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Background/AimsThe role of DHRS3 in human cancer remains unclear. Our study explored the role of DHRS3 in gastric cancer (GC) and its clinicopathological significance and associated mechanisms.MaterialsBisulfite-assisted genomic sequencing PCR and a Mass-Array system were used to evaluate and quantify the methylation levels of the promoter. The expression levels and biological function of DHRS3 was examined by both in vitro and in vivo assays. A two-way hierarchical cluster analysis was used to classify the methylation profiles, and the correlation between the methylation status of the DHRS3 promoter and the clinicopathological characteristics of GC were then assessed.ResultsThe DHRS3 promoter was hypermethylated in GC samples, while the mRNA and protein levels of DHRS3 were significantly downregulated. Ectopic expression of DHRS3 in GC cells inhibited cell proliferation and migration in vitro, decreased tumor growth in vivo. DHRS3 methylation was correlated with histological type and poor differentiation of tumors. GC patients with high degrees of CpG 9.10 methylation had shorter survival times than those with lower methylation.ConclusionDHRS3 was hypermethylated and downregulated in GC patients. Reduced expression of DHRS3 is implicated in gastric carcinogenesis, which suggests DHRS3 is a tumor suppressor.

Background: Studies have found that water-assisted colonoscopy (WAC) including water immersion colonoscopy (WIC) and water exchange colonoscopy (WEC) is superior to air insufflation colonoscopy (AIC) in terms of the cecal intubation rate. However, the application of WAC in ulcerative colitis (UC) has rarely been reported. This study aimed to explore the effectiveness of WAC without sedation in patients with UC. Methods: One hundred and seventy-two UC patients were randomly divided into the AIC group (n = 56), WIC group (n = 58), and WEC group (n = 58). The cecal intubation rate, abdominal pain score, operator difficulty, bowel cleanliness, insertion, and total time were compared. Results: The cecal intubation rate was higher in the WIC (91.4% vs. 75.0%; mean difference = 16.4%; 95% CI: 3.0–29.8%) and WEC (93.1% vs. 75.0%; mean difference = 18.1%; 95% CI: 5.0–31.2%) compared to the AIC group, while there was no difference between the WIC and WEC groups. The abdominal pain score and operator difficulty were lower in the WIC and WEC groups than in the AIC group, while there was no difference between the WIC and WEC groups. The bowel cleanliness during withdrawal was higher in the WIC and WEC groups than in the AIC group, while the WEC was superior to WIC. Compared with the AIC and WIC groups, the insertion time and total time were longer in the WEC group, and there was no difference in the AIC group and WIC group. Conclusion: In comparison with AIC, WAC can increase the cecal intubation rate, reduce abdominal pain scores and improve bowel cleanliness in patients with UC. [ABSTRACT FROM AUTHOR]

• This study investigated altered functional connectivity (FC) of the periaqueductal gray (PAG) subregions in CD patients with and without abdominal pain. • This study found that FC between PAG and certain regions had correlation relationship with the pain degree. • This study revealed the disrupt communication between the PAG and default mode network (DMN) in CD patients with abdominal pain. Abdominal pain in Crohn's disease (CD) has been known to be associated with changes in the central nervous system. The periaqueductal gray (PAG) plays a well-established role in pain processing. However, the role of PAG-related network and the effect of pain on the network in CD remain unclear.Resting-state functional magnetic imaging (fMRI) data were collected from 24 CD patients in remission with abdominal pain, 24 CD patients without abdominal pain and 28 healthy controls (HCs). Using the subregions of PAG (dorsomedial (dmPAG), dorsolateral (dlPAG), lateral (lPAG) and ventrolateral (vlPAG)) as seeds, the seed-based FC maps were calculated and one-way analysis of variance (ANOVA) was performed to investigate the differences among the three groups.Results showed that the group differences were mainly involved in the FC of the vlPAG with the precuneus, medial prefrontal cortex (mPFC) as well as orbitofrontal cortex (OFC), and the FC of the right lateral PAG (lPAG) with the precuneus, inferior parietal lobule (IPL), angular gyrus and premotor cortex. The FC values of all these regions decreased successively in the order of HCs, CD without abdominal pain and CD with abdominal pain. The pain score was negatively correlated with the FC of the l/vlPAG with the precuneus, angular gyrus and mPFC in CD patients with abdominal pain.This study implicated the disrupt communication between the PAG and the default mode network (DMN). These findings complemented neuroimaging evidence for the pathophysiology of visceral pain in CD patients. [ABSTRACT FROM AUTHOR]

