Gastroenterology and Hepatology From Bed to Bench最新文献

Aim: Determining critical dysregulated proteins in liver cancer was the main aim of this study.

Background: Liver cancer is a common health problem characterized by difficulties in early diagnosis and rapid progression. Due to the lack of targeted drugs and the other features of the disease, the survival rate for patients is extremely low.

Methods: The related dysregulated proteins for liver cancer were retrieved from the STRING database. The queried proteins were included in a network by Cytoscape software, and the central nodes of the network were enriched via gene ontology.

Results: Among 11 introduced central nodes (GAPDH, TP53, EGFR, MYC, INS, ALB, IL6, AKT1, VEGFA, CDH1, and HRAS), HRAS and AKT1 were highlighted as critical dysregulated proteins which can be considered as possible biomarkers.

Conclusion: Analysis revealed that AKT1, HRAS and the related biochemical pathways (especially "HIF-1 signaling pathway") are the possible diagnostic and therapeutic agents of liver cancer.

Aim: Due to weak diagnosis and treatment of pancreatic ductal adenocarcinoma (PDAC), detection of PDAC possible biomarkers in early stage is the main aim of this study.

Background: PDAC is known as an exocrine cancer with a 5-year overall survival of 11%.

Methods: Gene expression profiles of early stage of PDAC tissue and normal tissue are downloaded from gene expression omnibus (GEO) and evaluated via GEO2R. The significant differentially expressed genes (DEGs) are investigated via protein-protein interaction (PPI) network analysis and gene ontology.

Results: Among 104 DEGs, ALB, COL1A1, COL1A2, MMP1, POSTN, PLAU, and COL3A1 were pointed out as hub nodes. "Gelatin degradation by MMP1, 2, 3, 7, 8, 9, 12, 13" group of 52 biological terms were identified as the main affected terms.

Conclusion: In conclusion, ALB, MMP1, and COL1A1 genes were highlighted as possible biomarkers of early stage of PDAC. Dysfunction of extracellular matrix was identified as a main event in patients.

Aim: This study aims to evaluate whether biochemical alterations caused by methylglyoxal (MG), improves by the administration of gallic acid (GA), crocin (Cr), and metformin (MT) in the liver.

Background: MG is produced naturally through various physiological processes, but high levels of MG cause inflammation in hepatocytes. Normal liver function is essential for maintaining glucose homeostasis. Gallic acid and crocin can reduce inflammation.

Methods: This experiment was done in 5 weeks. 50 male NMRI mice were randomly divided into 5 groups (n=10): 1) Control, 2) MG (600 mg/Kg/d, p.o.), 3) MG+GA (30 mg/kg/day, p.o.), 4) MG+Cr (60 mg/kg/day, p.o.), 5) MG+MT (150 mg/kg/day, p.o.). After one week of habituation, MG was administered for four weeks. Gallic acid, crocin, and metformin were administered in the last two weeks. Biochemical and histologic evaluations were assessed after plasma collection and tissue sample preparation.

Results: Gallic acid and crocin-received groups significantly reduced fasting blood glucose, total cholesterol, triglyceride levels, and elevated insulin sensitivity. Administration of MG exerted a marked increase in the levels of hepatic enzymes. Treatment with gallic acid, crocin, and metformin significantly decreased them. The altered levels of inflammatory factors in the diabetic group were significantly improved in the diabetic-treated groups. High levels of steatosis and red blood cells (RBCs) accumulation in the MG group markedly recovered in other treated mice.

Conclusion: Harmful effects of accumulated MG in the liver of diabetic mice were effectively attenuated by using gallic acid and crocin.

Aim: In the current clinical trial study, the potency of mirtazapine and nortriptyline was compared in patients with Functional Dyspepsia (FD) who had anxiety or depression.

Background: FD usually accompanies other psychosocial disorders. According to previous studies, among these disorders, anxiety and depression have the most correlation.

Methods: This randomized clinical trial was organized in Taleghani hospital (Tehran, Iran). In two parallel groups, 42 patients were treated for 12 weeks, with 22 patients receiving 7.5 mg of mirtazapine and 20 patients receiving 25 mg of nortriptyline per day. To gain robust results, the patients with a positive history of antidepressant therapy, organic diseases, alcohol abuse, pregnancy, and major psychiatric disorders were excluded from the study. The subjects were examined by three questionnaires, including Nepean and Hamilton questionnaires. The patients were asked to answer the questions three times during the study: once before the onset of the treatment, second during the treatment, and third at the end of the treatment.

