Prognostic and predictive significance of p53 and ATRX in neuroendocrine neoplasms of GIT and pancreas and their utility as an adjunct to accurate diagnosis-An eight-year retrospective study.

INTRODUCTION: Neuroendocrine neoplasms of gastrointestinal tract (GIT) and pancreas are heterogenous tumors. World Health Organization (WHO) 2019 classification introduced Grade (G)3 neuroendocrine tumor (NET) distinct from neuroendocrine carcinoma (NEC), based on molecular differences and to triage the patients for appropriate therapy. This distinction largely relies on morphology, which can be challenging at times. Genomic profiling has revealed TP53 and RB1 mutations in NECs, while death domain-associated protein 6 (DAXX) and alpha-thalassemia/mental retardation X-linked (ATRX), in G3NET. Their role as biological markers in differentiating these entities and their significance as prognostic markers are not yet established. This study aims at analyzing the diagnostic and prognostic role of p53 and ATRX in neuroendocrine neoplasms of GIT and pancreas. METHODOLOGY: A single-centre, eight-year retrospective study of neuroendocrine neoplasm of GIT and pancreas comprised G2NET, G3NET and NEC. Tumor slides were stained by immunohistochemistry for p53 and ATRX. Strong nuclear staining of > 50% of tumor cells for p53 was considered mutated. Nuclear staining of ATRX in < 5% of tumor cells was considered ATRX loss. Expression of p53 and ATRX was analyzed and correlated with tumor grades and patient survival. RESULTS: Fifty-five patients with gastro-entero-pancreatic neuroendocrine neoplasm were studied, comprising G2NET (58%), G3NET (16%) and NEC (26%). Median age of diagnosis was 59 years with male predominance. The pancreas was the most common site followed by the small bowel. NEC showed lower survival compared to G3 and G2NET. Mutated p53 immunohistochemical expression was more frequent among NEC than G3NET. Patients with mutated p53 had significantly lower survival irrespective of the grade (p = 0.001). There was no association of ATRX loss with grade or survival. CONCLUSION: G3NETs are genetically different from NECs. Use of immunohistochemistry for p53 in addition to histomorphology may facilitate accurate categorization of NEC and G3NET. Mutated p53 may also be used as an independent prognostic marker in neuroendocrine tumors of GIT and pancreas.

Role of In Vitro Tests in the Characterisation of Locally Applied, Locally Acting Drugs in the Throat: Application to Flurbiprofen.

Background/Objectives: For locally applied, locally acting generic drug products, comparison to an originator product based on systemic exposure is usually not feasible due to low plasma concentrations and inadequate reflection of local exposure at the site of action. Where a validated PD model exists, a comparative clinical study can be performed in healthy subjects; where no surrogate endpoint is available, patients with the relevant indication need to be enrolled, with all the associated factors which could result in lack of sensitivity. Even though the need for alternative in vitro approaches has been acknowledged by both industry and regulatory bodies, the complexity of in vivo drug delivery processes makes the development of guidance documents particularly difficult. Our objective was to present in vitro approaches less classically used and to address in vivo relevance of the selected tests. Methods: This article analyses current regulatory approaches in Europe and the U.S., and highlights the key advantages of in vitro tests in terms of their sensitivity, reliability, reproducibility and in vivo relevance using locally applied flurbiprofen in various formulations. Results: The in vitro esophageal retention (IVOR) model demonstrates that the first 6-10 min after application of different flurbiprofen formulations is important for their comparison and also offers the best correlation with in vivo data using the partial area under the concentration-time curves (pAUCs). Rheological evaluations further demonstrated that the mucoadhesive properties of the gel spray formulation are based on interaction with mucin. Conclusions: Designing a relevant in vitro test requires adequate evaluation of the complexity of the drug substance, drug product, dosing conditions and delivery processes.

Gastrointestinal microbiota and metabolites responses to dietary cereal grains in an adult pig model.

