, essential to assess the potency, therapeutic and nutritional values of cannabis cultivars. Here, we implemented the SpiderMass technology for the in vivo detection of cannabidiol acid (CBDA) and tetrahydrocannabinol acid (THCA) and other endogenous organic plant compounds to access distribution gradients within the plants and differentiate cultivars. The SpiderMass system is composed of an IR- laser handheld microsampling probe connected to the mass spectrometer through a transfer tube. The analysis was performed in situ on different plant organs from freshly cultivated Cannabis plants in only a few seconds. SpiderMass analysis easily discriminated the two acid phytocannabinoid isomers by MS/MS and the built statistical models differentiated between four Cannabis cultivars. Different abundancies of acid phytocannabinoids were also found along the plant as well as between different cultivars. All together, these results introduce the direct analysis by SpiderMass as a compelling analytical alternative for forensic and hemp industrial analysis.

New generation antibiotics are needed to combat the development of resistance to antimicrobials. One of the most promising new classes of antibiotics is cannabidiol (CBD). It is a non-toxic and low-resistance chemical that can be used to treat bacterial infections. The antibacterial activity of Cannabis sativa L. byproducts, specifically CBD, has been of growing interest in the field of novel therapeutics. As research continues to define and characterize the antibacterial activity that CBD possesses against a wide variety of bacterial species it is important to examine potential interaction between CBD and common therapeutics such as broad-spectrum antibiotics. Here, we show that CBD-antibiotic co-therapy can effectively fight S. typhimurium via membrane integrity disruption. This research serves to examine the potential synergy between CBD and three broad-spectrum antibiotics for potential antibiotic-CBD co-therapy. In this study, we reveal that Salmonella typhimurium (S. typhimurium) growth is inhibited at very low dosages of CBD-antibiotic. This interesting finding demonstrates that CBD and CBD-antibiotic co-therapies are viable novel alternatives to combating Salmonella typhimurium.

Most neurodegenerative diseases, including Alzheimer's disease, ischemic stroke, subarachnoid hemorrhage, and intracerebral hemorrhage are associated with inflammation. Tumor necrosis factor (TNF) is a pleiotropic pro-inflammatory cytokine that regulates cerebral infarction in stroke pathology, and its action is influenced by the bioavailability of its membrane-bound receptors, TNFR1 and TNFR2, and microglial activation. During the initial onset of these diseases, the soluble variant of the cytokine presents with prolonged and excessive activation of TNFR1, resulting in cell death and long-term neurological impairments. Therapeutic interventions for neurodegenerative diseases have targeted TNF to limit the onset of neuroinflammation. First-generation therapeutics have been demonstrated to inhibit membrane-bound TNF to TNFR2 receptor binding, resulting in severe side effects such as infections and cancer. As such, second-generation drugs, including XPro1595, have been developed to selectively inhibit soluble TNF and impede the effects of TNFR1 while still allowing for TNFR2 activation. Early results in murine TBI models demonstrate reduced glial reactivity by 50%, reduced dendritic degeneration by 30%, increased plasticity by 15%, and improved functional outcomes by 20% post-TBI. This scoping review of TNF receptors in various neurodegenerative diseases seeks to evaluate current and future therapeutic strategies as well as highlight potential strategies to eliminate confounding variables present in the current literature.

Affinity reagents, or target-binding molecules, are quite versatile and are major workhorses in molecular biology and medicine. Antibodies are the most famous and frequently used type and they have been used for a wide range of applications, including laboratory techniques, diagnostics, and therapeutics. However, antibodies are not the only available affinity reagents and they do have significant drawbacks, including laborious and costly production. Aptamers are one potential alternative that have a variety of unique advantages. They are single stranded DNA or RNA molecules that can be selected for binding to many targets including proteins, carbohydrates, and small molecules – for which antibodies typically have low affinity. There are also a variety of cost-effective methods for producing and modifying nucleic acids in vitro without cells, whereas antibodies typically require cells or even whole animals. While there are also significant drawbacks to using aptamers in therapeutic applications, including low in vivo stability, aptamers have had success in clinical trials for treating a variety of diseases and two aptamer-based drugs have gained FDA approval. Aptamer development is still ongoing, which could lead to additional applications of aptamer therapeutics, including antitoxins, and combinatorial approaches with nanoparticles and other nucleic acid therapeutics that could improve efficacy.

The aim of our study was to evaluate the impact of T. gondii status on eosinophils count (PNE), eosinophil to lymphocyte ratio (ELR) and eosinophil to neutrophil to lymphocytes ratio (ENLR) before and after can-nabis cessation in patients with psychiatric disorders. One hundred and eighty-eight patients were includ-ed in the study. T. gondii, PNE, ELR, ENLR, and urinary cannabis were measured at baseline and after 4 weeks of cannabis cessation. Highest PNE (p = .02), ELR (p = .03) and ENLR levels (p = .031) and highest increase of PNE (p = .044), and ENLR (p = .036) levels were found in patients after cannabis cessation only in the Toxo+ group. At four weeks, significant interactions between cannabis and T. gondii status for PNE (p = .038), and for ENLR (p = .043) levels were found, as well as for the evolution between baseline and 4 weeks for ENLR level (p = .049). After cannabis cessation, we found a positive correlation between negative symptoms and PNE levels at 4 weeks in the Toxo+ group. This study shows that the increase of inflammation after cannabis cessation might be modulated by T. gondii seropositivity status in patient after cannabis cessation.

