Genetic transformation is a critical tool for gene manipulation and functional analyses in plants, enabling the exploration of key phenotypes and agronomic traits at the genetic level. While dicotyledonous plants offer various tissues for in vitro culture and transformation, monocotyledonous plants, such as rice, have limited options. This study presents an efficient method for genetically transforming rice (Oryza sativa L.) using seed-derived embryogenic calli as explants. Two target genes were utilized to assess regeneration efficiency: green fluorescent protein (eGFP) and the apple FLOWERING LOCUS T (FT)-like gene (MdFT1). Antisense MdFT1 was cloned into a vector controlled by the rice α-amylase 3D (Ramy3D) promoter, while eGFP was fused to Cas9 under the Ubi promoter. These vectors were introduced separately into rice embryogenic calli from two Korean cultivars using Agrobacterium-mediated transformation. Transgenic seedlings were successfully regenerated via hygromycin selection using an in vitro cultivation system. PCR confirmed stable transgene integration in the transgenic calli and their progeny. Fluorescence microscopy revealed eGFP expression, and antisense MdFT1-expressing lines exhibited notable phenotypic changes, including variations in plant height and grain quality. This study demonstrated the effective use of seed-derived embryogenic calli for rice transformation, offering a promising approach for developing transgenic plants in monocot species.

Adlay seed samples were collected from 3 adlay growing regions (Yeoncheon, Jeonnam and Eumseong regions) in Korea during 2012. Among all the samples collected, 400 seeds were tested for fungal occurrence by standard blotter and test tube agar methods and different taxonomic groups of fungal genera were detected. The most predominant fungal genera encountered were Fusarium, Phoma, Alternaria, Cladosporium, Curvularia, Cochliobolus and Leptosphaerulina. The occurrence of Fusarium species were 45.6% and based on the combined sequences of two protein coding genes, EF-1a, Beta-tubulin and phylogenetic analysis, 10 species were characterized as F. incarnatum (11.67%), F. kyushense (10.33%), F. fujikuroi (8.67%), F. concentricum (6.00%), F. asiaticum (5.67%), F. graminearum (1.67%), F. miscanthi (0.67%), F. polyphialidiom (0.33%), F. armeniacum (0.33%) and F. thapsinum (0.33%). The ability of these isolates to produce mycotoxins fumonisin (FUM) and zeralenone (ZEN) were tested by ELISA quantitative analysis method. The result revealed that fumonisin (FUM) was produced only by F. fujikuroi and zeralenone (ZEN) by F. asiaticum & F. graminearum. Mycotoxigenic species were then examined for their morphological characteristics to confirm their identity. Morphological observations of the species correlated well with their molecular identification and confirmed as F. asiaticum, F. fujikuroi and F. graminearum.

To develop aryloxyphenoxypropionate herbicides with novel structure and improved activity, a total of twenty-eight novel quinazolinone–phenoxypropionate derivatives containing a diester moiety were synthesized and tested for herbicidal activity. The bioassay results in the greenhouse showed that QPEP-I-4 exhibited excellent herbicidal activity against E. crusgalli, D. sanguinalis, S. alterniflora, E. indica, and P. alopecuroides with inhibition rates >80% at a dosage of 150 g ha-1, and displayed higher crop safety to G. hirsutum, G. max, and A. hypogaea than the commercial herbicide quizalofop-p-ethyl. Studying of the molecular mode of action by phenotypic observation, membrane permeability evaluation, and transcriptomic analysis revealed that a growth inhibition of plant by QPPE-I-4 was the result from damage of plants biomembrane. The evaluation of ACCase activity in vivo indicated that QPPE-I-4 could inhibit ACCase and may be a new type of ACCase inhibitor. The present work demonstrated that QPPE-I-4 could serve as a lead compound for further developing novel AOPP herbicides.

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.

Drugs are known to cause substantial liver injury, with hepatotoxicity ranging from asymptomatic increase of liver enzymes to hepatic failure. HIV/AIDS patients, with compromised immune systems, are especially vulnerable to opportunistic infections such as tuberculosis (TB). Patients with co-infection frequently get combined antiretroviral (ART) and antitubercular (ATD) regimens, which can cause hepatotoxicity. Hepatotoxicity has been linked to commonly administered antiretroviral drug regimens as well as first-line antitubercular agents such isoniazid, rifampin, and pyrazinamide, which are required for the treatment of both drug-sensitive and drug-resistant tuberculosis. As a result, there is an urgent need to investigate treatments based from traditional herbs known for their hepatoprotective abilities against ART and ATD-induced liver injury. Many researchers have investigated the effectiveness of medicinal plants in treating chemically caused hepatotoxicity. Medicinal plants are high in phytochemicals and secondary metabolites, both of which have a variety of medicinal benefits. Currently, there is a lack of specific therapeutic regimens to address this adverse effect, and management often relies on symptomatic treatment or therapy withdrawal. Traditional medicinal plants may have the potential to restore normal liver function, enzyme activity, and cellular structure in response to ART and ATD-induced hepatotoxicity. This review aims to examine the scientific evidence supporting the use of medicinal plants as hepatoprotective agents against liver damage induced by ART and ATDs.

The microbial contamination in food packaging have been a major concern that paved the way for the search for natural based new anti-microbial agents, such as modified α-mangostin. In the present work, twelve synthetic analogs were obtained via semi-synthetic modification of α-mangostin by Ritter reaction, reduction by palladium-carbon (Pd-C), alkylation, and acetylation. The evaluation of the anti-microbial potential of the synthetic analogs showed higher therapeutic value than the parent molecule. The anti-microbial studies proved that I E showed higher antibacterial activity whereas I I showed most significant antifungal activity. Due to their microbial properties, modified α-mangostin can be utilized as active anti-microbial agents in food packaging.

The efficient preparation of single-stranded DNA (ssDNA) rings, as a macromolecular construction approach with topological features, has aroused much interest due to their numerous applications in biotechnology and DNA nanotechnology. However, an extra splint is essential for enzymatic circularization, and by-products of multimers are usually present at high concentrations. Here, we proposed a simple and robust strategy of using permuted precursor (linear ssDNA) for circularization by forming an intramolecular dynamic nick using a part of the linear ssDNA substrate itself as the template. After the simulation of the secondary structure for desired circular ssDNA, the linear ssDNA substrate is designed to have its ends on the duplex part (≥5 bp). By using this permuted substrate with 5'-phosphate, the splint-free circularization is simply carried out by T4 DNA ligase. Very interestingly, formation of only several base pairs (2–4) flanking the nick is enough for ligation, although they form only instantaneously under ligation conditions. More significantly, the 5 bp intramolecular duplex part commonly exists in genomes or functional DNA, demonstrating the high generality of our approach. Our findings are helpful for understanding the mechanism of enzymatic DNA ligation from the viewpoint of substrate binding.

Litsea martabanica root's antioxidant and AChE activity showed promise as a pesticide detoxification agent in our previous study. In addition to roots, its leaves can help mitigate pesticide exposure, although there is limited scientific evidence supporting their efficacy. However, the use of roots in many countries, such as Thailand, could contribute to environmental degradation, as highland communities traditionally cut down whole trees to obtain them. This study aims to evaluate the antioxidant activity and anti-pesticide potential of water extracts from L. martabanica leaves instead of its roots through in vitro and in vivo investigations. The findings showed that L. martabanica water extracts and fractions demonstrated varied antioxidant activity. The water extract, obtained using traditional extraction methods, was chosen for in vivo experiments. Rats received the extract followed by chlorpyrifos exposure for 16 days. Results indicated reduced acetylcholinesterase activity in chlorpyrifos-exposed rats, while treatment with leaf extract led to increased activity, suggesting its potential as a detoxifying agent. Histopathological examination revealed no liver cell necrosis and showed liver cell regeneration, indicating potential protection against free radical-induced liver damage without affecting rat liver weight or biochemical profiles. Utilizing L. martabanica leaves for healthcare purposes holds promise without negative environmental impact.

Gastric inflammation-related disorders are commonly observed digestive system illnesses char-acterized by the activation of proinflammatory cytokines, particularly tumor necrosis factor-α (TNF-α). This results in the induction of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PEG2) and matrix metallopeptidase-9 (MMP-9). These factors contribute to the pathogenesis of gastric in-flammation disorders. We examined the preventive effects of Lonicera japonica Thunb. ethanol ex-tract (Lj-EtOH) on gastric inflammation induced by TNF-α in normal GES-1 cells. The GES-1 cell line was used to establish a model that simulated the overexpression of COX-2/PGE2 and MMP-9 proteins induced by TNF-α, to examine the anti-inflammatory properties of Lj extracts. The re-sults indicated that Lj-EtOH exhibits significant inhibitory effects on COX-2/PEG2 and MMP-9 ac-tivity, attenuates cell migration, and provides protection against TNF-α-induced gastric inflam-mation. The protective effects of Lj-EtOH are associated with the modulation of COX-2/PEG2 and MMP-9 through activation of TNFR–ERK 1/2 signaling pathways as well as the involvement of c-Fos and nuclear factor kappa B (NF-κB) signaling pathways. Based on our findings, Lj-EtOH ex-hibits a preventive effect on human gastric epithelial cells. Consequently, it may represent a novel treatment for the management of gastric inflammation.

In the course of our ongoing research targeting the identification of potential biocontrol agents from entomopathogenic fungi (EPF), we explored a solid-state rice fungal extract of Blackwellomyces roseostromatus BCC56290 derived from infected lepidopteran larvae. Chemical and biological prospections afforded four unprecedently reported natural products differentiated into one dimeric naphthopyran bioxanthracene ES-242 derivative (1) and three cyclodepsipeptides (2-4) in addition to two known cyclodepsipeptides, cardinalisamides B (5) and C (6). Chemical structures of the isolated compounds were elucidated through comprehensive 1D/2D NMR and HR-ESI-MS data together with comparisons to the reported literature. The absolute configuration of the isolated cyclodepsipeptide was determined using Marfey’s method. All isolated compounds were assessed for their antimicrobial, cytotoxic and nematicidal activities with some compounds revealed significant activities.

: Schizophrenia and schizoaffective disorder are generally treated with second-generation antipsychotic drugs. These drugs are mostly D2 and 5-HT2A antagonists. They improve positive schizophrenia symptoms sufficiently well; however, they ameliorate negative schizophrenia symptoms and cognitive functions to a small extent. We review novel antipsychotic drugs exerting a partial agonism at dopaminergic and serotonergic receptors such as cariprazine, brexipiprazole and lumateperone. Besides, the mechanisms of actions of non-anti-dopaminergic antipsychotic drugs are pointed out. Updated neural networks are used to explain the mechanism of action of M4 and M1 receptor agonists, for example xanomeline combined with trospium or emraclidine, and trace-amine-associated receptor 1 agonists (TAAR1), for example ulataront. Phase 3 clinical trials of new third generation antipsychotic drugs are presented. Novel antipsychotic drugs with a partial agonism at D2 and D3 receptors improve positive and negative schizophrenia symptoms as well as cognitive symptoms better than second generation antipsychotic drugs. Besides, they are well tolerated. M4 and M1 receptor agonists, i.e. xanomeline combined with trospium or emraclidine, and TAAR1 agonists, i.e. ulataront, have promising results in clinical trials; they well improve negative schizophrenia symptoms and cognitive functions. Phase 3 clinical trials offer promising results for anti-dopaminergic and non-anti-dopaminergic novel antipsychotic drugs. These new non-anti-dopaminergic antipsychotic drugs better emend negative schizophrenia symptoms, and they better improve cognitive functions than second-generation antipsychotic drugs. Promising new antipsychotic drugs are cariprazine, brexipiprazole, lumateperone, ulataront, and xanomeline combined with trospium. Although phase 3 clinical studies are not yet completed, they showed a therapeutic effect superior to those achieved by second-generation antipsychotic drugs. They are tolerated very well, and they better treat negative schizophrenia symptoms and improve cognitive functions.

The authors propose a novel approach for a comprehensive evaluation of neuroprotective effects using both in vitro and in vivo methods. This approach allows for the initial screening of numerous newly synthesized chemical compounds and substances from plant and animal sources while preserving animal life. In vitro techniques, including mitochondrial suspensions and neuronal cell cultures, enable assessment of neuroprotective activity, which can be challenging in intact organisms. The preliminary methods help outline the neuroprotection mechanism depending on the neurodestruction agent. The authors have validated a model of acute cerebrovascular accident, which simulates key cerebrovascular phenomena such as reduced cerebral blood flow, energy deficit, glutamate-calcium excitotoxicity, oxidative stress, and early gene expression. A significant advantage of this model is its ability to reproduce the clinical picture of cerebral ischemia: impaired motor activity, signs of neurological deficits (paresis, paralysis, etc.), as well as disturbances in attention, learning, and memory. Crucial to this approach is the selection of biochemical, molecular, and cellular markers to evaluate nerve tissue damage and characterize potential neuroprotective agents. Additionally, a comprehensive set of molecular, biochemical, histological, and immunohistochemical methods is proposed for evaluating neuroprotective effects and underlying mechanisms of potential pharmaceutical compounds.

A key component of nanomaterials, carbon dots (CDs) are zero-dimensional solids, smaller than 10 nm in size that include carbon as their backbone structure. Herbal medicine carbon dots (HM-CDs) are nanoparticles developed from medicinal plants. Owing to their advantageous properties, they are extensively employed in biological domains such as drug administration, bio-imaging, biosensors, and DNA interactions. It's interesting to note that, carbon dots pro-duced from herbal medicines as a raw material have surfaced as the most recent addition to the CD family. This article provides an overview of the several sources of green precursor, preparation tech-niques, characterization, and applications of CDs. It reviews recent advancements in synthe-sizing CDs made from green carbon materials and their potential uses as bioimaging, catalysts and sensing. Furthermore, several difficult issues and future directions for this potent and amazing content are also covered.

