Delayed Gastric Conduit Emptying (DGCE) occurs in 15-39% of patients who underwent esophagectomy. Intra-Pyloric Injection of Botulinum Toxin (IPBT), Pneumatic Balloon Dilation (PBD), and the same session combination (BTPD), represent the main endoscopic procedures, but comparative data are currently unavailable. We retrospectively analyzed prospectively collected data on all consecutive patients with DGCE treated endoscopically with IPBT, PBD, or BTPD. ISDE Diagnostic Criteria were used for DGCE diagnosis and classification. Gastric Outlet Obstruction Score was used for clinical staging. All patients undergoing IPBT received 100 UI of toxin, while those undergoing PBD were dilated up to 20mm. Clinical success (CS) was defined as the resolution of symptoms/resumption of feeding at discharge or expanding dietary intake at any rate. Recurrence was defined as symptom relapse after more than 15 days of well-being requiring endoscopic/surgical intervention. 64 patients (81.2% male, 90.6% Ivor-Lewis esophagectomy, 77.4% adenocarcinoma), median age 62 years (IQR 55-70), were enrolled: 18 (28.1%) in the IPBT group, 24 (37.5%) in the PBD group and 22 (34.4%) in the BTPD group. No statistically significant differences were found in the baseline characteristics, surgical techniques, and median follow-up among the three groups. BTPD showed a higher CS rate (100%) compared to the PD and BTPD groups (p=0.02) and Kaplan-Meier analysis with log-rank test revealed that the BTPD group was associated both with a significatively shorter mean time to refeed of 1.16 days (95% CI 0.8-1.5; p=0.001) and a shorter median time to discharge of 1 day (95% CI 1-3; p=0.0001). Endoscopic management of DGCE remains challenging. Waiting for further strong evidence, BTPD can offer patients a higher clinical efficacy rate and a shorter time to refeed and be discharged.

We report a case in which a 74-year-old man suffering from esophageal achalasia complicated with epiphrenic esophageal diverticulum was successfully treated with a simultaneous laparoscopic surgery. The gentleman was referred with symptoms suggestive of a passage disorder in lower esophagus from 5 years. Esophagogastroduodenoscopy demonstrated an epiphrenic diverticulum at the left wall of the lower esophagus, and esophagography led to the suspicion of a combined esophageal achalasia. A simultaneous laparoscopic surgery, with an abdominal approach was performed in which, following the opening of the esophageal hiatus, the diverticular wall was separated from the mediastinal organs and diverticulectomy was performed with linear staplers. After Heller’s myotomy, Dor’s fundoplication was subsequently performed in which both incisional line of muscle layer and the suturing line of diverticulectomy were wrapped by the fornix of stomach to make up for the wall strength and avoid the suture leakage. It was theoretically considered logical and effective to reinforce this vulnerable site with Dor’s fundoplication. He had an uneventful recovery and a rapid relief from symptoms following surgery.

Background: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide, and its incidence has been rising in parallel with the prevalence of obesity and diabetes. A critical marker for the progression of NAFLD is advanced hepatic fibrosis (AHF), which can result in cirrhosis and hepatocellular carcinoma. This study sought to investigate the potential associations between five nutrition-related indices—the geriatric nutritional risk index (GNRI), prognostic nutritional index (PNI), controlled nutritional score (CONUT), triglyceride-total cholesterol-body mass index (TCBI), and albumin/globulin ratio (AGR)—and the progression of NAFLD and AHF. Methods: This study analyzed the association between five nutrition-related indicators and the occurrence of NAFLD and AHF by utilizing data from the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020.03. After adjusting for demographic, lifestyle, clinical, and laboratory-related factors, the associations were examined employing various statistical techniques, including multivariate logistic regression, subgroup analysis, and smooth curve fitting analysis. Results: This study included 5,514 subjects, of whom 2,088 were diagnosed with NAFLD and 359 with AHF. After adjusting for potential confounding factors using multivariate logistic regression analysis, the results revealed that GNRI, PNI, and TCBI were positively associated with the incidence of NAFLD, while CONUT and AGR demonstrated negative associations with NAFLD. Additionally, GNRI, CONUT, and TCBI were positively associated with the incidence of AHF, while AGR demonstrated a negative association with AHF.Conclusions: The study demonstrates that nutritional status plays a dual role in the progression of NAFLD and AHF, serving as both a risk and protective factor. These findings offer a scientific foundation for the early identification of high-risk populations and the development of individualized nutritional intervention strategies.

Introduction: Vitamin B1 (thiamine) deficiency (TD) after metabolic and bariatric surgery (MBS) is often insidious and, if unrecognized, can lead to irreversible damage or death. As TD symptoms are vague and overlap with other disorders, we aim to identify predictors of recurrent TD and failure to collect B1 labs. Methods: We analyzed a large sample of data from patients with MBS (n=878) to identify potential predictors of TD risk. We modeled recurrent TD and failure to collect B1 labs using classical statistical and machine learning (ML) techniques. Results: We identified clusters of labs associated with increased risk of recurrent TD: micronutrient deficiencies, abnormal blood indices, malnutrition, and fluctuating electrolyte levels (aIRR range: 1.62-4.68). Additionally, demographic variables associated with lower socioeconomic status were predictive of recurrent TD. ML models predicting characteristics associated with failure to collect B1 labs achieved 75-81% accuracy, indicating that clinicians may fail to match symptoms with the underlying condition. Conclusion: Our analysis suggests that both clinical and social factors can increase the risk of life-threatening TD episodes in some MBS patients. Identifying these indicators can help with diagnosis and treatment.

Background and Objectives: A novel synthetic self-assembling peptide, PuraStat, has been introduced as a hemostatic agent. This case series aimed to evaluate the clinical efficacy of PuraStat for gastrointestinal bleeding during emergency endoscopy. Cases: Twenty-five patients with gastrointestinal bleeding who had undergone emergency endoscopy with PuraStat between August 2021 and December 2022 were retrospectively examined. Six patients were receiving antithrombotic agent, and ten patients with refractory gastrointestinal bleeding had undergone at least one endoscopic hemostatic procedure. The breakdown of bleeding was gastroduodenal ulcer/erosion in 12 cases, bleeding after gastroduodenal or colorectal endoscopic resection in 4 cases, rectal ulcer in 2 cases, postoperative anastomotic ulcer in 2 cases, and gastric cancer, diffuse antral vascular ectasia, small intestinal ulcer, colonic diverticular bleeding, and radiation proctitis in each case. The method of hemostasis was only PuraStat application in six cases, and hemostasis in combination with high-frequency hemostatic forceps, hemostatic clip, argon plasma coagulation, and hemostatic agents (i.e. thrombin) in the remaining cases. Rebleeding was observed in three cases. Hemostatic efficiency was observed in 23 cases (92%). Conclusions: PuraStat has the expected hemostatic effect on gastrointestinal bleeding during emergency endoscopy. The use of PuraStat should be considered in emergency endoscopic hemostasis of gastrointestinal bleeding.

In recent years there has been an increasing interest in developing novel materials based on natural biopolymers as a renewable alternative of petroleum-based plastics. The availability of proteins derived from agricultural by-products, along with their favourable properties, has fostered a renewed interest in protein-based materials, promoting research in innovative technologies. In this study we propose the use of rapeseed protein-rich meal as main ingredient for the preparation of novel sustainable materials combining excellent environmental properties such as biodegradability and renewable origin. Application as sustainable products in the present high-tech society needs modification of basic native properties of these natural compounds. The original route proposed in this paper consists in the preparation via compression moulding of flexible biomaterials stabilized by crosslinkers/chain extenders. Investigation of the effects of different denaturing and disulfide bond reducing agents, crosslinkers, and preparation conditions on the material mechanical behaviour demonstrated that the novel materials have appreciable strength and stiffness. The results show the potential of utilizing full meal from vegetable by-products to prepare protein-based materials with granted ecofriendly characteristics and mechanical properties adequate to specific structural applications.

Rett syndrome (RTT) is an X-linked neurodevelopment disorder associated with the single monogenic mutation in methyl-CpG binding protein 2 (MeCP2) in up to 95% of cases. The growing number of genome-wide association studies and incomplete concordance for autoimmune diseases in monozygotic twins concur to support the involvement of environmental factors, like infectious agents or chemicals, in the breakdown of tolerance leading to autoimmunity. In fact, the coexistence of a perturbation of the immune system in RTT patients has been previously hypothesized. We herein explored the hypothesis that an autoimmune component derived from environmental bacterial infection of non typeable Haemophilus influenzae may coexist in RTT. At this purpose we screened sera from RTT syndrome patients, non-RTT pervasive developmental disorders patients and healthy controls with the hyperglucosylated adhesin protein HMW1ct(Glc) used as a precise antigen in ELISA in order to identify specific antibodies to N-glucosylation sites. Results showed that HMW1ct(Glc) is able to significantly discriminate antibodies among RTT sera and controls. Competitive ELISA confirmed the specific interaction between antibodies characteristic of RTT syndrome and the N-glucosylation motifs of the bacterial adhesin protein HMW1ct(Glc).

Background/Objectives: Chemerin, which is a multifunctional cytokine and adipokine, has been implicated in inflammatory and metabolic processes and might play a role in upper gastrointes-tinal (GI) malignancies, particularly gastric and esophageal cancer. The aim of this review is to explore the role of chemerin in the pathophysiology of upper GI cancers, as well as its potential as a biomarker for early detection and as a therapeutic target. Methods: A comprehensive review of recent studies about chemerin's biochemical properties and interaction with its receptors, as well as its effects on inflammatory responses, immune regulation and metabolic processes was con-ducted. Clinical implications of chemerin on gastric and esophageal cancer were analyzed, whereas the potential therapeutic strategies targeting chemerin were discussed. Results: Elevated chemerin levels are associated with poor prognosis in gastric cancer and promote invasiveness and metastasis in esophageal cancer. Chemerin receptor antagonists show promising results in inhibiting cancer cell migration, invasion and progression. Conclusions: Chemerin could repre-sent a valuable prognostic biomarker and therapeutic target for upper GI cancers. Future observa-tional studies should validate its clinical applications and investigate the efficacy of chemerin in-hibitors as potential therapeutic targets.

The abstract should be a total of about 250 words and structured to contain the following headings: Background/Objectives, Methods, Results, Conclusions. Background/Objectives: Place the question addressed in a broad context and highlight the purpose of the study; Methods: Describe briefly the main methods or treatments applied. Include any relevant preregistration numbers, and species and strains of any animals used; Results: Summarize the article’s main findings; Conclusions: Indicate the main conclusions or interpretations. The abstract should be an objective representation of the article: it must not contain results which are not presented and substantiated in the main text and should not exaggerate the main conclusions. Clinical trial abstracts should include items that the CONSORT group has identified as essential.

Abstract: Peptide pools composed of short amino acid sequences have proven to be versatile tools in various research areas and clinical applications. They are powerful tools for epitope mapping, immunotherapy, and vaccine development. Their importance lies in their ability to map complex protein structures, enabling a comprehensive understanding of immune responses and facilitating the identification of potential therapeutic agents. The application of peptide pools also extends to the field of personalized medicine, offering tailored solutions for diseases such as cancer and infectious diseases. Peptide pools are complex mixtures of immunostimulatory antigens primarily intended for T-cell stimulation. They are commercially available in many different compositions and variants. However, unlike other reagents that consist of only one or a few compounds, peptide pools are highly complex products with limited stability. This makes their quality control a major challenge. Quantitative peptide analysis usually requires sophisticated methods, in most cases isotope-labeled standards and reference materials. None of these are routinely available for these products. Synthesis and purification of all labeled peptides might be required. Usually, this approach would be prohibitively laborious and expensive. Therefore, an approach is needed to provide a practical and feasible method for quality control of peptide pools. With insufficient quality control, the use of such products could lead to incorrect experimental results, which would worsen the well-known reproducibility crisis in the biomedical sciences. Here we propose the use of ultra-high performance liquid chromatography (UHPLC) with two detectors, a standard UV detector (at 214 nm) for quantitative analysis and a high-resolution mass spectrometer (HRMS) for identity confirmation. To be cost-efficient and fast, quantification and identification are performed in one chromatographic run. An optimized protocol is shown, and different peak integration methods are compared and discussed. This work was performed using a peptide pool known as CEF, which consists of 32 peptides derived from cytomegalovirus (CMV), Epstein-Barr virus (EBV) and influenza virus, ranging from 8 to 12 amino acids in length.

Bicyclic peptides have attracted the interest of pharmaceutical companies because of their remarkable properties putting them on a new path in medicine. Their conformational rigidity that improves proteolytic stability, leads to rapid penetration into tissues via any possible route of administration and elimination, occurring by renal metabolism, is of great importance for people with a history of liver diseases. In addition, each ring can function independently, making them extremely versatile molecules for further optimization. In this paper we compared the potentiometric and spectroscopic properties studied by UV-Vis, MCD, and EPR, of four synthetic analogues of the bi-cyclic peptide c(PKKHP-c(CFWKTC)-PKKH). In particular we correlated the structural and spectral properties of complexes with coordinating abilities toward Cu(II) ions of MCL (Ac-PKKHPc(CFWKTC)PKKH-NH2) that contains the unbinding cycle and N- and C-terminal linear parts, with two histidine residues, one per part; two monocyclic ligands containing one histidine residue, both in the N-terminal position i.e., MCL2 (Ac-PKKHPc(CFWKTC)PKKS-NH2) and in the C-terminal position i.e., MCL3 (Ac-PKKSPc(CFWKTC)PKKH-NH2), respectively, and the linear structure LNL (Ac-PKKHPSFWKTSPKKH-NH2).

Antimicrobial peptides represent a promising alternative to traditional drugs in relation to cost, toxicity and, primarily, the growing problem of drug resistance. Here we report on the activity against HSV-1 and HSV-2 of a previously described wide-spectrum synthetic decapeptide, Killer Peptide (KP). As determined by plaque reduction assays, treatment with KP at 100 μg/mL resulted in a reduction in the viral yield titer of 3.5 Logs for HSV-1 and 4.1 Logs for HSV-2. Further evaluation of KP antiviral activity focused on the early stages of virus replicative cycle, including the determination of the residual infectivity of viral suspensions treated with KP. A direct effect of the peptide on viral particles, impairing virus absorption and penetration, was shown. The toxicity profile proved to be extremely good with a selectivity index of 29.6 for HSV-1 and 156 for HSV-2. KP was also active against an acyclovir (ACV)-resistant HSV-1 strain, while HSV-1 subcultures in the presence of sub-inhibitory doses of KP did not lead to the emergence of resistant strains. Finally, the antiviral action of KP proved to be synergistic with that of ACV. Overall, these results demonstrate that KP could represent an interesting addition/alternative to acyclovir for antiviral treatment.