Background: Most modern studies about human marijuana use have been made under a set of arbitrary cultural standards and policies not related to drug harm potential, loosely called Prohibition. Here we asked if potential health hazards generated by Prohibition are addressed in research design and analysis. Methods: For this, we have searched PubMed database (from inception to December 2017) for citations of prevalent contaminants of illegal street cannabis: fungi and pesticides. In addition, we performed full text evaluation of 23 studies selected from, and including, 2 meta-analysis reviews investigating potential health hazards from cannabis use. Results: Different combinations of the keywords cannabis, prohibition, pesticides, fungi, contaminants, cancer, schizophrenia, psychosis, show that these words coincide in less than 1% of the cannabis human studies within the database. In the scope of 141 abstracts in which the terms, cannabis and pesticides coincide, none is directed to distinguish cannabis and pesticide adverse effects on CNS. A similar picture emerges when fungi is the paired word. Full text evaluation shows that all but one of the studies analyzed, completely neglect or comment on the nature of cannabis source, legal status, or contamination as a confounding factor. Discussion: Our results show a potential bias on scientific investigation that may affect data reliability in informing about the health hazards of cannabis use. This finding suggests that other aspects of the Prohibition environment may also go unacknowledged. Conclusion: Prohibition related health risks usually go unacknowledged and unaccounted for in biomedical research on Cannabis.

Mental healthcare conditions in India are severely deficient, particularly concerning the living conditions of patients. Post-treatment, numerous individuals with mental illness are abandoned by their families, who may lack the willingness or financial means to care for them. These recovered patients often experience setbacks due to the absence of facilities aimed at developing the skills necessary for reintegrating into society. The lack of separate accommodations for recovered individuals forces them to reside with other patients, worsening their condition. The government is struggling to accommodate and finance the care of recovered patients, affecting those in need of treatment as hospital bed space becomes overwhelmed by the increasing number of cured individuals. Therefore, there is an urgent need for halfway homes. These facilities offer a range of services, including social, medical, psychological, and educational support, alongside housing. The term "halfway houses" reflects their position between fully independent living and highly regulated in-patient or correctional facilities. Following treatment, many patients experience abandonment by their families or encounter difficulties returning home due to memory loss. Recovered patients often live in confined spaces, lacking essential social skills. Therefore, establishing a workspace focused on teaching social and other necessary skills before reintegrating them into society would be a beneficial approach. This would provide a structured environment for individuals who have spent significant time in seclusion, assisting them in developing the skills needed to navigate societal challenges effectively. Recent reports indicate that over 2,000 cured patients are still housed in mental hospitals across the country, according to the NHRC. The NHRC has raised concerns about the situation, noting that all 46 Government Mental Healthcare Institutions in India display very poor and inhumane treatment of patients, leading to the issuance of notices. NHRC visits have revealed deplorable conditions in all 46 mental institutes across the country.

Intratumoral immune cytolytic activity (CYT), measured as the geometric mean of the expression of Granzyme-A (GZMA) and Perforin-1 (PRF1), has emerged as a critical factor in cancer immunotherapy, with significant implications for patient prognosis and treatment outcomes. Here, we review how different immune checkpoint pathways, the composition of Tumor Microenvironment (TME), antigen presentation and metabolic pathways, all regulate CYT. We also discuss the various methods through which CYT can be assessed. The detection and analysis of tumor-infiltrating lymphocytes using flow cytometry or immunohistochemistry provide important information on the immune cell populations within the TME. Gene expression profiling and spatial analysis techniques, such as multiplex immunofluorescence and imaging mass cytometry, allow researchers to study CYT in the context of the TME. We further report the significant clinical implications that CYT has, as its increased levels are associated with positive clinical outcomes and a favorable prognosis. Moreover, CYT can be used as a prognostic biomarker and aid in patient stratification. Measuring CYT through different methods offers promising paths for improving treatment responses. Overall, we highlight that the understanding and modulation of CYT levels is critical for improving cancer immunotherapy. Research into CYT and the factors that influence it has the potential to transform cancer treatment and improve patient outcomes.