Halitosis can be defined as bad breath or a condition frequently characterized by a disagreeable or unpleasant odor emanating from the oral cavity. Most modern toothpaste used today cater for general oral hygiene and not for specific tooth-mouth maladies like halitosis. Therefore, the aim of this study was to produce herbal toothpaste for halitosis control. Using the method of Mamatha and Naveen (2007) for herbal toothpaste production, the following natural components; Bridelia ferrugeinea and alum were utilized. Different toothpaste samples were also produced using different components in different proportions. Bacteria were isolated from the oral cavity of selected respondents. To assay the efficacy of the herbal toothpaste produced, sensitivity tests, and physiochemical tests for toothpaste efficacy were used. Comparative analysis between the toothpaste produced and commercial toothpaste was also carried out. Physicochemical properties of the herbal toothpastes produced showed that they were purely alkaline, while the selected commercial toothpaste was slightly alkaline. Also, they had consistency in foaming ability, moisture contents, and volatile contents. Sensitivity tests of the herbal toothpastes produced showed that they were effective antimicrobial agents against Staphylococcus aureus isolates. From the results obtained our toothpaste showed efficacy in terms of halitosis control.

Despite the efforts made to stop the tuberculosis (TB) epidemic, it still remains one of the leading causes of death from an infectious disease. Previous work in the group uncovered a new family of amides which showed promising activities against Mycobacterium tuberculosis. A closer look at the literature showed that these compounds are structurally related to the DNB family of DprE1 inhibitors, so, we decided to study a wide range of substituted amides and determine their activity, focusing on unexplored structures related to the dinitrobenzamides (DNB) found in the literature. To synthesize our library of compounds we started from 3,5-dinitrobenzoic acid to form the nitroaromatic core that is characteristic of the DNB’s, to which we then added linear or cyclic amine moieties. Additionally, the impact of terminal aromatic moieties was also assessed for some derivatives, via an ether, ester, or amide bond. In order to obtain the desired derivatives, multiple synthetic approaches were used, mainly focused on nucleophilic addition/elimination reactions, SN2 reactions and Mitsunobu reactions. The activity was impacted mainly by two structural features, the addition of an aromatic moiety as a terminal group and the type of the linker. The most interesting compounds exhibited activities comparable to isoniazid and DNB1. Computational studies were also performed aimed at understanding their possible interactions with DprE1. The most active compounds are a good starting point for further development, and we plan to study an extended family of compounds based in those structures.

Long COVID is a phenomenon in which individuals experience persistent symptoms after recovering from COVID-19. The symptoms are discovered to be unique for every individual and can affect multiple organs systems in the body. This study aims to identify effective natural remedies for long COVID by analyzing hub genes associated with the symptoms of the condition and evaluating the repurposed drugs catered and used for treating the symptoms of long COVID. The most common and prevalent symptoms of long COVID were identified; Fatigue, Shortness of Breath, Loss of Smell, Headache, Brain Fog, Chest Pain, Insomnia, Heart Palpitations, Dizziness, Joint Pain, Depression, Anxiety, Tinnitus, Loss of Appetite. Hub genes for each of the symptoms provided an insight on the key biological pathways of the symptom. Repurposed drugs identified, provided the template to identify the natural compounds with similar structure as a potential therapeutic drug. The natural compounds were retrieved using fingerprint search of the repurposed drugs from the NPASS Database. The findings of this study suggest several natural remedies for each symptom based on the molecular docking of the hub gene and natural compound using iGEMDOCK. The identified natural remedies may hold promise in treating long COVID, but further research is required to explore the efficacy and effectiveness of the proposed natural compounds. The results of the study pose important implications for the development of effective treatments for long COVID.

Herbal Coffee is getting more popular due to its unique flavor and higher concentration of bioactive compounds, mainly polyphenols. Rosemary is a unique herb with potent antioxidant properties. A green technique called ultrasound aids in releasing bioactive substances from the plant cell wall. In this context, ultrasound-assisted herbal coffee prepared and their anti-diabetic, anti-Alzheimer, and antioxidant activities were measured while the LC/MS was used to determine the bioactive components from the herbal coffee infusion. A total of 95 secondary metabolites were putatively reported, including alkaloids, phenolic acids, and flavonoids, which we identified in the herbal coffee infusion. The total phenolic content (61.5 ± 5.1 mg GAE/g), total flavonoid content (19.3 ± 0.9 mg QE/g), and total condensed tannin (7.6 ± 0.7 mg CE/g) of herbal coffee infusion were observed to be highest of the two remaining samples. The herbal coffee extracts were used to determine all samples' antioxidant, anti-diabetic, and anti-Alzheimer activities. Using LC-MS/MS, we semi-quantified 19 phenolic metabolites. The results show numerous bioactive components in herbal coffee infusion with more potent antioxidant, antidiabetic, and anti-Alzheimer potential. Moreover, more studies must be conducted to confirm how the metabolomic profile of herbal coffee affects its flavor profile.

Canine parvovirus (CPV) infection is a widespread ailment among young dogs globally, characterized by high morbidity, mortality, and significant infectivity. Due to its grim prognosis, it is often likened to canine "cancer" with a medium-term mortality rate of 46.43% and late-stage mortality reaching up to 100%.Current treatment modalities primarily encompass fluid therapy, antiemetics, antimicrobial medications, pain relievers, and enteral nutrition. However, the absence of specific internationally recognized medications necessitates substantial care expenses. This review aims to elucidate recent advancements in pharmacological interventions for mitigating CPV infection symptoms, underscoring the potential of novel pharmaceutical technologies in veterinary medicine to enhance clinical outcomes for afflicted animals and their caregivers，lay a theoretical foundation for the development of specific drugs.

Gasca D herbal formulation is an antidiabetic medicine for the management of diabetes mellitus produced exclusively from natural ingredients. The level of some essential elements (Copper, chromium, Cobalt, Iron, Manganese, Nickel and zinc) and toxic (Cadmium, Arsenic, Mercury, and Lead) heavy metals were determined using microwave plasma-atomic emission spectrometry (MP-AES). The aim of this study is to evaluate the levels of essential and toxic heavy metals and also identify bioactive compounds present in Gasca D herbal formulation. The result shows no traces of Lead, Mercury, Zinc, Arsenic and Zinc, Iron was found to have highest concentration 67.16 + 7.5 µg/g and Cadmium lowest concentration 0.4 + 0.03µg/g. GC-MS analysis of Gasca D herbal formulation revealed the presence of 14 biologically active compounds which include N-Formyl-beta-alanine, Paromomycin, 3,4-Altrosan, Benzamide, 1,3,4-Thiadiazol-2-amine, Carbamodithioic acid, Carbonic acid, alpha-D-Glucopyranoside, Ethyl isocyanide, 2-Propanesulfinic acid, Propanamide, 2-Butenenitrile, Dicyclopropyl carbinol, Isoxazolidine, 1,5-Hexadiene 10-Azido-1-decanethiol. Conclusion: The result indicates that the mean levels of toxic metals in Gasca D herbal formulation were below WHO permissible levels. Gasca D herbal formulation also contains various bioactive compounds that can have various medicinal application which can be used for the treatment of various diseases.

Hypertension is a global public health challenge, with a high prevalence across various regions and significant implications for cardiovascular risk. This article reviews the effectiveness of herbal medicine as a potential therapeutic approach for hypertension, offering an alternative or complementary solution to conventional pharmacological treatments. It highlights several natural agents that have demonstrated efficacy in lowering systolic blood pressure (SBP) in clinical and meta-analytical studies. The methodology involved a systematic review of articles that discuss herbal therapeutics for hypertension, focusing on their efficacy compared to placebo and standard treatments. The findings suggest that certain nutraceuticals, such as garlic, hawthorn, and CoQ10, can significantly reduce SBP, presenting a viable option for managing hypertension. This review underscores the need for further research to validate these findings and optimize herbal treatment strategies, potentially expanding the use of these natural products in clinical practice. The article aims to increase awareness among medical professionals and patients about the benefits and applications of herbal medicines in treating hypertension.

The objective of this study was to investigate the impact of adding fermented herbal extracts (FHE) derived from mulberry leaf (Morus alba), Javanese turmeric (Curcuma xanthorrhiza), and fingerroot (Boesenbergia rotunda) to the diet of tiger shrimp (Penaeus monodon) on their growth, moulting performance, feed efficiency, and nutrient retention. The main feed used in this trial was a commercially manufactured pellet, then five different doses of FHE supplementation were used: 0 mg/kg feed (P0, control), 50 mg/kg feed (P1), 100 mg/kg feed (P2), 150 mg/kg feed (P3), and 200 mg/kg feed (P4). Weight gain, average daily gain, and length gain of shrimps fed P2 was significantly higher than that of those fed the control diet. Similar result was observed in moulting performance. The application of P2 showed superior results in enhancing the FE of cultured shrimp. Thus, the protein and energy retention of P. monodon was significantly better in P2 treatment groups. P0 had the lowest crude protein, while shrimp given P2 and P3 diets had the highest crude protein content of any treatment group. Based on the findings, it is recommended that the juvenile tiger shrimp diet contain 100 mg/kg of FHE for the best effects.

Abstract: The SARS-CoV-2 pandemic has reemphasized the urgent need for broad-spectrum antiviral therapies. We developed a computational workflow using scRNA-Seq data to assess cellular metabolism during viral infection. With this workflow we predicted the capacity of cells to sustain SARS-CoV-2 virion production in patients and found a tissue-wide induction of metabolic pathways that support viral replication. Expanding our analysis to influenza A and dengue viruses, we identified metabolic targets and inhibitors for potential broad-45 spectrum antiviral treatment. These targets were highly enriched for known interaction partners of all analyzed viruses. Indeed, phenformin, an NADH:ubiquinone oxidoreductase inhibitor, suppressed SARS-CoV-2 and dengue virus replication. Atpenin A5, blocking succinate dehydrogenase, inhibited SARS-CoV-2, dengue virus, respiratory syncytial virus, and influenza A with high selectivity indices. In vivo, phenformin showed antiviral activity against SARS-CoV-2 in a Syrian hamster model. Our work establishes host metabolism as druggable for broad-spectrum antiviral strategies, providing invaluable tools for pandemic preparedness.

Epithelial surfaces in humans are home to symbiotic microbes (i.e., microbiota) that influence the defensive function against pathogens depending on the health of the microbiota. Healthy microbiota contribute to the well-being of their host in general (e.g., via the gut-brain-axis), and their respective anatomical site in particular (e.g., oral, urogenital, skin or respiratory microbiota). Despite efforts towards a more responsible use of antibiotics, they are often prescribed for uncomplicated, self-limiting infections and can have a substantial negative impact on the gut microbiota. Treatment alternatives such as non-steroidal anti-inflammatory drugs may also influence the microbiota and thus can have lasting adverse effects. Herbal drugs offer a generally safe treatment option for uncomplicated infections of the urinary or respiratory tract. Additionally, their microbiota preserving properties allow for a more appropriate therapy of uncomplicated infections without contributing to an increase in antibiotic resistance or disturbing the gut microbiota. Here, herbal treatments may be a more appropriate therapy with a generally favorable safety profile.

The Italian herbal products market is the most prosperous in Europe. The proof is represented by the use of these products in several marketing categories, ranging from medicine to nutrition and cosmetics. Market and legislation in Italy are at the same time cause and consequence of this peculiar situation. In fact, the legislation on botanical food supplements in Italy is very permissive and at the same time the market shows an overall satisfaction of users and strong feedback in terms of consumption, which brings a widening use of medicinal plants, formerly the prerogative of pharmaceuticals, to other fields such as nutrition. This review summarizes the market and normative panorama of herbal products in Italy, highlighting the blurred boundaries of health indications, marketing authorizations and quality controls between herbal medicines and non pharmaceutical products, such as food supplements, cosmetics and other herbal-based “parapharmaceuticals”.

The formula Chong-Lou-Yao-Fang (CLYF) is an herbal medicinal formulation developed by the indigenous Naxi people for treating liver cancer. This study is to reveal the biological activity, potential targets, and molecular mechanisms of CLYF for cancer treatment through network pharmacology, molecular docking and in vitro experiments. 35 key compounds were screened from 176 active ingredients in CLYF, which played a vital role in the treatment of cancer, 20 core targets were filtered through protein–protein interaction (PPI) network analysis. The enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) indicated that PI3K-Akt, MAPK, hepatitis B, hepatitis C might be effective in liver cancer treatment. Mo-lecular docking revealed stable binding between EGFR, TP53, and AKT1 with active ingredients. Experiments with cell cultures confirmed that CLYF-A suppressed the proliferation of HepG2 cells, which is consistent with the network pharmacology approach undertaken and the predictions of molecular docking. CLYF-A also induced significant apoptosis and cell cycle arrest in HepG2 cells, which was associated with the loss of mitochondrial membrane potential. This study explored the biological activity, potential targets, and molecular mechanisms of CLYF for cancer treatment. Our results may provide a scientific basis for the clinical use of CLYF for cancer treatment and have important implications for developing pharmaceutical preparations, which also need more phar-macological experiments.

Drug residues that contaminate food and water represent a serious concern for human health, since their irrational use is constantly increasing the amplitude of exposure. Multiple sources contribute to the overall exposure to contaminants, including agriculture, domestic use, personal, public, and veterinary healthcare, increasing the possible origin of contamination. In this review, we focus on crop pesticides and veterinary drug residues because of their extensive use in modern agriculture and farming, which ensures food production and security for the ever-growing population around the world. We discuss crop pesticides and veterinary drug residues with respect to their worldwide distribution and impacts, with special attention on their harmful effects on human reproduction and embryo development, as well as their link to epigenetic alterations, leading to intergenerational and transgenerational diseases. Among the contaminants, the most commonly implicated in causing such disorders are organophosphates, glyphosate and antibiotics, with tetracyclines being the most frequently reported. This review highlights the importance of finding new management strategies for pesticides and veterinary drugs. Moreover, due to the still limited knowledge on inter- and transgenerational effects of these contaminants, we underlie the need to strengthen research in this field, so as to better clarify the specific effects of each contaminant and their long-term impact.

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.