Background/Objectives: Endometriosis represents substantial direct and indirect healthcare costs impacted by absent accurate, non-invasive uniformly diagnostic tools. We endeavored to demonstrate gastrointestinal myoelectrical activity (GIMA) biomarkers unique to endometriosis allow noninvasive, uniformly accurate diagnosis or exclusion of endometriosis. Methods: Prospective open-label comparative study of 154 patients, age >18, with or without diagnosed endometriosis. Population included 62 non-endometriosis controls (Cohort 1), 43 subjects with surgically histologically-confirmed endometriosis (Cohort 2), and 49 subjects with abdominal pain and negative imaging (Cohort 3). Electroviscerography (EVG) recorded GIMA biomarkers from three abdominal electrodes before and 30-minutes post water-load protocol. Cohort 2 had postoperative EVG and Cohort 3 had preoperative EVG. Calculated specificity, sensitivity, NPV, PPV and predictive probability or C-Statistic used univariate, multivariate, linear and logistical regression analyses of the area under the curve (AUC) at all frequency and time points, including age and pain covariants. Results: Non-endometriosis cohort differed significantly from endometriosis cohorts (p<0.001) for median (IQR), and AUC percent frequency distribution of power at baseline, 10-minute, 20-minute, and 30-minute post water-load at all frequency ranges 15-20cpm, 30-40cpm and 40-50cpm. Endometriosis cohorts were statistically similar (p>0.05). GIMA biomarker threshold scoring demonstrated 95%/91% sensitivity and PPV, 96%/95% specificity and NPV and C-statistic of >99%/98% respectively for age subsets. GIMA biomarkers in Cohort 3 predicted 47/49 subjects positive and 2/49 negative for endometriosis, confirmed surgically. Hormonal therapy, surgical stage, nor pain score affected diagnostic accuracy. Conclusions: Non-invasive electroviscerography with GIMA biomarker detection distinguished participants with and without endometriosis based upon endometriosis specific GIMA biomarkers threshold scoring.

Cell-penetrating peptides (CPPs), a group of small peptides capable of promoting the transport of molecular cargo across the plasma membrane, have become important tools in promoting the cellular uptake of exogenously delivered macromolecules. GV1001, a peptide derived from a reverse-transcriptase subunit of telomerase (hTERT) and developed as a vaccine against various cancers, reportedly has unexpected CPP properties. Unlike typical CPPs, such as the HIV-1 TAT peptide, GV1001 enabled the cytosolic delivery of macromolecules such as proteins, DNA and siRNA via extracellular heat shock protein 90 (eHSP90) and 70 (eHSP70) complexes. The eHSP-GV1001 interaction may have biological effects in addition to its cytosolic delivery function. GV1001 was originally designed as a MHC class II-binding cancer epitope, but its CPP properties may contribute to its strong anti-cancer immune response relative to other telomerase peptide-based vaccines. Cell signaling via eHSP-GV1001 binding may lead to unexpected biological effects, such as direct anticancer or antiviral effects. In this review, we focus on the CPP effects of GV1001 bound to eHSP90 and ehsp70.

Background and Aims: Obesity is a pervasive health issue in children. It affects multiple systems in the body including the gastrointestinal tract. Research on obesity-related gastrointestinal diseases has focused mostly on hepatobiliary disorders. However, non-hepatic gastrointestinal diseases such as gastroesophageal reflux, constipation, and functional abdominal pain, though common and debilitating, have not been highlighted in the context of obesity. These entities can downgrade the already compromised lifestyle of obese children. Some of these disorders are more difficult to treat in these children compared to their peers with normal body mass index. Method: We reviewed the available literature on the association between obesity and these three common gastrointestinal disorders. Results: - There appears to be a strong correlation between childhood obesity and constipation and gastroesophageal reflux, and a probable correlation with functional abdominal pain. Conclusion: We suggest that given the available literature, weight management should be an integral part of the management of gastroesophageal reflux, constipation, and functional abdominal pain in obese children. This gains relevance especially because of the recent availability of medications for the treatment of obesity in children.

Gastrointestinal bleeding (GIB) after heart transplantation (HT) remains a significant clinical issue. The study aimed to explore its incidence, trends, outcomes and clinical predictors of GIB in HT patients. Adult patients who underwent HT between 2015 and 2021 at Union Hospital were recruited and divided into two groups based on the presence or absence of postoperative GIB. Primary outcomes were evaluated by follow-up. Independent predictors of GIB after HT were identified by logistic regression analysis. A nomogram prediction model was constructed according to these independent variables, and the accuracy of the model was assessed using the receiver operating characteristic (ROC) curve and the calibration curve. Among 461 patients, 40 (8.7%) developed GIB post-HT. HT patients with postoperative GIB exhibited higher in-hospital, 30-day, 90-day and 1-year mortality (all P < 0.05). Multivariate analysis identified age, preoperative warfarin, postoperative continuous renal replacement therapy and postoperative nasogastric tube as independent risk factors for GIB following HT. The nomogram prediction model was performed using the 4 variables. The area under the curve (AUC) of this model was 0.852(95% CI: 0.787-0.917, P < 0.001) and the calibration curve was close to the ideal diagonal line. GIB following HT is associated with a poor clinical prognosis. The constructed nomogram, incorporating its independent risk factors, demonstrated a favorable predictive value for GIB.

Antiviral peptides (AVPs) represent a promising strategy for addressing the global challenge of viral infections and their growing resistance to traditional drugs. Lab-based AVP discovery methods are resource-intensive, highlighting the need for efficient computational alternatives. In this study, we developed five non-trained but supervised Multi-Query Similarity Search Models (MQSSMs) integrated into the StarPep toolbox. Rigorous testing and validation across diverse AVP datasets confirmed the models' robustness and reliability. The top-performing model, M13+, demonstrated impressive results with an accuracy of 0.969 and a Matthew’s correlation coeffi-cient of 0.71. To assess their competitiveness, the top five models were benchmarked against 14 publicly available machine learning and deep learning AVP predictors. The MQSSMs outper-formed these predictors, highlighting their efficiency in terms of resource demand and public ac-cessibility. Another significant achievement of this study is the creation of the most comprehensive dataset of antiviral sequences to date.

Gastrointestinal parasites (GIP) are diverse parasitic organisms known to have coevolved with bacterial populations inside the gut of mammalian hosts. These helminths produce small molecules, peptides and proteins to evade or fight their hosts' immune systems. Small molecules include polar compounds, amino acids, lipids and carbohydrates. Metabolomics is an emerging field of research recently applied to study helminth infections and host-parasite interactions. This review comprehensively discusses metabolomics studies of small molecules of GIP in animals, providing insights into the available tools and techniques, databases, and analytical software. Most metabolomics investigations employed LC-MS, MS or MS/MS, NMR, or a combination thereof. Recent advancements in metabolomics platforms, including artificial intelligence (AI)-assisted software tools and databases, have propelled helminth metabolomics forward, offering new avenues to explore host-parasite interactions, immunomodulation, and the intricacies of parasitism. As our understanding of helminth metabolomics continues to expand, it promises to unveil novel perspectives and enrich the knowledge of these complex host-parasite relationships.

Relative to several model bacteria, the ethanologenic bacterium Zymomonas mobilis is shown here to have an elevated resistance to exogenous antimicrobial peptides (AMPs) – both, with regard to peptide bulk concentration in the medium, and the numbers of peptide molecules per cell. By monitoring integration of the AMPs in the bacterial cell membrane and observing the resulting effect on membrane energy-coupling, it is concluded that the membranotropic effects of the tested AMPs in Z. mobilis and in Escherichia coli are comparable. The advantage of Z. mobilis over E. coli apparently results from its uncoupled mode of energy metabolism that, in contrast to E. coli, does not rely on oxidative phosphorylation, and hence, is less vulnerable to disruption of its energy-coupling membrane by AMPs. It is concluded that the high resistance to antimicrobial peptides (AMPs) observed in Z. mobilis not only proves crucial for its survival in its natural environment but also offers a promising platform for AMP production and sheds light on potential strategies for novel resistance development in clinical settings.

A useful perioperative nutritional therapy for highly invasive esophageal cancer surgical cases needs to be developed. We clarified the usefulness of amino acid-enriched nutritional therapy using glutamine (Gln)/arginine (Arg)/calcium β-hydroxy-β-methylbutyrate (HMB) products on the short-term postoperative outcomes of minimally invasive esophagectomy for esophageal cancer. Altogether, 114 patients (Gln/Arg/HMB group) received perioperative nutritional therapy with Gln/Arg/HMB products, and we retrospectively investigated the change in nutritional parameters including skeletal muscle mass, occurrence of postoperative complications, and short-term postoperative outcomes in this group. The results were compared between the Gln/Arg/HMB and control groups (79 patients not receiving the Gln/Arg/HMB products). The incidence of all postoperative complications, sputum expectoration disorder, and pleural effusion of grade ≥III was significantly lower in the Gln/Arg/HMB group (62.0% vs. 38.6%, p = 0.001; 44.3% vs. 28.1%, p = 0.020; 27.8% vs. 13.2%, p = 0.011, respectively). The psoas muscle area and postoperative body weight was significantly higher at 1 month and 1 year after surgery in the Gln/Arg/HMB group than in the control group (93.5% vs. 99.9%, p &lt; 0.001; 92.0% vs. 95.4%, p = 0.006). Perioperative amino acid-enriched nutritional therapy may improve the short-term postoperative outcomes, nutritional status, and skeletal muscle mass of esophageal cancer surgical patients.

Background/Aim: Stool gluten immunogenic peptides (GIP) determination is now considered a valuable tool for detecting dietary lapses in treated celiac disease (CeD) patients. Our study aims to explore the diagnostic performance of a qualitative lateral flow immunoassay point-of-care test (LFIA/PoCT) compared with a qualitative enzyme-linked immunosorbent assay (ELISA) for detection of stool GIP. Methods: The study is a post hoc analysis of stool samples collected in the real-life conditions from a cohort of gluten-free diet-treated CeD patients. Stool GIP was measured in µg/g of stool using an ELISA kit (iVYLISA GIP S®, Biomedal SL). For the qualitative evaluation of stool GIP, a LFIA/PoCT test (GlutenDetect®; Biomedal S.L) was employed, which reported results as positive or negative. The LFIA/PoCT performance was evaluated against ELISA, considered as the gold standard. GIP concentrations

In recent years, bacterial resistance to conventional antibiotics has become a major concern in the medical field. The global misuse of antibiotics in clinics, personal use, and agriculture has accelerated this resistance, making infections increasingly difficult to treat and rendering new antibiotics ineffective more quickly. Finding new antibiotics is challenging due to the complexity of bacterial mechanisms, high costs and low financial incentives for the development of new molecular scaffolds, and stringent regulatory requirements. Additionally, innovation has slowed, with many new antibiotics being modifications of existing drugs rather than entirely new classes. Antimicrobial peptides (AMPs) are a valid alternative to small molecule antibiotics offering several advantages, including broad-spectrum activity and a lower likelihood of inducing resistance due to their multifaceted mechanisms of action. However, AMPs face challenges such as stability issues in physiological conditions, potential toxicity to human cells, high production costs, and difficulties in large-scale manufacturing. A reliable strategy to overcome the drawbacks associate with the use of small molecule antibiotics and AMPs is the combination therapy, namely the simultaneous co-administration of two or more antibiotics or the synthesis of covalently linked conjugates. This review is intended to cover and critically analyze the design, synthetic strategies, antibacterial activity and, when possible, the cytotoxicity of antibiotic-AMPs conjugates.

Modern gastroenterology, which occupies the pages of scientific journals without alternative, began as an initiative of manufacturers of diagnostic equipment. For widespread advertising, they selected practical doctors who were not familiar with the methodology of science and superficial knowledge of physiology. This is how a group led by DeMeester arose, which in 1976 published the DeMeester score, i.e., the normal limit for esophageal pH monitoring. pH <4, less than 4% of the time per day was considered normal, i.e., it was unreasonably claimed that such reflux is physiological. This article proves that this study was carried out with numerous methodological errors, which led to an erroneous conclusion. For a long time, pH monitoring was considered the gold standard and with its help hypotheses were proposed that form the basis of modern gastroenterology. The article proves the fallacy of 13 hypotheses, which are presented as theories. Numerous articles using pH monitoring have publicized this method. Practitioners became "great scientists", equipment manufacturers became successful businessmen. Over time, they found other groups of practitioners to promote devices for impedance ph monitoring, high-resolution manometry, and many others. At the same time, a network of reviewers who believe in the infallibility of the luminaries do not allow studies that contradict their faith to be published. Thus, fundamental science was destroyed, which alone could assess the harm of false research both for science and for patients. Conclusion This study provides a list of hypotheses, that were previously considered theories, but since scientific evidence has proven these assumptions to be false, they should be excluded from subsequent use and citation.

Gastrointestinal cancers are a specific group of oncological processes in which the location and nature of growth are of key importance for clinical symptoms and prognosis. At the same time, as research shows, they can pose a very serious threat to the patient's life, especially at an advanced stage of development. The type of therapy used depends on the anatomical location of the cancer, its type and degree of progression. One of the modern forms of therapy used to treat gastrointestinal cancers is photodynamic therapy, which, as already mentioned, has been approved for the treatment of esophageal cancer in the United States. Despite the increasingly rapidly developing clinical use of this treatment method, the exact immunological mechanism it induces on cancer cells has not yet been known. This article presents the current findings on the mode of action of dynamic phototherapy on cells of various gastrointestinal cancers. There are most of them about the impact on colorectal cancer. The types of cell death induced by PDT include apoptosis, necrosis, and pyroptosis. The anticancer effect also results from the induction of destruction of tumor vessels and activation of the immune system. Most reports exist on the mechanism of apoptosis induction, in which the mitochondrial pathway is most often emphasized. Photodynamic therapy may also have a beneficial effect on such aspects of cancer as the ability to develop metastases, or contribute to reducing resistance to known pharmacological agents.