Cordycepin has good antitumor activity, but its clinical application is limited due to the easy deamination of N6 in structure. In this study, a large lipopolysis group was introduced at the cordycepin N6 to improve the problem, Cordycepin derivatives(3a-4c) were synthesized, and biological evaluation of compounds were studied. In the study, the vitro antitumor activity of the compounds against MCF7 cells, HepG2 cells and SGC-7901 cells was evaluated by MTT assay. In the results, compound 4a showed the most obvious inhibitory effect on MCF7 cells with IC50 value of 27.566±0.52 μM, which was much lower than cordycepin. Compound 4a showed high selectivity between MCF7 and normal MCF-10A cells. Further biological evaluation showed that compound 4a promoted apoptosis and blocked the cell cycle in G0/G1 phase. Then, Western Blot was used to detect related apoptotic proteins. It was found that Compound 4a could down-regulate the expression of Bcl-2 protein and up-regulate the expression of p53, Bax, Caspase-3, and Caspase-9 proteins. The mitochondrial membrane potential decreased continuously and the positive expression rate decreased. It was speculated that compound 4a induced the apoptosis of MCF7 cells through the mitochondrial pathway.

The perturbation in water balance rather than any change in salt content is the main cause of hyponatremia, the most frequent electrolyte abnormality defined as serum sodium concentration <135 mEq/L. Hyponatremia may be divided as mild (Na>120 mEq/L) or severe (Na<120 mEq/L) hyponatremia, most frequently observed in elderly ICU hospitalized patients. Based on tonicity hyponatremia may be hypotonic (decreased concentration of solute), isotonic, and hypertonic (falsely low sodium). According to the volume of the extracellular fluid (ECF) hyponatremia is further divided as hypovolemic, euvolemic, or hypervolemic hyponatremia. Finally, hyponatremia may develop rapidly as acute (<48 h) with usually severe symptoms, or slowly as chronic hyponatremia, being usually asymptomatic or with mild symptoms. Patient’s medical history and clinical symptoms and signs could point to a certain diagnostic direction. Acute severe hyponatremia is presented with headaches, vomiting, nausea, fatigue, impaired cognition, gait with increased falls symptoms etc., while the severe symptomatology due to hyponatremic encephalopathy is presented as confusion, agitation, seizures, or even coma and death. Nevertheless, an urgent evaluation of the volume and neurological status is essential for prevention of neurological damages. The treatment of hyponatremia should of course be based on the underlying cause, the duration and degree of hyponatremia, the observed symptoms, and volume status of patient.

Since the 1980s, a growing interest in goat milk was noticed due to the nutritional values and health benefits of this milk, which resulted in increasing goat populations and milk production worldwide. This comprehensive review elaborates on goat milk composition compared to other types of milk. It is also an overview of goat milk production, properties, nourishment-value, applications in dairy products, and potential health benefits. Goat milk composition and its characteristics are slightly different from other types of milk and can be utilized to manufacture many dairy products. Fresh goat milk and goat milk products (e.g., yogurt and kefir were found to provide various potential health benefits, such as anti-inflammatory, prevent cardiovascular disease, anti-diabetic and antihypertensive, strengthen bones, boost immunity, and improve metabolism.

The concerning worldwide increase of obesity and chronic metabolic diseases such as T2D, dyslipidemia, and cardiovascular disease motivates further investigations into preventive and alternative therapeutic approaches. Over the past decade, there is growing evidence that the formation and activation of thermogenic adipocytes (brown and beige) may serve as therapy to treat obesity and its associated diseases owing to its capacity to increase energy expenditure and to modulate circulating lipids and glucose levels. Thus, understanding the molecular mechanism of brown and beige adipocytes formation and activation will facilitate the development of strategies to combat metabolic disorders. Here, we provide a comprehensive overview of pathways and players involved in the development of brown and beige fat as well as the role of thermogenic adipocytes in energy homeostasis and metabolism. Also, we discuss the alterations in brown and beige adipose tissue function during obesity and, explore the therapeutic potential of thermogenic activation to treat metabolic syndrome.

Obesity and chronic low-grade inflammation are becoming global epidemics. The dysbiosis has a specific role in the metabolism and energy stocks of the host. The discovery that a low-grade of inflammation could be directly connected to the intestinal microbiota metabolic endotoxemia (elevated levels of plasma lipopolysaccharides) has allowed the identification of novel mechanisms involved in the control of the intestinal barrier. In this review, it will analyze the latest news to explain how human symbiotic microorganisms participate in the growth of the fat reserves and promote insulin resistance as a low-grade inflammation. Besides, it will discuss new treatments with probiotics and prebiotics as a promising therapeutic approach to reverse the host's metabolic changes linked to dysbiosis observed in obesity.