Background: To study the effect of microRNA‐383 (miR‐383) on cell proliferation, migration, and invasion of hepatocellular carcinoma (HCC) cells, and explore its mechanism. Methods: The expressions of miR‐383 and plant homology domain that refers to protein 8 (PHF8) were detected in tissues and cells by quantitative real‐time polymerase chain reaction (qRT‐PCR) or western blot respectively. The miR‐383 group (transfected miR‐383 mimics), miR‐con group (transfected miR‐con), si‐con group (transfected si‐con), si‐PHF8 group (transfected si‐PHF8), miR‐383 + ctrl group (cotransfected miR‐383 mimics and pcDNA‐3.1), miR‐383 + PHF8 group (cotransfected miR‐383 mimics and pcDNA‐3.1‐PHF8) were transfected into HepG2 cells by liposome method. Cell proliferation, migration and invasion were measured by 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide (MTT) or trans‐well assays respectively. The luciferase activity of each group was detected by dual luciferase reporter gene assay. Results: Compared with normal adjacent tissues, the expression of miR‐383 was significantly down‐regulated and the expression of PHF8 was significantly up‐regulated (p <.05). Compared with normal hepatocellular cell LO2, the expression of miR‐383 was significantly reduced (p <.05) in HCC cells. Moreover, overexpression of miR‐383 or silencing of PHF8 significantly inhibited the proliferation, migration, and invasion of HCC cells. In addition, PHF8 was targeted by miR‐383 and its restoration rescued the inhibitory effect of miR‐383 on cell proliferation, migration, and invasion of HCC cells. Conclusion: miR‐383 could inhibit the proliferation, migration, and invasion of HCC cells by targeting PHF8, which will provide a basis for miR‐383 targeted therapy for HCC. [ABSTRACT FROM AUTHOR]

A pathogenic role of serine/threonine protein kinase 25 (STK25) has been observed in several chronic liver diseases. However, whether STK25 participates in hepatocellular carcinoma (HCC) remains unexplored. The current work aimed to explore the role and mechanism of STK25 in HCC. A high STK25 level was found in HCC tissue, which was associated with reduced overall survival. HCC cells with STK25 silencing displayed a marked decrease in proliferative and invasive ability, but were highly sensitive to apoptosis induced by the chemotherapy drug sorafenib. Reciprocally, HCC cells with forced expression of STK25 displayed the opposite effects. Further data unveiled that STK25 silencing restrained the activation of Yes-associated protein 1 (YAP1) associated with regulation of mammalian STE20-like protein kinase 1/2 (MST1/2). Forced expression of constitutively active YAP1 abolished STK25 silencing-induced antitumor effects, while repression of YAP1 reversed STK25 upregulation-induced protumor effects. Additionally, HCC cells with STK25 silencing exhibited reduced tumorigenic potential in vivo. Collectively, the results show that STK25 exerts a protumor function in HCC by enhancing YAP1 activation via regulation of MST1/2. These findings propose STK25 as a viable target for the development of anti-HCC therapy. • STK25 is increased in HCC and correlated with poor prognosis. • Inhibition of STK25 has anticancer effects in HCC. • STK25 mediates the YAP1 signaling in HCC. • STK25 regulates HCC via the YAP1 signaling. [ABSTRACT FROM AUTHOR]