The gastrointestinal and genitourinary tracts share several similarities. Primarily, these tissues are composed of hollow structures lined by an epithelium through which materials need to flow with the help of peristalsis brought by muscle contraction. In the case of the gastrointestinal tract, solid or liquid food must circulate to be digested and absorbed and the waste products eliminated. In the case of the urinary tract, the urine produced by the kidneys must flow to the bladder, where it is stored until its elimination from the body. Finally, in the case of the vagina, it must allow the evacuation of blood during menstruation, accommodate the male sexual organ during coitus, and is the natural way to birth a child. The present review describes the anatomy, pathologies and treatments of such organs, emphasizing tissue engineering strategies.

Introduction: The gastrointestinal tract (GI) is the second most affected organ system in systemic sclerosis or systemic/localized scleroderma (SSc) and is an important topic for research. Approximately 90% of patients with scleroderma exhibit pathology of the GI tract. The systemic scleroderma has the potential to impact any part of the gastrointestinal tract, between the oral cavity and anorectum. The pathological complications of scleroderma adversely impact the health-related quality of life of the affected patients and increase the treatment burden of patients and medical professionals. Study Aim: We summarized the epidemiology, commonly reported clinical manifestations, complications, and available therapies for treating the GI pathology in systemic scleroderma patients. Methodology: We performed a literature review using the keywords "systemic sclerosis," "scleroderma," "GI manifestations in scleroderma," and "GI complications of scleroderma" across databases, including Google Scholar, Medline, Embase, and PubMed. We also analyzed a range of case reports concerning scleroderma manifestations and treatment modalities. Results: Our research revealed the annual incidence of SSc attributing to19.3 cases per million adults in the United States. We found the highest incidence of systemic scleroderma in patients within the age range of 44-55 years. Our results affirmed 5:1 incidence of systemic scleroderma that confirmed the higher impact of this disease condition in females than male populations. We found that the gastrointestinal manifestations of systemic scleroderma predominantly elevate the morbidity and mortality incidence among the affected patients. Esophageal and intestinal manifestations impact 90% and 40-70% of patients with systemic scleroderma. The small bowel hypomotility and small intestinal bacterial overgrowth (SIBO) in systemic scleroderma cases trigger the episodes of malabsorption and malnutrition that eventually add to 50% of the mortality rate. Systemic sclerosis is associated with the high incidence of fecal incontinence that triggers depression and its deleterious mental health manifestations in many clinical scenarios. Conclusion: The gastrointestinal complications in systemic sclerosis potentially deteriorate the daily living activities of the affected patients. The systematic management of the gastrointestinal complications of systemic scleroderma warrants multidisciplinary approaches. Prospective studies should focus on developing targeted therapies for improving the recovery patterns and prognostic outcomes in systemic scleroderma cases.

Symptoms attributed to the gastrointestinal manifestations of multi-system disorders play an important role in the long-term management of these conditions. Gastrointestinal complications of a variety of connective tissue disorders have been studied and there is an increased interest in the incidence and prevalence of these symptoms. Descriptions of the occurrence of gastrointestinal complications in Marfan syndrome have appeared infrequently in the medical literature. In this review article we focus on both structural and functional gastrointestinal pathology that may occur in patients with Marfan syndrome.

Aβ peptides are known to bind neural plasma membranes in a process leading to the deposit of Aβ-enriched plaques. These extracellular structures are characteristic of Alzheimer’s disease, the major cause of late-age dementia. The mechanisms of Aβ plaque formation and deposition are far from being understood. A vast amount of literature describes the efforts to analyze those mechanisms, using a variety of tools. The present review focuses on biophysical studies, mostly carried out with model membranes, or with computational tools. The review starts by describing basic physical aspects of lipid phases, and commonly used model membranes (monolayers and bilayers). This is followed by a discussion of biophysical techniques applied to these systems, mainly but not exclusively Langmuir monolayers, isothermal calorimetry, density-gradient ultracentrifugation, and molecular dynamics. The methodological section is followed by the core of the review, a summary of important results obtained with each technique. The last section is devoted to an overall reflection and an effort in understanding Aβ-bilayer binding. Concepts such as Aβ peptide membrane binding, adsorption, and insertion are defined and differentiated. The roles of membrane lipid order, nanodomain formation, and electrostatic forces in Aβ-membrane interaction are separately identified and discussed.

Abstract Octreotide is the first synthetic peptide hormone, consisted of eight amino acids, that mimics the activity of somatostatin, a natural hormone in the body. During the past decades, advanced instrumentation and crystallographic software established X-ray Powder Diffraction (XRPD) as a valuable tool for extracting structural information of biological macromolecules. The latter was demonstrated by the successful structural determination of octreotide at a remarkably high d-spacing resolution (1.87 Å) (PDB code: 6vc1). This study focuses on the response of octreotide to different humidity levels and temperatures, with a particular focus on the stability of the polycrystalline sample. XRPD measurements were accomplished employing an Anton Paar MHC-trans humidity-temperature chamber installed within a laboratory X’Pert Pro diffractometer (Malvern Panalytical). The chamber is employed to control and maintain precise humidity and temperature levels of samples during XRPD data collection. Pawley analysis of the collected data sets revealed that the octreotide polycrystalline sample is remarkably stable and no structural transitions were observed. The compound retains its orthorhombic symmetry (space group: P212121, a = 18.57744(4) Å, b = 30.17338(6) Å, c = 39.70590(9) Å, d~ 2.35 Å). However, a characteristic structural evolution in terms of lattice parameters and volume of the unit-cell is reported mainly upon controlled relative humidity variation. In addition, an improvement of signal-to-noise ratio in the XRPD data under a cycle of dehydration/rehydration is reported. These results underline the importance of considering the impact of environmental factors, as humidity and temperature, in the context of structure-based drug design, thereby contributing to the development of more effective and stable pharmaceutical products.

Anastomotic insufficiencies are severe complications of abdominal surgery, often leading to pro-longed hospitalization, serious tissue inflammation, even sepsis and the need for recurrent sur-gery. Current non-surgical treatments such as self-expanding metal stents (SEMS) and endoscopic vacuum therapy (EVT) have limitations, including stent migration or perforation. This review evaluates the effectiveness of the VacStent GITM, a novel medical device combining SEMS and negative-pressure wound therapy in treating gastrointestinal leaks. Data were gathered from four prospective studies and compared with existing treatments. Studies on the VacStent GITM applica-tion demonstrate technical success and competitive closure rates in upper gastrointestinal leaks, with minimal complications reported. Comparative analyses with SEMS and EVT reveal prom-ising and most importantly equally good outcomes while maintaining the possibility for sus-tained enteral nutrition and reducing stent migration risk. The VacStent GITM presents a promis-ing alternative to current non-surgical treatments. Ongoing research aims to validate its efficacy in lower gastrointestinal leaks and establish its role in leak management comprehensively. Fur-ther investigation is necessary to confirm these findings and optimize treatment protocols. Future usages of the VacStent GITM in colonic anastomotic insufficiencies promise an effective approach and might be able to lower the rates of necessary implementations of a stoma.

Amidst increasing awareness of diet-health relationships, plant-derived bioactive peptides are recognized for their dual nutritional and health benefits. This study investigates bioactive peptides released after Alcalase hydrolysis of protein from chachafruto (Erythrina edulis), a nutrient-rich South American leguminous plant, focusing on their behavior during simulated gastrointestinal digestion. Evaluating their ability to scavenge radicals, mitigate oxidative stress, and influence immune response biomarkers, the study underscores the importance of understanding peptide interactions in digestion. Methods included previous enzymatic hydrolysis with Alcalase to obtain peptides, and results show significant radical scavenging and oxidative stress protection by chachafruto peptides. These findings highlight the potential of chachafruto bioactive peptides in functional foods and nutraceuticals, supporting human health through dietary interventions.

Spinal muscular atrophy (SMA) is a severe neuromuscular disorder that is caused by mutations in the survival motor neuron 1 (SMN1) gene, hindering the production of functional survival motor neuron (SMN) proteins. Antisense oligonucleotides (ASOs), a versatile DNA-like drug, are adept at binding to target RNA to prevent translation or promote alternative splicing. Nusinersen is an FDA-approved ASO for the treatment of SMA. It can effectively promote alternative splicing in SMN2, an analog of SMN1, to produce a greater amount of full length SMN protein, to compensate for the loss of functional protein translated from SMN1. Despite its efficacy in ameliorating SMA symptoms, the cellular uptake of these ASOs is suboptimal and their inability to penetrate the CNS necessitates invasive lumbar punctures. Cell-penetrating peptides (CPPs), that can be conjugated to ASOs, represent a promising approach to improve the efficiency of these treatments for SMA and have the potential to transverse the blood-brain barrier to circumvent the need for intrusive intrathecal injections and their associated adverse effects. This review provides a comprehensive analysis of ASO therapy, their application for the treatment of SMA, and the encouraging potential of CPPs as delivery systems to improve ASO uptake and overall efficiency.

Gastrointestinal (GI) cancers, such as colorectal and gastric cancers, pose significant global health challenges due to their high rates of incidence and mortality. Even with advancements in treatment and early detection, many patients still face poor outcomes, highlighting the critical need for new biomarkers and therapeutic targets. Telomere length (TL) and telomerase activity (TA) have gained attention in this context. Telomeres, protective nucleotide sequences at chromo-some ends, shorten with each cell division, leading to cellular aging. Telomerase, a ribonucleoprotein enzyme, counteracts this shortening by adding telomeric repeats, a process tightly regulated in normal cells but often dysregulated in cancer. This review critically evaluates the role of TL and TA in the pathogenesis of GI cancers, examining their potential as diagnostic, prognostic, and predictive biomarkers. It explores how alterations in telomere biology contribute to the initiation and progression of GI tumors and assesses the therapeutic implications of targeting telomerase. By integrating findings from diverse studies, this review aims to elucidate the intricate relationship between telomere dynamics and gastrointestinal carcinogenesis, offering in-sights into how TL and TA could be leveraged to enhance the early detection, treatment, and prognosis of GI cancers.

2017 was an excellent year in terms of new drugs (chemical entities and biologics) approved by the FDA, with a total of forty-six. In turn, one of the highlights was the number of peptides (six) included in this list. Here, the six peptides are analysed in terms of chemical structure, synthetic strategy used for their production, source, biological target, and mode of action.

Commercial protein supplements are the main sources for the sports nutrition. Nowadays, those protein supplements mainly differ in the ingredients and formulations, possibly affecting the digestion behavior and protein absorption during gastrointestinal digestion. Herein, this work aimed to investigate the gastric digestion behavior and protein hydrolysis of commercial protein supplements by using an in vitro dynamic digestion model. Five commercial protein supplements were selected, including three protein powders and two liquid protein beverages. The results indicated that liquid protein beverages had smaller particle size than protein powder dispersions, and one of the protein powders existed as the microcapsules. During gastric digestion, all samples tended to form aggregates as the pH decreased, and the degree of aggregation was more pronounced in liquid protein beverages than in protein powders, where the intact structure of the microcapsules was gradually disrupted. Protein hydrolysis degree in liquid protein beverages was higher than that in protein powders. One of the liquid products (M20) had the highest protein hydrolysis degree of around 35.74% after 120 min gastric digestion and a half-empty time of 37.82 min. These findings suggest that the formulation and ingredients of commercial protein supplements will affect their digestion behavior, resulting in varying degree of protein hydrolysis. Hence, sports supplements should be carefully designed to provide precise nutrition for the athletes and exercisers.

The gastrointestinal tract contains multiple types of immune cells that maintain the balance between tolerance and activation at the first line of host defense facing non-self antigens, including dietary antigens, commensal bacteria, and sometimes unexpected pathogens. Maintaining homeostasis at the gastrointestinal tract requires stringent regulation of the immune responses against various environmental conditions. Diet can be converted into gut metabolites which have unique functional activities through host as well as microbial enzymatic activities. Accumulating evidences demonstrate that gastrointestinal metabolites have significant impacts on the regulation of intestinal immunity and further integrate immune response of distal mucosal tissue. Metabolites, especially derived from microbiota, regulate immune cell functions by various ways including recognition and activation of cell surface receptors, controlling of gene expression by epigenetic regulation and integration of cellular metabolism. These mucosal immune regulations are key to understand underlying mechanism for the development of gastrointestinal disorders. Here, we review the recent advancement of our understanding on the role of gut metabolites in the regulation of gastrointestinal immunity with highlighting the cellular and molecular regulatory mechanisms by macronutrients-derived metabolites.

Gastrointestinal stromal tumors are the mostly seen mesenchymal tumors of the gastrointestinal system. This rare tumor in duodenum is seen 5%. The diagnosis and treatment is hard because of its rarity and location. Case: A 63-year-old man with a solid mass at the third part of the duodenum, and local segmental resection of the tumor was performed. The histopathology was reported as gastrointestinal stromal tumor of the duodenum with negative surgical margins. Discussion: Gastrointestinal stromal tumors at the duodenum are seen rarely. They can be asymptomatic or may involve symptoms of upper GI bleeding and abdominal pain at presentation. Because of the misleading clinical presentation the differential diagnosis may be difficult. Tumors less than 2 cm can be followed by endoscopic ultrasound. Local segmental resection with 1cm clear margin is the treatment choice.

Worldwide, the demand for natural and synthetic sweeteners in the food industry as an alternative to refined sugar is increasing. This prompted more research to estimate its safety and effect on health. The gut microbiome is critical in metabolizing selected sweeteners, which might affect overall health. Recently, more studies evaluated the relationship between sweeteners and the gut microbiome. This review summarizes the current knowledge addressing the role played by the gut microbiome in metabolizing selected sweeteners. It also addresses the influence of the five selected sweeteners or their metabolites on GI cancer-related pathways. Overall, the observed positive effect of sweetener consumption on GI cancer pathways, such as apoptosis and cell cycle arrest, requires further investigation to understand the underlying mechanism. Furthermore, more research is needed to address the main challenges of studying the field, thus advancing it further.