Corn (C), wheat (W), and paddy rice (PR) are important energy sources and are commonly used in feed production for swine. This study mainly focuses on the variation and regularities of microbiota and metabolites in the gastrointestinal tract (GIT) of pigs in response to C, W, and PR. A total of 18 pigs were allotted into three dietary groups with six replicated pigs and received diets containing C, W, or PR as the sole energy source, respectively. The results showed that digestive parts significantly affected the diversity of microbial communities. Cereal grain sources significantly influenced the ß-diversity of microbial communities in the colon and rectum. Campylobacterota and Proteobacteria are mainly distributed in the duodenum, Lactobacillus in the jejunum, and Bacteroidota in the colon and rectum. The W diet increased the Bacteroidota, Spirochaetota, and Prevotellaceae_NK3B31_group abundances and showed the highest concentrations of all short-chain fatty acids (SCFAs) in the hindgut. Fibrobacterota, Bacteroidota, Spirochaetota, Prevotellaceae_NK3B31_group, Prevotella, and Treponema in the colon or rectum were positively correlated with acetate, propionate, butyrate, and total SCFAs. These findings suggested that aerobic bacteria and facultative anaerobes in the foregut will gradually be replaced by anaerobes in the hindgut. The W diet had the best fermentability and was beneficial to the colonization of microbial communities that mainly used carbohydrates. The hindgut flora of the PR diet group may be more balanced with fewer potential pathogenic bacteria. Many microbial communities have been identified to contribute positively to the SCFA production of the hindgut. Collectively, our study revealed the spatial variation regularities of GIT microbial communities in an adult pig model and provided new insights into GIT microbiota and responses of metabolites to cereal grain diets.

Corrigendum: Role of dietary fiber and lifestyle modification in gut health and sleep quality.

[This corrects the article DOI: 10.3389/fnut.2024.1324793.].

Cross-sectional study using the University of California, Los Angeles, Scleroderma Clinical Trials Consortium Gastrointestinal Tract Instrument 2.0 (UCLA SCTC GIT 2.0) for gastrointestinal disorders of systemic sclerosis.

This study aimed to identify severe gastrointestinal ailments in patients with systemic sclerosis (SSc), investigate the role of antibodies in gastrointestinal disorders, and explore the relationship between limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) in terms of gastrointestinal involvement and its association with skin stiffness. We used the University of California, Los Angeles, Scleroderma Clinical Trials Consortium Gastrointestinal Tract Instrument 2.0 (UCLA SCTC GIT 2.0) questionnaire to assess gastrointestinal disturbances in 100 patients with SSc. Gastrointestinal impairment was categorized into three levels: absence of or minor symptoms, moderate symptoms, and severe symptoms, as indicated by the total gastrointestinal tract (GIT) score. Comparing 27 patients with dcSSc and 73 patients with lcSSc, severe gastrointestinal disturbances were found in 7.4% of patients with dcSSc and 4.1% of patients with lcSSc. A total of 18.0% of anticentromere antibody (ACA)-positive patients exhibited moderate to severe symptoms, while 9.1% of antitopoisomerase 1 antibody-positive patients displayed similar symptoms. The average disease duration in patients with severe symptoms was 15.0 years, in those with moderate symptoms was 10.3 years, and in those who were symptom-free or mildly affected was 8.5 years. Among 16 patients with moderate to severe gastrointestinal disorders, a positive correlation was observed between the modified Rodnan skin thickness score (mRSS) and total GIT score. In addition, a positive correlation was identified between fecal incontinence and mRSS, with weaker correlations for reflux and bloating symptoms. Patients with gastrointestinal disorders showed a tendency to worsen over time, particularly in ACA-positive patients with dcSSc. Furthermore, a correlation was observed between mRSS and fecal incontinence, reflux, and abdominal bloating in patients with moderate to severe gastrointestinal disturbances.

Role of Artificial Intelligence in the Diagnosis of Gastroesophageal Reflux Disease.

Gastroesophageal reflux disease (GERD) is a disorder that usually presents with heartburn. GERD is diagnosed clinically, but most patients are misdiagnosed due to atypical presentations. The increased use of artificial intelligence (AI) in healthcare has provided multiple ways of diagnosing and treating patients accurately. In this review, multiple studies in which AI models were used to diagnose GERD are discussed. According to the studies, using AI models helped to diagnose GERD in patients accurately. AI, although considered one of the most potent emerging aspects of medicine with its accuracy in patient diagnosis, presents limitations of its own, which explains why healthcare providers may hesitate to use AI in patient care. The challenges and limitations should be addressed before AI is fully incorporated into the healthcare system.