Results: Based on Gastrointestinal (GI) manifestations, mirtazapine, in comparison to nortriptyline could significantly suppress the signs and symptoms of FD, including epigastric pains (P=0.02), belching (P=0.004), and bloating (P=0.01). Although the results from the use of mirtazapine compared to the use of nortriptyline (P=0.002) showed a lower mean depression score on the Hamilton questionnaire, no significant differences were found between the effects of these drugs on the anxiety scale of patients (P=0.091).

Conclusion: Mirtazapine is more effective for GI symptoms related to gastric emptying. Considering the level of anxiety, mirtazapine, compared to nortriptyline, revealed better outcomes in FD patients suffering from depression.

A substantial number of coeliac disease patients fail to respond to treatment with a gluten-free diet. Non-responsiveness might be multifactorial and the spectrum ranges from intentional or inadvertent gluten contamination as the main aetiology, to sensitivity to other nutrients (in addition to additives and preservatives). If the diagnosis of coeliac disease is correctly made and cross contamination and other factors have been excluded, then the aetiology behind the symptoms of a small group of coeliac patients might be refractory coeliac disease. The journey to ensure gluten contamination is not behind the persistent symptoms, is very challenging and requires in-depth training and skills. We therefore present potential guidance for the healthcare professional, in particular dietitians, on how to navigate these challenges on this journey.

Aim: The aim of this study was to explore the aetiology of severe duodenal mucosal abnormality in consecutive patients who underwent gastroscopy and duodenal biopsy over the past 10 years.

Background: A range of differential diagnoses have been reported for severe duodenal architectural distortion.

Methods: Clinical and laboratory data of all the patients with severe duodenal architectural distortion diagnosed at MidCentral District Health Board (DHB), New Zealand were collected and statistically analysed. Ninety-five percent confidence intervals (CI) are shown.

Results: Between September 2009 and April 2019, 229 patients were diagnosed with severe enteropathy. The median patient age was 41 years (range 6-83 years). Two hundred and twenty-four of these patients (97.8%, 95.0-99.3%) were diagnosed with coeliac disease (CeD), with one of these patients having gluten induced T-cell lymphoma. From the remaining five patients, one had a diagnosis of tropical sprue and four did not have a clear aetiology. There were 180 patients from 191 (94.2%, 89.9-97.1%) with at least one positive coeliac marker, all with a diagnosis of CeD. Eleven patients (5.8% of 191, 2.9-10.1%) had negative markers for both tissue transglutaminase IgA (tTG-IgA) and IgA-endomysial antibodies (EMA-IgA) with six having a diagnosis of seronegative CeD.

Conclusion: Although the spectrum of histological changes in CeD may range from normal to a flat mucosa, severe duodenal architectural distortion seems to occur mainly in CeD. Idiopathic enteropathy was recorded as the second but by far less frequent presentation of severe enteropathy. This study highlights that infection and other aetiologies are rarely implicated in severe enteropathy, with one case (0.4%) of refractory CeD/T-cell lymphoma.

Aim: This study aimed to detect relationships among quality of life (QoL) and anxiety and demographic factors in patients with celiac disease (CD).

Background: CD is a type of autoimmune small intestine diseases caused by gluten ingestion. In Iran, the prevalence of CD is considered to be 1% in the general population. As physical problems and behavioral disorders of CD can lead to a reduction in QoL.

Methods: This cross-sectional study was performed on 533 patients with Celiac Disease from 9 cities of Iran. Data collected were analyzed by SPSS version 22. Quality of life and anxiety respectively evaluated by (GHQ-28) and SAS questionnaires. Predictors of quality of life (sex, age, age of diagnosis, city of life, education level, family history of celiac, occupation and anxiety) were tested by multiple linear regression.

Results: Our results showed a significant relationship between poor quality of life and anxiety (correlation= -0.143, P=0.001). The mean of the quality of life index in celiac diseases was 126.2±30.4 and women had a lower quality of life than men (P=0.003) importantly in emotions and worries scores. There was no significant difference between male and female in terms of anxiety level.