Cancer being a multi-factorial disease, a multi-target approach is needed to treat it with minimal side-effects. Therefore, combined use of a proven herbal formula with chemo-therapy could be the better therapeutic. It may maintain homeostasis by synergistically targeting multiple signaling pathways involved in tumorigenesis, thus circumventing recurrence, resistance, and immunosuppression. Here we aim to determine the effectiveness and safety of an FDA-approved herbal formula, SR033 in combination with 5-fluorouracil (5FU) and paclitaxel (PTX). We report chemo-sensitization and chemo-synergy in HeLa and MCF-7 cell lines, immunomodulation of COX-2, PD-L1, VEGF and TGFβ and overall survival in-vitro and in-vivo via oral and topical delivery of SR033. In-vitro, SR033/5FU significantly reverses 5FU and PTX-resistance, lower COX-2, and PD-L1, resulting in TGFβ/ VEGF axis modulation. Furthermore, the study suggests that due to anti-oxidative potential of SR033, oral administration exerts chemo-preventive activity and restores cellular compartment in solid tumor and ascites-bearing mice models. Furthermore, the topical application, SR033L with low-dose 5FU increases survival rate, reduces tumor growth, and completely restores local and peripheral neutrophil-lymphocyte ratio in solid tumor mice model. The study indicates that SR033 could be a strong candidate in combination with low-dose 5FU and PTX for a holistic approach to cancer management.

Transdermal drug delivery systems (TDDS) are designed to administer a consistent and effective dose of medication through the patient's skin. These pharmaceutical preparations are self-contained, discrete dosage forms designed to be placed topically on intact skin to release the active component at a controlled rate by penetrating the skin barriers. This medication provides a continuous and prolonged administration of a substance at a consistent rate. TDDS, or transdermal drug delivery system, has gained significant attention as a non-invasive method of administering drugs to vulnerable patient populations, such as pediatric and geriatric patients. This approach is considered easy to administer and helps overcome bioavailability issues associated with conventional drug delivery, which can be hindered by poor absorption and metabolism. TDDS has various advantages compared to conventional methods of drug administration. It is less intrusive, more patient-friendly, and can circumvent first-pass metabolism and the corrosive acidic environment of the stomach that happens when medications are taken orally. Multiple methodologies have been devised to augment the transdermal permeability of diverse pharmaceutical substances. Recent advancements in transdermal drug delivery systems have facilitated the precise delivery of medications to the intended site of action by improving the penetration of drugs through the outermost layer of the skin, known as the stratum corneum, resulting in enhanced drug availability throughout the body. This review seeks to provide a concise overview of the several methods employed in the production of TDDS, as well as their evaluation, therapeutic uses, clinical considerations, and current advancements. These advancements have resulted in the development of intelligent, biodegradable, and highly efficient transdermal drug delivery systems.

Vascular cell adhesion molecule-1 (VCAM-1) is closely associated with tumor progression and metastasis. However, the relevance and role of VCAM-1 in lung cancer have not been clearly elucidated. In this study, we found that VCAM-1 was highly overexpressed in lung cancer tissue compared with that of normal lung, and high VCAM-1 expression correlated with poor survival of lung cancer patients. VCAM-1 knockdown reduced invasion in A549 human lung cancer cells, and competitive blocking experiments targeting the Ig-like domain 6 of VCAM-1 (VCAM-1-D6) demonstrated that the VCAM-1-D6 domain was critical for VCAM-1-mediated A549 cell invasion. Next, we developed a human monoclonal antibody specific to human and mouse VCAM-1-D6 (VCAM-1-D6 huMab), which was isolated from a human synthetic antibody library using phage display technology. Finally, we showed that VCAM-1-D6 huMab had a nanomolar affinity for VCAM-1-D6 and that it potently suppressed invasion in A549 and NCI-H1299 lung cancer cell lines. Taken together, these results suggest that VCAM-1-D6 is a novel therapeutic target in VCAM-1-mediated lung cancer invasion and that our newly developed VCAM-1-D6 huMab will be a useful tool for inhibiting VCAM-1-expressing lung cancer cell invasion.

Considering the harmful effects of cannabis on individuals with a severe mental disorder and the limited effectiveness of current interventions, this case report showcases the beneficial results of a 10-session Avatar intervention for cannabis use disorder (CUD) on a polysubstance user with a comorbid schizoaffective disorder. Virtual reality allowed the creation of an Avatar representing a person significantly related to the patient’s drug use. Avatar intervention for CUD aims to combine exposure, relational, and cognitive behavioral therapies while practicing real-life situations and learning how to manage negative emotions and cravings. Throughout therapy and later on, Mr. C managed to maintain abstinence from all substances. Also, an improvement in the severity of CUD as well as a greater motivation to change consumption, were observed after therapy. As observed by his mother, his psychiatrist, and himself, the benefits of Avatar intervention for CUD extended to other spheres of his life. The drastic results observed in this patient could be promising as an alternative to the current treatment available for people with a dual diagnosis of cannabis use disorder and psychotic disorder, which generally lack effectiveness. A single-blind randomized control trial comparing the treatment with a classical intervention in a larger sample is currently underway to evaluate whether the results are reproducible on a larger sample.