The odds of having obesity in Egyptian children with autism spectrum disorders is higher than stunting compared to healthy developing peers: a national survey.

BACKGROUND: The nutritional status and growth of children with Autism spectrum disorders (ASD) is influenced significantly by two factors; food selectivity behaviors due to their consumption of a limited variety of food and the high incidence of gastrointestinal (GIT) disorders. AIM: This study aimed to assess the nutritional adequacy and growth pattern of ASD children aged three to twelve years compared to their healthy developing peers. METHODS: A national comparative, facility-based cross-sectional study was conducted in eight Egyptian governorates on 285 Egyptian children diagnosed with ASD and 224 children who are their relatives as healthy developing peers. Anthropometric measurements were obtained, including weight, height, head circumference, and mid-upper arm circumference. Body Mass Index (BMI) was calculated and all numbers were plotted on WHO growth charts. Assessment of food preferences, and nutrient intake adequacy of children was done using the Food preference questionnaire, and the Dietary Reference Intakes (DRIs) of Egyptian children. RESULTS: Calorie-dense food and sugar intake were higher among ASD children than their healthy developing peers. ASD children omit some important protein sources such as dairy (COR = 5.2, 95% CI:2.7-9.9), meat, and poultry (COR = 2.7, 95% CI: 1.6-4.7), and a lower intake of fruits and vegetables than their healthy developing peers. For children with ASD in all age groups, a deficiency in the range of 50-60% was detected for vitamins (C, D, B6, thiamine, riboflavin, niacin) and minerals (iron). A deficiency in the range of 60-70% was detected for folate and calcium. A deficiency of vitamin C calcium and iron was also detected for both children with ASD and their healthy developing relatives aged 6 to 12 years. GIT disorders were common among ASD children compared to healthy developing peers (COR = 2.8 to 10.3). Children with ASD had four-fold higher odds of stunting (COR = 4.1, CI: 1.7-10.1), threefold higher odds of being overweight (COR = 3.3, CI: 1.48-7.32), and nearly eleven-fold higher odds of obesity (COR = 11.4, CI: 4.05-32.17) compared to their healthy developing peers. CONCLUSION: ASD children are prone to overweight and protein malnutrition. Their intake of fruits and vegetables is inadequate and hence their intake of vitamins and minerals is insufficient, contributing to stunting.

The Discovery of GIT1/ß-Pix Inhibitors: Virtual Screening and Biological Evaluation of New Small-molecule Compounds with Anti-invasion Effect in Gastrointestinal Neoplasms.

Background and Objective: GIT1 (G-protein-coupled receptor kinase interacting protein-1) has been found to be highly related with cancer cell invasion and metastasis in many cancer types. ß-Pix (p21-activated kinase-interacting exchange factor) is one of the proteins that interact with GIT1. Targeting GIT1/ß-Pix complex might be a potential therapeutic strategy for interfering cancer metastasis. However, at present, no well-recognized small-molecule inhibitor targeting GIT1/ß-Pix is available. Thus, we aim to discover novel GIT1/ß-Pix inhibitors with simple scaffold, high activity and low toxicity to develop new therapeutic strategies to restrain cancer metastasis. Methods: GIT1/ß-Pix inhibitors were identified from ChemBridge by virtual screening. Briefly, the modeling of GIT1 was performed and the establishment of GIT1/ß-Pix binding pocket enabled the virtual screening to identify the inhibitor. In addition, direct binding of the candidate molecules to GIT1 was detected by biolayer interferometry (BLI) to discover the hit compound. Furthermore, the inhibitory effect on invasion of stomach and colon cancer cells in vitro was carried out by the transwell assay and detection of epithelial-mesenchymal transition (EMT)-related proteins. Finally, the binding mode of hit compound to GIT1 was estimated by molecular dynamics simulation to analyze the key amino residues to guide further optimization. Results: We selected the top 50 compounds from the ChemBridge library by virtual screening. Then, by skeleton similarity analysis nine compounds were selected for further study. Furthermore, the direct interaction of nine compounds to GIT1 was detected by BLI to obtain the best affinitive compound. Finally, 17302836 was successfully identified (KD = 84.1±2.0 µM). In vitro tests on 17302836 showed significant anti-invasion effect on gastric cancer and colorectal cancer. Conclusion: We discovered a new GIT1/ß-Pix inhibitor (17302836) against gastrointestinal cancer invasion and metastasis. This study provides a promising candidate for developing new GIT1/ß-Pix inhibitors for tumor treatment.