Since there is not a clear consensus about the possibility for COVID-19 to be an airborne disease, exists a controversy regarding the need to use surgical masks to prevent its spread. Here, using the Kepler conjecture for ideal packaging, the number of virions of different sizes that can be accommodated inside droplets was calculated and are proportional to the 3^rd potency of the droplet/virion diameter. The differences between particles of 5 um and 100 μm are around four orders of magnitude, explaining why the airborne spread is much more difficult but still possible. There is no solid evidence yet that the airborne coronaviruses may reach enough concentration to infect, but this may be the case under certain circumstances. The WHO partially recognizes now this fact in a warning to health workers (from my point of view too late, as it was the declaration of a pandemic). Another issue is whether the virus stays infective in aerosols generated from patients. This has not been directly proved yet except with artificial aerosols, but there are no reasons why the virus cannot remain in the air and be infective if the viral charge and time of exposure are enough. We must also consider whether the virus can infect the intestine; there are some signs in this sense. Finally, and most importantly, we need to reduce interactions by using surgical masks to flatten the curve, leave the quarantine and avoid a rebound. For cultural reasons, a social distance of 2 meters (2M) is extremely hard to manage. Surgical masks do reduce the interactions in conditions of proximity and, therefore, help to “flatten the curve”. The WHO and CDC “laissez-faire” on this matter do not help and we are running out of time. Anticipated actions, such as the use of surgical masks for the general population, are critical.

Minigastrin (MG) analogs for therapy of CCK2R-expressing malignancies are limited by low stability in vivo or excessive accumulation in non-target organs. By modifying the C-terminal receptor-binding sequence, metabolization could be prevented and tumor targeting significantly improved. In this work, N-terminal changes of the peptide length were evaluated. Based on the amino acid sequence of DOTA-MGS5 (DOTA-DGlu-Ala-Tyr-Gly-Trp-(N-Me)Nle-Asp-1Nal-NH₂), two new MG analogs were synthesized, by either introduction of a penta-DGlu moiety or depletion of the four N-terminal amino acids and introduction of a non-charged hydrophilic linker. Two CCK2R-expressing cell lines were used to demonstrate receptor interaction. Stability of the ¹⁷⁷Lu-labeled peptide analogs was evaluated in human serum up to 24 h after incubation and in BALB/c mice up to 30 min after injection. The biodistribution profile and tumor targeting potential was evaluated in xenografted BALB/c nude mice. For both new MG analogs, the combination of strong receptor-specific cell interaction, high stability and enhanced tumor targeting could be demonstrated. Shortening of the peptide sequence lowered the absorption in the dose-limiting organs, whereas elongation increased uptake in renal tissue.

Multiple lines of research have led to the hypothesis that antimicrobial peptides (AMPs) are an important component of the innate immune response, playing a vital role in the defense against a wide range of infectious diseases. In this review we explore the occurrence and availability of antimicrobial proteins and peptides across various species, highlighting their natural abundance and evolutionary significance. The design of AMPs has been driven by the identification of key structural and functional features, which are essential for optimizing their antimicrobial activity and reducing toxicity to host cells. We discuss various approaches, including rational design, high-throughput screening, and computational modeling, that have been employed to develop novel AMPs with enhanced efficacy. A particular focus is given to the identification and characterization of peptide fragments derived from naturally occurring host defense proteins, which offer a promising avenue for the discovery of new AMPs. The incorporation of artificial intelligence (AI) and machine learning (ML) tools into AMP research has further accelerated the identification, optimization, and application of these peptides. This review also discusses the current status and therapeutic potential of AMPs, emphasizing their role in addressing the growing issue of antibiotic resistance. The conclusion highlights the importance of continued research and innovation in AMP development to fully harness their potential as next-generation antimicrobial agents.

The RV144 trial represents the only vaccine trial to demonstrate any protective effect against HIV-1 infection. While the reason(s) for this protection are still being evaluated, it serves as justification for widespread efforts aimed at developing new, more effective HIV-1 vaccines. Advances in our knowledge of HIV-1 immunogens and host antibody responses to these immunogens are crucial to informing vaccine design. While the envelope (Env) protein is the only viral protein present on the surface of virions, it exists in a complex trimeric conformation and is decorated with an array of variable N-linked glycans, making it an important but difficult target for vaccine design. Thus far, efforts to elicit a protective humoral immune response using structural mimics of native Env trimers have been unsuccessful. Notably, the aforementioned N-linked glycans serve as a component of many of the epitopes crucial for the induction of potentially protective broadly neutralizing antibodies (bnAbs). Thus, a greater understanding of Env structural determinants, most critically Env glycosylation, will no doubt be of importance in generating effective immunogens. Recent studies have identified the HIV-1 Env signal peptide (SP) as an important contributor to Env glycosylation. Further investigation into the mechanisms by which the SP directs glycosylation will be important, both in the context of understanding HIV-1 biology and in order to inform HIV-1 vaccine design.

Transplant oncology is a relatively new field in which transplantation is used to treat patients who would otherwise be unresectable. New anticancer treatment paradigms using tumor and transplant immunology and cancer immunogenomics are emerging. In turn, liver transplantation (LT) has become a potential therapy for certain patients with colorectal cancer (CRC) with liver metastasis, hepatocellular (HCC), cholangiocarcinoma (CCA), and metastatic neuroendocrine tumor (NET) to the liver. Although there are established criteria for LT in HCC, the evidence regarding LT as a treatment modality for certain gastrointestinal malignancies is still debated. The aim of this review is to highlight updates in the role of LT for certain malignancies, including HCC, metastatic CRC, hilar CCA, and neuroendocrine tumor (NET), as well as contextualize LT use and discuss controversies in transplant oncology.

Malignant neoplasm is one of the most incurable diseases among inflammatory diseases. Researchers have been studying for decades to win over this lethal disease and provide the light of hope to humankind. The gastrointestinal bacteria of human hold a complex ecosystem and maintain homeostasis. One hundred trillion microbes are residing in the gastrointestinal tract of human. Disturbances in the microbiota of human’s gastrointestinal tract can create immune response against inflammation and also can develop diseases , including cancer. The bacteria of the gastrointestinal tract of human, can secrete a variety of metabolites and bioproducts which aid in the preservation of homeostasis in the host and gut. During pathogenic dysbiosis, on the other hand, numerous microbiota subpopulations may increase and create excessive levels of toxins, which can cause inflammation and cancer. Furthermore, the immune system of host and the epithelium cell can be influenced by gut microbiota. Probiotics, which are bacteria that live in the gut, have been protected against tumor formation. Probiotics are now studied to see if they can help fight dysbiosis in cancer patients undergoing chemotherapy or radiotherapy because of their capacity to maintain gut homeostasis. Countless numbers of gut bacteria have demonstrated anti-cancer efficiency in cancer treatment, prevention, and boosting the efficiency of immunotherapy. The review article has briefly explained the anti-cancer immunity of gut microbes and their application in treating a variety of cancer. This review paper also highlights the pre-clinical studies of probiotics against cancer and the completed and ongoing clinical trials on cancers with the two most common and highly effective probiotics Lactobacillus and Bacillus spp.

Gastrointestinal stromal tumors are the mostly seen mesenchymal tumors of the gastrointestinal system and mostly seen at the stomach. We report a case of giant gastrointestinal stromal tumor of the stomach in a 71-year-old woman. The physical examination and radiological findings revealed that a giant mass occupied most of the abdominal cavity. The patient underwent an en-block resection of this giant mass with partial resection of the distal stomach and transverse colon and, reconstruction with gastro-jejunostomy and end-to end colo-colic anatomoses. The histopathologic diagnosis was revealed as gastrointestinal stromal tumor of the stomach. We suggest that complete surgical resection is the only effective radical treatment approach for giant gastrointestinal stromal tumors of the stomach.

The antimicrobial peptide LRGG (LLRLLRRGGRRLLRLL-NH2) was designed and chemically synthesized in a study conducted by Jia et al. Gram-negative bacteria were found to be sensitive to LRGG and exhibited a high therapeutic index. Genetic engineering methods were used to create the prokaryotic fusion expression vector pQE-GFP-LRGG, and the resulting corresponding fusion protein GFP-LRGG was subsequently expressed and purified. The precursor GFP was then removed by TEV proteolysis, and pure LRGG was obtained after another round of purification and endotoxin removal. The prokaryotic-expressed antimicrobial peptide LRGG displays a broad-spectrum antibacterial effect on gram-negative bacteria and can eliminate 99.99% of E. coli within 100 minutes at the minimal MIC concentration. Compared to the chemically synthesized LRGG, the prokaryotic-expressed LRGG exhibits similar temperature, pH, salt ion, serum stability, and cell selectivity. Furthermore, prokaryotic-expressed LRGG showed excellent therapeutic effects in both the infection model of cell selectivity and no embryotoxicity in a Galleria mellonella infection model. The mechanism by which LRGG causes bacterial death was found to be disruption of Gram-negative cell membrane.

GI endoscopy forms an important part in a daily practice of a gastroenterologist. Musculoskeletal injuries related to GI endoscopy are on the rise. Observational studies and surveys depict the importance of proper ergonomical environment when performing GI endoscopy. Our aim is to outline preventive measures in gastrointestinal (GI) endoscopy in reducing possibility for occupational injury. We review most relevant studies that outline the gravity of the problem. A detailed analysis of proposed ergonomical recommendations is performed, outlining crucial steps in injury prevention. Proper ergonomical education is a key-step in preventing occupational injury. Robotics and other mechanical solutions offer a variety of approaches tackling the ergonomical challenge. Implementing proper ergonomical education and mechanical solutions lowers the possibility if occupational injury. Strategies and appliances presented are beneficial to all GI endoscopy practitioners.

After screening nearly 1000 synthetic peptides, a synthetic peptide termed JAL-AK22 (KYEGHWYPEKPYKGSGFRCIHI) derived from the BoxA domain in Tob1 protein was found to activate both unfolded and folded proMMP-7. In addition, JAL-AK22 showed auto-proteolytic activity. Interestingly, the smaller derivative of JAL-AK22 termed JAL-TA9 (YKGSGFRMI) also possessed auto-proteolytic activity and cleaved 2 fragment peptides (MMP18-33 and MMP18-40) derived from the prodomain of proMMP-7 under physiological conditions. These proteolytic activities were inhibited by AEBSF, a serine protease inhibitor. Our results demonstrate that a small synthetic peptide consisting of only 9 amino acids has serine protease-like activity and activates proMMP-7 by cleaving the prodomain region. We thus propose calling small peptides possessing with protease-like activity Catalytides (catalytic peptides). We expect that our findings will stimulate the development of novel Catalytides and related applications.

Identifying the correct dosage and time are key factors to successful implementation of anthelmintic. Comparing differential evolution of infection between anthelmintic treated animals against untreated ones, we present a mathematical model that first calibrates data collected and analyzed over an extended period of 10 years (2011-2019), and then predicts the dynamical evolution of gastrointestinal parasites in livestock, focusing specifically on Stronglye \& Coccidia oocysts, the two prime negative contributors to cattle health, measured using the standard Eggs-Per-Gram (EPG) index. The model incorporates information about all three critical regimes of infection - low infection regime ($< 50$ EPG), medium infection regime ($50-100$ EPG) and high infection regime ($>100$ EPG), including fatally large doses of infection ($> 500$), and probabilistically estimates the variation in animal weight due to infection propagation. A key success of our model is its ability to accurately predict the appropriate anthelmintic treatment times for cattle from a numerical solution of the model presented. The generic model can be applied to other agroclimatic conditions and can serve as a major diagnostic tool for anthelmintic strategizing.

Despite the extensive research conducted on ruminal methanogens and anti-methanogenic intervention strategies over the last 50 years, most of the currently researched enteric CH4 abatement approaches have shown limited efficacy. This is largely because of the complex nature of animal production and the ruminal environment, host genetic variability of CH4 production, and an incomplete understanding of the role of the ruminal microbiome in enteric CH4 emissions. Recent sequencing-based studies suggest the presence of methanogenic archaea in extra-gastrointestinal tract tissues, including respiratory and reproductive tracts of cattle. While these sequencing data require further verification by culture-dependent methods, the consistent identification of methanogens with relatively greater frequency in the airway and urogenital tract of cattle plus increasing appreciation of the microbiome-gut-organ axis highlight the potential interactions between ruminal and extra-gastrointestinal methanogenic communities. Thus, a traditional singular focus on ruminal methanogens may not be sufficient, and a holistic approach which takes into consideration of the transfer of methanogens between ruminal, extra-gastrointestinal, and environmental microbial communities is of necessity to develop more efficient and long-term ruminal CH4 mitigation strategies. In the present review, we provide a holistic survey of the methanogenic archaea present in different anatomical sites of cattle and discuss potential seeding sources of the ruminal methanogens.

The incidence of gastrointestinal cancers has seen a significant increase in recent years. Current treatments present numerous challenges, including drug resistance, non-specificity, and severe side effects, among others. These issues have necessitated the exploration of new therapeutic strategies. One promising avenue is the use of magnetic nanoparticles, which have gained considerable interest due to their ability to generate heat in tumor regions upon the application of an external alternating magnetic field, a process known as hyperthermia. This review conducted a systematic search of in vitro and in vivo studies published in the last decade that employ hyperthermia therapy mediated by magnetic nanoparticles for treating gastrointestinal cancers. After applying various inclusion and exclusion criteria, a total of 40 articles were analyzed. The results revealed that iron oxide is the preferred material for magnetism generation in the nanoparticles, and colorectal cancer is the most studied gastrointestinal cancer. Interestingly, novel therapies employing nanoparticles loaded with chemotherapeutic drugs demonstrated an excellent antitumor effect. In conclusion, hyperthermia treatments mediated by magnetic nanoparticles appear to be an effective approach for the treatment of gastrointestinal cancers, offering advantages over traditional therapies.

Copper(II), nickel(II) and zinc(II) complexes of various peptide fragments of tau protein were studied by potentiometric and spectroscopic techniques. All peptides contained one histidyl residue and represented the sequences of tau(91-97) (Ac-AQPHTEI-NH2), tau(385-390) (Ac-KTDHGA-NH2) and tau(404-409) (Ac-SPRHLS-NH2). Imidazole-N donors of histidine were the primary metal binding sites for all peptides and all metal ions but in case of copper(II) and nickel(II) the deprotonated amide groups were also involved in metal binding by increasing pH. The most stable complexes were formed with copper(II) ion but the presence of prolyl residues resulted in significant changes in the thermodynamic stability and speciation of the systems. It was also demonstrated that nickel(II) and especially zinc(II) complexes have relative low thermodynamic stability with these peptides. Copper(II) catalyzed oxidation of the peptides was also studied. In the presence of H2O2 the fragmentation of peptides can be detected in all cases. In the simultaneous presence of of H2O2 and ascorbic acid the extent of the fragmentation of the peptide is less preferred, and the formation of 2-oxo-histidine also occurs.