Currently, there are no pharmacological treatments able to reverse nigral degeneration in Parkinson’s disease (PD), hence the unmet need for the provision of neuroprotective agents. Cannabis-derived phytocannabinoids (CDCs) and resveratrol (RSV) may be useful neuroprotective agents for PD due to their anti-oxidative and anti-inflammatory properties. To evaluate this, we undertook a systematic review of the scientific literature to assess the neuroprotective effects of CDCs and RSV treatments in pre-clinical in vivo animal models of PD. The literature databases MEDLINE, EMBASE, PsychINFO, PubMed and Web of Science core collection were systematically searched to cover relevant studies. A total of 1034 publications were analyzed, of which 18 met the eligibility criteria for this review. Collectively, the majority of neurotoxin-induced PD rodent studies demonstrated that treatment with CDCs or RSV produced a significant improvement in motor function and mitigated the loss of dopaminergic neurons. Biochemical analysis of rodent brain tissue suggested that neuroprotection was mediated by anti-oxidative, anti-inflammatory, and anti-apoptotic mechanisms. This review highlights the neuroprotective potential of CDCs and RSV for in vivo models of PD, and therefore suggests their potential translation to human clinical trials to either ameliorate PD progression and/or be implemented as a prophylactic means to reduce the risk of development of PD.

It is commonly believed that exposing Cannabis sativa (cannabis) plants to ultraviolet (UV) radiation can enhance Δ⁹-tetrahydrocannabinol (Δ⁹-THC) concentrations in female inflorescences and associated foliar tissues. However, a lack of published scientific studies has left knowledge-gaps in the effects of UV on cannabis that must be elucidated before UV can be utilized as a horticultural management tool in commercial cannabis production. In this study we investigated the effects of UV exposure level on photosynthesis, growth, inflorescence yield, and secondary metabolite composition of two indoor-grown cannabis cultivars: ‘Low Tide’ (LT) and ‘Breaking Wave’ (BW). After growing vegetatively for 2 weeks under a canopy-level photosynthetic photon flux density (PPFD) of ≈225 μmol·m^–2·s^–1 in an 18-h light/6-h dark photoperiod, plants were grown for 9 weeks in a 12-h light/12-h dark “flowering” photoperiod under a canopy-level PPFD of ≈400 µmol·m^–2·s^–1 and 3.5 h·d^–1 of supplemental UV radiation with UV photon flux densities (UV-PFD) ranging from 0.01 to 0.8 μmol·m^–2·s^–1 provided by light-emitting diodes (LEDs) with a peak wavelength of 287 nm (i.e., biologically-effective UV doses of 0.16 to 13 kJ·m^–2·d^–1). The severity of UV-induced morphology (e.g., whole-plant size and leaf size reductions, leaf malformations, and stigma browning) and physiology (e.g., reduced leaf photosynthetic rate and reduced F_v/F_m) symptoms worsened as UV exposure level increased. While the proportion of dry inflorescence yield that was derived from apical tissues decreased in both cultivars with increasing UV exposure level, total dry inflorescence yield only decreased in LT. The equivalent Δ⁹-THC and cannabidiol (CBD) concentrations also decreased in LT inflorescences with increasing UV exposure level. While the total terpene content in inflorescences decreased with increasing UV exposure level in both cultivars, the relative concentrations of individual terpenes varied by cultivar. The potential for using UV to enhance cannabis quality must still be confirmed before it can be used as a production tool for modern, indoor-grown cannabis cultivars.

DKA represents an acute, severe complication of relative insulin deficiency and a common presentation of Type 1 Diabetes Mellitus (T1DM) primarily and, occasionally, T2DM in children and adolescents. It is characterized by the biochemical triad of hyperglycaemia, ketonaemia and/or ketonuria, and acidaemia. Clinical symptoms include dehydration, tachypnoea, gastrointestinal symptoms, and reduced level of consciousness, precipitated by a variably long period of polyuria, polydipsia and weight loss. The present review aims to summarize potential pitfalls in the diagnosis and management of DKA. A literature review was conducted using the Pubmed/Medline databases including articles published from 2000 onwards. Diagnostic challenges include differentiating between T1DM and T2DM, DKA and hyperosmolar hyperglycaemic state (HHS), or between DKA and alternative diagnoses presenting with overlapping symptoms, such as pneumonia, asthma exacerbation, urinary tract infection, gastroenteritis, acute abdomen and central nervous system infection. The mainstays of DKA management include careful fluid resuscitation, timely intravenous insulin administration and restoration of shifting electrolyte disorders and underlying precipitating factors. However, evidence suggests that optimal treatment remains a therapeutic challenge. Accurate and rapid diagnosis, prompt intervention and meticulous monitoring are of major importance to break the vicious cycle of life-threatening events and prevent severe complications during this potentially fatal medical emergency.