Background: Infections of Coronavirus Disease-2019 (COVID-19) can cause long-term effects known as long COVID. This pilot study aimed to evaluate the feasibility of a clinical study as well as the efficacy and safety of traditional East Asian herbal medicines in alleviating fatigue and cognitive dysfunction “brain fog” in patients with long COVID. Methods: This prospective pilot study investigated the use of three types of herbal medicines, Bojungikki-tang (BIT), Kyungok-go (KOG), and Cheonwangbosim-dan (CBD), for a 12-week period as potential treatments for fatigue and cognitive dysfunction in patients with long COVID. Forty-five patients with long COVID were recruited, and one of three drugs was given based on the patient’s symptoms and pattern identification. The effect of herbal medications on fatigue and cognitive function outcomes was assessed over a 36-week period, with patient adherence closely monitored. Results: After 12 weeks of herbal drug administration, fatigue symptoms improved significantly across all groups, with treatment success rates of 80%, 53.33%, and 46.67% in the BIT, KOG, and CBD groups, respectively. However, “brain fog” symptoms showed less improvement, with treatment success rates of 40%, 46.67%, and 13.33% in the BIT, KOG, and CBD groups, respectively. All adverse events reported were mild and unrelated to the medication. The study design was found to be feasible with high medication adherence. Conclusions: This study demonstrated the feasibility of conducting a clinical trial with three herbal medicines to treat long COVID symptoms like fatigue and “brain fog.”

Glaucoma, a group of diseases characterized by progressive retinal ganglion cell loss, cupping of the optic disc and by a typical pattern of visual field defects, is a leading cause of severe visual impairment and blindness worldwide. Elevated intraocular pressure (IOP) is the leading risk factor for glaucoma development. However, glaucoma can also develop at normal pressure levels. An increased susceptibility of retinal ganglion cells to IOP, systemic vascular dysregulation, endothelial dysfunction and autoimmune imbalances have been suggested to play a role in the pathophysiology of normal tension glaucoma. Since inflammation and oxidative stress play a role in all forms of glaucoma, the goal of this review article is to resent an overview on the inflammatory and prooxidant mechanisms in the pathophysiology of glaucoma and to discuss immunomodulatory and antioxidant treatment approaches.

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.

Research has shown that the consumption of herbal teas is linked with positive effects on the regulation of postprandial blood glucose level. In this study, a comparative analysis of aqueous and ethanol extractions is performed on four herbal teas (Mallotus, Cyclocarya, Rubus, Vine) to evaluate their phytochemical profiles and functional activities. Investigations of phytochemical contents, antioxidant activities, α-glucosidase inhibitory activities and chemical compositions are carried out through colorimetric analyses and UPLC-Q-Orbitrap HRMS/MS, respectively. Results showed that among the studied herbal teas, Vine exhibited the highest glucose re-gulating abilities under both aqueous and ethanol extractions. Overall, ethanol extracted samples yielded higher phytochemicals content, but the compositions of the phytochemicals varied. Meanwhile, aqueous extracts showed surprisingly strong antioxidant activities and comparable α-glucosidase inhibitory activities with ethanol extracts. Phytochemicals contents presented a positive correlation with antioxidant activities and α-glucosidase inhibitory activities. Nevertheless, antioxidant activities displayed a weak positive correlation with α-glucosidase inhibitory activities. Results from this study provided evidence that aqueous extracts from herbal teas possessed valuable phytochemicals composition for antioxidants and the hyperglycemic populations, and are promising candidates for potential applications as functional ingredients with health promoting effects and as natural additives to boost the nutritional value of herbal food products.

Alkaloid-based urea derivatives were produced with high yield through the reaction of anabasine and cytisine with isoxazolylphenylcarbamates in boiling benzene. Their antitumor ac-tivity in combination with the commonly used six anticancer drugs namely cyclophosphane, fluorouracil, etoposide, cysplatine, ribomustine with different mechanisms of action was investi-gated. Based on the quantum chemical calculations data and molecular docking, hypotheses have been put forward to explain their mutual influence when affecting on the С6 rat glioma model cells.

Background: We prepared reference materials of fentanyl and amphetamines in hair, and established methods for the certification of reference materials of fentanyl and amphetamines in hair samples. Methods: Hair samples containing 15 drugs were prepared by immersion method (water-dimethylsulfoxide). On the basis of single-factor experiment, Box-Behnken design-response surface was used to optimize the pre-treatment conditions of samples. In MRM/SIM mode, 15 drugs were quantitatively analyzed by LC-MS/MS and GC-MS/MS methods. Results: The contents of 15 drugs in the mixed hair samples were: 1.050 ng mg-1~7.771 ng mg-1, RSDs<7%(n=11). The results showed that the two analytical methods developed were highly sensitive (LODs as low as 0.05 pg mg-1), reproducible (intra-day and inter-day precision RSDs were<10%) and accurate. F-test was performed on the prepared hair samples and the results showed that the homogeneity of the prepared hair samples was good. Conclusions: The established methods were used for the detection of fentanyl and amphetamine drugs in human hair, with high sensitivity, accuracy and specificity. It can be used as a certified method for the development of fentanyl and amphetamine matrix certified reference materials. The developed hair reference materials are expected to be applied in forensic drug abuse detection and laboratory quality control.

Purpose: Inflammation of various degrees is common among humans. There are associated side effects with orthodox delivery systems and anti-inflammatory agents hence the study investigated the characteristics of herbal lipospheres and the anti-inflammatory potency of the lipospheres formulated from Pentaclethra macrophylla with the view to having a drug with a better delivery system and lesser side effects.Methods: Herbal lipospheres were formulated using solidified reverse micellar solutions (SRMS) of P90H and goat fat and characterized for particle size and morphology, pH – time dependent analysis, encapsulation efficiency (EE%) and Fourier Transform infrared spectroscopy. The in vitro antinociceptive and anti-inflammatory study were carried out using membrane stabilization by hypotonicity induced haemolysis and determination of anti-platelet aggregatory activity models. The in-vivo anti-nociceptive and anti-inflammatory studies on egg albumin and formaldehyde induced arthritis models were done. Total white blood cell count and differential blood count were carried out on the rats. Results: The results showed that there was no change in pH for the PM unloaded lipospheres and 2.5g of PM-loaded lipospheres from Day 1 to Day 7, but mild variation in the rest of the formulations. The EE ranged from 35.2% to 94% increasing according to the drug concentration. The photomicrographs of the lipospheres showed that the particles were spherical in shape. The particle sizes were within the acceptable range for lipospheres. FTIR showed no interaction. In the arthritis study, PM-loaded lipospheres inhibited edema consistently throughout the duration of observation. Inhibition of membrane increased steadily with an increase in concentration of PM in the lipospheres and the standard drug. The platelet aggregatory inhibition decreased steadily with an increase in concentration of the PM in the lipospheres as well as the standard. The T50 dose of PM had the highest percentage of WBC and it decreased as the treatment doses increased from T100 to T200. There was no significant differences among the Neutrophil counts of the different groups.Conclusion: The study, therefore, showed that the methanol extract of Pentaclethra macrophylla formed efficient herbal lipospheres with antinociceptive and anti-inflammatory activities.

The network pharmacology (NP) approach is a valuable novel methodology for understanding the complex pharmacological mechanisms of medicinal herbs. In addition, various in silico analysis techniques combined with the NP can improve the understanding of various issues in natural product research. This study assessed the therapeutic effects of Arum ternata (AT), Poria cocos (PC), and Zingiber officinale (ZO) on hyperlipidemia after network pharmacologic analysis. A protein–protein interaction (PPI) network of forty-one key targets was analyzed to discover core functional clusters of the herbal compounds. The KEGG pathway and gene ontology (GO) term enrichment analysis identified significant categories of hypolipidemic mechanisms. The STITCH database indicated a high connection with several statin drugs deduced by the similarity in targets. AT, PC, and ZO regulated the genes related to the energy metabolism and lipogenesis in HepG2 cells loaded with free fatty acids (FFAs). Furthermore, a combinational effect of the mixture of three herbs was found. The herbal combination exerted superior efficacy compared to a single herb, particularly in regulating acetyl-CoA carboxylase (ACC) and carnitine palmitoyltransferase 1 (CPT-1). In conclusion, the network pharmacologic approach was used to assess potential targets of the herbal combination for treatment. Experimental data from FFAs-induced HepG2 cells suggested that the combination of AT, PC, and ZO might attenuate hyperlipidemia and its associated hepatic steatosis.

Maintenance of intestinal barrier integrity is crucial for preventing inflammatory bowel diseases (IBDs) onset and exacerbations. In this work we study the effect of a fixed combination of Lactobacillus reuteri and Lactobacillus acidophilus and herbal extracts in an in vitro inflammation experimental model. Caco-2 cell monolayer was exposed to INF-γ+TNF-α or to LPS; Trans Epithelial Electrical Resistance (TEER) and paracellular permeability were investigated. ZO-1 and occludin tight junctions (TJs) were also investigated by mean of immunofluorescence. The pre-treatment with the fixed combination of probiotics and herbal extracts prevented the inflammation-induced TEER decrease, paracellular permeability increase and TJs translocation. In summary the fixed combination of probiotics and herbal extracts investigated in this research was found to be an interesting candidate for targeting the re-establishment of intestinal barrier function in IBDs conditions.

Coronavirus disease (COVID-19) is the current global public health threat with no specific, effective, and approved treatment available till date. The outbreak of COVID-19 has led the world into an unimagined and uncertain situation by disrupting the economies, claiming human lives, and leaving many into secondary mental health problems. As per the latest WHO report, approximately 8.2 million people are infected, and nearly 0.44 million lives are lost to COVID. The infection has spread to over 200 countries and territories around the world. The world is in search of efficient diagnostics and therapeutics, including vaccines, biologics and drugs. With the rapid increase in rates of infection and time constraints, drug repurposing seems to be a potential and viable option to find the promising anti-COVID therapeutics. In the wake of a rapid increase in the number of clinical trials involving drugs for repurposing, we aim to provide information on the safety concerns related to the drugs currently investigated in trials. This review also highlights the possible mechanisms of actions, adverse drug reactions, and contraindications of the drugs under repurposing evaluation.

The present minireview assessed the benefits of using artificial intelligence applications in healthcare at predicting the targets of bioactive small molecules in human. Method. The tool is a tuned algorithm, with novel data in web interface. Results. We used tables to order the information of Swiss Target Prediction that allow predictions on combination of chemotherapies and probable side effects. This tool is useful to understand the molecular mechanisms underlying a given phenotype or bioactivity, to rationalize possible favorable or unfavorable side effects and to predict off-targets of known molecules as well as to clear the way for drug repurposing. Predictions are done using a ligand-based approach to compare the similarity between a query molecule and the known ligands of a large collection of protein targets. Conclusion. This study allowed us to formulate recommendations for the use of some of the chemotherapeutic agent groups in cancer patients at a low cost. It is very important and beneficial for patients that take medicine for a longer period and on whose lives depend on such treatment.

Despite recent public health and hygiene advancements, enteric fever, commonly referred to as typhoid fever, remains a common disease in developing nations. The common mode of infection is contaminated water or food. Additionally, person-to-person transmission through poor hygiene and sewage contamination of water supplies has been blamed for most outbreaks. The exact burden of typhoid has yet to be discovered because of the lack of surveillance systems in many developing nations. This makes it difficult to estimate the number of cases. Recent studies have shown that the actual number of cases of typhoid has been estimated to be around 21.6 million annually. The mortality studies suggest that the incidence of typhoid is highest in children under five years old. Typhoid fever and paratyphoid fever have been demonstrated to be life-threatening illnesses. Salmonella serotype Typhi (S. Typhi) is the causative organism of typhoid fever whereas Salmonella serotype Paratyphi is the causative organism for paratyphoid fever. The S. Typhi bacterium is known to be resistant to various drugs. There is a dire need to develop new drugs to treat and overcome the current drug-resistant S. Typhi. The identification of new targets marks the beginning of the process of developing new anti-S. Typhi drugs. The S. Typhic genome sequencing and recent cutting-edge molecular biology tools have led to the discovery of numerous new inhibitors and targets. The goal of this review is to identify the most critical targets in the S. Typhi that are targeted by drugs. It also highlights the various promising vaccines on the market or are still in preclinical studies. A detailed understanding of the targets could help researchers develop safer and more efficient antibacterial agents against S. Typhi.Additionally, the advancement of molecular techniques and the knowledge of the Salmonella pathogenesis pathways have opened better avenues to develop effective antibiotics and vaccines against this pathogen. This review also sought to identify and summarize critical structures of this pathogen that play significant roles in the maturation, development, and pathogenesis of S. Typhi. The endpoint of this work is to provide valuable information on potential therapeutic targets of S. Typhi for drug and vaccine developers.

Influenza viruses cause acute respiratory infections responsible for significant mortality and morbidity around the world. Various factors, such as antigenic drift, allow influenza strains to avoid being fully suppressed by seasonal vaccines. This has led to the increased scrutiny of antivirals as treatment and prophylaxis options for seasonal outbreaks and potential pandemics. Unfortunately, many influenza antivirals suffer from a lack of adequate clinical trials, as well as a lack of toxicity data. This is especially true of umifenovir (arbidol), a drug popularly used for the prevention and treatment of influenza strains in China and Russia. Neuraminidase inhibitors, though widely prescribed, display a potential for future resistance. Adamantanes, while proven to be effective in treating influenza A, are already encountering rapid and widespread cross-resistance and are effectively obsolete. Baloxavir marboxil, a newer antiviral, shows promise in treating acute uncomplicated influenza and may avoid the development of resistance when co-administered with other antiviral drugs. Indeed, the low genetic barrier to resistance associated with influenza antivirals could potentially be overcome by co-administration with other antivirals. This review explores the most widely prescribed antivirals for influenza treatment, their mechanisms of action, and the data currently available about their susceptibility to resistance and efficacy.

The pathophysiology of irritable bowel syndrome in children involves multiple factors. Thus, treatment options are variable, targeting diet and the child’s and parents’ behav-ior, involving pharmacological and psychological interventions or neuromodulation. Parents are increasingly interested in complementary and alternative therapies for children with irritable bowel syndrome, especially when other treatments have been tried without relieving the child’s symptoms. This paper looks into current evidence for the benefits and side effects of herbal remedies and spices in pediatric patients with IBS. The benefits of peppermint oil, STW5, Psyllium fiber, Curcuma, ginger, and other herbal medicines are discussed based on findings in the current literature.

