Gastroenterology and Hepatology From Bed to Bench最新文献

Primary Familial Intrahepatic Cholestasis type 3 is an exceedingly rare genetic cholestatic disorder characterized by the defective hepatocanaliculr bile acid transport leading to progressive liver disease. In this case report, we describe the course of treatment for a 12-year-old kid diagnosed with Wilson disease based on Leipzig score and copper investigations. The child did not improve with chelation therapy and was subsequently genetically classified as PFIC-3. This case highlighted the caveats in Wilson disease diagnostic scoring system. The diagnostic odyssey, therapeutic interventions, and outcome of this case underscore the intricate interplay between clinical suspicion, investigative strategies, and the pivotal role of genetic testing to elucidate rare liver disorders in children.

Aim: This study aimed to evaluate the effect of moderate exercise on the healing of acetic acid-induced gastric ulcers in male rats.

Background: Gastric ulcers include benign mucosal and submucosal lesions of the gastric wall. Exercise regulates a wide range of physiological processes.

Methods: 48 male Wistar rats were randomly divided into three experimental groups (n=16 per group) as follows: control, which was left untreated after causing stomach ulcers; experimental group 1, the rats were first exercised and then received acetic acid; experimental group 2, the rats received acetic acid, and then exercised. The ulcer was caused by injecting 0.12 ml of a 60% acetic acid solution after 24 hours of not eating. The rats had a period of moderate treadmill activity either before or after the development of ulcers, lasting for a duration of 30 days. On the seventh and fourteenth days after the experiment, the rats were sacrificed, their stomach was removed, and the wound healing parameters, and wound depth were determined.

Results: Exercise before and after inducing gastric ulcers significantly decreased the depth of gastric ulcers in the experimental groups. The average number of PMN in the control group decreased in comparison to the seventh and fourteenth days following the experiment. Conversely, the number of fibroblasts, epithelialization, and new vessels increased. It seems that exercise before the appearance of ulcers has a greater effect on gastric ulcers compared to exercise after inducing gastric ulcers.

Conclusion: Exercise can prepare the gastric mucosa for forthcoming injuries, and heal gastric ulcers. Moderate aerobic exercise has significant restorative effects on gastric ulcers caused by acetic acid and is recommended.

Aim: The potency of Adenovector expressing Mda7-tLyp1 (Ad-Mda7-tLyp1) for death induction was evaluated on the breast (MCF7), liver (HepG2), and gastric (MKN45) cancer cell lines.

Background: Mda-7 could be a possible complementary to traditional cancer therapy, and tethering to tumor-homing peptides (THPs) might improve its therapeutic efficacy.

Methods: After the preparation of recombinant Ad-Mda7-tLyp1 and Ad-Mda7, the expression of recombinant proteins was analyzed by ELISA. Adenovectors were transduced (MOI=2-5) into Hep-G2, MCF7, MKN45, and normal skin fibroblast, then tumor-killing effect was measured by cytopathic effect (CPE) monitoring, MTT viability test, BAX gene expression analysis, and Caspase3/7 assay.

Results: ELISA assay revealed a sustained level of recombinant protein secretion following Adenovector transduction. In CPE microscopy, all cancer cell lines showed a significant reduction (≥50%) in their normal phenotype after receiving Ad-Mda7-tLyp1 and Ad-Mda7. The viability was significantly lower compared to the control, indicating an anti-proliferating effect. In parallel, the viability test showed that Ad-Mda7 and Ad-Mda7-tLyp1 have a significant killing effect (≥50%) on MCF-7, Hep-G2, and MKN45 compared to normal fibroblast (P≤0.05). BAX gene expression analysis showed that both Ad-Mda7-tLyp1 and Ad-Mda7 vectors induced >2-fold increase of apoptosis (P<0.05), particularly in MCF7. Similarly, caspase3/7 activity showed a significant increase (P<0.05) following Ad-Mda7, and Ad-Mda7-tLyp1 transduction into cancer cell lines, but not in normal fibroblasts.

Conclusion: The newly constructed Ad-Mda-tlyp1 showed a suitable tumor cell killing activity and enough specificity on studied cell lines.

Aim: A systematic review and meta-analysis were performed to investigate posterior tibial nerve electrical stimulation application methods in patients with chronic constipation.

Background: Posterior tibial nerve electrical stimulation is a management procedure for chronic constipation.