Neurofibromatosis type 2 (NF2) is a genetic syndrome characterized by the growth of benign tumors in the nervous system, particularly bilateral vestibular schwannomas, meningiomas, and ependymomas. This review consolidates the current knowledge on NF2 syndrome, emphasizing the molecular pathology associated with the mutations in the gene of the same name, the NF2 gene, and the subsequent dysfunction of its product, the Merlin protein. Merlin, a tumor suppressor, integrates multiple signaling pathways that regulate cell contact, proliferation, and motility, thereby influencing tumor growth. The loss of Merlin disrupts these pathways, leading to tumorigenesis. We discuss the roles of another two proteins potentially associated with NF2-deficiency as well as Merlin: Yes-associated protein 1 (YAP), which may promote tumor growth, and Raf kinase inhibitory protein (RKIP), which appears to suppress tumor development. Additionally, this review discusses the efficacy of various treatments, such as molecular therapies that target specific pathways or inhibit neomorphic protein-protein interaction caused by NF2-deficiency. This overview not only expands on the fundamental understanding of NF2 pathophysiology but also explores the potential of novel therapeutic targets that affect the clinical approach to NF2 syndrome.

Prostate cancer lung metastasis represents a clinical conundrum due to their implication of advanced disease progression and the complexities they introduce in treatment planning. As the disease progresses to distant sites such as the lung, the clinical management becomes increasingly intricate, requiring tailored therapeutic strategies to address the unique characteristics of metastatic lesions. This review seeks to synthesize the current state of knowledge surrounding prostate cancer metastasis to the lung, shedding light on the diverse array of clinical presentations encountered, ranging from subtle radiological findings to overt symptomatic manifestations. By examining the diagnostic modalities utilized in identifying this metastasis, including advanced imaging techniques and histopathological analyses, the review aims to provide insights into the diagnostic landscape and the challenges associated with accurately characterizing lung metastatic lesions in prostate cancer patients. Moreover, the review delves into the nuances of therapeutic interventions employed in managing prostate cancer lung metastasis, encompassing systemic treatments such as hormonal therapies and chemotherapy, as well as metastasis-directed therapies including surgery and radiotherapy.

Advances in gastric cancer screening and endoscopic technology have made it possible to detect and treat gastric cancer at an early stage. As a result, about 40% of all gastric cancers have now been resected by endoscopic treatment in Japan. In endoscopic diagnosis, magnifying endoscopic observation using band-limited light such as narrow band imaging (NBI) has significantly improved the accuracy of gastric cancer diagnosis. At the same time, in endoscopic treatment, endoscopic submucosal dissection (ESD) has contributed to increase explosively the number of gastric cancers which could be resected endoscopically. In recent years, the construction of algorism for endoscopic diagnosis and treatment with a view to personalized medicine has been explored, and endoscopic use for gastric cancer managements is expected to develop further in the future. Keywords (5 words):

Many of the potential immune therapeutic targets are similarly affected in adult-onset neurodegenerative diseases such as Alzheimer’s (AD) disease, Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD), but also in a seemingly distinct Niemann-Pick type C disease with primarily juvenile-onset. This strongly argues for an overlap in pathogenic mechanisms. The commonly researched immune targets include various immune cell subsets such as microglia, peripheral macrophages, or regulatory T cells (Tregs), the complement system, and other soluble factors. In this review, we will compare these neurodegenerative diseases from a clinical point of view and point out the common pathways and mechanisms of protein aggregation, neurodegeneration and/or neuroinflammation that could potentially lead to shared treatment strategies. We also describe the common therapeutic approaches in treating the immune dysfunctions in these disorders, moving from immunization to microbiome regulation and stem cell treatment.

Monoterpenes as natural products are the subject of increased attention in the search for new pharmacological agents because of their numerous biological activities including antifungal, antibacterial, antioxidant, anticancer, antispasmodic, hypotensive, vasodilating effects, etc. In vitro and in vivo studies reveal their antidepressant, anxiolytic, and memory-enhancing in experimental dementia and Parkinson’s disease effects. Chemical modification of natural substances by conjugation with various synthetic components is a modern method of obtaining new biologically active compounds. The discovery of new potential drugs among monoterpene derivatives is a progressive direction in experimental pharmacology and a promising approach to the therapy of various pathologies. Biologically active substances such as monoterpenes borneol, camphor, geraniol, pinene, and thymol, were used to synthesize compounds with different properties, including analgesic, anti-inflammatory, anticonvulsant, anti-depressant, anti-Alzheimer’s, anti-parkinsonian, antiviral and antibacterial (anti-tuberculosis). Myrtenal is a perspective monoterpenoid with therapeutic potential in various fields of medicine. Its chemical modifications often lead to new or more pronounced biological effects. As an example, conjugation of myrtenal with the known pharmacophore adamantane allows one to enhance some of its key properties. Myrtenal-adamantane derivatives exhibited a variety of beneficial properties – antimicrobial, antifungal, antiviral, anticancer, anxiolytic, and neuroprotective, which are worth examining in more detail and at length.