According to the International Union for Conservation of Nature Red List, the scalloped hammerhead (Sphyrna lewini) is a critically endangered species, primarily due to intense fishing and other anthropogenic effects such as pollution. Nowadays, plastic debris contamination is a subject of concern due to its extensive presence in the sea and the digestive tracts of many fish species. The possible effects of plastic debris as a vector of other pollutants are still unknown. We analyzed the digestive tract of hammerhead sharks to investigate the correlation between plastic and other anthropic debris contamination and feeding habits in the eastern region of the Gulf of California. A total of 58 specimens were analyzed from the coastal area, revealing a plastic occurrence frequency of 79.3%. Of these, 91.4% corresponded to fibers, and 8.6% to fragments. The composition of the polymers was primarily cellulose (64.4%). According to their diet, these organisms exhibit benthopelagic habits, feeding both in the water column and on the seabed. These results indicate a high level of contamination of anthropogenic cellulosic microfibers in the area. This changed according to the year, indicating that the anthropic debris ingestion is related to the discharges of human activities and their seasonality rather than to a selection process by the sharks. Although cellulosic microfibers are recognized as a biomaterial, they can harm marine species, posing an additional threat to this iconic shark.

Polymeric nanoparticles (NPs) have garnered significant interest due to their potential in drug delivery. Specifically, nanopolymers functionalized with molecules such as proteins or peptides serve as versatile vehicles for this purpose. Curcumin (Cur) is a widely studied anticancer compound known for its positive effects on human health. Nevertheless, its insolubility and low bio-distribution hinder the exploitation of its beneficial traits. In this study, our team developed a nanodelivery system using a nanopolymer called poly(ε-caprolactone)-poly(ethylene glycol) (PCL-PEG), functionalized with A6 peptide to enable targeted delivery of Cur. The designed system exhibited favorable characteristics, including a stable zeta potential of -13.8 mV, a small size of 76.4 nm, uniform surface morphology, and high hydrophilicity with a contact angle of 31.53°. Additionally, the targeted delivery system demonstrated high encapsulation efficiency (EE%) (93 ± 0.89%), drug loading (DL%) (16.7 ± 0.9%), and a slow and gradual release profile with a release of approximately 83.1 ± 0.12%. The MTT assay results showed significant cell death in MDA-MB-231 cancer cells (IC₅₀ = 21.3 ± 1.57 µM) when treated with the Cur-NPs-A6 formulation, while the toxicity of the designed NPs was reduced on non-cancerous MCF-10A cells. Moreover, both the RT-qPCR and invasion assays demonstrated the system's effectiveness in activating apoptosis pathways and inhibiting cell invasion. These findings suggest that the engineered intelligent delivery system, equipped with the A6 peptide, which has a strong affinity for CD44 (a protein with increased expression in malignancy), could be an exceptionally effective strategy for cancer treatment.

The healing of osteochondral defects (OCD) resulting from injury, osteochondritis, or osteoarthritis in middle- and old-age individuals, bearing lesions in the cartilage and bone, pain, and loss of joint function, presents challenges to the clinical practitioners because of non-regenerative cartilage and the limitations of current therapies. Bioactive peptide-based osteochondral (OC) tissue regeneration is becoming more popular because it does not have the immunogenicity, misfolding, or denaturation problems associated with original proteins. Periodically, reviews are published on the regeneration of bone and cartilage; however, none of them address the simultaneous healing of these tissues in the complicated heterogeneous environment of the OC interface. As regulators of cell adhesion, proliferation, differentiation, angiogenesis, immunomodulation, and antibacterial activity, potential therapeutic strategies for OC defects utilizing bone and cartilage-specific peptides should be examined and investigated. Therefore, the main goal of this review is to study how they contribute to the healing of OC defects, either alone or in conjunction with other peptides and biomaterials.

Despite significant strides in prevention, diagnosis, and treatment, cardiovascular diseases remain the number one cause of mortality in the United States, with rates climbing at an alarming rate in the developing world. Targeted delivery of therapeutics to the heart has been a lofty goal to achieve with strategies ranging from direct intra-cardiac or intra-pericardial delivery, intra-coronary infusion, to adeno-associated viral vectors which have preference, if not complete cardio-selectivity, for cardiac tissue. Cell penetrating peptides (CPP) are 5-30 amino acid long peptides that are able to breach cell membrane barriers while carrying cargoes up to several times their size, in an intact functional form. Identified nearly three decades ago, the first of these CPPs came from the HIV coat protein transactivator of transcription. Although a highly efficient CPP, its clinical utility is limited by its robust ability to cross any cell membrane barrier, including crossing the blood-brain barrier and transducing neuronal tissue non-specifically. Several strategies have been utilized to identify cell or tissue specific CPPs, one of which is phage display. Using this latter technique, we identified a cardiomyocyte targeting peptide (CTP) more than a decade ago, a finding that has been corroborated by several independent labs across the world that have utilized CTP for myriad different purposes in pre-clinical animal models. The goal of this publication is to provide a comprehensive review of the identification, validation, and application of CTP, and outlining its potential in diagnostic and therapeutic applications especially in the field of targeted RNA interference.

Based on a new model of a possible origin of life, we establish an efficient and stable system undergoing structural reproduction, self-optimization and molecular evolution. This system is being formed under realistic conditions by the interaction of two cyclic processes, one of which offering vesicles as the structural environment, the other supplying peptides from a variety of amino acids as versatile building blocks. We demonstrate that structures growing in a combination of both cycles have the potential to support their own existence, to undergo chemical and structural evolution and to develop unpredicted functional properties. The key mechanism is the mutual stabilization of the peptides by the vesicles and of the vesicles by the peptides together with a constant production and selection of both. The development of the proposed system over time not only would represent one of the principles of life, but could also be a model for the formation of self-evolving structures ultimately leading to the first living cell. The experiment yields clear evidence on a vesicle-induced accumulation of membrane-interacting peptide which could be identified by liquid chromatography combined with high-resolution mass spectroscopy. We found that the selected peptide has an immediate effect on the vesicles, leading to i) reduced vesicle size, ii) increased vesicle membrane permeability, and iii) improved thermal vesicle stability.

Gastrointestinal (GI) tract disorders, ranging from benign polyps to aggressive forms of cancer, pose significant health challenges globally. Early detection and precise classification of these conditions are crucial for effective treatment and improving patient survival rates. This study employs the Hyper-Kvasir dataset, a comprehensive collection of endoscopic images, to develop deep learning models that harness the power of the YOLO (You Only Look Once) architecture for real-time detection and classification of GI abnormalities. The focus is on overcoming inherent challenges such as class imbalance and limited annotated data availability. Advanced machine learning strategies, including data augmentation and semi-supervised learning, are utilized to enhance the model's performance. Our experiments demonstrate notable improvements in the detection of pre-cancerous lesions and other GI abnormalities, confirming the potential of integrating AI into endoscopic practices to support clinicians, reduce diagnostic errors, and contribute to more accurate and timely diagnoses. The implications of these findings are significant, offering a pathway to more reliable diagnostic processes and ultimately, better patient management in gastroenterology.

The spectrum, intensity and overlap of symptoms between FGIDs and other gastrointestinal disorders characterize patients with FIGDs, who are incredibly different in their backgrounds. An additional challenge with regard to the diagnosis and treatment's applicability is the ongoing expansion of the risk factors believed to be connected to these disorders. Many cytokines and inflammatory cells have been found causing the continuous existence of low-inflammation, which is thought to be a basic pathophysiological process. The idea of the gut-brain axis has been created to offer a basic framework for the complex interactions that occur between the nervous system and intestinal functions, including the involvement of the gut bacteria. In this review paper, we intend to promote a hypothesis that FGIDs, should be seen through the perspective of the network of the neuroendocrine, immunological, metabolic and microbiome pathways. Hypothesis arises from an increased understanding of chronic inflammation as a systemic disorder, being omnipresent in chronic health conditions. Better understanding of inflammation role in the pathogenesis of FGIDs can be achieved by clustering markers of inflammation with data indicating symptoms, comorbidities, and psycho-social factors. Finding subclasses among related entities of FGIDs, may reduce patient heterogeneity and help clarify pathophysiology for better treatment.

In Mexico, 1.9% of child mortality among children aged 3 to 15 years is attributed to waterborne gastrointestinal diseases (WGD). This study employs a generalized bivariate logit econometric model to simulate the relationships between mortality risks and seven explanatory variables. Based on the model results and sensitivity analysis of the estimated parameters, a set of policies was designed to reduce the likelihood of child mortality. The proposed strategy involves im-plementing the following public policies, primarily targeting communities with extreme and high marginalization: increasing access to drinking water, improving housing conditions, expanding parental basic education coverage, and providing nutrition and healthcare to children from an early age. The findings reveal that children who speak an indigenous language face a mortality risk from WGD that is three times higher than those who do not, while children who receive medical services have a 29% lower risk of mortality compared to those who do not have access to them. It is recommended to offer free medical care in indigenous languages within high-marginalization communities. The combined impact of these policies is expected to signifi-cantly reduce child mortality due to WGD.

Crohn’s disease (CD) is a progressive, multifactorial, immune-mediated disease characterized by chronic inflammation of any part of the gastrointestinal (GI) tract. Pediatric patients present with a more extensive form of the disease, especially in the upper GI tract with various histopathological inflammatory patterns. Our study aims to analyze the endoscopic and histopathological findings in children with diagnosed CD and compare results on the initial and follow-up tests. Our study included 100 children and adolescents with CD, with performed endoscopic and histopathological (HP) procedures. The results of multiple biopsies performed in these 8 years were matched and compared. We found a statistically significant decrease in stool changes, weight loss, and abdominal pain as presenting symptoms, and in the fecal calprotectin levels. On esophagogastroduodenoscopy and ileo-colonoscopy 36.59% and 64.86% patients had specific findings, respectively. Non-caseating granulomas were found on 9% of oesophageal, 18% of gas-tric, and 12% of duodenal biopsies. In the lower GI tract, we have observed a disease progression in the rectum and descending colon between the first and second biopsies. Our study showed that more than a third of patients had specific endoscopic (36.59%) and histopathologic (32%) findings in the upper GI tract, and an additional 23% had HP findings highly suggestive of CD. We demonstrated the importance of regular endoscopic and histopathological assessments of pediatric CD patients.

Advances in nanomedicine bring the attention of researchers to the molecular targets which can play a major role in the development of novel therapeutic and diagnostic modalities for cancer management. The choice of a proper molecular target can decide on the efficacy of the treatment and endorse the personalized medicine approach. Gastrin-releasing peptide receptor (GRPR) is a G-protein-coupled membrane receptor, well known to be overexpressed in numerous malignancies including pancreatic, prostate, breast, lung, colon, cervical and gastrointestinal cancers. Therefore, many research groups express a deep interest in targeting GRPR with their nanoformulations. A broad spectrum of the GRPR ligands has been described in the literature, which allows tuning of the properties of the final formulation, particularly in the field of the ligand affinity to the receptor and internalization possibilities. Hereby the recent advances in the field of applications of various nanoplatforms which are able to reach the GRPR expressing cells are reviewed.

The gut-brain axis (GBA) represents a complex, bidirectional communication network that intri-cately connects the gastrointestinal tract with the central nervous system (CNS). Understanding and intervening in this axis opens a pathway for therapeutic advancements. In light of this, the current review assesses the effectiveness of neuromodulation techniques in treating neurological and gastrointestinal disorders by modulating the GBA, involving key elements such as gut micro-biota, neurotrophic factors, and proinflammatory cytokines. Through a comprehensive literature review encompassing PubMed, Google Scholar, Web of Science, and the Cochrane Library, and analyzing 182 relevant articles, this research highlights how neuromodulation can positively impact the management of functional gastrointestinal disorders (FGIDs), chronic pain, inflammation, and a range of GI disorders like Crohn's disease and ulcerative colitis. Despite existing challenges, the ability of neuromodulation to adjust disrupted neural pathways, alleviate pain, and mitigate in-flammation is significant in improving the quality of life for patients, thereby offering exciting prospects for future advancements in patient care.

This is growing recognition of early onset gastrointestinal (GI) malignancies in young adults

The gastrointestinal (GI) tract is a continuous channel through the body that consists of the esophagus, the stomach, the small intestine, the large intestine, and the rectum. Its primary functions are to move the intake of food for digestion before storing and ultimately expulsion of feces from the rectum through the anal sphincter. The mechanical behavior of GI tissues thus plays a crucial role for GI function in health and disease. The mechanical properties are typically characterized by a constitutive biomechanical model, which is a mathematical representation of the relation between load and deformation in a tissue. Hence, validated biomechanical constitutive models are essential to characterize and simulate the mechanical behavior of the GI tract under physiological and pathological conditions. Numerous constitutive models have consequently been proposed over the past three decades, mainly inspired by work done in cardiovascular tissues. Here, a comprehensive review of these constitutive models is provided. This review is limited to studies where a model of the strain energy function is proposed to characterize the stress-strain relation of a GI tissue. Several needs are identified for more advanced modeling of GI biomechanics including: 1) Microstructural models that provide actual structure-function relations; 2) Validation of coupled electro-mechanical models accounting for active muscle contractions; 3) Human data under physiological and pathological conditions to develop and validate models. The findings from this review provide guidelines for using existing constitutive models as well as perspective and directions for future studies aimed at establishing new constitutive models for GI tissues.

The incidence of gastrointestinal diseases (cancer in particular) has increased progressively with considerable morbidity, mortality, and a high economic impact on the healthcare system. Dietary intake of natural bioactive phytochemicals showed to have cancer-preventing and therapeutic effects. This includes the cruciferous vegetable derivative phenethyl isothiocyanate (PEITC), a bioactive compound from watercress. PEITC antioxidant, anti-inflammatory and anti-cancer properties are of particular importance. This review summarizes the current knowledge on the role of PEITC as a potential natural nutraceutical or an adjuvant against oxidative/inflammatory-related disorders in the gastrointestinal tract. We also discuss the safe and recommended dose of PEITC. Besides, we establish a framework to guide the research and development of sustainable methodologies for obtaining and stabilizing this natural nutraceutical for industrial use. This is a topic that still needs more scientific development, but with the potential to lead to a viable strategy in the prevention of cancer and other associated diseases of the gastrointestinal tract.