Methods: A comprehensive search was conducted on Ovid, PubMed, Scopus, ProQuest, Web of Science, and The Cochrane Library based on the PICO formation of the study. All randomized controlled trials and quasi-experimental studies in which patients with chronic constipation were treated with transcutaneous tibial nerve stimulation (TTNS) or percutaneous tibial nerve stimulation (PTNS) were included in this study. Two independent reviewers screened all titles, abstracts, and full texts. The selected studies' quality was assessed critically using the Joanna Briggs Institute checklists. The data synthesis was conducted using Review Manager Software.

Results: Out of 1016 records, 11 studies were included in this study. The results showed that TTNS was effective in improving constipation symptoms (SMD: -1.52, CI 95%: -2.81 to -0.22, p< 0.0001) and reducing defecation time of patients with chronic constipation (SMD: -0.86, CI 95%: -1.60 to -0.13, p= 0.17). Additionally, PTNS was found to improve the quality of life of these patients (SMD: -1.32, CI 95%: -2.05 to -0.59, p< 0.00001).

Conclusion: Both TTNS and PTNS can be effective interventions for chronic constipation. To suggest a definitive and standard treatment plan, further research is needed to determine optimal parameters for TTNS and PTNS applications.

Aim: The present study examined the protective potential of human adipose tissue-derived mesenchymal stem cells (hASCs) modified to overexpress alpha-1 antitrypsin (AAT), in a mouse model of the liver fibrosis.

Background: For the treatment of end-stage liver diseases, cell therapy has emerged as a promising noninvasive alternative to liver transplantation. Mesenchymal stem cells (MSCs) are being evaluated due to their dual capabilities of promoting liver regeneration and modulating the pathogenic inflammation of the immune system.

Methods: Liver fibrosis was induced in mice via the intraperitoneal injection of carbon tetrachloride (CCl4). MSCs were extracted from the human adipose tissue. After stemness confirmation, the cells were transduced with the lentiviruses containing the AAT gene, and then injected into the mice's tail vein. Fourteen days' post-transplantation, mice were sacrificed, and blood and tissue samples were collected for analysis. Important liver enzymes, including alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin, and total bilirubin (TB), were measured. Histological studies were carried out using the hematoxylin and eosin (H&E), as well as Masson's trichrome (MT) staining.

Results: Compared to hASCs, treatment with AAT-hASCs resulted in greater reductions in ALT, AST, ALP, and TB, as well as normalized albumin levels. AAT-hASCs promoted enhanced liver regeneration histologically, likely attributable to anti-inflammatory and anti-proteolytic properties of AAT.

Conclusion: These findings indicate AAT-engineered hASCs as a promising cell-gene therapy candidate for further study in liver cirrhosis models.

The incorporation of AI models into bioinformatics has brought about a revolutionary era in the analysis and interpretation of biological data. This mini-review offers a succinct overview of the indispensable role AI plays in the convergence of computational techniques and biological research. The search strategy followed PRISMA guidelines, encompassing databases such as PubMed, Embase, and Google Scholar to include studies published between 2018 and 2024, utilizing specific keywords. We explored the diverse applications of AI methodologies, including machine learning (ML), deep learning (DL), and natural language processing (NLP), across various domains of bioinformatics. These domains encompass genome sequencing, protein structure prediction, drug discovery, systems biology, personalized medicine, imaging, signal processing, and text mining. AI algorithms have exhibited remarkable efficacy in tackling intricate biological challenges, spanning from genome sequencing to protein structure prediction, and from drug discovery to personalized medicine. In conclusion, this study scrutinizes the evolving landscape of AI-driven tools and algorithms, emphasizing their pivotal role in expediting research, facilitating data interpretation, and catalyzing innovations in biomedical sciences.

Aim: This study aimed to evaluate the expression of tcdA, tcdB, and binary toxin genes (cdtA and cdtB) by Real-Time PCR and molecular typing of Clostridioides difficile isolated from patient diarrhea samples from Hamadan Hospitals, west of Iran.

Background: The concentration of C. difficile toxins (CDTs) is associated with the severity of the disease and the mortality rate. Measuring CDT levels could provide a reliable and objective means of determining the severity of C. difficile infection (CDI).

Methods: From November 2018 to September 2019, 130 diarrhea samples were collected from hospitalized patients in three hospitals in Hamadan. C. difficle isolates were detected by culture and PCR. The presence of the genes encoding the toxin was identified by PCR, whereas the measurement of toxin expression was conducted using a relative Real-Time PCR technique. Genetic linkage of the isolates was also assessed by Ribotyping and Repetitive Extragenic Palindromic (rep-PCR) methods.