Recent studies have shown that spindle and kinetochore-associated protein 2 (SKA2) is dysregulated in multiple tumors and acts as a key regulator of tumor progression. However, whether SKA2 plays a role in hepatocellular carcinoma (HCC) has not been fully elucidated. The purpose of this study was to explore the expression, function and underlying molecular mechanism of SKA2 in HCC. We found that SKA2 was highly expressed in HCC tissues and cell lines. Knockdown of SKA2 caused marked reductions in the proliferative, colony-forming and invasive capacities of HCC cells, while SKA2 overexpression had opposite effects. Further experiments revealed that overexpression of SKA2 enhanced expression levels of phosphorylated glycogen synthase kinase-3β (GSK-3β) and active β-catenin in HCC cells. Moreover, SKA3 overexpression enhanced transcriptional activity mediated by Wnt/β-catenin signaling. Knockdown of SKA3 downregulated the activation of Wnt/β-catenin signaling, and the effect was significantly reversed by the inhibition of GSK-3β. Notably, inhibition of Wnt/β-catenin signaling markedly abrogated SKA2-mediated promotion effect on HCC proliferation and invasion. In addition, knockdown of SKA2 impeded tumor formation and growth in HCC cells in a nude mouse in vivo model. Overall, these findings indicate that SKA2 accelerates the progression of HCC through the upregulation of Wnt/β-catenin signaling. Our study highlights a potential role of SKA2 in HCC progression and suggests it as a possible target for HCC treatment. Image 1 • SKA2 is highly expressed in HCC. • SKA2 knockdown inhibits proliferation and invasion in HCC cells. • SKA2 promotes Wnt/β-catenin via modulation of GSK-3β. • SKA2 exerts the function in HCC cells by Wnt/β-catenin signaling. [ABSTRACT FROM AUTHOR]

Background and Study Aims: Adherent invasive Escherichia coli (AIEC) are enriched in IBD (inflammatory bowel disease) patients, but the role and mechanism of AIEC in the intestinal epithelial barrier is poorly defined. We evaluated the role of the AIEC strain E. coli LF82 in vitro and investigated the role of Th17 in this process., Material and Methods: After coincubation with AIEC, the epithelial barrier integrity was monitored by epithelial resistance measurements. The permeability of the barrier was evaluated by TEER (trans-epithelial electrical resistance) and mucosal-to-serosal flux rate. The presence of interepithelial tight junction proteins ZO-1 and Claudin-1 were determined by immunofluorescence and western blot analysis. Cytokines in the cell culture supernatant were assayed by enzyme-linked immunosorbent assay (ELISA)., Results: AIEC infection decreased TEER and increased the mucosal-to-serosal flux rate of Lucifer yellow in the intestinal barrier model in a time- and dose-dependent manner. AIEC infection decreased the expression and changed the distribution of ZO-1 and claudin-1. It also induced the secretion of cytokines such as TNF-α and IL-17., Conclusion: AIEC strain E. coli LF82 increased the permeability and disrupted the tight junctions of the intestinal epithelial barrier, revealing that AIEC plays an aggravative role in the inflammatory response., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.)