Effect of parasitic infection on microplastic ingestion in a native leuciscid hybrid species (Alburnus derjugini x Squalius orientalis) from Kürtün Dam Lake, Türkiye.

Microplastic (MP) pollution is currently one of the most serious environmental issues. MPs were investigated in the Kürtün Dam Lake in healthy individuals of the native leuciscid hybrid (Alburnus derjugini x Squalius orientalis) species and individuals infected with the Ligula intestinalis parasite. Although MP abundance appeared to be higher in non-infected fish (NIF) than in L. intestinalis (L) and infected fish (IF), the MP abundance in IF was higher, because the parasite theoretically belongs to IF. In addition to the observation of MPs in the gastrointestinal tract (GIT) of fish, the diffusion of MPs by parasites settled in the body cavity indicates that MPs are not only present in the GIT. Therefore, predation on existing fish by birds causes MP dispersion. In the present study, the most common MP shape was fiber (100% for NIF and IF, 85.7% for L), the MP color was black (57.1% for IF and L) and orange (50% for NIF), and the polymer type was polyamide (57.1% for IF, 50% for NIF) and polyethylene terephthalate (28.5% for L). These MP compositions led us to believe that textile effluents and aquaculture operations in dam lakes could be sources of pollution. Therefore, this study provides insights for future research to elucidate the connection between MP consumption and parasite infection.

The Gut Microbiota-Brain Axis: A New Frontier in Alzheimer's Disease Pathology.

Dr. Aloysius Alzheimer, a German neuropathologist and psychiatrist, recognized the primary instance of Alzheimer's disease (AD) for a millennium, and this ailment, along with its related dementias, remains a severe overall community issue related to health. Nearly fifty million individuals worldwide suffer from dementia, with Alzheimer's illness contributing to between 60 and 70% of the instances, estimated through the World Health Organization. In addition, 82 million individuals are anticipated to be affected by the global dementia epidemic by 2030 and 152 million by 2050. Furthermore, age, environmental circumstances, and inherited variables all increase the likelihood of acquiring neurodegenerative illnesses. Most recent pharmacological treatments are found in original hypotheses of disease, which include cholinergic (drugs that show affective cholinergic system availability) as well as amyloid-accumulation (a single drug is an antagonist receptor of Nmethyl D-aspartate). In 2020, the FDA provided approval on anti-amyloid drugs. According to mounting scientific data, this gut microbiota affects healthy physiological homeostasis and has a role in the etiology of conditions that range between obesity and neurodegenerative disorders like Alzheimer's. The microbiota-gut-brain axis might facilitate interconnection among gut microbes as well as the central nervous system (CNS). Interaction among the microbiota-gut system as well as the brain occurs through the "two-way" microbiota-gut-brain axis. Along this axis, the stomach as well as the brain develop physiologically and take on their final forms. This contact is constant and is mediated by numerous microbiota-derived products. The gut microbiota, for instance, can act as non-genetic markers to set a threshold for maintaining homeostasis or getting ill. The scientific community has conducted research and found that bowel dysbiosis and gastrointestinal tract dysregulation frequently occur in Alzheimer's disease (AD) patients. In this review, the effects of the microbiota- gut-brain axis on AD pathogenesis will be discussed.