Antibody-Drug Conjugates (ADCs) are a powerful therapeutic modality for cancer treatment. ADCs are multi-functional biologics in which a disease-targeting antibody is conjugated to an effector payload molecule through a linker. The success of currently used ADCs has been largely attributed to the development of linker systems which allow targeted release of cytocidal payload drugs inside cancer cells. Many lysosomal proteases are over-expressed in human cancers. They can effectively cleave a variety of peptide sequences, which can be exploited in the design of ADC linker systems. As a well-established linker, valine-citrulline-p-aminobenzyl carbamate (ValCitPABC) is used in many ADCs that are already approved or under preclinical and clinical development. Although ValCitPABC and related linkers are readily cleaved by cathepsins in the lysosome while remaining reasonably stable in human plasma, many studies have shown that they are susceptible to carboxylesterase 1C (Ces1C) in mouse and rat plasma, which hinders preclinical evaluation of the ADCs. Furthermore, neutropenia and thrombocytopenia, two of the most commonly observed dose-limiting adverse effects of ADCs, are believed to result from the premature hydrolysis of ValCitPABC by human neutrophil elastase. In addition to cathepsin-cleavable linkers, there is also growing interest in legumain-sensitive linkers for ADC development. Increasing plasma stability while maintaining lysosomal cleavability of ADC linkers is an objective of intensive current research. This review reports recent advances in the design and structure-activity relationship studies of various peptide/peptidomimetic linkers in this field.

The determination of the three-dimensional structure is a key step for the identification of new targets as well as the rational design of bioactive compounds. Herein, we report the synthesis and the structural elucidation of novel tetrameric macrocycles. Measurements were taken in solid and solution states with the help of X-ray scattering and NMR spectroscopy. The investigations made will help to find diverse applications for this new, promising compound class.

Granular cell tumors (GCTs), known also as Abrikossoff tumors, are rare tumors that originates from Schwann cells that primarily localize in the tongue, skin, and submucosal tissues and involve the gastrointestinal tract in 11% of cases. We present a case of a young woman who first presented to our centre in 2018, for an EGDS to assess a thickening of the esophageal wall, seen on a CT. In that occasion, a diagnosis of Abrikossoff tumor was made. She underwent endoscopic resection with subsequent yearly follow-up without evidence of recurrence. 5 Years later, on a routine colonoscopy, we found numerous white submucosal formations in all of the explored tracts, with a histological examination compatible with GCT. Her daughter presented with a white nodule on her tongue, also diagnosed as GCT. Her daughter was also diagnosed with GCT of the tongue a few months later.

(1) Background: Little research is done on the link of diabetic kidney disease (DKD) progression and diabetic gastroenteropathy in type 1 diabetes (T1D). (2) Methods. We performed a cross-sectional study with 100 T1D patients, 27 of them had progressive DKD, defined as estimated glomerular filtration rate (eGFR) decline≥3 ml/min/year or increased albuminuria stage over the mean follow-up time of 5.89±1.73 years. Newly developed score with 17 questions on gastrointestinal (GI) symptoms was used. Faecal calprotectin was measured by ELISA. Lower GI endoscopies were performed in 21 patients. (3) Results: Gastrointestinal symptom score demonstrated high reliability (Cronbach's α=0.78). Patients with progressive DKD had higher GI symptom scores compared to those with stable DKD (p=0.019). The former group demonstrated more frequent bowel movement disorders (p=0.04). The scores correlated negatively with eGFR (r = -0.335; p = 0.001), positively with albuminuria (r=0.245; p=0.015), Hba1c (r=0.305, p=0.002), diabetes duration (r=0.251, p=0.012). Faecal calprotectin levels did not differ between DKD groups significantly. The most commonly reported histopathological findings of enteric mucosa were infiltration with eosinophils, lymphocytes, plasmacytes, presence of lymphoid follicles and lymphoid aggregates. Conclusion: progression of DKD positively correlated with gastrointestinal symptoms, but more research is needed to clarify the causal relationships of the gut-kidney axis in T1D.

The study of biologically active substances from natural sources shows the prospect of obtaining a new type of antimicrobial agents, highly effective against pathogenic microorganisms and non-toxic to humans. Our study reveals for the first time that Cornu aspersum mucus has the potential to act as a source of antibacterial agents against bacterial pathogens such as Bacillus cereus 1085, Propionibacterium acnes 1897, Salmonella enterica 8691, Enterococcus faecalis 3915, and Enterococcus faecium 8754. Both mucus fractions with MW<20 kDa and MW>20 kDa showed antimicrobial activity and antioxidant properties that’s why they can be turned into an alternative agent to expensive synthetic antibacterial compounds. Using de novo sequencing 16 novel peptides with potential antibacterial activity were identified by in a fraction with MW<20 kDa. The results of electrophoretic and proteomic analysis of mucus fraction with MW >20 kDa presented proteins with potential antibacterial activity highly homologous to hemocyanins, mucus protein Aspernin, lectins, L-amino acid oxidase-like protein, and mucins (mucin-5AC, mucin-5B, mucin-2 and mucin-17). Thanks to the synergistic action of the bioactive components, the mucus fraction with MW > 20 kDa in low concentrations per 8–2 µg/mL showed promising antimicrobial activity against the tested bacteria, comparable to Vancomycin and without unwanted cytotoxic effects against non-target cells. Additionally, C. aspersum mucus fractions were found to have a positive effect on eukaryotic organisms by reducing the levels of intracellular oxidative damage and increasing the antioxidant capacity of the cell. These findings could serve as a basis for the development of a potent non-cytotoxic antibacterial agent to replace conventional antibiotics and avoid the development of antibiotic resistance.

The cytosolic PNGase (peptide:N-glycanase; Png1 in yeast; NGLY1/Ngly1 in human/mice), also known as peptide-N4-(N-acetyl-beta-glucosaminyl)-asparagine ami-dase, is a well-conserved deglycosylation enzyme (EC 3.5.1.52) which catalyzes the non-lysosomal hydrolysis of an N(4)-(acetyl-β-D-glucosaminyl) asparagine residue into N-acetyl-β-D-glucosaminylamine and a peptide containing an aspartate residue. This enzyme (NGLY1) plays essential roles in clearance of misfolded or unassembled gly-coproteins through a process named ER-associated degradation (ERAD). Accumulating evidence also points out that NGLY1 deficiency can cause an autosomal recessive hu-man genetic disorder associated with abnormal development and congenital disorder of deglycosylation. In addition, the loss of NGLY1 can affect multiple cellular pathways, including but not limited to NFE2L1 pathway, Creb1/Atf1-AQP pathway, BMP path-way, AMPK pathway, and SLC12A2 ion transporter, which might be the underlying reasons for a constellation of clinical phenotypes of NGLY1 deficiency. The current comprehensive review indeed uncovers the detailed NGLY1’s structure and its im-portant roles for participation in ERAD, involvement in CDDG and potential treatment for NGLY1 deficiency.

Description of a novel bovine antimicrobial peptide and its antimicrobial spectrum. RNA isolation and RT-PCR were done from various tissues. DCD peptide was synthesized, and antimicrobial activity was analyzed. Bovine dermcidin gene contains five exons intermittent by 4 introns. Bovine DCD-mRNA was 398 bp with ORF 336 bp. Bovine DCD was expressed in skin and blood. Analysis of the amino acid compositions revealed that cysteine was repeated 6 times indicating the presence of 3 disulfide bonds that play role in the peptide stability. Staphylococcus epidermidis, Streptococcus bovis, and Enterococcus faecalis were affected by Bovine DCD peptide. Highest antimicrobial effect was at 50 and 100 µg/ml. The effect on Escherichia coli and Candida albicans was slightly low. In all bacteria, Bovine DCD peptide activity did not affect by varying pH values, but in Staphylococcus aureus, the activity was affected greatly at pH 4.5 and 5.5. The optimum salt concentrations were 100 and 50 mM NaCl with all bacterial strains and E. coli, respectively. In case of C. albicans, the antimicrobial activity of Bovine DCD peptide decreased with increasing the pH value regardless the NaCl concentration. The pH 6.5 of the sweat buffer was the optimum for the Bovine DCD peptide activity.

Background: Gastrointestinal stromal tumors (GIST) are rare mesenchymal neoplasms of the gastrointestinal tract (GIT) that represent approximately 1 to 2 percent of primary gastrointestinal (GI) cancers. Owing to their rarity, very little is known about the overall epidemiology and prognostic factors of the pathology. The purpose of this study is to investigate the clinical characteristics, survival outcomes, and independent prognostic factors of patients with GIST in the past decade. Methods: A total of 2,374 patients diagnosed with GIST, between 2010 and 2017, were ultimately enrolled in our study by retrieving the Surveillance, Epidemiology, and End Results (SEER) database. We analyzed demographics, clinical characteristics, and overall mortality (OM) as well as cancer-specific mortality (CSM) of GIST. Variables with a p value < 0.01 in the univariate Cox regression were incorporated into the multivariate Cox model to determine the independent prognostic factors, with a hazard ratio (HR) of greater than 1 representing adverse prognostic factors. Results: Multivariate cox proportional hazard regression analyses of factors affecting all-cause mortality and GIST related mortality among US patients between 2010 and 2017 revealed higher overall mortality in Non-Hispanic Blacks (HR= 1.516, 95% CI 1.172-1.961, p= 0.002), age 80+ (HR= 9.783, 95% CI4.185-22.868, p= 0), followed by age 60-79 (HR= 3.408, 95% CI 1.488-7.807, p=0.004); male patients (HR= 1.795 , 95% CI 1.461-2.206, p=0); advanced disease with distant metastasis (HR= 3.865 , 95% CI 2.977-5.019, p=0), followed by regional involvement by both direct extension and lymph node involvement (HR= 3.853, 95% CI 1.551-9.57, p=0.004); and widowed patients (HR= 1.975, 95% CI 1.494-2.61, p= 0), followed by single patients (HR= 1.53, 95% CI 1.154-2.028, p=0.003). The highest CSM was observed in the same groups, except widowed patients and patients aged 60-79. The highest CSM was also observed among patients that underwent chemotherapy (HR= 1.687, 95% CI 1.19-2.392, p= 0.003). Conclusion: In this United States population-based retrospective cohort study using the SEER database, we found that non-Hispanic blacks, male patients, and patients older than 60 years have a higher mortality with GIST. Furthermore, patients who received chemotherapy have a higher GIST specific mortality and married patients had a lower mortality. However, we do not know to what extent these independent prognostic factors interact with each other to influence mortality. This study paves the way for future studies addressing those interactions. The results of this study may help treating clinicians to identify patient populations associated with dismal prognosis as those may require closer follow-up and more intensive therapy; furthermore, with married patients having a better survival, we hope to encourage clinicians to involve family members of the affected patients early in the disease course as the social support might impact the prognosis.

The impact of a non-anticholinergic spasmolytic drug (drotaverine hydrochloride) on 23 heart rate (HR), HR variability (HRV) and gastrointestinal tract (GIT) motility in the normal, resting 24 horses was determined. Ten adult riding horses had ECG recordings for 180 minutes after treat-25 ment with drotaverine (180 mg) or saline. Horses from the drotaverine group presented a de-26 creased of GIT contraction for two hours after treatment, but also showed drowsiness. Drotaverine 27 caused a reduction in cardiac vagal modulation of HR at T30 (P=0.050) and T60 (P=0.008) compared 28 to those receiving saline. RMSSD and high frequency (HF) recorded significantly low values after 29 drotaverine treatment by the end of the study, suggesting a decrease in parasympathetic activity. 30 HRV analysis indicated that drotaverine decreased both the low frequency (LF) and Lf/HF ratio 31 reflecting a decrease in sympathetic system. Non linear parameters registered low values after 32 drotaverine administration pointing a diminished in parasympathetic (for SD1) and sympathetic 33 (for SD2) activity. Decreased HRV was suggestive for a pervasive state of sympathetic hypervigi-34 lance of horses. The marked effect of drotaverine on HRV and GIT function in horses should be 35 taken into consideration when evaluating a clinical response to this drug in diseases associated 36 with smooth muscle spasm.

Background: The prevalence of obesity, defined as body mass index (BMI) ≥ 30 kg/m2, has reached epidemic levels. Obesity is associated with an increased risk of various cancers, including gastrointestinal ones. Recent evidence has suggested that obesity disproportionately impacts males and females with cancer, resulting in varied transcriptional and metabolic dysregulation. Methods: This study aimed to elucidate the differences in the metabolic milieu of adenocarcinomas of the gastrointestinal (GI) track both related and unrelated to sex in obesity. To demonstrate these obesity and sex-related effects, we utilized three primary data sources: serum metabolomics from obese and non-obese patients assessed via the Biocrates MxP Quant 500 mass spectrometry-based kit, the ORIEN tumor RNA-sequencing data for all adenocarcinoma cases to assess the impacts of obesity, and publicly available TCGA transcriptional analysis to assess GI cancers and sex-related differences in GI cancers specifically. We applied and integrated our unique transcriptional metabolic pipeline in combination with our metabolomics data to reveal how obesity and sex can dictate differential metabolism in patients. Results: Differentially expressed genes (DEG) analysis of ORIEN obese adenocarcinoma as compared to normal-weight adenocarcinoma patients resulted in large-scale transcriptional reprogramming (4029 DEGs, adj. p < 0.05 and |logFC|>0.58). Gene Set Enrichment and metabolic pipeline analysis showed genes enriched for pathways relating to immunity (inflammation, and CD40 signaling, among others) and metabolism. Specifically, we found alterations to steroid metabolism and tryptophan/kynurenine metabolism in obese patients, both of which are highly associated with disease severity and immune cell dysfunction. These findings were further confirmed using the TCGA colorectal adenocarcinoma (CRC) and esophageal adenocarcinoma (ESCA) data, which showed similar patterns of increased tryptophan catabolism for kynurenine production in obese patients. These patients further showed disparate alterations between males and females when comparing obese to non-obese patient populations. Alterations to immune and metabolic pathways were validated in 6 patients (2 obese and 4 normal weight) via CD8+/CD4+ peripheral blood mononuclear cell RNA-sequencing and paired serum metabolomics, which showed differential kynurenine and lipid metabolism, which corresponded with altered T-cell transcriptome in obese populations. Conclusions: Overall, obesity is associated with differential transcriptional and metabolic program in various disease sites. Further, these alterations, like kynurenine and tryptophan metabolism, which impact both metabolism and immune phenotype, vary with sex and obesity together. This study warrants further in-depth investigation into obesity and sex-related alterations in cancers that may better define biomarkers of response to immunotherapy.