Organ transplantation remains the only treatment option for patients with end-stage organ dysfunction. However, there are numerous limitations that challenge its clinical application, including the shortage of organ donations, the quality of donated organs, injury during organ preservation and reperfusion, primary and chronic graft dysfunction, acute and chronic rejection, infection, and carcinogenesis in post-transplantation patients. Acute and chronic inflammation and cell death are two major underlying mechanisms for graft injury. Necroptosis is a type of programmed cell death involved in many diseases and has been studied in the setting of all major solid organ transplants, including the kidney, heart, liver, and lung. It is determined by the underlying donor organ conditions (e.g., age, alcohol consumption, fatty liver, hemorrhage shock, donation after circulatory death, etc.), preservation conditions and reperfusion, as well as allograft rejection. Specific molecular mechanisms of necroptosis have been uncovered in the organ transplantation setting, and potential targeting drugs have been identified. We hope this review article will promote more clinical research to determine the role of necroptosis and other types of programmed cell death in solid organ transplantation to alleviate the clinical burden of ischemia-reperfusion injury and graft rejection.

Characterized in biomedical terms, stretching exercises have been defined as movements applied by external and/or internal forces – to increase muscle and joint flexibility, decrease muscle stiffness, to elevate joint range of motion (ROM), to increase the length of the morpho-functional unit “muscle-tendon”, to improve joint, muscle and tendon movements, contraction and relaxa-tion. The present review examines and summarizes the initial and recent literature data related to the biomechanical, physiological and therapeutic effects of static stretching (SS) on flexibility and other physiological characteristics of the main structural and functional unit “joint-ligaments-tendon-muscle”. The healing and therapeutic effects of SS, soon combined with other rehabilitation techniques (massage, foam rolling – with and without vibrations; hot/cold therapy, etc.) are discussed in relationship to creation of individual (patient-specific) or group programs for treatment and prevention of joint injuries as well as for improving performance in sports. From a theoretical point of view, the role of SS as positively affecting the composition of the connective tissue matrix is pointed out: type I-III collagen synthesis, hyaluronic acid and glucosaminoglycans (GAGs) turnover – under influence of the transforming growth factor beta-1 (TGF-β-1). Different variables as collagen type, biochemistry, elongation and elasticity are used as molecular biomarkers. Recent studies evaluated that the static progressive stretching therapy could prevent/reduce the development of arthrogenic contractures, joint capsule fibrosis, muscle stiffness and need new clinical applications. Combined stretch techniques are proposed and ap-plied in medicine and sports, depending on their long- and short-term effects on variables such as ROM, EMG activity, muscle stiffness, etc. The results obtained are of theoretical and practical interest for development of new experimental, mathematical and computational models and creation of efficient therapeutic programs. The healing SS effects on the main structural and functional unit – “joint-ligament-tendon-muscle” need further investigations, which could clarify and evaluate benefits of SS in prophylaxis and treatment of joint injuries - in healthy and ill in-dividuals, in older adults, as compared to young, active and well-trained persons, as well as to professional athletes.

MicroRNAs (miRNAs) are single-stranded, noncoding RNA molecules that regulate gene expression post-transcriptionally by binding to messenger RNAs. miRNAs are important regulators of gene expression, and their dysregulation is implicated in many human and dog diseases. Most cancers tested, to date, have been shown to express altered miRNA levels, which indicates their potential importance in the oncogenic process. Based on this evidence, numerous miRNAs have been suggested as potential cancer biomarkers for both diagnosis and prognosis. miRNA-based therapies have also been tested in different cancers and have provided measurable clinical benefits to patients. In addition, understanding miRNA biogenesis and regulatory mechanisms in cancer can provide important knowledge about resistance to chemotherapies, leading to more personalized cancer treatment. In this review, we have comprehensively summarized the importance of miRNA in human and dog cancer research. We have discussed the current state of development and potential for miRNA as both a diagnostic marker and a therapeutic target.

Reinventing approved therapeutic proteins for a new dose, a new formulation, a new route of administration, an improved safety profile, a new indication, or a new conjugate with a drug or a radioactive source is a creative approach to benefit from the billions spent on developing new therapeutic proteins. These new opportunities were created only recently with the arrival of AI/ML tools and high throughput screening technologies. Furthermore, the complex nature of proteins offers mining opportunities that are not possible with chemical drugs; bringing in newer therapies without spending billions makes this path highly lucrative financially while serving the dire needs of humanity. This paper analyses several practical reinventing approaches and suggests regulatory strategies to reduce development costs significantly. This should enable the entry of hundreds of new therapies at affordable costs.

Transposable elements (TEs) ubiquitously exist in the human genome, and some have the ability to copy and paste themselves to other locations, resulting in new insertions. Organisms have evolved with mechanisms and machineries to repress such activity. TEs are also co-opted for beneficial functions by the host and are thus maintained in the genome. During the lifetime of humans, aberrant TE activity might cause or contribute towards diseases including neurological conditions such as Alzheimers Disease (AD) and cancer. While inflammatory pathways linked to TEs may be a part of the disease pathology, on the other hand altered TE activity involving inflammatory pathways could be recognised by disease suppression mechanisms. For this reason, TEs could be targeted for therapeutic applications aiming to prevent TE activity or reduce initial inflammatory pathways as well as to activate disease suppression mechanisms. In this review, we describe the contributory and potential preventative roles of TEs in neurological conditions and cancer from a molecular and evolutionary perspective. Evolutionary paradigms both at the unicellular and organismal level aid understanding the role of TEs in disease. These observations could pave the way for the development of novel therapeutic approaches targeting TEs.