The multifactorial nature of some diseases, and in particular neurodegenerative diseases such as Alzheimer’s disease, frequently requires the use of several drugs. These drug cocktails are not without drawbacks in terms of increased adverse effects, drug-drug interactions or adherence to treatment. The concept of pleiotropic drugs, which combine, within a single molecule, several activities directed against distinct therapeutic targets, makes it possible to overcome some of these problems. In addition, these pleiotropic drugs, generally, lead to the expression of a synergy of effects, sometimes greater than that observed with a combination of drugs. This article will review, through recent examples, the different kinds of pleiotropic drugs being studied or already present on the market of medicines.

In this work, we report the synthesis of a new thiosemicarbazone-based drug of N'-(di(pyridin-2-yl)methylene)-4-(thiazol-2-yl)piperazine-1-carbothiohydrazide (HL) featuring a thiazole spectator for the efficient coordination with Cu(II) to give [CuCl(L)]2 (1) and [Cu(NO3)(L)]2 (2). Both 1 and 2 exhibit dimeric structures ascribed to the presence of di-2-pyridylketone moieties that demonstrate dual functions of chelation and intermolecular bridging. HL, 1 and 2 are highly toxic against hepatocellular carcinoma cell lines Hep-G2, PLC/PRF/5, and HuH-7, with half maximal inhibitory concentration (IC50) values as low as 3.26 nmol/mL (HL), 2.18 nmol/mL (1), and 2.54 × 10−5 nmol/mL (2) for PLC/PRF/5. While the free ligand HL may elicit its anticancer effect via sequestration of bio-relevant metal ions (i.e. Fe3+ and Cu2+), 1 and 2 are also capable of generating cytotoxic reactive oxygen species (ROS) to inhibit cancer cell proliferation. Our preliminary pharmacokinetic studies revealed that oral administration (per os, PO) of HL has a significantly longer half-life t1/2 of 21.61 ± 9.4 h, nearly doubled as compared to that of the intravenous (i.v.) administration of 11.88 ± 1.66 h, certifying HL as an effective chemotherapeutic drug via PO administration.

Magnaporthe oryzae is a filamentous heterothallic ascomycete fungus globally distributed in rice-growing regions and serves as the causative agent of rice blast disease. Populations shaped by environmental factors and human intervention play important roles in the formation of genetic structure. In this study, population structures and spatiotemporal dynamics were investigated based on the large-scale whole genomic sequences of rice-infecting M. oryzae around the world. By analyzing the genetic structures, we identified divergent clades that crossed geographic boundaries. While we observed associations between the isolates and their geographic origins, we also found that there were frequent migration events occurring worldwide. The populations in Asia demonstrated the highest genetic diversity due to the continent’s history of rice domestication, followed by separate gene flows to Africa, North America, South America and Europe. Within Asia, China was the migration origin, facilitating gene flows to Japan and South Korea. Additionally, our analysis of the evolutionary history of global M. oryzae populations provided insights into the population expansion that has taken place in recent decades. Overall, our findings indicate that human-mediated gene flows played a pivotal role in shaping the genetic structure of M. oryzae.

This study compared the efficacy of alfaxalone and propofol to induce anesthesia in bitches undergoing an ovariohysterectomy or cesarean sections. 34 healthy and pyometra-affected females were induced with IV propofol administration, 35 healthy and pyometra-affected bitches were induced with the IV administration of alfaxalone. For the cesarean sections, females were induced with propofol (n=14) or alfaxalone (n=14). Maternal physiological parameters (heart rate, blood pressure, temperature) were recorded throughout surgeries; the viability and a modified Apgar score was recorded in the neonates at 5, 60 and 120 minutes after delivery. The use of propofol and alfaxalone did not show relevant differences over parameters assessed, when ovariohysterectomy was performed in healthy bitches or females with pyometra, as well as when cesarean sections were compared; only, a transient tachycardia appeared after alfaxalone administration. However, a higher percentage of bitches needed extra-doses of propofol. Neonatal mortality was similar between both groups, but when alfaxalone was used a higher neonatal viability was observed. Propofol and alfaxalone showed similar efficacy to perform the ovariohysterectomy in all bitches. Both protocols were optimal for cesarean sections, but alfaxalone was associated with a higher neonatal viability and a higher neonatal survival rate.

The mammalian or mechanistic target of rapamycin (mTOR) integrates multiple intracellular and extra-cellular upstream signals involved in the regulation of anabolic and catabolic processes in cells, and plays a key regulatory role in cell growth and metabolism. Activation of the mTOR signaling pathway has been reported to be associated with a wide range of human diseases. A growing number of in vivo and in vitro studies have demonstrated that the gut microbes and its complex metabolites can regulate host metabolic and immune responses through the mTOR pathway, and result in disorders of host phys-iological functions. In this review, we summarize the regulatory mechanisms of gut microbes and mTOR in different diseases, and discuss the crosstalk between gut microbes and their metabolites and mTOR in the disorders in gastrointestinal tract, liver, heart and other organs. We also discuss the promising appli-cation of multiple potential drugs that can adjust the gut microbiota and mTOR signal pathways. Despite the limited findings between gut microbes and mTOR, elucidating their relationship may provide new clues for the prevention and treatment of various diseases.

It is currently recognized that an injudicious strategy in the last decades has been not only focusing of research typically on caries in children, but also the narrow focusing on fluoride, because despite sufficient availability of fluoride in water and oral healthcare products, caries levels escalate steadily as people get older and caries remain a main public health issue to be settled. In the last two decades the scientific community intensified efforts of exploring other products for caries prevention, herbal products being one of these approaches. Because preliminary evidence indicated that clinical trials for caries prevention with herbal products are heterogeneous in design, quality and products evaluated, we performed a scoping review intended to explore the main characteristics of such clinical trials. From an initial collection of 1986 unique papers from different literature databases, 56 articles satisfied the inclusion and exclusion criteria. The species investigated, dosage forms, study designs, duration of intervention, controls, endpoints, quality of reporting and risk of bias are discussed. 85.71% of the trials reviewed here reported positive results but given the methodological flaws and biases affecting them, it is difficult to conclude on the efficacy of those products based on the studies published thus far.

There is proliferation of alcoholic beverages flavoured with herbal-extracts perceived to have medicinal values. Information on the phytochemical and heavy metal contents of these products is scarce. This study assessed the phytochemical properties and heavy metal contents of herbal-extract flavoured alcoholic beverages in major motor parks in Ibadan, Nigeria. The phytochemical properties of the beverages were determined in triplicate using standard methods while the heavy metal contents were assessed using atomic absorption spectrophotometry. Data were analyzed using descriptive statistics and means were compared using ANOVA at p<0.05. The pH range of the beverages was 3.28-6.57 and the alcohol content was 34.0-51.5%. Detected major phytochemicals and concentration ranges were phytic acid (0.72-2.37 mg/g), alkaloids (0.42-4.11 mg/g), flavonoids (0.22-3.64 mg rutin equivalents/g), total phenols (1.13-3.66 mg gallic acid equivalents/g), anthraquinones ((0.74-1.93 mg/g) and triterpenoids (0.74-1.93 mg/g). The phytochemical contents were within the acceptable limits while the heavy metals were: Pb (2.13-4.70 mg/L), Cd (0.06-0.07 mg/L), Co (0.12-0.23 mg/L), Zn (0.14-0.40 mg/L) and Fe (0.72-4.22 mg/L); all except Pb and Cd were within permissible limits. The herbal-extract flavoured alcoholic beverages contain beneficial phytochemicals and traces of heavy metals. Safety awareness of these products for improved consumers’ health would be of public health importance.

Toxoplasma gondii (T. gondii) is one of the most common parasites that infect humans. The parasite exists in approximately 40 million people in the United States. Latent infections are frequently associated with tissue cysts of T. gondii in the skeletal muscle and brain tissue that can lead to mental disorders, congenital disorders, and vision dysfunction. Furthermore, self-directed violence, impulsivity, and aggression are associated with T. gondii infection. Dopamine is associated with human behavior including pleasure, aggression, memory, and substance use disorder; however, the result of the studies on the association of T. gondii infection and drugs of abuse are not well understood. The frequency of substance use may be associated with substance-induced modification of dopamine-receptor densities and basal dopaminergic activity. Likewise, T. gondii can directly or indirectly influence dopaminergic activity in infected cells. Based on this hypothesis, the current paper aimed to systematically review all published literature on the association between drugs of abuse and T. gondii infection. Systematic review of controlled studies on T. gondii infection and substance use effects in adults were searched on the electronic databases. Studies have shown that individuals infected with T. gondii display increased risky behavior, such as excessive alcohol consumption. Furthermore, it was observed that T. gondii seropositive subjects had a reduced likelihood of self-reported substance use compared to T. gondii seronegative subjects. This study confirms that SUD is a potential risk factor for behavioral and psychiatric complications associated with T. gondii infection. Ultimately T. gondii infection in the context of drug dependence and the development of SUD remain to be elucidated. Therefore, it is necessary to conduct further research characterizing the mechanisms associated with dopamine metabolism of drug dependence and withdrawal in the context of a T. gondii infection, evaluating the role of inflammation, and identifying potential drug-and-sex specific underpinnings of these associations.

Hydrogels, hydrophilic polymeric compounds, have been recently put under investigation as regenerative medicine applications and delivery systems for antineoplastic drugs, particularly chemotherapeutics (anthracyclines, alkylating agents), target drugs (trastuzumab) and immunotherapies. Porosity, conductivity, biodegradability and physical states are some of the peculiarities that render hydrogels suitable for therapies implementation. Chemically-modifying agents and enzymes can be also coupled to hydrogels for pharmacokinetical parameters improvement and side effects avoidance. Cardiotoxicity is in fact one of the major issues for oncological patients after treatment efficacy. Heart failure, myocarditis and hypertension are causes of morbidity and mortality that can possibly be avoided. Specific reaching of the target tumor site has been achieved by several authors in preclinical in vivo studies but clinical studies are currently under design processes. Polydioxanone, a hydrogel-mimicking agent, is capable to interact with the elastic properties of pulmonary artery. An advantageous characteristic is that can be also reabsorbed within biological systems and can cause a remodeling process of the vessel wall. Hydrogels currently represent a strong topic of interest for researchers and probably will guide future clinical investigations and practice.

Agricultural waste is rich in bioactive molecules. In evaluating the viability of circular models for the development of health-promotional substances and final products, it is important to highlight that the processing industry of fruits and other valuable herbal materials generates a considerable number of by-products and waste containing health-promoting components. These by-products can be utilized purposefully used in pharmaceuticals and related areas for the development of health promotional products. The linear utilization of agricultural waste results in the loss of a range of valuable bioactive compounds, including polyphenols (anthocyanins, flavonoids, phe-nolic acids, and related compounds), antioxidants from other groups, as well as phytosterols, tocopherols and fatty acids. As an illustrative example, the waste materials of species belonging to the Vaccinium genus represent a notable secondary resource that can be purposefully applied to the development of health-promoting substances. The fruits of these wasted herbal materials have been found to contain reliable polyphenols, which play a pivotal role in the prevention of various chronic conditions, including precancerous conditions, inflammatory diseases and other ailments. In addition, the fruits of blackberries, elderberries, and purple corn which are similarly rich in anthocyanins also provide a promising avenue for further developments. Phenolic compounds suitable for recycling are also found in sugarcane harvesting by-products. Tomato waste contains a significant amount of the valuable carotenoid lycopene. The additional value of the above-mentioned fruit processing by-products may attribute to specified physiological functions, which, if used properly, can contribute to the prevention of certain diseases, and improving of quality of life. This review assessed the scope and gaps in the existing principles on the isolation of health-promoting substances from herbal secondary materials.

Reducing carbohydrates digestion by having low glycaemic index (GI) foods has been linked to weight loss. Inhibiting related enzymes is an alternative way to decrease carbohydrate digestion. RCM-107, an eight-herb formula that is modified from the RCM-104, has indicated significant weight-loss action in clinical trials. However, no research has been conducted to study its effect on the activity of porcine pancreatic alpha-amylase (PPA), which is involved in carbohydrate absorption. In this paper, we used fluorescence PPA inhibition assay to investigate the inhibitory effects of RCM-107 and the individual herbs present in this herbal mixture on amylase activity. Subsequently, molecular docking predicted the key active compounds that may be responsible for the enzyme inhibition. According to our results, both the RCM-107 formula and several individual herbs displayed α-amylase inhibitory effects. Also, marginal synergistic effects of RCM-107 were also detected. In addition, alisol B, (-)-epigallocatechin-3-gallate (EGCG) and plantagoside have been predicted as the key active compounds that may be responsible for the α-amylase inhibition effect of RCM-107 according to inter-residue contact analysis. Finally, Glu233, Gln63, His305, Asp300 and Tyr151 are predicted to be markers of important areas with which potential amylase inhibitors would interact.

In this study, we repositioned thiopurine drugs used for the treatment of acute leukaemia as new tyrosinase inhibitors. Tyrosinase catalyses two distinct and successive oxidations in melanin biosynthesis: the conversions of tyrosine to dihydroxyphenylalanine (DOPA) and DOPA to dopaquinone. Continuous efforts are underway to discover small molecule inhibitors of tyrosinase for therapeutic, cosmetic, and agricultural purposes. Structure-based virtual screening has predicted inhibitor candidates for mushroom tyrosinase from drugs approved by the US Food and Drug Administration (FDA). Enzyme assays have confirmed the thiopurine leukaemia drug, thioguanine, as a tyrosinase inhibitor. Two other thiopurine drugs, mercaptopurine and azathioprine, were also evaluated for their tyrosinase inhibitory activity; mercaptopurine caused stronger inhibition than thioguanine did, whereas azathioprine was a poor inhibitor. The inhibitory constants of thioguanine and mercaptopurine were calculated as 52 and 16 µM, respectively, and the value of mercaptopurine was comparable to that of the well-known inhibitor kojic acid (13 µM). The cell lysate and melanin content assay in B16F10 melanoma cells confirmed that the compounds inhibited mammalian tyrosinase. In particular, 50 µM thioguanine reduced the melanin content by 57% without cytotoxicity. Furthermore, the thiopurine drugs shared little chemical similarity with the known tyrosinase inhibitors.