The discovery of more bioactive compounds for non-invasive administration has been the goal of research groups focused on pharmacotherapy. Phytonutrients have always been attractive for researchers because they are a significant source of bioactive phytochemicals, but it is challenging to determine which components show high biomedical activity. However, based on the chemical structure of these active compounds, their physicochemical properties can be calculated to predict the probability of gastrointestinal (GI) absorption after oral administration. Indeed, different researchers have proposed several rules (e.g., Lipinski's, Veber's, Ghose's, and Muegge's rules) to attain these predictions for synthetic compounds. Most phytochemicals do not fully comply with these rules even though they show high bioactivity and high GI absorption experimentally. Here, we provide a detailed methodology using web-based platforms to determine the physicochemical properties of five phytochemicals in the phytonutrients ginger, echinacea, and tobacco. Furthermore, we analyzed the calculated data and established a protocol based on the combination and integration of these rules, plus other extended parameter ranges, to reliably predict the GI absorption of natural compounds. The presented data and methodology can be beneficial for evaluating bioactive natural compounds as potential drug candidates and predicting their oral bioavailability in patients.

Cyanobacterial blooms occur with increasing frequency in freshwater ecosystems, posing a hazard to human and environmental health. Exposure of human to cyanobacterial metabolites occurs mostly via accidental ingestion through contaminated drinking water or during recreational activities and, most frequently, results in gastrointestinal symptoms. Despite the clinical manifestation, cyanobacterial metabolites are rather investigated for their toxicity towards specific organs or tissues, especially hepato-, nephro- and neurotoxicity, then for effects on the gastrointestinal tract and the associated lymphoid tissue. The aim of this review was to systematically summarize available literature on the effects on the gastrointestinal tract and the mucosal innate immune system and compile the data from both, in vitro and in vivo studies, focusing on human-health relevant models. Our systematic literature review revealed significant data gaps in the understanding on metabolites breaching the gastrointestinal barrier and the role of the immune system in the establishment of clinical symptoms. Microcystins and cylindrospermopsin were linked to gastrointestinal symptoms, immune system effects or both. Furthermore, implications for cyanobacterial bloom lipopolysaccharides in gastrointestinal inflammation were reported in several cases, while other metabolites received only minor attention. The collected data indicate the need for a reassessment of potential enterotoxicity of microcystins and cylindrospermopsin. Additionally, the carcinogenic potential of cyanotoxins, especially microcystins, has to be clarified, as an increasing amount of epidemiological studies show correlations between cyanobacterial blooms and gastrointestinal cancer incidence. Furthermore, other, often highly abundant bioactive metabolites like aeruginosins, have to be toxicologically evaluated at levels also accounting for (sub-)chronic exposure to low concentrations and in combination with naturally co-occurring metabolites, as can be expected in drinking water supplies. studies, focusing on human-health relevant models. Our systematic literature review revealed significant data gaps in the understanding on metabolites breaching the gastrointestinal barrier and the role of the immune system in the establishment of clinical symptoms. Microcystins and cylindrospermopsin were linked to gastrointestinal symptoms, immune system effects or both. Furthermore, implications for cyanobacterial bloom lipopolysaccharides in gastrointestinal inflammation were reported in several cases, while other metabolites received only minor attention. The collected data indicate the need for a reassessment of potential enterotoxicity of microcystins and cylindrospermopsin. Additionally, the carcinogenic potential of cyanotoxins, especially microcystins, has to be clarified, as an increasing amount of epidemiological studies show correlations between cyanobacterial blooms and gastrointestinal cancer incidence. Furthermore, other, often highly abundant bioactive metabolites like aeruginosins, have to be toxicologically evaluated at levels also accounting for (sub-)chronic exposure to low concentrations and in combination with naturally co-occurring metabolites, as can be expected in drinking water supplies.

Maintenance of integrity and function of the gastric mucosa (GM) requires a high regeneration rate of epithelial cells during the whole life span. The health of the gastric epithelium highly depends on redox homeostasis, antioxidant defense and activity of detoxifying systems within the cells as well as robustness of blood supply. Bioactive products of lipid peroxidation, in particular second messengers of free radicals, the bellwether of which is 4-hydroxynonenal (HNE), are important mediators in physiological adaptive reactions and signaling but they are also thought to be implicated in the pathogenesis of numerous gastric diseases. Molecular mechanisms and consequences of increased production of HNE and its protein adducts in response to stressors during acute and chronic gastric injury are well studied. However, several important issues related to the role of HNE in gastric carcinogenesis, tumor growth and progression, the condition of GM after eradication of Helicobacter pylori, or the relevance of antioxidants for HNE-related redox homeostasis in GM still need more studies and new comprehensive approaches. In this regard, preclinical studies and clinical intervention trials are required, which should also include the use of state-of-the-art analytical techniques such as HNE determination by immunohistochemistry and ELISA as well as modern mass-spectroscopy methods.

OBJECTIVES: To assess the predictive value of serum trypsin and Trypsinogen Activation Peptide (TAP) for the severity of AP by means of a single center cohort study as well as a systematic review of the current literature. METHODS: The literature search was conducted using Medline (PubMed), EMBASE and the Cochrane Central Register. A total of 142 patients with acute pancreatitis (AP) were included in the cohort study and parameters of the revised Atlanta criteria of 2012 and the APACHE II were assessed. RESULTS: The review showed promising results for the predictive value of serum trypsinogen-2, but conflicting results for serum TAP and trypsin. In the cohort study, patients were observed for 4 days after diagnosis of AP: 9 patients had severe AP, 35 patients had moderate AP and 81 patients had mild AP. The ratio of the geometric mean of severe vs mild AP for trypsin was 0.72 (95% CI: 0.51-1.00), p=0.053 and for TAP 0.74 (95% CI: 0.54-1.01), p=0.055 respectively. CONCLUSION: The cohort study showed an inverse correlation of serum levels of TAP and trypsin with severity of AP. Serum TAP and trypsin have an inferior predictive value of severity of AP compared to the clinical APACHE II score.

We introduced a novel biotin-binding peptide for sensing biotin, biotinylated proteins, and nu-cleotides. From a 15-mer library displayed on the RNA coliphage Qβ, a 15-amino acid long peptide (HGHGWQIPVWPWGQG) hereby referred to as nanotag was identified to selectively bind biotin. The targets selection was achieved through panning with elution by infection. The selected peptide was tested as a transducer for an immunogenic epitope of the foot-and-mouth disease virus (FMDV) on Qβ phage platform separated by a linker. The biotin-tag showed no significant in-fluence on the affinity of the epitope to its cognate antibody (SD6). The nanotag bound biotin selectively when fused either to the C- or N-terminus of the epitope. The epitope would not bind or recognize SD6 while positioned at the N-terminus of the nanotag. Additionally, the biotin com-peted linearly with the SD6 antibody in a competitive ELISA. Competition assays using the se-lected recombinant phage itself as a probe, or transducer, enable the operationalization of this technology as a biosensor toolkit to sense and quantify SD6 analyte. Herein, the published Strep II nanotag (DVEWLDERVPLVET) was used as a control and has similar functionalities to our pro-posed novel biotin-tag thereby providing a new platform for developing devices for diagnostic purposes.

Hepcidin-25 was identified as the main iron regulator in the human body by binding to the sole iron-exporter ferroportin. Studies showed that the N-terminus of hepcidin is responsible for this interaction, the same N-terminus that encompasses a small copper(II)-binding site known as ATCUN (amino terminal Cu(II)- and Ni(II)- binding) motif. Interestingly, this copper-binding property is largely ignored in most papers dealing with hepcidin-25. In this context, detailed investigations of the formed complex of hepcidin-25 with copper could reveal insights into its biological role. The present work is mainly focused on the study of the metal-bound form of hepcidin-25, which could be considered the biologically active form. The first part is devoted to the reversed-phase chromatographic separation of copper-bound and copper-free hepcidin-25, which was achieved by applying basic mobile phases containing 0.1% ammonia. Further, mass spectrometry (tandem mass spectrometry MS/MS, high resolution mass spectrometry HRMS) and nuclear magnetic resonance (NMR) spectroscopy were employed to characterize the copper-peptide. Lastly, a 3D model of hepcidin-25 with bound copper(II) is presented. The identification of metal complexes and potential isoforms and isomers, from which the latter usually are left undetected by mass spectrometry, led to the conclusion that complementary analytical methods are needed to characterize a peptide calibrant or reference material comprehensively. Quantitative nuclear magnetic resonance (qNMR), inductively-coupled plasma mass spectrometry (ICP-MS), ion-mobility spectrometry (IMS) and chiral amino acid analysis (AAA) should be considered among others.

The oncological outcomes are improving in gastrointestinal cancer with advancement in systemic therapies, and there is notable potential in combining immunotherapy and radiation therapy (RT)to allow for further improvements in outcomes. Various preclinical and early phase II studies have shown promising synergy with immunotherapy and RT in gastrointestinal cancer. Consolidative nivolumab in esophageal cancer after neoadjuvant chemoradiation (CRT) and complete resection has recently been approved as standard treatment after improved disease free survival in phase III study. Immunotherapy has shown promising results in hepatocellular carcinoma and colorectal cancer as well. We have reviewed the published and ongoing studies of the combinations of immunotherapy and RT in gastrointestinal cancers.

Different kinds of freshwater fish soups show a diverse range of health functions, due to their different nutritional substances and corresponding bioactivities. Crucian carp soup and snakehead soup have different dietotherapy functions, crucian carp soup is suitable for lactating women and snakehead soup is suitable for postoperative patients. In the current study, the changes of nutrient profiles in the different fish soups, such as chemical composition, free amino acids, mineral and fatty acid contents, were investigated. The antioxidant activities of the fish soups were evaluated by using the DPPH radical scavenging activity, the ferrous ion chelating activity, the hydroxyl radical-scavenging activity and the reducing power effect. In order to learn the theoretical basis of the potential role fish soup plays in diet therapy functions after being digested by the human body, the nutrient profiling and bioactivities of the fish soup samples after simulated gastrointestinal digestion were also explored. The intensive profiles of nutritional composition and antioxidant activities of these two kinds of fish soups were expected to partly provide the theoretical basis of therapeutic effects.

The objective of this study was to identify genomic regions and genes associated with resistance to gastrointestinal nematodes in Australian Merino sheep in Uruguay, using the single-step GWAS methodology (ssGWAS), which is based on genomic estimated breeding values (GEBVs) obtained from a combination of pedigree, genomic and phenotypic data. This methodology converts GEBVs into SNP effects. Analysis included 26,638 animals with fecal egg count (FEC) records obtained in two independent parasitic cycles (FEC1 and FEC2), and 1,700 50K SNP genotypes. Comparison of genomic regions was based on genetic variances (gVar(%)) explained by non-overlapping regions of 20 SNPs. For FEC1 and FEC2, 18 and 22 genomic windows exceeded the significance threshold (gVar(%) ≥ 0.22%), respectively. The genomic regions with strong associations with FEC1 were located on chromosomes OAR 2, 6, 11, 21 and 25, and for FEC2 on OAR 5, 6 and 11. The proportion of genetic variance attributed to the top windows was 0.83% and 1.9% for FEC1 and FEC2, respectively. The 33 candidate genes shared between the two traits were subjected to enrichment analysis, revealing a marked enrichment in biological processes related to immune system functions. These results contribute to the understanding of the genetics underlying gastrointestinal parasite resistance and its implications for other productive and welfare traits in animal breeding programs.

Background: Patients undergoing dual antiplatelet therapy (DAPT) may experience recurrent gastrointestinal bleeding (GIB). We investigated the clinical characteristics and risk factors for recurrent non-variceal upper gastrointestinal bleeding (NVUGIB) in patients who had experienced NVUGIB during receiving DAPT. Methods: We enrolled patients diagnosed with NVUGIB during receiving DAPT between 2006 and 2020. Definite bleeding was confirmed by esophagogastroduodenoscopy in all NVUGIB patients. Results: A total of 124 patients were diagnosed with NVUGIB during receiving DAPT. Male was predominant (n = 103, 83.1%), bleeding mostly from the stomach (n = 94, 75.8%) and peptic ulcers (n = 72, 58.1%). After successful hemostasis of NVUGIB, 36 patients (29.0%) experienced at least one episode of recurrent upper GIB, 19 patients (15.3%) died, and 7 (5.6%) patients had a bleeding-related death. Multivariate analysis showed that age was a significant factor for re-bleeding (odds ratio [OR],1.050; 95% confidence interval [CI]:1.001-1.102, P-value:0.047), all-cause mortality (OR,1.096; 95% CI:1.020-1.178, P=0.013), and re-bleeding related mortality (OR,1.187; 95% CI:1.032-1.364, P-value:0.016). In Kaplan-Meier analysis, the cumulative probabilities of re-bleeding, death, and bleeding-related death were significantly higher in patients aged 70 and older (P=0.008, &lt;0.001, and 0.009, respectively). Conclusion: Clinicians should be cautious about re-bleeding and mortality when elderly patients who experienced NVUGIB during receiving DAPT.Keywords: dual antiplatelet therapy; upper gastrointestinal tract; bleeding; mortality

SARS-CoV-2 infects a range of host species. However, the susceptibility of companion animals to SARS-CoV-2 and their potential ability to transmit the virus to humans remains unclear. Here, we present a detailed clinical description of an immunosuppressed dog that was infected with SARS-CoV-2. The dog had severe gastrointestinal (GI) clinical signs, coagulopathy, elevated hepatic transaminases, and met canine systemic inflammatory response syndrome criteria, without respiratory clinical signs, mirroring a subset of humans with GI-restricted COVID-19. Viral sequencing demonstrated divergence from other reported sequences, based on phylogenetic analysis. The dog shed high levels of virus for a prolonged time period with positive virus isolation. The dog’s immunosuppressed state may have increased both susceptibility to infection and disease progression. Together, our findings suggest that certain individual companion animals may be at higher risk for severe SARS-CoV-2 infection, COVID-19-like disease, and high viral shedding, which may pose a transmission risk to humans.

