Turkish Journal of Gastroenterology最新文献

Background/Aims: The prevalence of sarcopenia and osteopenia/osteoporosis is increased in chronic pancreatitis (CP). This study aims to evaluate the prevalence and related factors of osteosarcopenia in CP patients. Materials and Methods: Eighty-three CP patients were included in this cross-sectional observational study. Sarcopenia was assessed by measuring the surface area of the paravertebral muscles at the third lumbar region. Pancreatic fecal elastase (PFE) tests evaluated exocrine pancreatic insufficiency (EPI), while dual-energy x-ray absorptiometry scans assessed osteopenia/osteoporosis. EORTC PAN26 and a symptom questionnaire were administered, alongside nutritional marker assessments concurrent with PFE. Results: The prevalence of sarcopenia and osteopenia/osteoporosis was found to be 22.9% (n = 19) and 68.7% (n = 44), respectively. Factors associated with sarcopenia included male gender (OR: 4.9, P = .044), severe EPI (OR: 4.2, P = .043), smoking (OR: 4.6, P = .040), and zinc deficiency (OR: 2.2, P = .029). Severe EPI was significantly associated with osteopenia/osteoporosis (P = .010), diabetes mellitus (P = .001), sarcopenia (P = .016), and zinc deficiency (P = .012). Individuals with osteoporosis had higher PAN26 scores (P = .029). Factors independently associated with osteopenia/osteoporosis included female gender (OR: 7.8, P = .004), severe EPI (OR: 8.1, P = .003), and sarcopenia (OR: 5, P = .037). The prevalence of osteosarcopenia was 19.2%. Conclusion: Osteosarcopenia is common in CP patients. Smoking, zinc deficiency, EPI, and male gender are strongly associated with sarcopenia. Screening for osteosarcopenia is essential in CP patients to facilitate appropriate interventions.

Background/Aims: The study focuses on examining the impact of Helicobacter pylori (H. pylori) on the modulation of the miRNA expression profiles while also unraveling the associated pathways that play a significant role in initiating and driving the development of gastric cancer (GC). Materials and Methods: An in-depth analysis of miRNA expression profiles in gastric tissue samples from patients with chronic superficial gastritis (CSG), chronic atrophic gastritis (CAG), dysplasia (Dys), or GC was conducted. The carbon-13 urea breath test was used to identify H. pylori infection, and the participant cohort was characterized by the presence of H. pylori infection. Additionally, the role of miR-196a/b-5p in GC carcinogenesis was investigated. Results: A total of five miRNAs-miR-196a-5p, 196b-5p, 224-5p, 424-3p, and 941-demonstrated marked elevation in CSG, CAG, Dys, and GC. miR-196a/b-5p was observed to be upregulated in GC cells following H. pylori infection, as well as in Dys and GC tissue samples from patients harboring H. pylori. miR-196a/b-5p can expedite GC progression. Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), the target gene of miR-196a/b-5p, diminishes the proliferation capability of GC cells; however, miR-196a/b-5p can partially counteract this effect. miR-196a/b-5p activates the PI3K-Akt pathway, while IGF2BP1 inhibits the expression of these proteins. Conclusion: The levels of miR-196a/b-5p were observed to escalate following H. pylori infection, subsequently fostering the progression of GC by specifically targeting IGF2BP1 and triggering the PI3K-Akt signaling cascade.