Synthetic antivirals and corticosteroids have been used to treat both influenza and the SARS-CoV-2 disease named COVID-19. However, these medications are not always effective, produce several adverse effects, and are associated with high costs. Medicinal plants and their constituents act in several different targets and signaling pathways involved in the pathophysiology of Influenza and COVID-19. This study aimed to perform a review to evaluate the effects of medicinal plants on Influenza and COVID-19 and to investigate the potential delivery systems for new antiviral therapies. EMBASE, PubMed, GOOGLE SCHOLAR, and COCHRANE databases were searched. The studies included in this review showed that medicinal plants, in different formulations, can help decrease viral spread and time of full recovery. Plants reduced the incidence of acute respiratory syndromes and the symptom scores of the illnesses. Moreover, plants are related to few adverse effects and have low costs. In addition to their significance as natural antiviral agents, medicinal plants and their bioactive compounds may exhibit low bioavailability. This highlights the need for alternative delivery systems, such as metal nanoparticles, that can effectively transport these compounds to infected tissues.

Water and sanitation facilities in sub-Saharan Africa and Africa in general are appalling and for the most part absent. Progress continues with respect to the development of plant materials as potent adsorbents, disinfectants, coagulants, flocculants, wetland species and lots more as substitutes for the dangerous chemical disinfectants. This research presents the potential of phyto-active components of Zanthoxylum zanthoxyloides and Gongronema latifolium as effective biocides against water microbial contaminants. Dry powder of Zanthoxylum zanthoxyloides and Gongronema latifolium were extracted and prepared into different concentrations with ethyl acetate and chloroform, ranging from 25 to 500 mg/ml. These fractions were then examined for antimicrobial activities against inherent bacterial and fungal water contaminants using disc diffusion assay. Fractions were afterwards screened for phytochemical active compounds using standard methods. Crude extracts of the different plant examined selectively comprise saponins, tannins, reducing sugars, anthraquinones, flavonoids, terpenoids, phlobatanins and alkaloids. All plant extracts showed broad spectrum antibiosis against selected gram positive and gram negative bacteria including E. coli, P. aeruginosa, Klebsiella sp, S. pneumoniae and B. cereus, as well as tested fungi, including A. niger, A. flavus, Trichoderma sp and Candida sp. While all extracts exhibited maximum antibiosis at 500 mg/ml, the chloroform extracts compared well than ethyl acetate extracts. The overall results revealed that antimicrobial activities of the plant extracts are dose dependent with comparative activity greater than that of commercial antibiotics at the concentration of extracts tested. E.coli was the most susceptible microbial isolate tested and represents the potential of the extract against a group of coliform which are important indicators of microbial pollution in water. Other microbial isolates also recorded sensitivity to extracts tested at varying degrees. The findings indicate that microbes tested were mostly susceptible to chloroform extract of Z. zanthoxyloides and G. latifolium except for the activity of ethyl acetate extract of Z. zanthoxyloide against E.coli. Results of phytochemical screening of the extract also showed the varied presence of alkaloids, saponins, tannins, flavonoids, terpenoids and anthraquinones The results indicated that plant materials investigated can be developed as effective biocides against water microbial contaminants

Parkinson-like events are side effects that may persist for an extended period even after drug administration is discontinued. Although these events can be triggered by various drugs, the mechanisms underlying their diverse symptoms remain largely unclear. To investigate this, we used the Japanese Adverse Drug Event Reporting Database, which is maintained by the Phar-maceuticals and Medical Devices Agency, to analyze the risk factors associated with Parkinson-like events along with associated drug trends and characteristics. Our findings indicate that similar to　Parkinson’s disease, age-related differences affect the onset of these events, with older individuals being more susceptible. Hierarchical clustering and principal component analysis revealed that the mechanisms triggering these Parkinson-like events are consistent across reports, suggesting a common underlying cause. However, even with a consistent mechanism, side effects can vary depending on the site of action. These insights underline the importance of swift identification of the drugs suspected of causing these events and implementation of measures to reduce their side effects.

The low water solubility of any pharmacoactive molecules limits their pharmacological potential but the solubility parameter cannot compromise, so different approaches are employed to enhance their bioavailability. Pharmaceutically active molecules with low solubility convey a higher risk of failure for drug innovation and development. Pharmacokinetics, pharmacodynamics, and several other parameters, such as drug distribution, protein binding and absorption, are majorly affected by their solubility. Among all pharmaceutical dosage forms, the oral dosage forms cover more than 50 %, and the drug molecule should be water-soluble. For good therapeutic activity by the drug molecule on the target site, solubility and bioavailability are crucial factors. The pharmaceutical industry screening programs identified that around 40% of new chemical entities (N.C.E.s) face various difficulties at the formulation and development step. These pharmaceuticals are attributed to their less solubility and bioavailability. The bioavailability and drug solubility enhancement are significant challenges in the area of pharmaceutical formulations. According to the Classification of Biopharmaceutics, Class II and IV drugs (APIs) exhibits poor solubility, lower bioavailability, and less dissolution. Various technologies are discussed in this article to improve the solubility of the poorly water-soluble drug, for example, complexation of active molecules, utilization of emulsion formation, micelles, microemulsions, cosolvents, polymeric micelles preparation, particle size reduction technologies, pharmaceutical salts, prodrugs, solid-state alternation technique, soft gel technology, drug nanocrystals, solid dispersion methods, crystal engineering techniques and nanomorph technology. This review mainly describes several other advanced methodologies for solubility and bioavailability enhancement, such as crystal engineering, micronization, solid dispersions, nano sizing, use of cyclodextrins, solid lipid nanoparticles, colloidal drug delivery systems and drug conjugates, by some appropriate research reports.

Brazil chicken production is around 13 million tons and about a third is exported to over 150 countries, placing Brazil as the world largest chicken meat producer, and therefore it is crucial to follow the legislation of all importer markets. This study conducted a survey by chance in 45 meat industries able to export. Therefore, 2580 chicken meat samples were collected and submitted to 11 analyte extraction and chromatographic verification of compliance in an accredited laboratory. Ten chemical residues (amoxicillin, bacitracin, colistin, dinitolmide + zoalene, spectinomycin, roxarsone, tiamulin, tylosin, trenbolone acetate and virginiamycin) were investigated in chicken meat and one (halofuginone hydrobromide) in chicken liver. The results showed that no compound exceeded the maximum residue limits established by seven legislations. All residue concentrations found were below the method quantification limit, thereby confirming the capability of Brazilian chicken meat industries in complying to foreign markets.

Many approaches have been developed over time to counter the bioavailability limitations of poorly soluble drugs. With advances in nanotechnology in recent decades, science and industry have been approaching this issue through the formulation of drugs as nanocrystals, which consist of pure drugs and a minimum of surface active agents required for stabilization. They are carrier-free submicron colloidal drug delivery systems with a mean particle size in the nanometer range, typically between 10 and 800 nm. By reducing particle size to nanoscale, the particle surface area available for the molecule dissolution in the direction of dissolution medium is increased, and thus bioavailability is enhanced. This approach has proven successful, as demonstrated by the number of such drug products on the market. R&D and industry have offered many technological solutions to reduce the particle size to nanoscale, and also devised solutions for the handling of particle of nanodimensions, such as methods to accurately measure nanoparticle size and techniques to prevent physicochemical and stability related problems, such as aggregation. The present work provides an overview of the more recent achievements in improving the bioavailability of poorly soluble drugs according to their administration route, and describes the methods developed to overcome physicochemical and stability related problems.

Diabetes mellitus is a cluster of metabolic diseases characterized by hyperglycemia. Since this epidemic growing worldwide, the usage of phototherapeutics to manage diabetes is vital. Coccinia grandis (Aka ivy gourd) belongs to cucumber family is identified as a most effective herb, especially for diabetes and many other disease conditions. Hence, an instant herbal porridge cube incorporating Coccinia grandis leaf powder was produced and sensory acceptability of the porridge was evaluated using trained panelists. The bioactive activity of Coccinia grandis leaf powder showed that 66.77±0.74 mg/g GAE of Total Phenolic Content, 27.65±6.79% of DPPH radical scavenging activity, 5.72% of alpha-amylase inhibition activity and 59.64% of alpha-glucosidase inhibition activity. The effect on postprandial blood sugar levels after consuming the developed porridge was measured using healthy adults and it was observed there was no blood sugar elevation during the 2 hours of time. As a further development, Coccinia grandis leaf extract was nano-encapsulated with food grade Sodium alginate and it was incorporated into the same porridge as a safe delivery method of bioactive compounds. In-vitro digestion assay was conducted and the results show that alpha-amylase inhibition activity for the gastric phase and alpha-glucosidase inhibition activity for the intestinal phase was higher in nano-encapsulated porridge. The study concludes that, consuming nano-encapsulated Coccinia grandis leaf extract with porridge is more beneficial for diabetic patients.

The incidence of lung cancer has increased in recent years and causes major mortalities across the globe. Besides, the availability of the several chemotherapeutics modalities in the management, there is still a challenge to find out an efficient remedy with lesser or no toxic effects. Hence, there is a necessity to employ complementary research to establish effective management for lung cancer. In this study, we have implemented a novel herbal informatics model to find out the alternative remedy in the treatment of lung cancer. This model utilizes five major steps of the bioprospection process based on the classical surge followed by the binary index and rationale-based selection of herbal products targeting the cancer-causing factors which are explained in detail in the methodology section of this model. This study revealed 07 herbals such as Withania somnifera (Ws), Berberis vulgaris(Bv), Glycyrrhiza glabra(Gg), Andrographis paniculate(Ap), Azadirachta indica(Ai), Cinnamomum Verum(Cv), Piper longum(Pl) based on the fuzzy set optimization scoring(0.6-1) that could be further studied in vitro and in vivo level for utilization in the management of lung cancer.

In most countries, the incidence of nasopharyngeal carcinoma (NPC) is no more than 1 per 100,000 for both men and women; however, it is much higher for men and women in Taiwan. The use of traditional Chinese medicine (TCM) as complementary and alternative medicine for the treatment of NPC and its treatment-related side effects has been increasing. The National Health Insurance (NHI) covers 99.6% of Taiwan’s residents. In the present population-based cohort study, we aimed to investigate the pattern of utilization of Chinese herbal products (CHPs) for NPC from 2001 through 2011 in Taiwan. We identified a total of 30294 patients with newly diagnosed NPC from the Registry for Catastrophic Illnesses Patient Database (RCIPD). Descriptive statistics and multiple logistic regression analysis were employed to estimate the adjusted odds ratios (aORs) for CHP utilization. From 2001 through 2011, 17816 patients aged ≥20 years were newly diagnosed with NPC. Of these, 4749 patients used TCM outpatient services for NPC treatment. TCM users were more likely to be women, young, residents of Central Taiwan, and white-collar workers. The most commonly prescribed formula CHP was Gan-Lu-Yin, followed by Xin-Yi-Qing Fei-Tang and Shan-Shen-Mai-Men-Dong-Tang. The most commonly prescribed single CHP was Hedyotis diffusa, followed by Radix Scrophulariae and Radix Ophiopogonis. These findings provide information regarding personalized therapies for NPC and can promote further clinical experiments and pharmacological research on CHPs for NPC treatment in Taiwan. Further well-designed randomized controlled studies and basic mechanistic studies should assess the safety and effectiveness of CHPs for NPC treatment.

Human metapneumovirus is one of major causes of common cold among children, especially infants. Its key enzyme is RNA-dependent RNA-polymerase, which performs both replication and transcription, including capping and cap methylation. The goal of the work is to find possible inhibitors of RNA-dependent RNA-polymerase across the active compounds of Rosaceae plants. The candidates were selected by molecular docking to cap-transferring domain of RNA-polymerase (PDB ID: 4UCZ) in Autodock VINA. Among all the substances tested by docking, ellagic acid derivatives showed the most promising results (affinity values below -10 kcal/mol). Hence, they could be treated as possible candidate drugs against metapneumoviral infection after experimental examination. The main advantage of using these substances should be their low toxicity, which is quite uncommon for selective RNA polymerase inhibitors used in clinical practice. Occurrence of ellagic acid derivatives among the plants from Rosaceae family like raspberry could explain their effect during common cold.

Overexpression of BRF2, a selective subunit of RNA polymerase III, has been shown to be crucial in the development of several types of cancers, including breast cancer and lung squamous cell carcinoma . Predominately, BRF2 acts as a central redox-sensing transcription factor (TF) and is involved in rescuing oxidative stress (OS) -induced apoptosis. Here, we showed a novel link between BRF2 and DNA damage response. Due to the lack of BRF2 specific inhibitors, through virtual and molecular dynamics screening, we identified potential drug candidates that interfere with BRF2-TATA-binding Protein (TBP)-DNA complex interactions based on binding energy, intermolecular, and torsional energy parameters. We experimentally tested Bexarotene as a potential BRF2 inhibitor. We found that Bexarotene (Bex) treatment resulted in a dramatic decline in oxidative stress (Tert-butylhydroquinone (tBHQ))-induced levels of BRF2 and consequently, lead to a decrease in cellular proliferation of cancer cells which may in part be due to drug pretreatment induced reduction of ROS generated by the oxidizing agent. Our data thus, provide the first experimental evidence that BRF2 is a novel player in DNA damage response pathway and Bexarotene can be used as a potential inhibitor to treat cancers with the specific elevation of oxidative stress.

Objectives: The mechanism of action of drugs that depress the central nervous system (CNS) was unknown until molecular pharmacology discovered each drug's exact role. The benefit of knowing the mechanism of action is to design a new drug that could have the same efficacy as the prototype drug but with fewer side effects. Some of the available CNS depressant drugs that were abused or illegally used could be modified to make them used medically. Methods: We reviewed various published articles in PubMed and Google Scholar that focused on CNS depressants' molecular pharmacology.Results: It was clear that at specific plasma concentrations of ethyl alcohol showed almost same mode of action of propofol by targeting the extrasynaptic GABA-A receptors, which causes tonic GABAergic inhibition. Besides, the High affinity of some benzodiazepines (e.g., midazolam) to α1 subunit of GABA-A receptor causes sedative, hypnotic, amnesic, and some antiepileptic effects; however, some other benzodiazepines (e.g., diazepam) have high affinity to α3 subunits, which causes anxiolytic, muscle relaxant, and strong antiepileptic effects. The CB1 receptor partial agonism effect of tetrahydrocannabinol has a sedative advantage over full agonism due to desensitization of CB1 receptors. Conclusion: From the molecular pharmacology prospect, it is possible to design new drugs with more specific CNS depressants effect and fewer side effects by targeting particular receptors with a precise reaction.