Conclusion: According to the results, both quality of life and anxiety correlated together and women seem to suffer more than men from celiac disease. Therefore, greater attention to women who have celiac disease are suggested.

Aim: This study aimed to find lncRNAs and mRNAs that were expressed differently by combining microarray datasets from different studies. This was done to find important target genes in gastric cancer for anti-cancer therapy.

Background: Gastric cancer (GC) is the fourth most frequent and second-most deadly malignancy worldwide. Thus, genetic diagnosis and treatment should focus on genetic and epigenetic variables. Based on several studies, disordered expression of non-coding RNAs (ncRNAs), such as lncRNAs, regulate gastric cancer invasion and metastasis. Besides, lncRNAs cooperatively regulate gene expression and GC progression.

Methods: We obtained differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) from three GC tissue microarray datasets by meta-analysis and screened genes using the "Limma" package. Then, using the RNAInter database, we allocated DEmRNAs to each DElncRNA. ClusterProfiler and GOplot programs were used to analyze function enrichment pathways and gene ontologies for final DEmRNAs.

Results: A total of 9 differentially expressed lncRNAs (DElncRNAs) (5 up-regulated and 4 down-regulated), and 856 DEmRNAs (451 up-regulated and 405 down-regulated) between tumor and adjacent normal samples were found. Finally, 117 differentially expressed mRNAs were predicted as interactors of six DElncRNAs (H19, WT1-AS, EMX2OS, HOTAIR, ZEB1-AS1, and LINC00261).

Conclusion: In order to promote cancer therapeutics and give knowledge on the process of carcinogenesis, our study projected a network of drug-gene interactions for discovered genes and presented relevant prospective biomarkers for the prognosis of patients with stomach cancer.

Aim: To assess the role of granulocyte colony-stimulating factor (GCSF) in the patients with severe alcoholic hepatitis (SAH) using real world experience in the United States.

Background: There are few effective treatments for severe alcoholic hepatitis, which has a significant fatality rate. GCSF has been associated with improved survival in a small number of Indian studies, while there is a dearth of information from other parts of the globe.

Methods: We performed a single-center retrospective study of consecutive patients admitted to a tertiary care, liver transplant center with severe alcoholic hepatitis from May 2015 to February 2019. The patients receiving GCSF (5μg/kg subcutaneously every 12 hours for 5 consecutive days) (n=12) were compared to the patients receiving standard of care (n=42).

Results: Thirty-day, 90-day and 1-year mortality rates was similar among groups (25% vs. 17%, P=0.58; 41% vs 29%, P=0.30; 41% vs 47%, P=0.44, respectively). There was no difference in liver transplant listing and orthotopic transplantation among groups.

Conclusion: In this real-world, United States-based study, GCSF does not improved survival in the patient with several alcoholic hepatitis compared to standard of care.

Aim: In this study, we aim to propose consensus-based interpretations to enhance both automatic, and manual analysis and then present our recommendations about reflux-related variables to enhance Multichannel Intraluminal (MII) measurements.

Background: Multichannel Intraluminal Impedance-pH (MII-pH) monitoring is the most sensible option to evaluate Gastroesophageal Reflux Disease (GERD), specifically for the patients with normal endoscopy findings, and persistent symptoms without response to Proton Pomp Inhibitor therapy. There were only a few studies on the interpretation of reflux events in MII tracings.

Methods: Several 200 episodes of reflux events were reviewed during several meetings in five steps, to discuss and categorize unresolved issues within existing interpretations, and propose technical principles for accurate characterization of reflux events.

Results: In this study, we show that baseline impedance is determined using a moving average procedure to the impedance data of each channel with a time window of 60 seconds based on this finding; a liquid reflux event is defined as a retrograde 50% drop in baseline impedance, gas reflux event is defined as a rapid increase in impedance greater than 5 kΩ, Mixed liquid-gas reflux is defined as gas reflux occurring immediately before or during liquid reflux.

Conclusion: The reliability of final diagnosis is significantly dependent on the accurate detection of reflux events, which is currently confronting technical limitations. A pathological reflux event propagates to at least three of the impedance sites, according to the literature. We think that taking three impedance locations into account might be too strict.