Background/Aims: This research aimed at probing the mechanism of long non-coding RNA small nucleolar RNA host gene 4 (SNHG4) in regulating lipid metabolism and inflammation in non-alcoholic fatty liver disease (NAFLD). Materials and Methods: L02 and THLE-2 cells were stimulated with free fatty acids (FFA) and transfected. Lipid accumulation was detected through Oil Red O staining, measurements of triglyceride and total cholesterol were taken, and the levels of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 were assessed using enzyme-linked immunosorbent assays. The assessment of gene expression was conducted using real-time reverse transcriptase-polymerase chain reaction and Western blot techniques. The interplay between SNHG4 and miR-34b-5p/X-linked inhibitor of apoptosis protein (XIAP) was evaluated. Results: Free fatty acids downregulated SNHG4 and XIAP and upregulated miR-34b-5p in L02 and THLE-2 cells, leading to lipid metabolism disorder and inflammation. SNHG4 overexpression mitigated the lipid metabolism disorder and inflammation triggered by FFA, while this effect was suppressed by silencing XIAP. In contrast, SNHG4 knockdown aggravated FFA-induced lipid metabolic and inflammatory disorders, whilst this effect was rescued by inhibiting miR-34b-5p. Conclusion: SNHG4 regulates lipid metabolism and inflammatory disorders in NAFLD by targeting the miR-34b-5p/XIAP axis.

Background/aims: The function and mechanism of ubiquitin-specific protease 34 (USP34) in hepatocellular carcinoma (HCC) were explored to provide new molecular targets for treating HCC.

Materials and methods: In the present study, bioinformatics techniques, quantitative real-time polymerase chain reaction, and western blot were used to detect the level of USP34 in HCC tissues and cell lines. Small interfering RNA of USP34 was transfected into HCC cells, and then Cell Counting Kit-8 (CCK-8) assay, wound healing assay, and transwell assay were performed to verify the proliferation, migration and invasion of HCC cells. Enzyme-linked immunosorbent assay was utilized to assess the glycolysis level in HCC cells. Co-immunoprecipitation was used to evaluate the ubiquitination level of cellular Myc (c-Myc).

Results: The expression of USP34 was upregulated in HCC patients and strongly associated with worse outcomes. Meanwhile, interference with USP34 suppressed the proliferation, migration, and invasion of HCC cells. In addition, silencing of USP34 reduced the glucose uptake, lactate production and ATP content in HCC cells, as well as downregulated the expression levels of glycolysis-related proteins (hexokinase 2, glucose transporter 1, pyruvate kinase M2, and lactate dehydrogenase A). Furthermore, the knockdown of USP34 enhanced the ubiquitination level of c-Myc and increased the degradation of c-Myc. Overexpression of c-Myc reverted the inhibitory effects of si-USP34 on the malignant biological behavior in HCC cells.

Conclusion: The USP34 regulates aerobic glycolysis and inhibits the progression of HCC by accelerating c-Myc ubiquitinated degradation.

Background/aims: Hepatocellular carcinoma (HCC) is significantly influenced by the immune system, which plays a key role in its development, progression, treatment, and prognosis. While observational studies have revealed correlations between circulating immune traits and HCC, their genetic basis and causal links remain unclear. This study aims to investigate the genetic associations and bidirectional causal relationships between immune traits and HCC risk using Mendelian randomization (MR) approaches.

Materials and methods: Genome-wide association study summary statistics from the FinnGen cohort (R9, including 453 HCC cases and 287137 controls) were used to perform a bidirectional two-sample MR analysis. The causal effects of immune traits on HCC, as well as reverse causality, were assessed. Sensitivity analyses, including heterogeneity and pleiotropy tests, were used to ensure the robustness and validity of the results.

Results: Thirty-nine immune traits were identified to be significantly associated with HCC risk. Elevated levels of 10 immune traits were positively associated with increased HCC risk, while the abundance of 29 immune traits was inversely correlated with HCC incidence. Furthermore, the reverse MR analysis revealed significant causal effects of HCC on 11 immune traits.

Conclusion: This study provides strong evidence of genetic links between systematic immune cell profiles and HCC, shedding light on the mechanisms underlying its onset and progression. These findings identify potential immune biomarkers for early diagnosis and immune-targeted therapies.

Background/aims: Hepatic ischemia-reperfusion injury (HIRI) refers to the damage caused by metabolic imbalance post-ischemia upon reperfusion, often occurring in scenarios like hemorrhagic shock, liver resection, and liver transplantation. Due to the complex nature of the mechanisms underlying metabolic imbalance, specific treatment options are lacking. Peroxisome proliferator activated receptor gamma (PPARγ) is a group of metabolic regulatory receptors that can influence HIRI by regulating autophagy, although the precise mechanism remains contentious.