Folk medicine is widely used in Angola, even for human African trypanosomiasis (sleeping sickness) in spite of the fact that the reference treatment is available for free. Aiming to validate herbal remedies in use, we have selected nine medicinal plants and assessed their antitrypanosomal ac-tivity. 122 extracts were prepared using different plant parts and solvents. 15 extracts from seven different plants exhibited in vitro activity against Trypanosoma brucei rhodesiense bloodstream forms >70% at 20 µg/ml. The dichloromethane extract of Nymphaea lotus (leaves and leaflets) and the ethanolic extract of Brasenia schreberi (leaves) had IC50 values ≤10 µg/ml. These two aquatic plants are of particular interest. They are being co-applied in the form of a decoction of leaves because they are considered by local healers as male and female of the same species, the ethnotaxon “longa dia simbi”. Bioassay-guided fractionation led to the identification of eight active molecules: gallic acid (IC50 0.5 µg/ml), methyl gallate (IC50 1.1 µg/ml), 2,3,4,6-tetragalloyl-glucopyranoside, ethyl gallate (IC50 0.5µg/ml), 1,2,3,4,6-pentagalloyl-β-glucopyranoside (IC50 20µg/ml), gossypet-in-7-O-β-glucopyranoside (IC50 5.5µg/ml), and hypolaetin-7-O-glucoside (IC50 5.7µg/ml) in B. schreberi, and 5-[(8Z,11Z,14Z)-heptadeca-8,11,14-trienyl] resorcinol (IC50 5.3µg/ml) not described to date in N. lotus. Five of these active constituents were detected in the traditional preparation. This work provides the first evidence for the ethnomedicinal use of these plants in the management of sleeping sickness in Angola.

Background: Gastric cancer (GC) is the second most prevalent cancer in Korea, significantly impacting morbidity and mortality. While advancements in early detection and treatment have improved survival rates, managing post-surgical recovery remains vital. Herbal medicine (HM) has emerged as a potential adjunct therapy to enhance recovery and quality of life (QoL) in patients post-GC surgery. Methods: This systematic review and meta-analysis evaluated the efficacy and safety of HM in the post-surgical recovery of GC patients. We searched both Korean and international databases, identifying 16 randomized controlled trials (RCTs) meeting our criteria. We assessed study quality using the Cochrane Risk of Bias tool and analyzed data with Review Manager Software (RevMan). Results: Our analysis included 1,546 patients from the selected studies, demonstrating that HM significantly improved gastrointestinal recovery times, including time to first flatus, bowel movement, and return of bowel sounds. Significant improvements were also seen in nutritional markers such as albumin and prealbumin, alongside beneficial effects on immune markers like CD3+ and CD4+ levels. QoL assessments using WHOQOL-BREF and QLQ-C30 scores indicated substantial improvements. HM had a favorable safety profile, showing a reduced incidence of adverse effects compared to controls. Conclusion: The findings suggest that HM can significantly enhance recovery and improve the quality of life following gastric cancer surgery, with a favorable safety profile. However, due to considerable heterogeneity in study results, extended clinical trials and rigorous follow-ups are recommended to assess long-term effects and side effects comprehensively.

The aim of this study is to solve the problems of complicated pretreatment and high analytical cost in the detection technology of trace drug toxicants in municipal wastewater. A high-performance magnetic sorbent was synthesized for enrichment of trace drug substances in wastewater to develop magnetic solid-phase extraction pretreatment combined with the acoustic ejection mass spectrometry (AEMS) analytical methods for the molecules in wastewater drug toxicants. The magnetic nanospheres was successfully prepared by magnetic nanoparticles modified with divinylbenzene and vinyl pyrrolidone.The results showed that the linear dynamic range of 17 drugs was 1-500 ng/L, the recovery was 43%-105%, the matrix effect was more than 67%, the limit of quantitative detection was 1-2 ng/L, and the detection time of each sample was 2.98s. It can be seen that the developed magnetic solid-phase extraction (MSPE) method is a good solution to the problem of complicated pre-treatment and analytical cost in the detection of drugs in wastewater. The developed magnetic material and acoustic excitation coupled mass spectrometry analysis method can realize the low-cost, efficient enrichment and fast analysis of different kinds of drug molecules in urban sewage.

We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD), to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies for such investigations. PubMed was searched using specified search terms. One small prospective study on diet and anti-TNF treatment in 56 patients with CD found similar remission rates after 56 weeks among 32 patients with good compliance that received concomitant enteral nutrition and 24 with poor compliance that had no dietary restrictions (78% versus 67%, p = 0.51). A meta-analysis of 295 patients found higher odds of achieving clinical remission and remaining in clinical remission among patients on combination therapy with specialised enteral nutrition and Infliximab (IFX) compared with IFX monotherapy (OR 2.73; 95% CI: 1.73–4.31, p < 0.01, OR 2.93; 95% CI: 1.66–5.17, p < 0.01, respectively). In conclusion, evidence-based knowledge on impact of diet on anti-TNF treatment response for clinical use is scarce. Here we propose a mechanism by which Western style diet high in meat and low in fibre may promote colonic inflammation and potentially impact treatment response to anti-TNF drugs. Further studies using hypothesis-driven and data-driven strategies in observational, animal and interventional studies are warranted.

Artificial Intellignece (AI) is a platform lending immense assistance in discovering and developing drugs and thus, various such approaches have been developed with the intent of simplifying and improving biomedical operations such as drug repurposing and drug discovery. In the past decade, AI-based investigation of nanomedicines, as well as non-nanomedicines has reached the clinical level. In semblance with the traditional methods of therapy, nanomedicine therapy is employed at limited doses. The study of a variety of drugs resulted in the conclusion that the effect of each drug is variable for every patient and, evaluating that perfect drug combination manually is a time-consuming as well as an inefficient treatment method. Therefore, the use of AI simplifies and reduces the time consumption in determining the perfect customized drug combination for nano-therapy. The area with the most potential for meeting this reality is to optimize the drug and dosage parameters. It is a universally known fact that cancer is dangerous and unique because of the exacting challenges it poses during treatment and, to achieve a better treatment, the therapeutic effect on each patient must be delineated even if the volume of data generated is massive. The article aims at analyzing the AI technologies that help yield results much quicker, make the analyses simple, and efficient.

During the current COVID-19 pandemic caused by SARS-CoV-2, clinicians and scientists are working assiduously to unravel its pathophysiology and find effective treatments. An impressive number of papers has been published on SARS-CoV-2, exposing the complexity of the disease, the tendency of scientists to form hypotheses within their area of expertise, and the lack of orchestration of research. Hypotheses and research findings mainly complement each other, though sometimes controversies can be discerned among various theories and study results. Our overview aims to portray the ‘big picture’ of COVID-19, visualising the interwovenness of different pathophysiological pathways, with a focus on cytokine-induced pathology, the sequelae of ACE2 downregulation, and thrombosis associated with microvascular injury. It aids in overseeing the effects of repurposed drugs on intended targets, but also alerts to the (adverse) effects on interacting pathways. The overview shows how comorbidities probably increase susceptibility to (severe) COVID-19 and provides the possible pathophysiological origin of signs, symptoms, and biochemical abnormalities.

Assessment of drugs toxicity and associated biomarker genes is one of the most important tasks in the pre-clinical phase of drug development pipeline as well as in the toxicogenomic studies. There are few statistical methods for the assessment of doses of drugs (DDs) toxicity and their associated biomarker genes. However, these methods consume more time for computation of the model parameters using the EM (Expectation-Maximization) based iterative approaches. To overcome this problem, in this paper, an attempt is made to propose an alternative approach based on hierarchical clustering (HC) for the same purpose. There are several types of HC approaches whose performance depends on different similarity/distance measures. Therefore, we explored suitable combinations of distance measures and HC methods based on Japanese Toxicogenomics Project (TGP) datasets for better clustering/co-clustering between DDs and genes as well as to detect toxic DDs and their associated biomarker genes. We observed that Word’s HC method with each of Euclidean, Manhattan and Minkowski distance measures produces better clustering/co-clustering results. For an example, in case of glutathione metabolism pathway (GMP) dataset LOC100359539/Rrm2, Gpx6, RGD1562107, Gstm4, Gstm3, G6pd, Gsta5, Gclc, Mgst2, Gsr, Gpx2, Gclm, Gstp1, LOC100912604/Srm, Gstm4, Odc1, Gsr, Gss are the biomarker genes and Acetaminophen_Middle, Acetaminophen_High, Methapyrilene_High, Nitrofurazone_High, Nitrofurazone_Middle, Isoniazid_Middle, Isoniazid_High are their regulatory (associated) DDs explored by our proposed co-clustering algorithm based on the distance and HC method combination Euclidean: Word. Similarly, for the PPAR signaling pathway (PPAR-SP) dataset Cpt1a, Cyp8b1, Cyp4a3, Ehhadh, Plin5, Plin2, Fabp3, Me1, Fabp5, LOC100910385, Cpt2, Acaa1a, Cyp4a1, LOC100365047, Cpt1a, LOC100365047, Angptl4, Aqp7, Cpt1c, Cpt1b, Me1 are the biomarker genes and Aspirin_Low, Aspirin_Middle, Aspirin_High, Benzbromarone_Middle, Benzbromarone_High, Clofibrate_Middle, Clofibrate_High, WY14643_Low, WY14643_High, WY14643_Middle, Gemfibrozil_Middle, Gemfibrozil_High are their regulatory DDs. These results are validated by the available literature and functional annotation.

Background: Identification of cancer biomarkers that are differentially expressed (DE) under two biological conditions is an important task in many microarray studies. There exist several methods in the literature in this regards and most of these methods designed especially for unpaired samples, which does not satisfy the requirements of paired samples where the gene expressions are taken from the same patients before and after treatment. Furthermore, the traditional biomarker identification methods based on either p-values or fold change (FC) values. However, sometimes, p-value based results do not comply with FC based results due to the smaller variance of gene expressions. There are some methods that combine both p-values and FC values to solve this problem. But, these methods also show weak performance for small-sample case in presence of outlying expressions. To overcome this problem, in this paper an attempt is made to develop a hybrid robust SAM-FC approach by combining rank of FC values and rank of p-values based on SAM statistic using minimum β-divergence method, which is designed for paired samples. This method introduces a weight function known as β-weight function. This weight function produces larger weights corresponding to usual/normal expressions and smaller weights for unusual/outlying expressions. The β-weight function plays the significant role on the performance of the proposed method. Results: The proposed method uses β-weight function as a measure of outlier detection by setting β=0.2. We unify both classical and robust estimates using β-weight function such that maximum likelihood estimators (MLEs) are used in absence of outliers and minimum β-divergence estimators are used in presence of outliers to obtain reasonable p-values and FC values in the proposed method. We examined the performance of proposed method in a comparison of some popular methods (t-test, SAM, LIMMA, Wilcoxon, WAD, RP and FCROS) using both simulated and real gene expression profiles for both small-and large-sample cases. From the simulation and a real spike in data analysis results we observed that the proposed method outperforms other methods for small-sample case in presence of outliers and it keeps almost equal performance with other robust methods (Wilcoxon, RP and FCROS) otherwise. From a head-and-neck cancer (HNC) dataset the proposed method identified 2 genes (CYP3A4, NOVA1) that are significantly enriched in linoleic acid metabolism, drug metabolism, steroid hormone biosynthesis and metabolic pathways. The survival analysis through Kaplan-Meier curve revealed that combined effect of these 2 genes has prognostic capability and they might be promising biomarker of HNC. Moreover, we retrieved the 12 candidate drugs based on gene interaction from glad4u and drug bank databases. Conclusion The identified drugs showed statistical significance and critical role of the proteins indicate that these proteins might be therapeutic target in cancer. Thus, elucidating the associations between the drugs identified in the present study require further investigations.

Long-acting (LA) drug-delivery system (DDS) successes are linked to their abilities to harness biocompatible polymers and materials for sustained and predictable release of therapeutic agents over an extended period of time. For human immune deficiency virus type one (HIV-1) infections, LA DDSs hold great promise in closing the gaps of daily oral therapy for treatment and prevention. Examples are Cabenuva, Apretude and Sunlenca, which have been shown to be safe and effective. Alternative promising drug delivery technologies such as implants, prodrugs, vaginal rings, and microarray patches are being explored to further meet patients’ needs. We posit that improved physicochemical properties of the formulation payloads and material chemistry design with optimal drug release kinetics holds the potential to optimize release profiles. Furthermore, for the treatment and prevention of HIV-1 infection, the landscape of LA medicines now in clinical or preclinical development offers hope that the strategic design of polymers will further improve upon controlled delivery of drugs to simplify dosing schedules.

Abstract: The kallikrein-kinin system consists of the two kininogen substrates, present in blood plasma, and of two serine proteases, the plasma and tissue kallikreins. The action of the latter on kininogens produce small peptides, the kinins, short lived but endowed by powerful pharmacologic actions on blood vessels and other tissues. Many recent and exciting therapeutic developments in the field are briefly summarized. Notably, various novel strategies are being clinically developed to inhibit the formation of bradykinin or block its receptors in the management of hereditary angioedema. The interventions include orally bioavailable drugs, biotechnological proteins, and gene therapy. These approaches are currently explored in a variety of other inflammatory and thrombotic disorders. Harnessing controlled kinin formation is also of potential therapeutic interest as shown by the clinical development of recombinant tissue kallikrein for ischemic stroke and renal disease. Biomarkers of a kinin-mediated disorders, frequently implicating edemas, include the consumption of kininogen(s), plasma kallikrein activity, and the detection of circulating kinin metabolites such as fragments BK_1-5 and BK_2-9. Novel opportunities to clinically apply the underexploited drugs of the kallikrein-kinin system are briefly reviewed. This personal perspective is offered by an observer of, and a participant in drug characterization during the last 4 decades.

