Gastroenterology and Hepatology From Bed to Bench最新文献

Aim: This study reports differential expression of Antisense RNAs (asRNAs) by analyzing transcriptomic profiles in gallbladder cancer (GBC).

Background: asRNAs play crucial roles in developing various tumors. However, the presence and biological mechanism of asRNAs in GBC development are still unknown.

Methods: Differentially expressed asRNAs (DE-asRNAs) were systematically identified from RNA sequencing data from ten GBC patients. Functional enrichment analysis was performed, followed by the identification of mRNAs targeted by asRNAs and the construction of a gene regulatory network of asRNAs targeting mRNAs.

Results: Of the 891 asRNAs identified, 17 DE-asRNAs were statistically significant. Out of 17, 12 asRNAs were upregulated, and five asRNAs were downregulated. Functional enrichment analysis showed their role in methylation and developmental processes. Of the 17 asRNAs, 14 are novel (UNC5B-AS1, SLC2A1-AS1, BBOX1-AS1, SOX21-AS1, ELFN1-AS1, TRPM2-AS, DNAH17-AS1, DCST1-AS1, VPS9D1-AS1, MIR1-1HG-AS1, HAND2-AS1, PGM5P4-AS1, PGM5P3-AS1, and MAGI2-AS). Enrichment analysis of asRNAs with target mRNAs showed enrichment in biological regulation and developmental processes involved in the PI3K, p53, apoptosis, and VEGF signaling pathways.

Conclusion: This study identified 14 asRNAs for the first time and showed that asRNAs targeting mRNAs strongly associated with tumor development in GBC through the PI3KCA and TP53 pathways.

Functional gastrointestinal disorders (FGID) are prevalent illnesses associated with diminished quality of life and increased healthcare utilization. These conditions influence gut sensitivity, motility, microbiota, immunological function, and nervous processing in the brain. Chronic symptoms, including pain and dyspepsia, are exacerbated by maladaptive patient behaviors, stress, and co-morbidity. Studies of functional neuroimaging reveal increased brain responses in regions associated with gut sensory processing and salient cues, altered central regulation of endocrine and autonomic nerve responses, and aberrant connections in pain processing and the default mode network. This neuroimaging helps us understand the pathophysiology and outcomes of patients better. From the standpoint of brain connection, research in this area can further our understanding of the central pathophysiology of FGID and pave the way for the objective diagnosis and development of novel therapeutics for FGID. Prospective Neuroimaging research may change from brain mapping to clinical prognosis prediction due to technological advances in machine learning algorithms used in imaging. The usefulness and revelations of functional brain imaging are highlighted in this review, along with the areas that require development and, lastly, recommendations for future research.

Aim: This study assessed the prognostic value of sarcopenia and myosteatosis for survival following liver transplantation using CT-derived skeletal muscle index (SMI) and skeletal muscle radiation attenuation (SMRA).

Background: Sarcopenia and myosteatosis are common in liver transplant (LT) candidates and may affect postoperative outcomes.

Methods: This retrospective cohort study analyzed 79 LT recipients (aged 17-75 years) at Taleghani Hospital, Tehran, Iran, from October 2019 to November 2023, excluding patients with malignancy or cardiovascular disease. Non-contrast-enhanced CT scans at the third lumbar vertebra were analyzed using SliceOmatic software to quantify SMI and SMRA. Sarcopenia was defined using AWGS-adapted criteria for CT: low SMI (<42 cm²/m² for men, <38 cm²/m² for women), reduced handgrip strength (<30 kg for men, <20 kg for women), or reduced gait speed (<1 m/s). Sarcopenia was classified as pre-sarcopenia (low SMI), sarcopenia (low SMI with either deficit in hand grip strength or gait speed), severe sarcopenia (low SMI with both deficits), or sarcopenic obesity (sarcopenia with BMI ≥30 kg/m²). Myosteatosis was defined by SMRA (<41 HU for BMI <25 kg/m²; <33 HU for BMI ≥25 kg/m²). The Cox proportional hazards model and Kaplan-Meier analysis assessed survival predictors (P<0.05).