Background: Immunologic and neuro-inflammatory pathways have been found to play a major role in the pathogenesis of many neurological disorders such as epilepsy, proposing the use of novel therapeutic strategies. In the era of personalized medicine and in the face of the exhaustion of anti-seizure therapeutic resources it is worth looking at the current or future possibilities that neuroimmunomodulator or anti-inflammatory therapy can offer us in the management of patients with epilepsy. Methods: We performed a narrative review on the recent advances on the basic epileptogenic mechanisms related to the activation of immunity or neuroinflammation with special attention to current and future opportunities for novel treatments in epilepsy. Results: Neuroinflammation can be considered a universal phenomenon and occurs in structural, infectious, post-traumatic, autoimmune, or even genetically based epilepsies. The emerging research developed in recent years has allowed us to identify the main molecular pathways in-volved in these processes. These molecular pathways could constitute future therapeutic targets for epilepsy. Conclusions: Different drugs current or in development have demonstrated their capacity to inhibit or modulate molecular pathways involved in the immunologic or neuroinflammatory mechanisms described in epilepsy. Some of them should be tested in the future as possible antiepileptic drugs.

Understanding of the molecular mechanisms of prostate cancer has led to development of therapeutic strategies targeting androgen receptor (AR). These androgen-receptor signaling inhibitors (ARSI) include androgen synthesis inhibitor- abiraterone and androgen receptor antagonists- enzalutamide, apalutamide, and darolutamide. Although these medications provide significant improvement in survival among men with prostate cancer, drug resistance develops in nearly all patients with time. This could be through androgen-dependent or androgen-independent mechanisms. Even weaker signals and non-canonical steroid ligands can activate AR in the presence of truncated AR-splice variants, AR overexpression, or activating mutations in AR. AR splice variant, AR-V7 is the most studied among these and is not targeted by available ARSIs. Non-androgen receptor dependent resistance mechanisms are mediated by activation of an alternative signaling pathway when AR is inhibited. DNA repair pathway, PI3K/AKT/mTOR pathway, BRAF-MAPK and Wnt signaling pathway and activation by glucocorticoid receptors can restore downstream signaling in prostate cancer by alternative proteins. Multiple clinical trials are underway exploring therapeutic strategies to overcome these resistance mechanisms.

Medicinal mushrooms have got much attention from biologists in the last decades. Leucocalocybe mongolica Imai remains one of the famous clinical and edible mushrooms used in traditional Chinese medicine and Mongolian medicine to treat various diseases. It also commonly consumes in Chinese and Mongolian daily dishes. Numerous biochemical components exist in L. mongolica, especially in the fruiting bodies include; polysaccharides, sterol, lectins, laccase, amino acids, terpenes, volatile compounds, and so on. These biomedical components possess a lot of medicinal properties and provide diverse therapeutical effects for human health, such as anti-tumor activity, antiproliferative activity, anti-diabetes properties, hypotensive effect, hepatoprotective effect, antioxidant activity, cardioprotective effect, and so on. However, this review's main objectives are to illustrate some basics about the bioactive components in L. mongolica and its pharmacological effects on the human body. In addition to giving forward some suggestions for future research on this medicinal mushroom.

The treatment of peptides has played an important role in clinical practice since the discovery of insulin therapy in the 1920s. Over 60 peptide drugs are approved in the United States (US and other regional mar-kets, and peptides continue to undergo drug discovery steadily. Peptide research and development has lev-eraged a wider range of structures known from other plant sources, via pharmacology and medicinal molecular biology, beyond its conventional focus on individual endogenous peptides. We build a comprehensive database of peptides that have met scientific studies with more than 150 constantly evolving peptides. Here we provide a simple overview of the peptide-based drug therapy environment, comprising evolutionary points of view, structural properties, operational thresholds, and explanation of the therapeutic area.

The recent pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread so rapidly and severely affected the people of almost every country in the world. The highly contagious nature of this virus makes it difficult to take control of the present pandemic situation. With no specific treatment available, the coronavirus disease 2019 (COVID-19) presents a threat to people of all ages including the elderly people and people with other medical complications as a vulnerable group to this disease. Better understanding of viral pathogenesis, appropriate preventive measures, early diagnosis and supportive treatments of the infected patients are now the general solutions to fight against this viral transmission. But, as an emerging disease, most about it remains still poorly understood. This article holds an overview on the origin and structure, pathogenesis, diagnosis and possible therapeutic options for the causative agent, SARS-CoV-2 and disease, COVID-19. However, few therapeutic options, laboratory experiments and other strategies proposed here need to be further clinically tested.