The use of spirocycles in drug discovery and medicinal chemistry has been booming in the last two decades. This has clearly translated in the landscape of approved drugs. Among two dozen clinically used medicines containing a spirocycle, 50% have been approved in the 21st century. The present review focuses on the notable synthetic routes to such drugs invented in industry and academia and is intended to serve as a useful reference source of synthetic as well as general drug information for researchers engaging in the design of new spirocyclic scaffolds for medicinal use or embarking upon analog syntheses inspired by the existing approved drugs.

Many ligands directly target adenosine receptors (ARs). Here we review the effects of noncanonical AR drugs on adenosinergic signaling. Non-AR mechanisms include raising adenosine levels by inhibiting adenosine transport (e.g. ticagrelor, ethanol, cannabidiol), affecting intracellular metabolic pathways (e.g. methotrexate, nicotinamide riboside, salicylate, 5‐aminoimidazole‐4‐carboxamide riboside), or undetermined means (e.g. acupuncture). Yet other compounds bind ARs in addition to their canonical ‘on-target’ activity (e.g. mefloquine). The strength of experimental support for an adenosine-related role in a drug’s effects varies widely. AR knockout mice are the ‘gold standard’ method for investigating an AR role, but few drugs have been tested in these mice. Given the interest in AR modulation for treatment of cancer, CNS, immune, metabolic, cardiovascular, and musculoskeletal conditions, it is informative to consider AR and non-AR adenosinergic effects of approved drugs and conventional treatments.

Nano-drugs and nano-delivery systems are rapidly evolving, with new strategies emerging in the current practices. The evolution of these technologies began with modifying the chemical structure, progressing to supramolecular ionic complexes, and culminating in elegant ad hoc delivery systems. Nanoparticles have numerous benefits as a carrier system for delivering therapeutic agents to intra-arterial sites. These benefits include their subcellular size, targeted surfaces, good suspensibility, and uniform dispersity, making them an ideal choice for catheter-based delivery. Despite the advancements made in the field of nano-drugs and nano-delivery systems, there are still some hurdles to overcome in terms of their commercial availability.The current review presents an updated summary of recent advancements in nano-drugs and nano-delivery systems, including their commercial availability. We aim to discuss the present challenges and prospects of commercially available nano-drugs and nano-delivery systems. Here, we provide a precise and informative overview of the current state of these technologies and underscore the potential they hold for future developments. Further, we have categorized commercially available modifications, name, parent company and their main applications in nano-drugs.

Mental health issues can have significant impacts on individuals and communities and hence on social sustainability. There are several challenges facing mental health treatment, however, more important is to remove the root causes of mental illnesses because doing so can help prevent mental health problems from occurring or recurring. This requires a holistic approach to understanding mental health issues that are missing from the existing research. Mental health should be understood in the context of social and environmental factors. More research and awareness are needed, as well as interventions to address root causes. The effectiveness and risks of medications should also be studied. This paper proposes a big data and machine learning-based approach for the automatic discovery of parameters related to mental health from Twitter data. The parameters are discovered from three different perspectives, Drugs & Treatments, Causes & Effects, and Drug Abuse. We used Twitter to gather 1,048,575 tweets in Arabic about psychological health in Saudi Arabia. We built a big data machine learning software tool for this work. A total of 52 parameters were discovered for all three perspectives. We defined 6 macro-parameters (Diseases & Disorders, Individual Factors, Social & Economic Factors, Treatment Options, Treatment Limitations, and Drug Abuse) to aggregate related parameters. We provide a comprehensive account of mental health, causes, medicines and treatments, mental health and drug effects, and drug abuse, as seen on Twitter, discussed by the public and health professionals. Moreover, we identify their associations with different drugs. The work will open new directions for social media-based identification of drug use and abuse for mental health, as well as other micro and macro factors related to mental health. The methodology can be extended to other diseases and provides a potential for discovering evidence for forensics toxicology from social and digital media.

Acute myeloid leukemia (AML) is the most common and incurable leukemia subtype. Despite extensive research into the disease's intricate molecular mechanisms, AML have not yet identified effective treatments or expanded diagnostic or prognostic markers. The morphological, immunophenotypic, cytogenetic, biomolecular, and clinical characteristics of AML patients are extensive and complex. Leukemia stem cells (LSC) consist of hematopoietic stem cells (HSC) and cancer cells transformed by the complex, finely-tuned interaction that causes the complexity of AML. Microenvironmental regulation of LSC dormancy, its diagnostic and therapeutic implications for identifying and targeting LSCs due to their significance in the pathogenesis of AML were discussed in this review. It is essential to perceive the relationship between the niche for LSCs and HSC, which together cause the progression of AML. Notably, methylation is a well-known epigenetic change that is significant in AML, and our data also reveals that microRNAs are a unique factor for LSC. Furthermore, multiple-targeted approaches to reduce the risk of epigenetic factors, such as the administration of natural compounds for the elimination of local LSC, may prevent potentially fatal relapses. Furthermore, the survival analysis of overlapping genes revealed that specific targets had significant effects on the survival and prognosis of patients. We predicted that the multiple-targeted effects of herbal products on epigenetic modification are governed by different mechanisms in AML and prevent potentially fatal relapses. Thus, these strategies can facilitate the incorporation of herbal medicine and natural compounds into the advanced drug discovery and development processes enabled achievable by Network Pharmacology research.

Daily vitamin D supplementation using higher than normal dosing (up to the upper limit, UL) and intermittent (once or twice per week) dosing were studied in patients with increased risk of vitamin D deficiency. Using a PubMed database an adequate search for published randomized control trials and other studies was done and results were analyzed. This review provides overview of use of 7000 IU daily, 30,000 IU per week or twice weekly and 50,000 IU weekly of vitamin D on rapid restore of 25(OH)D concentrations to at least 30 ng/mL in different groups of patients at high risk of vitamin D deficiency. The above mention dosing should be considered in adults with obesity or multi-diseased patients on requiring multi-treatment with the use of several drugs, including drugs affecting vitamin D metabolism. The simple schedule for 7000 IU/day, 30,000 IU/week or twice weekly or 50,000 IU/week, all for 6-8 weeks of use by patients representing the increased risk of vitamin D deficiency were provided for consideration. It appeared that higher daily doses or intermittent doses suggested above are effective, safe and responsive for patient’s preferences.

Introduction: Pharmaceutical tablets are solid forms administrated orally and they constitute 80% of the market because of its best stability and ease of large-scale production, adherence and treatment. The Brazilian Legislation establishes that for a drug to be registered as a similar or generic drug is necessary to verify the pharmaceutical equivalence in relation to the reference drug, indicated by ANVISA, through quality control tests, ensuring that the drug is approved with satisfactory quality. Objective: to evaluate the reference, generic and similar glibenclamide tablets through quality control tests, comparing the results with each other and relate clinical impacts on the patient in the face of changes in the quality control of medicines. Methodology: tests of average weight, friability and disintegration were done, according to the Brazilian Pharmacopoeia VI Edition, in uncoated tablets of Glibenclamide 5mg Reference (Daonil), Generic (Glibenclamide) and Similar (Glionil), and the results obtained were compared with the that advocates the scientific literature. Results: Data referring to the average weight: Reference 0.1591g, Generic 0.1002g and Similar 0.0996g; For friability: Reference value 0.54%, Generic value 0.49% and Similar value 0.28%. The disintegration tests showed the following times: Reference 35 seconds, Generic 29 seconds and Similar 33 seconds. Conclusion: the tests to which the glibenclamide tablets were submitted showed results within the parameters established by the Brazilian Pharmacopoeia.

Multiple drugs administration is a common practice in hospitals and clinics. This is the case when heavy pathologies are treated. In this context, frequently, antivirals and antibiotics are co-administrated either simultaneously or sequentially ignoring potential incompatibilities. In this study, we focused on an antiviral (Acyclovir) and an antibiotic (Ciprofloxacin) compatibility/incompatibility when they co-administrated with special interest on the effect of drugs ratio, pH and delay. By implementing robust HPLC method, we determined the main factors leading to potential modification of concentration of one of the two drugs in the mixture. The results showed that acyclovir is quantitatively recovered in all conditions related to pH, concentration and time (up to 24 hours). However, ciprofloxacin is strongly altered in acidic and basic conditions, the quantity of ciprofloxacin and time after mixing the two drugs. The most valuable piece of information is that the ratio of acyclovir/ciprofloxacin is crucial. The latter should be calculated and managed to provide at least two fold quantity of acyclovir versus ciprofloxacin in order to maintain the administrated doses and warrant efficient therapeutic effect.

Abstract: Presence in a recipient of antibodies directed against donor specific antigens represent a major obstacle in transplanting such patients. Removal of these antibodies represents a challenge for physicians dealing with kidney transplantation. Several strategies, techniques and old and new drugs are to date used to desensitize these patients. Desensitization may occur before transplantation or at the time of transplantation or after transplantation according whether physicians deal with living or deceased donors. Different techniques may be used to reveal the presence of antibodies in the recipients; each technique has different sensitivity and specificity, different advantages and disadvantages. The target of the drugs used to desensitize are B cells, Plasma cells, the antibodies themselves and finally, the complement that is the final actor causing tissue disruption. If B cells are relatively easy to be targeted, more difficult are the plasma cell. Indeed, several new drugs are used in randomized trials also to defeat plasma cells. Antibodies may be removed rather easily, but often their removal is followed by a rebound. Complement is not easy to be defeated and new drugs are to date used to be successful in this action. However is to date possible to desensitize many patients and to obtain successful transplantation.

Insulin resistance, as a common pathological process of many metabolic diseases, including diabetes and obesity, has attracted much attention due to its relevant influencing factors. To date, studies have mainly focused on the mechanisms between mitochondrial stress and insulin resistance, and they are now pursued as a very attractive therapeutic target due to their extensive involvement in many human clinical settings. In view of the complex pathogenesis of diabetes, natural drugs have become new players in diabetes prevention and treatment because of their wide targets and few side effects. In particular, plant phenolics have been paid more attention because of their close relationship with oxidative stress. In this review, we briefly review the mechanisms by which mitochondrial stress leads to insulin resistance. Moreover, we list some cytokines and genes that have recently been found to play roles in mitochondrial stress and insulin resistance. Furthermore, we describe several natural drugs that are currently widely used and give a brief overview of their therapeutic mechanisms. Finally, we suggest possible ideas for future research related to the unique role that natural drugs play in the treatment of insulin resistance through the above targets.

Adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) contains various phytonutrients for treating many diseases in Asia. To investigate whether orally administered of adlay bran oil (ABO) can cause drug interactions, the effects of ABO on the pharmacokinetics of five cytochrome P450 (CYP) probe drugs were evaluated. Rats were given a single oral dose (2.5 mL/kg BW) of ABO 1 h before administration of a drug cocktail either orally or intravenously, and blood was collected at various time points. A single oral dose of ABO administration did not affect the pharmacokinetics of five probe drugs when given as a drug cocktail intravenously. However, ABO increased plasma theophylline, dextromethorphan, and diltiazem when co-administered an oral drug cocktail. After 7-days of feeding with an ABO-containing diet, plasma concentrations of theophylline and chlorzoxazone were increased after oral administration of drug cocktail. The major CYP enzyme activities in liver and intestinal were not affected by ABO treatment. Results from this study indicate that a single oral dose or short-term administration of ABO may increase plasma drug concentrations when ABO is given concomitantly with drugs. ABO is likely to enhance intestinal drug absorption. Therefore, caution is needed to avoid food-drug interactions between ABO and co-administered drugs.

Traditional methods for discovery and development of new drugs can be a very time-consuming and expensive process because it includes several stages such as compound identification, pre-clinical and clinical trials before the drug is approved by the US Food and Drug Administration (FDA). Therefore, drug repurposing, namely using currently FDA-approved drugs as therapeutics for other diseases than what they are originally prescribed for, is emerging to be a faster and more cost-effective alternative to current drug discovery methods. In this paper, we have described a three-step in silico protocol for analyzing transcriptomics data using online databases and bioinformatics tools for identifying potentially repurposable drugs. The efficacy of this protocol was evaluated by comparing its predictions with the findings of two case studies of recently reported repurposed drugs: HIV treating drug Zidovudine for the treatment of Dry Age-Related Macular Degeneration and the antidepressant Imipramine for Small-Cell Lung Carcinoma. The proposed protocol successfully identified the published findings, thus demonstrating the efficacy of this method. In addition, it also yielded several novel predictions that have not yet been published, including the finding that Imipramine could potentially treat Severe Acute Respiratory Syndrome (SARS), a disease that currently does not have any treatment or vaccine. Since this in-silico protocol is simple to use and does not require advanced computer skills, we believe any motivated participant with access to these databases and tools would be able to apply it to large datasets to identify other potentially repurposable drugs in the future.

Long COVID is a persistent symptom that appears in many COVID-19 patients, regardless of whether they are asymptomatic, mild, or severe. At least 10% worldwide are suffering from long COVID. The anti-inflammatory effect was evaluated in LPS-treated RAW264.7 cells using six Korean national insurance-covered herbal prescriptions with therapeutic potential for mitigating inflammation in the respiratory tract, and additional network pharmacology analysis was performed. Soshihotang (SST) significantly downregulated iNOS and COX2 expression, reduced the production of NO (nitric oxide) and inflammatory cytokines, such as TNFα, IL-1β, and IL-6, and inhibited IκBα phosphorylation and reduced the nuclear translocation of NF-κB in LPS-treated RAW264.7 cells. Network pharmacological analysis showed that SST was closely related to the NF-κB signaling pathway. Further study on the potential of herbal prescriptions will be needed before they can be used clinically by long COVID patients.