Results: Among 79 recipients (58.2% male, mean age 47.2±13.7 years), 77.2% had myosteatosis and 34.2% had pre-sarcopenia. Over 60,173 person-days, 17 deaths occurred. Myosteatosis (HR 2.15, 95% CI 1.03-4.48), elevated bilirubin (HR 1.04, 95% CI 1.02-1.07 per unit), and female sex (HR 2.29, 95% CI 1.19-4.14) were associated with increased mortality hazard (all P<0.05). Kaplan-Meier curves showed 5-year survival of 70-80%.

Conclusion: Myosteatosis, elevated bilirubin, and female sex are significant predictors of mortality post-LT in this cohort. CT-derived SMRA assessment offer valuable tools for pre-transplant risk stratification, supporting targeted interventions to improve early outcomes.

Aim: This study seeks to determine, for the first time, whether these mechanisms account for the indirect effects of trauma on gastrointestinal symptom severity within a psychosomatic framework.

Background: Gastroesophageal reflux disease (GERD) is one of the most common disorders of the digestive system, and various psychological factors may contribute to its development and exacerbation. The present study will examine these factors within a unified analytical model. Specifically, the study aimed to examine a path analysis model of the relationship between trauma and gastrointestinal symptoms in patients with GERD, with a focus on the mediating roles of emotional processing and mentalization.

Methods: This cross-sectional study included 207 people with gastroesophageal reflux disease referred to Tehran Behbood Clinic, aged 18 to 60 years, selected through convenience sampling. The study was carried out between September and October 2024. The subjects completed the Gastrointestinal Symptom Rating Scale (GSRS), Mentalization Questionnaire (MQ), Childhood Trauma Questionnaire, and Emotional Information Processing Questionnaire (EIPQ). Data were analyzed using path analysis in R (lavaan package) with the Maximum Likelihood Robust (MLR) estimator to account for non-normality. Model fit was evaluated using chi-square, CFI, TLI, RMSEA, and SRMR, and direct, indirect, and total effects were calculated to examine the mediating role of emotional processing and mentalization.

Results: Trauma had a significant direct effect on gastrointestinal symptoms (β = 0.242, p < 0.001). Emotional processing significantly mediated this relationship (indirect effect β = 0.039, p < 0.05). Mentalization did not show a significant direct or mediating effect on gastrointestinal symptoms (β = 0.074, p = 0.255). Model fit indices indicated excellent fit (CFI = 1.000, TLI = 1.198, RMSEA = 0.000, SRMR = 0.003).

Conclusion: Based on the findings, it can be concluded that trauma and emotional processing predict gastrointestinal symptoms in patients with gastroesophageal reflux disease and need to be considered in therapeutic interventions.

Aim: This study investigated the microbiological profile, risk factors, antimicrobial resistance, and clinical outcomes in patients with acute cholangitis.

Background: Acute cholangitis is a critical infection resulting from biliary obstruction, with risks of sepsis and high mortality.

Methods: This prospective study included 105 patients undergoing biliary drainage for acute cholangitis via endoscopic retrograde cholangiopancreatography or percutaneous transhepatic drainage. Bile and blood cultures were collected. Antimicrobial susceptibility testing was performed. In-hospital outcomes were analysed.

Results: Bacteriologically confirmed cholangitis was identified in nearly half of the patients, with Gram-negative bacteria predominating in both bile and blood cultures. Klebsiella pneumoniae and Escherichia coli were the most common Gram-negative isolates, Staphylococcus aureus was the leading Gram-positive organism, and a small number of Candida species (n=5) were also recovered. Malignant biliary obstruction and higher SOFA scores were associated with positive cultures. Multidrug-resistant organisms (51.8% of isolates), including ESBL-producers and carbapenem-resistant strains, were common. Enterobacteriaceae remained sensitive to carbapenems and tigecycline, whereas Staphylococci were sensitive to linezolid and vancomycin. Culture-positive patients experienced longer hospital stays (P< 0.001) and higher mortality (10%, P= 0.016) compared with negative-culture patients.