Git2 deficiency promotes MDSCs recruitment in intestine via NF-κB-CXCL1/CXCL12 pathway and ameliorates necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease in preterm infants and the most common cause of neonatal death, whereas the molecular mechanism of intestinal injury remains unclear accompanied by deficiency of effective therapeutic approaches. GIT2 (G-protein-coupled receptor kinase interacting proteins 2) can affect innate and adaptive immunity and has been involved in multiple inflammatory disorders. In this study, we investigated whether GIT2 participates in the pathogenesis of NEC. Here we found that intestinal Git2 gene expression was significantly increased in NEC patients and NEC mice, which positively correlated with the tissue damage severity, and Git2 deficiency could potently protect against NEC development in mice. Mechanistically, Git2 gene knockout dramatically increased the recruitment of MDSCs in the intestine, and in vivo depletion of MDSCs almost completely abrogated the protective effect of Git2 deficiency on NEC. Moreover, Git2 deficiency induced MDSCs intestinal accumulation mainly relied on CXCL1/CXCL12 signaling, as evidenced by the significant increment of CXCL1 and CXCL12 levels in intestinal epithelium of Git2-/- mice and dramatically decrease of MDSCs accumulation in intestine as well as increase of NEC severity upon treatment of CXCL1/CXCL12 pathway inhibitors. In addition, Git2 deficiency induced up-regulation of CXCL1 and CXCL12 is at least partially mediated through activating NF-κB signaling. Thus, our findings suggest that GIT2 is involved in the pathogenesis of NEC, and targeting GIT2 may be a potential preventive and therapeutic approach for NEC.

Spatial profiles of the bacterial microbiota throughout the gastrointestinal tract of dairy goats.

The gastrointestinal tract (GIT) is stationed by a dynamic and complex microbial community with functions in digestion, metabolism, immunomodulation, and reproduction. However, there is relatively little research on the composition and function of microorganisms in different GIT segments in dairy goats. Herein, 80 chyme samples were taken from ten GIT sites of eight Xinong Saanen dairy goats and then analyzed and identified the microbial composition via 16S rRNA V1-V9 amplicon sequencing. A total of 6669 different operational taxonomic units (OTUs) were clustered, and 187 OTUs were shared by ten GIT segments. We observed 264 species belonging to 23 different phyla scattered across ten GITs, with Firmicutes (52.42%) and Bacteroidetes (22.88%) predominating. The results revealed obvious location differences in the composition, diversity, and function of the GIT microbiota. In LEfSe analysis, unidentified_Lachnospiraceae and unidentified_Succinniclassicum were significantly enriched in the four chambers of stomach, with functions in carbohydrate fermentation to compose short-chain fatty acids. Aeriscardovia, Candidatus_Saccharimonas, and Romboutsia were significantly higher in the foregut, playing an important role in synthesizing enzymes, amino acids, and vitamins and immunomodulation. Akkermansia, Bacteroides, and Alistipes were significantly abundant in the hindgut to degrade polysaccharides and oligosaccharides, etc. From rumen to rectum, α-diversity decreased first and then increased, while ß-diversity showed the opposite trend. Metabolism was the major function of the GIT microbiome predicted by PICRUSt2, but with variation in target substrates along the regions. In summary, GIT segments play a decisive role in the composition and functions of microorganisms. KEY POINTS: • The jejunum and ileum were harsh for microorganisms to colonize due to the presence of bile acids, enzymes, faster chyme circulation, etc., exhibiting the lowest α-diversity and the highest ß-diversity. • Variability in microbial profiles between the three foregut segments was greater than four chambers of stomach and hindgut, with a higher abundance of Firmicutes dominating than others. • Dairy goats dominated a higher abundance of Kiritimatiellaeota than cows, which was reported to be associated with fatty acid synthesis.

A Hospital-Based Cross-Sectional Study on the Histopathology of Upper Gastrointestinal Tract Endoscopic Biopsy in Dyspeptic Patients.