Background. Many anticancer drugs used in clinical practice cause adverse events such as oral mucositis, neurotoxicity, and extravascular leakage. We have reported that two 3-styrylchromone derivatives, 7-methoxy-3-[(1E)-2-phenylethenyl]-4H-1-benzopyran-4-one (compound A) and 3-[(1E)-2-(4-hydroxyphenyl)ethenyl]-7-methoxy-4H-1-benzopyran-4-one (compound B) showed the highest tumor-specificity against human oral squamous cell carcinoma (OSCC) cell lines among 291 related compounds. After confirming their superiority by comparing their tumor specificity with newly synthesized 65 derivatives, we investigated the neurotoxicity of these compounds, in comparison with 4 popular anticancer drugs. Methods: Tumor-specificity (TSM, TSE, TSN) was evaluated as the ratio of mean CC50 for human normal oral mesenchymal (gingival fibroblast, pulp cell), oral epithelial cells (gingival epithelial progenitor), and neuronal cells (PC-12, SH-SY5Y, LY-PPB6, differentiated PC-12) to OSCC cells (Ca9-22, HSC-2), respectively. Results: Compounds A and B showed one-order of magnitude higher TSM as compared with newly synthesized derivatives, confirming its prominent tumor-specificity. Docetaxel showed one order of magnitude higher TSM, but two order of magnitude lower TSE than compounds A and B. Compounds A and B showed higher TSM, TSE and TSN values than doxorubicin, 5-FU and cisplatin, damaging OSCC cells at concentrations that do not affect the viability of normal epithelial and neuronal cells. QSAR prediction based on the Tox21 database suggested that compounds A and B may inhibit the signaling pathway of estrogen-related receptors.

Anticonvulsant drugs are widely used in the management of epilepsy and other neurological disorders. However, their concomitant use with other medications can lead to significant drug interactions, impacting both efficacy and safety. This article aims to provide a comprehensive overview of common anticonvulsant interactions with other frequently used drugs. It discusses the mechanisms of these interactions, their clinical implications, and strategies for managing them. The article also highlights the importance of monitoring and patient education in minimizing adverse outcomes.

Activated platelets are involved in blood coagulation by exposing phosphatidylserine (PS), which serves as a substrate for assembling coagulation complexes. Platelets accelerate fibrin formation and thrombin generation, two final reactions of the coagulation cascade. We investigated the effects of antiplatelet drugs on platelet impact in these reactions and platelet ability to expose PS. Washed human platelets were incubated with acetylsalicylic acid (ASA), ticagrelor, ASA in combination with ticagrelor, ruciromab (glycoprotein IIb-IIIa antagonist) or prostaglandin E1 (PGE1). Platelets were not activated or activated by collagen, sedimented in multiwell plates and plasma was added after supernatant removal. Fibrin formation (clotting) was monitored in a recalcification assay by light absorbance and thrombin generation in a fluorogenic test. PS exposure was assessed by annexin V staining using flow cytometry. Ticagrelor (alone and in combination with ASA), ruciromab and PGE1, but not ASA prolonged the lag phase and decreased the maximum rate of plasma clotting, and decreased the peak and maximum rate of thrombin generation. Inhibition was observed when platelets were not treated with exogenous agonists (activation by endogenous thrombin) and pretreated with collagen. Ticagrelor (alone and in combination with ASA), ruciromab and PGE1, but not ASA decreased PS exposure on washed platelets activated by thrombin and by thrombin + collagen. PS exposure on activated platelets in whole blood was lower in patients with acute coronary syndrome receiving ticagrelor + ASA in comparison with donors free of medications. These results indicate that antiplatelet drugs are able to suppress platelet coagulation activity not only in vitro but also after administration to patients.

Presently, nano-crystallization is widely accepted for increasing the solubility and biological barrier permeability of poorly soluble drugs. It improves the bioavailability of therapeutic agents, increasing the effectiveness for treating diseased conditions, and could be safely administered by oral, parenteral, or transdermal routes. Drug nanocrystals are drug particles coated with a thin polymer layer to enhance their stability and could be decorated with ligands for active targeting. In addition, nanocrystals, due to their morphological properties, improve cell internalization. Therefore, passive targeting by high cellular uptake and retention in the mononuclear phagocyte system (MPS) may be expected. Drug nanocrystals are formulated by either top-down or bottom-up methods and could be scaled up for industrial manufacturing. In the past few decades, nanocrystal formulation has been increasingly studied to overcome the limitations of BCS Class II and IV chemotherapeutic agents. The study of cytotoxic effects of drug formulation on cell lines gives an insight for estimating its in-vivo biodistribution. This review highlights the role of morphology, stabilizer, and ligand conjugation on drug targeting and cellular uptake in cancer cells, as well as a brief discussion on nanocrystal production.

More than 15,000 prescriptions and over the counter drugs are available according to the US Food and Drug Administration website. Moreover, several herbal medicines and dietary supplements are readily available to add to the list of possible drugs, which can potentially cause adverse drug interactions. These are a pressing concern for all as they can interfere with many dental procedures. Additionally, the number of geriatric patients seen in routine dental practice has increased over time. This implies that there are more patients with multiple diseases and health conditions like hypertension, diabetes, problems associated with the cardiovascular, renal and gastrointestinal systems, arthritis, osteoporosis, etc. All these require patients to be on certain medications. Furthermore, advancement in the dental field has led to more complex dental procedures (implants, grafts) being carried out in a general dental practice. These advanced and slightly more invasive treatments require the use of certain drugs before, during and after the treatment like local anesthetics, vasoconstrictors, anxiolytics, analgesics and antibiotics. All of these can possibly interact with medications a patient is already taking and can also interfere with the current dental treatment and create complications. This article aims to provide necessary information about commonly encountered systemic diseases and associated treating medications, their mechanism of action, possible complications and their management. The classes of drugs discussed include anti-platelet agents, vitamin K antagonists, novel oral anticoagulants, bisphosphonates, disease-modifying anti-rheumatic drugs and oral contraceptives.

Specialized, reductionist, and linear approaches are applied in clinical research; they are based on linear logic and used towards therapeutic molecule-based targets. However, those approaches do not consider a systemic vision that describes the remote cause of the pathogenic activation. We propose new theoretical and practical methods for the next drug generation development. Self-organization, network structure, hierarchical organization, non-linearity, feedback circuits, reactions to information, and the view of drugs as information clarify the existing pharmacological methods. We suggest a perspective and hierarchical vision of the human organism based on six levels (mechanic and structural; metabolic; bodily dynamic; emotional, cognitive, spiritual). The therapy should restore the self-organization of every level using the “intelligent” modulation of the network responses. Multi-targeted drugs should act on the remote cause of the pathogenic cascade and be administered based on personal variability and networks. This approach may help the development of individualized, precise, and integrated medicine.

Extracellular vesicles (EVs), such as exosomes or oncosomes are released with molecules unfavorable for survival from cells. In addition, accumulating evidence has shown that tumor cells often eject anti-cancer drugs such as chemotherapeutics and targeted drugs within EVs, a novel mechanism of drug resistance. The EV-releasing, drug resistance phenotype is often coupled with cellular dedifferentiation and transformation, cells undergoing epithelial-mesenchymal transition (EMT) and taking on a cancer stem cell phenotype. Recent studies have shown that the release of EVs is also involved in immunosuppression. The concept of the resistance-associated secretory phenotype (RASP) is reviewed herein.

Elemental sulfur, commonly known for its wide range of biological activity, has a long history of being used to protect all garden and vegetable crops from a range of pests and diseases, including powdery mildew, ascochyta blight, clubroot, plant mites, oidium, anthracnose, and scab. In the present study, a quick and environmentally friendly approach has been developed for the synthesis of sulfur nanoparticles with antibacterial activity. Sulfur nanoparticles (SNPs) were prepared by modifying the surface of elemental sulfur using various polyelectrolyte-surfactant mixtures (PSM) including NaCMC-SDBS and PHMG-CTAB. The SNPs were characterized by UV–visible spectrophotometry, X-ray diffraction (XRD), and thermogravimetric analysis (TG/DSC), scanning electron microscopy (SEM), with the SNPs showing an almost spherical shape with an average size in the range of 150-200 nm. The antibacterial activity of the sulfur nanoparticles was tested using against gram-positive S. aureus and E. faecium and gram-negative E. coli and P. aeruginosa bacteria. From this, it could be seen that SNPs exhibited significant antimicrobial activity against gram-positive bacteria, i.e., S. aureus and E. faecium. The in vitro cytotoxicity of the SNPs-1 and SNPs-2 studied to normal (MeT-5A) and tumorous (MCF-7) human cell lines was assessed in the concentration range from 500 μg/ml to 0.12 mg/ml, from which it was determined as being non-cytotoxic. The received products can be considered for potential application in agriculture and medicine.

(1) Background: To substantiate the clinical efficacy and investigate the real-world effectiveness of the herbal medicinal product BNO 1016 in acute rhinosinusitis (ARS) in the context of antibiotic stewardship. (2) Methods: Clinical efficacy: We performed a meta-analysis of the clinical trials ARhiSi-1 and ARhiSi-2 comprising 676 patients, analysing the reduction of the Major Symptom Score (MSS) and improvement of SNOT-20. Real-world effectiveness: In addition, we performed a retrospective cohort study including 203,382 patients, comparing the real-life effectiveness of BNO 1016 in reducing ARS-related adverse outcomes in comparison to antibiotics and several other established therapies. (3) Results: Clinical efficacy: Treatment with BNO 1016 ameliorated symptoms of ARS by reducing MSS by 1.9 points (p&lt;0.0001) and improved quality of life (QoL) for patients by improving SNOT-20 by 3.5 points (p=0.001) in comparison to placebo. In patients with moderate/severe symptoms, the positive effects of BNO 1016 were even more pronounced (MSS: –2.3 points (p&lt;0.0001); SNOT-20: –4.9 points (p=0.0158)) compared to placebo. Real-world effectiveness: Treatment with BNO 1016 was as effective or significantly more effective in reducing the risk for adverse ARS-related outcomes such as follow-up antibiotic prescriptions, sick leave ≥7 days or medical appointments due to ARS, especially when compared to antibiotics. (4) Conclusions: BNO 1016 is a safe and effective treatment for ARS that can help reduce the overuse of antibiotics.

Lung cancer is one of the most important health risks worldwide for human. Non-small cell lung cancer (NSCLC) is the most common cause of premature death from malignant disease. This study provides in-depth insights from systems biology analyses to identify molecular to inform systemic drug targeting in NSCLC. Gene expression profiles from non small cell lung cancer were analyzed with genome-scale biomolecular networks (I,e., protein-protein interaction, transcriptional and post transcriptional regulatory networks). The aim of the study was to determine the pathways and expression profile of the genes to discover molecular signature at RNA and protein levels which could serve as potential drug targets for therapeutics innovation and the identification of novel targets. Eight proteins, six TFs and seven miRNAs came into prominence as potential drug targets. The differential expression profiles of these reporter biomolecules were cross-validated by independent RNA-Seq and miRNA-Seq. Risk discrimination performance of the reporter biomolecules NPR3, JUN, PPARG, TP53, CKMT1A, SP3 and TFAP2A were also evaluated. Total 213 drugs and 7 proteins were found for non small cell lung cancer through dgidb. Among these identified drugs seven drugs such as- Gemcitabine, Carboplatin, paclitaxel, Docetaxel, Crizotinib, Bevacizumab and Gemcitabine is used for NSCLC which is approved by National Cancer Institute. The molecular signatures and repurposed drugs presented here permit further attention for experimental studies which are offer significant potential as biomarkers and candidate therapeutics for precision medicine approaches to clinical management of NSCLC.

This study assesses the effectiveness of HCV self-testing (HCVST) distribution models compared to provider-led HCV testing (PL-HCVT), including the standard of care facility-based HCVT (SOC-HCVT) and community-based organization HCVT (CBO-HCVT) among people who inject drugs (PWID) in Vietnam. A cross-sectional study was conducted as part of a larger implementation science study in Hanoi and Ho Chi Minh City from September 2023 to April 2024. We engaged 8 CBOs and 10 public and private clinics in offering choice of HCVST through community-based and facility-based distribution, and secondary distribution), or PL-HCVT via SOC-HCVT and CBO-HCVT. Among 1,165 PWID, 693 opted for HCVST and 472 for PL-HCVT. The proportion of first-time testers was significantly higher in HIVST community-based and secondary distribution as well as CBO-HCVT compared to SOC-HCVT and facility-based HCVST (87.1%, 93.3% and 82.7% vs. 41.9% and 35.7%, respectively; p < 0.001). Overall, HCV seropositivity rate was lower in HCVST than PL-HCVT, however, higher in HCVST facility-based and community-based distribution compared to HCVST secondary distribution (28.1% and 20.4% vs. 5.7%, respectively). Community-based HCVST was most effective, followed by facility-based HCVST and secondary distribution. Our findings indicate that HCVST effectively reaches first-time testers and results in more people diagnosed and treated among PWID.

To reveal the relationship between metallodrugs and cancer malignancy, molecular networks of anti-cancer drugs were analyzed. Molecular networks in several types of cancers were analyzed in Ingenuity Pathway Analysis (IPA). Analysis of carboplatin revealed the causal network in diffuse large B-cell lymphoma. Analysis of 12 analyses of cisplatin treatment identified causal networks including camptothecin and NUPR1. The causal network of camptothecin, which includes PTEN, FAS, and IRF1, was inactivated in diffuse-type GC and activated in intestinal-type GC. Upstream regulator analysis of cisplatin revealed an increase in FAS, BTG2, SESN1 and CDKN1A, and the involvement of the tumor microenvironment pathway. Upstream regulators of cisplatin-treated lung adenocarcinoma included a histone deacetylase inhibitor, trichostatin A (TSA). Causal network of arsenic was inactivated in diffuse-type GC and activated in intestinal-type GC, and included ERK, EGFR, SRC, IKK and TP53. Prediction of RNA-RNA interactions with the causal network of arsenic identified 10 microRNAs including mir-101, mir-103, and mir-22. The results revealed the involvement of EMT in arsenic treatment. Analysis of oxaliplatin, a platinum drug, revealed that the SPINK1 pancreatic cancer pathway is inactivated in ischemic cardiomyopathy. The study showed the importance of the relationship between platinum drugs or arsenic trioxide and the tumor microenvironment in the treatment of resistant cancer in humans.