Materials and methods: In vivo and in vitro experiments were conducted to simulate hypoxic conditions, evaluating the effects of PPARγ overexpression plasmids, autophagy inhibitors, phosphatidylinositol 3-kinase (PI3K) activators, and PPARγ agonists on HIRI. The activation status of the PI3K-AKT1-FOXO3 signaling pathway, autophagy levels, inflammatory responses, and liver cell/organ damage were analyzed using western blot, ELISA, flow cytometry, H&E staining, and TUNEL experiments.

Results: Peroxisome proliferator activated receptor gamma can mitigate cell damage caused by hypoxia by activating autophagy, with the activation of autophagy being associated with the inhibition of the PI3K-AKT1-FOXO3 signaling pathway. Additionally, pretreatment of mice with the PPARγ agonist rosiglitazone can alleviate HIRI induced by ischemia by inhibiting the activation of the PI3K-AKT1-FOXO3 signaling pathway to induce autophagy.

Conclusion: Peroxisome proliferator activated receptor gamma inhibited the PI3K-AKT1-FOXO3 signaling pathway, which in turn activated autophagy to alleviate HIRI.

Background/aims: Hepatocellular carcinoma (HCC) is significantly influenced by the immune system, which plays a key role in its development, progression, treatment, and prognosis. While observational studies have revealed correlations between circulating immune traits and HCC, their genetic basis and causal links remain unclear. This study aims to investigate the genetic associations and bidirectional causal relationships between immune traits and HCC risk using Mendelian randomization (MR) approaches.

Materials and methods: Genome-wide association study summary statistics from the FinnGen cohort (R9, including 453 HCC cases and 287137 controls) were used to perform a bidirectional two-sample MR analysis. The causal effects of immune traits on HCC, as well as reverse causality, were assessed. Sensitivity analyses, including heterogeneity and pleiotropy tests, were used to ensure the robustness and validity of the results.

Results: Thirty-nine immune traits were identified to be significantly associated with HCC risk. Elevated levels of 10 immune traits were positively associated with increased HCC risk, while the abundance of 29 immune traits was inversely correlated with HCC incidence. Furthermore, the reverse MR analysis revealed significant causal effects of HCC on 11 immune traits.

Conclusion: This study provides strong evidence of genetic links between systematic immune cell profiles and HCC, shedding light on the mechanisms underlying its onset and progression. These findings identify potential immune biomarkers for early diagnosis and immune-targeted therapies.

Background/aims: Distinct virological relapse (VR) has occurred after stopping the use of nucleos(t)ide analogues treatment in patients with chronic hepatitis B (CHB) who are positive for Hepatitis B e antigen (HBeAg). Here, we aimed to identify serum miR-146a and miR155 in HBeAg-positive patients with CHB and their relationship with VR after entecavir (ETV) discontinuance.

Materials and methods: Ninety-eight patients with CHB and positive for HBeAg before initiating treatment were analyzed. Virological relapse was defined as 2 consecutive examinations (3 months apart) after treatment discontinuance, both showing an HBV DNA load of more than >2000 IU/mL.

Results: Compared to control, CHB patients were observed with increases in serum miR-146a and miR-155 before starting ETV treatment (P < .001). There were 52 patients (53.1%) experiencing VR at 12 months after discontinuance of ETV treatment. The VR group was demonstrated with increases in serum miR-146a and miR-155 than the non-VR group before starting ETV treatment (P < .001). Whether at the beginning of ETV discontinuance or at 12 months after ETV discontinuance, the VR group was noted with elevations in serum miR-146a and miR-155 than the non-VR group (P < .001).

Conclusion: The findings demonstrated that miR-146a and miR-155 levels in the circulation may be promising assessment tools for identifying sustained-virological responders after ETV discontinuance in CHB patients.