Results: Among 130 diarrhea samples, 16 (12.3%) were positive for C. difficile. Genes encoding cdtA and tcdB were detected in all isolates, and 8 (50%) and 6 (37.5%) isolates were positive for the cdtA and cdtB genes. Real-time PCR results showed different expression levels of the toxin genes. A significant increase in the expression of the tcdA gene was observed compared with the control strain (P<0.05). Besides, more expression of cdtA gene was observed in the strains compared with cdtB gene. Ribotyping and rep-PCR results showed high genetic diversity of C. difficile among hospitals investigated.

Conclusion: We encountered toxigenic C. difficile strains with various toxin expression levels, ribotypes, and rep types based on the findings of this study. This indicated that various clones from various sources circulate in the hospitals and among patients.

Aim: This study aimed to introduce a biomarker panel to detect pancreatic ductal adenocarcinoma (PDAC) in the early stage, and also differentiate of stages from each other.

Background: PDAC is a lethal cancer with poor prognosis and overall survival.

Methods: Gene expression profiles of PDAC patients were extracted from the Gene Expression Omnibus (GEO) database. The genes that were significantly differentially expressed (DEGs) for Stages I, II, and III in comparison to the healthy controls were identified. The determined DEGs were assessed via protein-protein interaction (PPI) network analysis, and the hub-bottleneck nodes of analyzed networks were introduced.

Results: A number of 140, 874, and 1519 significant DEGs were evaluated via PPI network analysis. A biomarker panel including ALB, CTNNB1, COL1A1, POSTN, LUM, and ANXA2 is presented as a biomarker panel to detect PDAC in the early stage. Two biomarker panels are suggested to recognize other stages of illness.

Conclusion: It can be concluded that ALB, CTNNB1, COL1A1, POSTN, LUM, and ANXA2 and also FN1, HSP90AA1, LOX, ANXA5, SERPINE1, and WWP2 beside GAPDH, AKT1, EGF, CASP3 are suitable sets of gene to separate stages of PDAC.

Aim: This study is done to investigate the hypolipidemic and hepatoprotective effects of corn silk extract in nicotine-administered male mice.

Background: Nicotine can induce pathophysiological effects in the liver tissue through oxidative stress and damage cells. Corn silk can improve liver function with its antioxidant effects.

Methods: In this experimental study, 30 male NMRI mice (25-30 gr) were divided into 5 groups: controls, sham, nicotine 2.5 mg/kg, nicotine+aqueous extract of corn silk 400 mg/kg, and nicotine+methanolic extract of corn silk 400 mg/kg for 1 month. One day after the last nicotine and extracts consumption, the serum samples were performed for biochemical measurement, and the supernatant of the homogenized liver was administered for antioxidant variables assessment.

Results: There was no significant difference in the body weight of different groups. Liver weight and GSH decreased in the nicotine group compared to the control group (P<0.05). Triglycerides, total cholesterol, HDL-C, LDL-C, liver enzymes, and MDA increased in the nicotine group compared to the control group (P<0.05). Also, the expansion of sinusoids, the presence of inflammatory cells, and necrosis of liver cells were observed in the nicotine group compared to the control group. Using aqueous and methanolic extracts of corn silk in mice receiving nicotine led to the improvement of the mentioned variables (P<0.05).

Conclusion: The results of this study showed that the use of nicotine can lead to the induction of hepatotoxicity. The use of aqueous and methanolic extracts of corn silk improved them through its antioxidant activity.

Polyomaviruses are a group of small, double-stranded DNA viruses that are known to be associated with the development of certain human diseases, but there is evidence that these viruses might be associated with gastrointestinal (GI) cancers. Several polyomaviruses have been identified, such as JC polyomavirus (JCPyV), BK polyomavirus (BKPyV) and recently Merkel cell polyomavirus (MCPyV). Although the direct effects of polyomaviruses on transformation of human cells and cancer development are not clearly recognized, their association with certain human diseases including GI cancers has been proposed through several molecular and epidemiological studies. For example, JCPyV and BKPyV have been linked to colorectal cancer, as there is growing evidence of finding viral genomes in cancerous tissues. Nevertheless, the major role of JCPyV, BKPyV and MCPyV in colorectal cancer progression is still under extensive investigation, and further surveys is required to establish a conclusive cause-and-effect relationship. Understanding the role of these viruses in cancer development has significant implications for diagnosis, treatment, and prevention strategies. It seems that proving a causal link between polyomaviruses and GI cancers might provide a novel path for targeted therapies or design and development of specific therapeutic vaccines. In addition, performing research on the possible link can provide insights into the underlying molecular mechanisms of carcinogenesis, potentially leading to the identification of novel biomarkers. This review focuses on polyomaviruses, in particular a recently discovered polyomavirus, MCPyV, and their possible link with human gastrointestinal disorders.