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Cellular energy metabolism dysregulation is associated with colorectal cancer (CRC) development and progression. Discoidin domain receptor 1a (DDR1a), one of the five DDR1 isoforms, is closely related to cell proliferation, invasion, and apoptosis in various tumors. Whether it participates in cellular metabolic reprogramming and regulates CRC initiation and progression remains unclear. In this study, we compared the expression of DDR1 in CRC tissues and adjacent tissues from 126 postoperative CRC samples. Moreover, lentivirus-mediated DDR1a overexpression and knockdown were performed in LoVo cells, and cell viability and proliferation were determined by CCK-8 and BrdU assays, respectively. Oxygen consumption rate, extracellular acidification rate, and lactate production were used to determine the effect of DDR1a on metabolic reprogramming. Clinically, CRC patients with high DDR1 expression had poor differentiation and were at an advanced TNM stage. DDR1a promoted LoVo cell proliferation, mitochondrial function, and extracellular acidification. Moreover, DDR1a knockdown inhibited intracellular lactic acid production in LoVo cells, while a pyruvate kinase inhibitor (diamide, 200 μM) significantly reversed this progression. Taken together, our results reveal that DDR1 plays a crucial role in maintaining intracellular environment homeostasis through metabolic reprogramming.

Objective To explore the function of discoidin domain receptor 1 (DDR1) in intestinal inflammation and fibrosis in mice with chronic colitis. Methods A 20 bp gRNA sequence targeting exon4 of DDR1 gene was designed and synthesized, and subsequently microinjected into the fertilized eggs of C57BL/6 mice after being mixed with Cas9 mRNA in order to generate DDR1 mutant mice. The F4-generation homozygous mice (DDR1-/-) as well as wild-type C57BL/6 mice (WT) were used to induce chronic colitis model by being given 2.5% dextran sodium sulfate (DSS) in drinking water. Disease activity index (DAI), body weight, colon length and histopathological changes were compared between the 2 groups. The contents of pro-inflammatory cytokines in peripheral blood were detected by ELISA. The severity of intestinal fibrosis and the expression of fibrosis related proteins were observed by Masson staining and Western blotting, respectively. Results PCR results identified that DDR1-/- mutant mice were successfully generated using CRISPR/Cas9 technology. As compared with the WT group, the DDR1-/- mice exhibited slower body weight loss, lower DAI scores and intestinal histopathology scores, and mild colon shortening (5.81±0.11 vs 5.19±0.05 cm, P < 0.05) after DSS drinking. The serum levels of IL-1β, TNF-α and TGF-β were decreased (P < 0.01), with down-regulated expression of TGF-β, α-SMA and COL1A1 proteins in the colon tissues of DDR1-/- mice. Masson staining displayed that collagen volume fraction was higher in the WT group than the DDR1-/- mice (41.43±0.08 vs 21.37±0.07 cm, P < 0.01). Conclusion DDR1 is probably involved in the development of chronic colitis, and DDR1 deletion may mitigate the symptoms and disease progression of chronic intestinal inflammation and fibrosis.

Cases and studies of protruding early gastric cancer (EGC) combined with spontaneous bleeding are relatively rare. The current study present a female patient aged 70 to 75 years old with hemorrhagic shock caused by spontaneous bleeding from EGC type 0-Isp, which was successfully cured by rapid emergency endoscopic submucosal dissection (ESD). [ABSTRACT FROM AUTHOR]

Background and purpose: Growing evidence suggests that abnormalities in brain–gut–microbiome (BGM) interactions are involved in the pathogenesis of irritable bowel syndrome (IBS). Our study aimed to explore alterations in dynamic functional connectivity (DFC), the gut microbiome and the bidirectional interaction in the BGM. Methods: Resting‐state functional magnetic resonance imaging (rs‐fMRI), fecal samples and clinical chacteristics were collected from 33 IBS patients and 32 healthy controls. We performed a systematic DFC analysis on rs‐fMRI. The gut microbiome was analyzed by 16S rRNA gene sequencing. Associations between DFC characteristics and microbial alterations were explored. Results: In the DFC analysis, four dynamic functional states were identified. IBS patients exhibited increased mean dwell and fraction time in State 4, and reduced transitions from State 3 to State 1. Aberrant temporal properties in State 4 were only evident when choosing a short window (36 s or 44 s). Decreased functional connectivity (FC) variability was found in State 1 and State 3 in IBS patients, two of which (independent component [IC]51‐IC91, IC46‐IC11) showed significant correlations with clinical characteristics. Additionally, we identified nine significantly differential abundances in microbial composition. We also found that IBS‐related microbiota were associated with aberrant FC variability, although these exploratory results were obtained at an uncorrected threshold of significance. Conclusions: Although future studies are needed to confirm our results, the findings not only provide a new insight into the dysconnectivity hypothesis in IBS from a dynamic perspective, but also establish a possible link between DFC and the gut microbiome, which lays the foundation for future research on disrupted BGM interactions. [ABSTRACT FROM AUTHOR]

Background: Glycosylation involved in various biological function, aberrant glycosylation plays an important role in cancer development and progression. Glycosyltransferase 8 domain containing 1 (GLT8D1) and GLT8D2, as members of the glycosyltransferase family proteins, are associated with transferase activity. However, the association between GLT8D1/2 and gastric cancer (GC) remains unclear. We aimed to investigate the potential prognostic value and oncogenic role of GLT8D1/2 in GC. Methods: The relationship between GLT8D1/2 and GC was evaluated through comprehensive bioinformatics approaches. A series of factors like gene expression patterns, Kaplan-Meier survival analyses, Cox regression analyses, prognostic nomogram, calibration curves, ROC curves, function enrichment analyses, tumor immunity association, genetic alterations, and DNA methylation were included. Data and statistical analyses were performed using R software (v3.6.3). Results: Both GLT8D1 and GLT8D2 expression were significantly upregulated in GC tissues(n = 414) compared with normal tissues(n = 210), and high expression of GLT8D1/2 was remarkably correlated with poor prognosis for GC patients. Cox regression analyses implied that GLT8D1/2 could act as independent prognostic factors in GC. Furthermore, gene function analyses indicated that multiple signaling pathways involving tumor oncogenesis and development enriched, such as mTOR, cell cycle, MAPK, Notch, Hedgehog, FGF, and PI3K-Akt signaling pathways. Moreover, GLT8D1/2 was significantly associated with immune cell infiltration, immune checkpoint genes, and immune regulators TMB/MSI. Conclusion: GLT8D1/2 may serve as potential prognostic markers of poor prognosis in GC correlated with tumor immunity. The study provided an insight into identifying potential biomarkers and targets for prognosis, immunotherapy response, and therapy in GC. [ABSTRACT FROM AUTHOR]