Background Dyspepsia is one of the most common GI complaints encountered in clinical practice. Histopathological assessment of endoscopic gastric mucosa biopsy is crucial to delineate the exact cause of dyspepsia to guide patients' management. Objectives The aim of this study was to determine the histopathological spectrum of upper gastrointestinal (GI) tract endoscopic biopsies and to study the age and sex distribution of the predominant upper GI lesions. Methods A cross-sectional study was conducted in the Department of Pathology, Rajendra Institute of Medical Sciences, Ranchi, Jharkhand, India, from January 2022 to December 2023. All endoscopic mucosal biopsies of the esophagus, stomach, and duodenum (first and second parts) lesions were examined under a microscope for histopathological findings. Results Out of 250 endoscopic biopsies studied, there were 76 cases of esophageal biopsies, 149 cases of gastric biopsies, and 25 cases of duodenal biopsies. The male-to-female ratio was 1.2:1. Non-neoplastic lesions were more common than neoplastic lesions. The most common lesions encountered were esophagitis in the esophagus, gastritis in the stomach, and duodenitis in the duodenum. Conclusion The main organic cause of dyspepsia in our setting was chronic gastritis. We conclude that endoscopy of the upper GI tract and histopathological examination help in the earlier detection of both benign and malignant lesions. This aids in better timely management of the patients and improves the overall treatment provided resulting in a better prognosis.

Epidemiology and diversity of gastrointestinal tract helminths of wild ruminants in sub-Saharan Africa: a review.

This review summarises studies on distribution, diversity, and prevalence of gastrointestinal helminth infections in wild ruminants in sub-Saharan Africa. The results showed that 109 gastrointestinal tract (GIT) helminth species or species complexes were recorded in 10 sub-Saharan African countries. South Africa reported the highest number of species because most studies were carried out in this country. Eighty-eight nematode species or species complexes were recorded from 30 wild ruminant species across eight countries. The genus Trichostrongylus recorded the highest number of species and utilised the highest number of wild ruminant species, and along with Haemonchus spp., was the most widely distributed geographically. Fifteen trematode species or species complexes were reported from seven countries. The genus Paramphistomum recorded the highest number of species, and Calicophoron calicophoron was the most commonly occurring species in sub-Saharan African countries and infected the highest number of hosts. Six cestode species or species complexes from one family were documented from 14 wild hosts in seven countries. Moniezia spp. were the most commonly distributed in terms of host range and geographically. Impala were infected by the highest number of nematodes, whilst Nyala were infected by the highest number of trematode species. Greater kudu and Impala harbored the largest number of cestodes. The prevalence amongst the three GIT helminths taxa ranged between 1.4% and 100% for nematodes, 0.8% and 100% for trematodes, and 1.4% and 50% for cestodes. There is still limited information on the distribution and diversity of GIT helminths in wild ruminants in most sub-Saharan African countries.

Metastatic Urothelial Cancer Presenting as Small Bowel Obstruction: A Case Report.

Neoplasms are among the common causes of small bowel obstruction (SBO). Metastatic disease is the most common cause of neoplastic SBO and is most commonly the result of colon, ovarian, pancreatic, and gastric neoplasms. Metastatic SBO secondary to metastatic urothelial carcinoma is exceedingly rare, with only a few cases described in the literature. It is important for physicians to be aware of urothelial carcinoma as a potential etiology of SBO.

Removal of GIT lesions and the role of impedance of the injection solution-an innovative approach to known methods.

In this work, for the first time, the specific impedances of various injection solutions as well as the surface and tissue impedance after injection of these solutions were analyzed and compared regarding the radio-frequency surgical cutting process. The impedances of 0.9% NaCl, 4% gelatine, 6% hydroxyethyl starch, 10% glycerol/5% fructose, 10% glucose, 5% and 20% albumin, blood, and blood plasma as well as aqua destillata have been tested in vitro. Even if EMR and ESD are routinely used in clinical practice, there is so far no easy, fast, and safe method to remove larger lesions en bloc. We show that the impedance of the injected solution shows to be a crucial factor for safe removal, especially of larger lesions (Ø > 20 mm) and more importantly in accordance with the requirements of oncology and pathology. KEY MESSAGES: Impedance is playing a crucial factor in the radio-frequency (RF)-surgery. With a higher Impedance there will be less current necessary to reach the aimed voltage. Injection solution Aqua destillata and 10% Glucose, show significantly higher Impedances. Higher impedances lead to less surgical related complications. Minor changes in existing method to improve patent safety.

Macrophage GIT1 promotes oligodendrocyte precursor cell differentiation and remyelination after spinal cord injury.