Pancreatic cancer (PC) is a highly aggressive malignancy with a poor prognosis, making early diagnosis crucial for improving patient outcomes. While the gut microbiome, including bacteria and viruses, is believed to be essential in cancer pathogenicity, the potential contribution of the gut virome to PC remains largely unexplored. In this study, we conducted a comparative analysis of the gut viral compositional and functional profiles between PC patients and healthy controls, based on fecal metagenomes from two publicly available data sets comprising a total of 101 patients and 82 healthy controls. Our results revealed a decreasing trend in the gut virome diversity of PC patients with disease severity. We identified significant alterations in the overall viral structure of PC patients, with a meta-analysis revealing 219 viral operational taxonomic units (vOTUs) showing significant differences in relative abundance between patients and healthy controls. Among these, 65 vOTUs were enriched in PC patients, and 154 were reduced. Host prediction revealed that PC-enriched vOTUs preferentially infected bacterial members of Veillonellaceae, Enterobacteriaceae, Fusobacteriaceae, and Streptococcaceae, while PC-reduced vOTUs were more likely to infect Ruminococcaceae, Lachnospiraceae, Clostridiaceae, Oscillospiraceae, and Peptostreptococcaceae. Furthermore, we constructed random forest models based on the PC-associated vOTUs, achieving an optimal average area under the curve (AUC) of up to 0.879 for distinguishing patients from controls. Through additional 10 public cohorts, we demonstrated the reproducibility and high specificity of these viral signatures. Our study suggests that the gut virome may play a role in PC development and could serve as a promising target for PC diagnosis and therapeutic intervention. Future studies should further explore the underlying mechanisms of gut virus-bacteria interactions and validate the diagnostic models in larger and more diverse populations., (© 2024 Wiley Periodicals LLC.)

Objective: The incidence of UC has increased yearly. Many studies have suggested that patients with ulcerative colitis have abnormal vitamin D levels. A systematic review and meta-analysis were conducted to investigate the association between vitamin D levels and ulcerative colitis., Methods: We searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang and China Science and Technology Journal Database (VIP) from inception to December 2022. We included case-control studies comparing the differences in vitamin D levels between patients with ulcerative colitis and healthy populations. Meta-analysis was performed using Review Manager5.4, Stata17.0 and other software., Results: Sixteen eligible observational studies were selected from 473 articles involving 2234 subjects, and they included 987 patients with ulcerative colitis and 1247 controls. The results showed that the serum level of vitamin D in patients with ulcerative colitis was significantly lower than that in healthy controls (SMD = -0.83, 95% CI: -1.18, -0.48). Vitamin D deficiency was reported in five studies. The prevalence of vitamin D deficiency was significantly higher in the ulcerative colitis group than in the healthy control group (OR = 1.90, 95% CI: 1.38, 2.62)., Conclusion: Serum vitamin D levels were significantly lower in patients with ulcerative colitis than in healthy controls., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Competing interests: None declared.

Background: Crohn's disease (CD) is a clinically chronic inflammatory bowel disease, which has been shown to be closely related to the brain-gut axis dysfunction. Although traditionally considered to be a limbic region, the insula has also been commonly identified as an abnormal brain region in previous CD-related studies., Methods: Structural magnetic resonance imaging (MRI) and resting-state functional MRI images were acquired from 45 CD patients in remission and 40 healthy controls (HCs). Three neuroimaging analysis methods including voxel-based morphometry (VBM), structural covariance, and functional connectivity (FC) were applied to investigate structural and functional alterations of the insulae between the CD patients and HCs. Pearson correlation was then used to examine the relationships between neuroimaging findings and clinical symptoms., Results: Compared with the HCs, CD patients exhibited decreased gray matter volume (GMV) in the left dorsal anterior insula (dAI) and bilateral posterior insula (PI). Taking these three areas including the left dAI, right PI, and left PI as regions of interest (ROIs), differences were observed in the structural covariance and FC of the ROI with several regions between the two groups. After controlling for psychological factors, the differences of several regions involved in emotional processing in GMV in the left dAI, the FC of the dAI, and the right PI were not significant. The FC of the parahippocampus/hippocampus with dAI and PI were negatively correlated with the CD activity index (CDAI)., Conclusions: We suggest that the insula-centered structural and/or functional changes may be associated with abnormal visceral sensory processing and related emotional responses in CD patients., Competing Interests: Conflicts of Interest: All authors have completed the International Committee of Medical Journal Editors (ICMJE) uniform disclosure form (available at https://dx.doi.org/10.21037/qims-21-509). The authors have no conflicts of interest to declare., (2022 Quantitative Imaging in Medicine and Surgery. All rights reserved.)