It was previously reported that the peptide derived from LfcinB, R-1-R exhibited anti-Candida activity and this activity was enhanced in combination with an extract from the Bidens pilosa plant. However, the mechanism of action has not been studied. In the current study, a proteomic study was carried out, followed by a bioinformatic analysis and biological assays in both SC5314 strain and a fluconazole-resistant isolate of Candida albicans, after incubation with R-1-R. The proteomic data showed that after treatment with R-1-R in the two study strains, most of the differentially expressed proteins in comparison to controls were up-regulated. These proteins were mainly involved in membrane and cell wall biosynthesis, membrane transporters, oxidative stress, the mitochondrial respiratory chain, and response to DNA damage. Besides, the proteomic analysis of C. albicans parental strain SC5314 treated with R-1-R in combination with an ethanolic extract of B. pilosa was also undertaken. The proteins differentially expressed after this treatment were involved in similar functional processes as the proteins differentially expressed after treatment with R-1-R peptide alone, but at different levels and were mostly down-regulated. The biological assays allowed validation of the proteomic results, evidencing damage to the cell surface, generation of reactive oxygen species and decrease in mitochondrial membrane potential. The results provide information to begin to unlock the understanding of the complex antifungal mode of action of the R-1-R peptide, its combination with the extract, and possibly other derivatives of natural products.

New strategies for enhancing drug delivery to the blood–brain barrier (BBB) represents a major challenge in treating cerebral diseases. Nano-emulsion based nanocarriers represent an ideal candidate to improve drug delivery thanks to their versatility in functionalization and cargo protection. In this work, a paclitaxel loaded nano-emulsion has been firstly functionalized and stabilized with two layers constituted of chitosan and hyaluronic acid, and, secondly, the latter has been conjugated to the CRT peptide. CRT is a bioactive peptide that selectively recognizes bEnd.3 cells, model of the BBB, thanks to its interactions with transferrin (Tf) and its receptor (TfR). Cytotoxic results showed a higher uptake of CRT functionalized nano-emulsion 41.5 % more than the negative control, demonstrating the ability of this novel tool to be accumulated on the brain endothelium tissue. Thanks to these results, our approach can be fully generalizable to the design of multifunctional nanocarriers for delivery of therapeutic agents to the central nervous systems.

Myocardial infarction (MI) remains the leading cause of death in the western world. Although medical advancements have been made in interventional revascularization technologies, a large percentage of patients are not candidates for them due to co-morbidities or lack of local resources. Thus, there remains a need for the development of novel non-invasive strategies to treat MI. Approaches to accelerate revascularization within ischemic tissues through angiogenesis by providing Vascular Endothelial Growth Factor (VEGF) in protein or gene form has been shown to be effective in animal models but not in humans likely due to its short half-life and systemic toxicity. We previously showed that a small peptide (PR1P) we developed stabilizes VEGF in its active dimer state, increases VEGF binding to its receptors and potentiates VEGF activity. Here we show that systemic PR1P treatment targeted, stabilized and upregulated endogenous VEGF within ischemic myocardium following left coronary artery surgery in mice and rats. Targeted VEGF upregulation led to augmentation of heart function at two weeks following surgery. We conclude that PR1P is a potential candidate therapeutic for MI.

Purpose: To assess the clinical safety and possible effectiveness of Vasoactive Intestinal Peptide in the treatment of Acute Respiratory Distress Syndrome (ARDS) related to sepsis. Methods: Under FDA Investigational New Drug clearance, 8 patients with ARDS related to sepsis were treated with 50 pmole/kg/hr – 100 pmole/kg/hr of Vasoactive Intestinal Peptide by intravenous infusion for 12 hours. All patients were on mechanical ventilation and full telemetery. Results: No drug-related serious adverse events were seen. Hypotension was seen in association with two infusions and diarrhea in association with one, but did not necessitate cessation of therapy. Bigeminy was seen in association with one infusion without sequelae. Seven of eight patients demonstrated a successful course during intensive care and were successfully removed from mechanical ventilation and discharged from intensive care. The eighth patient succumbed to purulent secretions in the lungs. Of those who were discharged from the ICU, six demonstrated successful 30 day survival. The seventh died from a cerebral infract at day 30, deemed unrelated to treatment with VIP. Serum levels of Tumor Necrosis Factor α were obtained in 6 patients at baseline and 24 hours and were seen to decrease with treatment in five patients. Conclusions: Initial clinical results of treatment with VIP in patients with ARDS demonstrated a safety profile consistent with previous studies in normal volunteers. The successful clinical course seen in 7 of 8 patients in the setting of an expected 50% survival may suggest that VIP shows promise in the treatment of other infectious conditions that damage the pulmonary epithelium, particularly COVID-19.

Beyond factors such as smoking and obesity, the risk of getting gastrointestinal cancer is passed down from parents to offspring, inherited by a gene mutation, predisposing them to develop cancer in their lifetime. Here we describe the clinical history of family members affected by gastrointestinal pathologies often leading to cancer. In the epidemiological study, the cohort of members of this family shared a high risk of developing gastrointestinal diseases. The subjects were monitored from May 2006 to December 2017 by collecting periodically clinical and endoscopic data, and determining both auto-modification of lymphocyte Poly(ADP-ribose)Polymerase as early signal of DNA damage, and erythrocyte membrane lipid composition (Fat Profile). Both biomarkers were demonstrated to be non invasive and easy tools, to monitor over time family members, first the oldest members (nine siblings), and thereafter their offspring, whose cell status evolved from physiological even to cancerous one. All subjects developed gastrointestinal pathologies of different kind and seriousness. Some diseases evolved to cancer, sometimes as a sudden and lethal event. The results of the two molecular approaches, agreed and even predicted the clinical and imaging paths. This cohort study supported the hypothesis that both noninvasive molecular analyses can predict altered cell states and support clinical and imaging tests.

This study aimed to introduce a novel machine learning (ML) model designed to predict the need of interventions during endoscopy in patients with upper gastrointestinal bleeding (UGIB). The risk stratification tools in current use, such as the Glasgow Blatchford Score (GBS) and pre-endoscopic Rockall score, have limitations in accurately predicting the need for endoscopic interventions. All patients diagnosed with UGIB from January 2013 to October 2023 who underwent endoscopy were included in the study. Variables extracted included demographics, social history ,clinical history, clinical presentation and symptoms, drug history, management prior to endoscopy, findings during endoscopy, laboratory variables and vitals, and post-endoscopic results. Three machine learning models including Random Forest Classifier (RFC), Gradient Boosting Classifier (GBC), and AdaBoost Classifier were used to evaluate the need for intervention during endoscopy in our study. A total of 1372 patients were included from three major hospitals in Jordan, of whom 242 underwent endoscopic intervention. The GBC outperformed all other models and pre-endoscopic scores in predicting the need for endoscopic intervention with an area under the curve of 0.861. Findings during endoscopy, platelet count, pulse rate and systolic blood pressure during admission were the most contributing features in predicting the need for the need of endoscopic intervention. This study highlights the potential of machine learning models in enhancing decision making for UGIB management.

This research explores a novel encapsulating agent for establishing a synbiotic relationship with Bacillus (B.) coagulans by combining different ratios of wall materials, including skim milk powder (S), maltodextrin (M), and cellulose acetate phthalate (C). The ratio options are represented as SMC1 (1:2:1), SMC3 (3:2:1), SMC5 (5:2:1), and SMC7 (7:2:1). These wall materials are incorporated with 5% inulin (a prebiotic). The results show that these agents effectively protect B. coagulans spores during spray-drying, resulting in spore vitality exceeding 6 log cfu/g; SMC5 and SMC7 yielded the highest spore viability values. Furthermore, SMC5 demonstrated the highest levels of antioxidant activity, encompassing the scavenging of DPPH, hydroxy radicals, and superoxide radicals. Additionally, it displayed notable antidiabetic effects, including inhibitions of α-amylase and α-glucosidase. In comparison, SMC7 exhibited the most potent antidiabetic activity by inhibiting DPP-IV. Subsequently, after simulated gastrointestinal digestion, SMC5 and SMC7 showed a slight decrease in spore viability during the 6-hour simulation. Therefore, the most suitable condition for synbiotic production was found to be SMC5, which can potentially protect B. coagulans spores and exhibit bioactive activities after microencapsulation and passage through gastrointestinal digestion. This innovative product can be utilized as an advanced food delivery system and as a functional ingredient in functional food products.

Modulating the gut microbiota with probiotics has been identified as a promising therapeutic method for the management of gastrointestinal illnesses. The effectiveness of probiotics in the treatment of gastrointestinal disorders can only be determined by delving into their underlying mechanisms of action. Through an analysis of the underlying processes, this study hopes to provide light on the potential benefits of probiotics for treating a variety of gastrointestinal conditions. The study covers a wide variety of gastrointestinal conditions, such as IBS, IBD, and antibiotic-associated diarrhea. Modifying the gut microbiota composition, strengthening the gut barrier function, modulating the immune system, and producing beneficial metabolites are among mechanisms of action that have been investigated. The strain- and dose-specific variables essential to getting the best treatment results are also highlighted. This review, which synthesizes the current information, gives a thorough overview of the effectiveness of probiotics in treating a variety of gastrointestinal illnesses and illuminates potential avenues for further study and therapeutic use.

The central nervous system (CNS) and the human gastrointestinal (GI) tract communicate through the gut-brain axis (GBA). Such communication is bi-directional and involves neuronal, endocrine and immunological mechanisms. The scientific data are mounting that gut microbiota is a source of a number of neuroactive and immunocompetent substances, which shape the structure and function of brain regions involved in control of emotions, physical activity and cognition. Most of GI maladies are associated with altered transmission within the GBA and influenced both by genetic and environmental factors. Current treatment protocols widely advocated for the treatment of GI disorders may positively or adversely affect the composition of intestinal microbiota with diverse impact on therapeutic outcome. The alterations of gut microbiota have been associated with mood and depressive disorders. and mental health is frequently altered in the course of many GI and non-GI ailments. Deregulation of the GBA may constitute a grip point for the development of diagnostic tools and personalized microbiota-based therapy. For example next generation sequencing (NGS) offers detailed analysis of microbiome footprints in patients with mental and GI disorders. Psychobiotics are new class of beneficial bacteria, with documented efficacy in the treatment of gut-brain axis disorders.

Following traumatic brain injury (TBI), secondary brain damage due to chronic inflammation is the most predominant cause of the delayed onset of mood and memory disorders. Currently no therapeutic approach is available to effectively mitigate secondary brain injury after TBI. One reason is the blood-brain barrier (BBB), which prevents passage of most therapeutic agents into the brain. Peptides have been among the leading candidates for CNS therapy due to their low immunogenicity and toxicity, bioavailability, and ease of modification. In this study, we demonstrated that non-invasive intranasal administration of KAFAK, a cell penetrating anti-inflammatory peptide, traversed the BBB in a murine model of diffuse, moderate TBI. Notably, KAFAK treatment reduced the production of pro-inflammatory cytokines that contribute to secondary injury. Furthermore, behavioral tests showed improved or restored neurological, memory, and locomotor performance in KAFAK-treated mice. This study demonstrates KAFAK's ability to cross the blood-brain barrier, to lower pro-inflammatory cytokine levels in vivo, and to restore function after a moderate TBI.

Peptide-based opioid ligands are important candidates for the development of novel, safer, and more effective analgesics to treat pain. To develop peptide-based safer analgesics, we synthesized a mixture-based cyclic pentapeptide library containing a total of 24,624 pentapeptides and screened the mixture-based library samples using a 55 °C warm-water tail-withdrawal assay. Using this phenotypic screening approach, we deconvoluted the mixture-based samples to identify a novel cyclic peptide Tyr-[D-Lys-Dap(Ant)-Thr-Gly] (CycloAnt), which produced dose- and time-dependent antinociception with an ED50 (and 95% confidence interval) of 0.70 (0.52-0.97) mg/kg i.p. mediated by the mu-opioid receptor (MOR). Additionally, higher doses (≥ 3 mg/kg, i.p.) of CycloAnt antagonized delta-opioid receptors (DOR) at least 3 hours. Pharmacological characterization of CycloAnt showed the cyclic peptide did not reduce breathing rate in mice at doses up to 15 times the analgesic ED50 value, and dramatically less hyperlocomotion than the MOR agonist, morphine. While chronic administration of CycloAnt resulted in antinociceptive tolerance, it was without opioid-induced hyperalgesia and significantly reduced signs of naloxone-precipitated withdrawal suggestive of reduced physical dependence as compared to morphine. Collectively, the results suggest this dual MOR/DOR multifunctional ligand is an excellent lead for the development of peptide-based safer analgesics.

For more than twenty years chemists use peptidic organocatalysts to transfer acyl groups onto alcohols. The goal was and still is the increase of selectivity towards the substrate of choice. One carefully designed example is a highly enantioselective tetrapeptide organocatalyst for the kinetic resolution of trans-cycloalkane-1,2-diols. Until now, the intermediate responsible for the acyl transfer of this tetrapeptide has never been directly observed. It was proposed computationally that a π-methylhistidine moiety is acylated as an intermediate step in the catalytic cycle. In this study we set out to investigate whether we can detect and characterize this key intermediate using NMR-spectroscopy and mass spectrometry. Different mass spectrometric experiments using a nano-ElectroSpray Ionization (ESI) source and tandem MS-techniques allowed the identification of tetrapeptide acylium ions using different acylation reagents. The complexes of trans-cyclohexane-1,2-diols with the tetrapeptide were also detected. Additionally, we were able to detect acylated tetrapeptides in solution using NMR-spectroscopy and monitor the acetylation reaction of a trans-cyclohexane-1,2-diol. These findings are important steps towards the understanding of this organocatalyst and its high enantioselectivity.

Background: In rheumatoid arthritis (RA), anti-citrullinated protein/peptide antibodies (ACPAs) are responsible for disease onset and progression, however, our knowledge is limited on ligand binding affinities of autoantibodies with different citrulline-peptide specificity. Methods: Citrulline-peptide specific ACPA IgGs were affinity purified and tested by ELISA. Binding affinities of ACPA IgGs and serum antibodies were compared by surface plasmon resonance (SPR) analysis. Bifunctional nanoparticles harboring a multi-epitope citrulline-peptide and a complement activating peptide were used to induce selective depletion of ACPA producing B cells. Results: KD values of affinity purified ACPA IgGs varies between 10-6-10-8 M and inversely correlate with disease activity. Based on their cross-reaction with citrulline-peptides we designed a novel multi-epitope peptide, containing Cit-Gly and Ala-Cit motifs in two-two copies, separated with a short, neutral spacer. This peptide detects antibodies in RA sera with 66 % sensitivity and 98 % specificity in ELISA and is recognized by 90% of RA sera, while none of the healthy samples in SPR. When coupled to nanoparticles, the multi-epitope peptide specifically targets and depletes ACPA producing B cells ex vivo. Conclusions: The unique multi-epitope peptide designed on the basis of ACPA cross-reactivity might be suitable to develop better diagnostics and novel therapies for RA.