Spinal cord injury (SCI) can result in severe motor and sensory deficits, for which currently no effective cure exists. The pathological process underlying this injury is extremely complex and involves many cell types in the central nervous system. In this study, we have uncovered a novel function for macrophage G protein-coupled receptor kinase-interactor 1 (GIT1) in promoting remyelination and functional repair after SCI. Using GIT1flox/flox Lyz2-Cre (GIT1 CKO) mice, we identified that GIT1 deficiency in macrophages led to an increased generation of tumor necrosis factor-alpha (TNFα), reduced proportion of mature oligodendrocytes (mOLs), impaired remyelination, and compromised functional recovery in vivo. These effects in GIT1 CKO mice were reversed with the administration of soluble TNF inhibitor. Moreover, bone marrow transplantation from GIT1 CWT mice reversed adverse outcomes in GIT1 CKO mice, further indicating the role of macrophage GIT1 in modulating spinal cord injury repair. Our in vitro experiments showed that macrophage GIT1 plays a critical role in secreting TNFα and influences the differentiation of oligodendrocyte precursor cells (OPCs) after stimulation with myelin debris. Collectively, our data uncovered a new role of macrophage GIT1 in regulating the transformation of OPCs into mOLs, essential for functional remyelination after SCI, suggesting that macrophage GIT1 could be a promising treatment target of SCI.

Propofol alleviates spinal cord ischemia-reperfusion injury by preserving PI3K/AKT/GIT1 axis.

Spinal cord ischemia-reperfusion injury (SCIRI) is a major contributor to neurological damage and mortality associated with spinal cord dysfunction. This study aims to explore the possible mechanism of Propofol and G-protein-coupled receptor-interacting protein 1 (GIT1) in regulating SCIRI in rat models. SCIRI rat models were established and injected with Propofol, over expression of GIT1 (OE-GIT1), or PI3K inhibitor (LY294002). The neurological function was assessed using Tarlov scoring system, and Hematoxylin & Eosin (H&E) staining was applied to observe morphology changes in spinal cord tissues. Cell apoptosis, blood-spinal cord barriers (BSCB) permeability, and inflammatory cytokines were determined by TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, evans blue (EB) staining, and enzyme-linked immuno sorbent assay (ELISA), respectively. Reverse transcription-quantitative polymerase chain reaction and western blot were used to detect the expression levels of GIT1, endothelial nitric oxide synthase (eNOS), PI3K/AKT signal pathway and apoptosis-related proteins. SCIRI rats had decreased expressions of GIT1 and PI3K/AKT-related proteins, whose expressions can be elevated in response to Propofol treatment. LY294002 can also decrease GIT1 expression levels in SCIRI rats. Propofol can attenuate neurological dysfunction induced by SCIRI, decrease spinal cord tissue injury and BSCB permeability in addition to suppressing cell apoptosis and inflammatory cytokines, whereas further treatment by LY294002 can partially reverse the protective effect of Propofol on SCIRI. Propofol can activate PI3K/AKT signal pathway to increase GIT1 expression level, thus attenuating SCIRI in rat models.

Erratum: Role of dietary fiber and lifestyle modification in gut health and sleep quality.

[This corrects the article DOI: 10.3389/fnut.2024.1324793.].

The Potential of Fecal and Urinary Biomarkers for Early Detection of Pancreatic Ductal Adenocarcinoma: A Systematic Review.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer often diagnosed at advanced stages, highlighting the urgent need for early detection strategies. This systematic review explores the potential of fecal and urinary biomarkers for early PDAC detection. A comprehensive search identified eight relevant studies investigating various biomarkers, including proteins, metabolites, microbial profiles, DNA mutations, and non-coding RNAs. Promising findings suggest that urinary biomarkers related to metabolic alterations, inflammatory processes, fecal microbiome profiles, and fecal miRNAs hold diagnostic potential even at early stages of PDAC. Combining biomarkers into panels may enhance diagnostic accuracy. Challenges such as validation in larger cohorts, standardization of protocols, and regulatory approval must be addressed for clinical translation. Despite these hurdles, non-invasive urinary and fecal biomarkers represent a promising avenue for improving PDAC outcomes through early detection.