Conclusion: -negative bacteria are the primary pathogens in acute cholangitis, and the high burden of multidrug resistance is linked to worse clinical outcomes, particularly in patients with malignant obstruction. Ongoing antibiotic stewardship and local resistance are crucial to optimize empiric therapy and improve patient outcomes.

Aim: This study aimed to investigate the effect of coffee or coffee extract on serum ALT and AST levels in patients with non-alcoholic fatty liver disease (NAFLD), by compiling data from randomized controlled trials up to November 2024.

Background: NAFLD represents the most prevalent hepatic disorder, characterized by the accumulation of lipids within hepatocytes in the absence of substantial alcohol consumption or viral infections. Effective management relies on lifestyle changes, such as diet and exercise. Recent studies have suggested that coffee consumption may offer liver-protective benefits, potentially helping to reduce serum levels of liver enzymes.

Methods: Two researchers conducted an independent search across PubMed, Web of Science, and Scopus, including clinical trials that assessed the effects of coffee or coffee extract on liver function tests (LFTs) in individuals diagnosed with NAFLD. Meta-analysis was carried out using STATA software.

Results: After screening titles, abstracts, and full texts, four studies comprising five placebo-treatment pairs were included in the meta-analysis. Coffee or coffee extract did not significantly affect serum ALT (p= 0.45) and AST (p= 0.54) levels.

Conclusion: There is insufficient evidence to support the effectiveness of coffee or coffee extract on serum ALT and AST levels. Due to the limited number of studies, small sample sizes, and short follow-up durations, further randomized controlled trials with adequate sample sizes and more extended follow-up periods are recommended.

Aim: To assess national and provincial trends in pancreatic cancer (PC) incidence, mortality, and mortality-to-incidence ratio (MIR) in Iran (1990-2021) using Global Burden of Disease (GBD) 2021 data.

Background: PC is highly lethal, and recent burden estimates for Iran are limited.

Methods: Age-standardized and age-specific incidence and mortality rates were obtained from the GBD Results Tool; MIR was calculated. Joinpoint regression was used to estimate average annual percentage change (AAPC) overall, by sex, and in adults aged ≥55 years.

Results: From 1990 to 2021, age-standardized incidence and mortality increased by 80% (1.98 to 3.57 per 100,000) and 73% (2.12 to 3.65 per 100,000), respectively, while the MIR declined slightly (1.07 to 1.02) but remained above 1. Among adults ≥55 years, incidence and mortality nearly doubled (8.31 to 16.84 and 8.73 to 17.38 per 100,000, respectively), with minor MIR reductions (1.05 to 1.03). Joinpoint regression confirmed significant national increases in incidence (AAPC:1.88%) and mortality (AAPC:1.73%), alongside a modest decline in MIR (AAPC:-0.14%). Provincially, all regions exhibited rising age-standardized incidence and mortality, most steeply in Ilam and the lowest in Tehran. MIR generally declined, notably in Tehran, Lorestan, and Chaharmahal and Bakhtiari, though slight increases occurred in South/North Khorasan, Markazi, and Sistan and Baluchestan.

Conclusion: PC burden in Iran has increased subs`tantially over the past three decades, especially among older adults and in certain provinces. Persistently high MIR indicates late diagnosis and poor survival, highlighting the need to strengthen cancer registries, improve early detection and diagnostic capacity, and address modifiable risk factors.

Aim: This narrative review synthesizes current evidence on the association between Celiac disease (CD) and pulmonary disorders, explores underlying mechanisms, and highlights clinical implications and future research directions.

Background: CD is a chronic autoimmune enteropathy triggered by gluten ingestion in genetically predisposed individuals. Although it primarily affects the small intestine, emerging evidence implicates extraintestinal involvement, particularly of the respiratory system, suggesting a potential gut-lung axis.

Methods: This narrative review was conducted using PubMed, Scopus, and Web of Science, covering literature published in English up to October 2025. Search terms combined 'celiac disease' OR 'coeliac disease' with ('lung disease' OR 'pulmonary' OR 'respiratory tract' OR 'asthma' OR 'bronchiectasis' OR 'COPD' OR 'interstitial lung disease' OR 'pulmonary hemosiderosis'). Inclusion criteria were peer-reviewed human studies reporting pulmonary manifestations in celiac disease. Exclusion criteria included non-English language, in vitro or animal studies, abstracts without full text, and insufficient clinical or mechanistic data. This was not a systematic review, and therefore no PRISMA flow diagram was generated."

Results: Large-scale registry studies in Scandinavia and case-based evidence across Europe and Asia support a spectrum of pulmonary manifestations in celiac disease, ranging from asthma and chronic cough to rare but life-threatening idiopathic pulmonary hemosiderosis. Asthma and chronic cough were the most commonly observed associations, with population-based studies reporting an elevated risk. Case reports and small cohorts described co-occurrence with bronchiectasis and interstitial lung disease, while rare cases confirmed links to idiopathic pulmonary hemosiderosis (Lane-Hamilton syndrome). Proposed mechanisms include systemic immune activation, increased intestinal and pulmonary permeability, micronutrient deficiencies, IgA deficiency, and chronic inflammation. Notably, several studies reported symptom improvement or resolution following a gluten-free diet (GFD).

Conclusion: Pulmonary manifestations of CD, though relatively uncommon, are clinically significant and often reversible with dietary intervention. Greater awareness, early recognition, and mechanistic research are essential to optimize patient outcomes.

Celiac disease is an enteropathy caused by intolerance to gluten, with genetic and environmental factors playing a key part in its pathogenesis. This review addresses the use of the gluten-free diet as the primary treatment for patients with celiac disease and the use of probiotics as an adjunctive therapy. The gluten-free diet is the sole treatment for preventing symptoms and allowing the inflamed intestinal mucosa to recover. The gluten-free diet, however, also has some very significant challenges like its complexity, the need for ongoing monitoring by dieticians, and the risk of contamination with gluten even in gluten-free labelled foods. At the same time, the growing interest in the use of probiotics as an adjunct therapy in celiac disease management is based on the hypothetical contribution of the gut microbiota to the pathophysiology of the disease. It has been hypothesized that gut dysbiosis could be involved in the development and maintenance of celiac disease symptoms. Probiotics, in particular the genera Lactobacillus and Bifidobacterium, are among the promising adjuvants for the improvement of gut health. These beneficial microorganisms may play an essential important, crucial role in the breakdown or modification of gluten polypeptides and in the reduction of intestinal epithelial cell damage caused by gliadin. While probiotic use is not a replacement for a gluten-free diet, it can have additive benefits by assisting in the preservation of a healthy balance of gut microbiota and lessening some chronic gastrointestinal symptoms.

Aim: This study aimed to assess the impact of a six-week gluten-free diet (GFD) on the iron profiles of patients with non-celiac gluten sensitivity (NCGS) and CD.

Background: Iron-deficiency anaemia (IDA) is a significant clinical feature of gluten-related disorders, especially Celiac disease (CD).

Methods: The study included 29 CD patients (mean age 40.28 ± 15.57 years) and 29 NCGS patients (mean age 30.31 ± 7.78 years) presenting with IDA who were enrolled in the study during 2023-2024. Haemoglobin, serum iron, serum ferritin, total iron-binding capacity (TIBC), and transferrin saturation (TSAT) levels were assessed at the beginning and after six weeks of GFD. HLA typing was conducted using the Real-time PCR-based SYBR Green method.

Results: Ferritin levels significantly increased in both CD and NCGS groups after the GFD, from 43.7807 to 50.5279 ng/mL and 23.0862 to 42.9910 ng/mL, respectively. Moreover, serum iron and TSAT levels significantly increased in the NCGS group, from 64.8034 to 81.3466 μg/dL and 19.29 ± 11.70 to 23.99 ± 9.05, respectively (p = 0.003).

Conclusion: The most frequent symptoms in CD and NCGS patients were bloating/bone disease (62.1%) and bone disease (37.9%), respectively. GFD was effective in improving IDA in both CD and NCGS patients. Further research is necessary to assess the therapeutic effect of GFD in patients with gastrointestinal symptoms and IDA.