METTL3 modulates colonic epithelium integrity via maintaining the self-renewal and differentiation of Lgr5+ stem cell.

The development and homeostasis of intestinal epithelium are mediated by actively proliferating Lgr5+ stem cells, which possess a remarkable self-renewal and differentiation capacity. Recently, our study demonstrated that m6A methylation was essential for the survival of colonic stem cells. Here, we show that METTL3 expression is downregulated in the colon mucosa in ulcerative colitis (UC) patients and strongly associated with the differentiation and maturation of goblet cells during inflammation.

A phosphoglycerate mutase 1 allosteric inhibitor restrains TAM-mediated colon cancer progression.

Colorectal cancer (CRC) is a prevalent malignant tumor often leading to liver metastasis and mortality. Despite some success with PD-1/PD-L1 immunotherapy, the response rate for colon cancer patients remains relatively low. This is closely related to the immunosuppressive tumor microenvironment mediated by tumor-associated macrophages (TAMs).

Alternative mRNA polyadenylation regulates macrophage hyperactivation via the autophagy pathway.

Macrophage hyperactivation is a hallmark of inflammatory diseases, yet the role of alternative polyadenylation (APA) of mRNAs in regulating innate immunity remains unclear. In this study, we focused on 3'UTR-APA and demonstrated that Nudt21, a crucial RNA-binding component of the 3'UTR-APA machinery, is significantly upregulated in various inflammatory conditions. By utilizing myeloid-specific Nudt21-deficient mice, we revealed a protective effect of Nudt21 depletion against colitis and severe hyperinflammation, primarily through diminished production of proinflammatory cytokines.

A Natural Peptide from A Traditional Chinese Medicine Has the Potential to Treat Chronic Atrophic Gastritis by Activating Gastric Stem Cells.

Chronic atrophic gastritis (AG) is initiated mainly by Helicobacter pylori infection, which may progress to stomach cancer following the Correa's cascade. The current treatment regimen is H. pylori eradication, yet evidence is lacking that this treatment is effective on later stages of AG especially gastric gland atrophy.

Novel mRNA Signature for Anti-TNF-α Therapy Primary Response in Patients With Ulcerative Colitis.

Background: Ulcerative colitis (UC), an idiopathic, chronic inflammatory disorder of the colonic mucosa, is commonly treated with antitumor necrosis factor α (anti-TNF-α) agents. However, only approximately two-thirds have an initial response to these therapies.

Methods: We integrated gene expression profiling from 3 independent data sets of 79 UC patients before they began anti-TNF-α therapy and calculated the differentially expressed genes between patient response and nonresponse to anti-TNF-α therapy and developed a de novo response-associated transcription signature score (logOR_Score) to demonstrate the predictive capability of anti-TNF-α therapy for therapeutic efficacy.

Analysis and purification of innate lymphoid cells in human intestine and blood by flow cytometry.

The role of innate lymphoid cells (ILCs)-including natural killer cells, helper-like ILC1s, ILC2s, ILC3s, and lymphoid tissue inducers-in human cancer is still poorly understood due to the scarcity of cell number. To address this, we present a protocol to analyze or purify ILCs from human blood, adjacent intestine, and colorectal tumor tissue. We describe steps for tissue and blood treatment, density centrifugation, antibody staining, and cell sorting.

Preoperative Prognostic Nutritional Index and Nomogram for Predicting the Risk of Postoperative Complications in Patients With Crohn's Disease.

Introduction: Patients with Crohn's disease (CD) are at a high risk of having postoperative complications. Preoperative prognostic nutritional index (PNI) has been extensively studied for postoperative complications in malignancies but seldom for CD.

Methods: Patients who underwent CD-related bowel surgery for the first time in our hospital were retrospectively enrolled from January 2013 to October 2019.

Berberine increases stromal production of Wnt molecules and activates Lgr5 stem cells to promote epithelial restitution in experimental colitis.

Background: Inflammatory bowel diseases (IBDs) are characterized by sustained inflammation and/or ulcers along the lower digestive tract, and have complications such as colorectal cancer and inflammation in other organs. The current treatments for IBDs, which affect 0.3% of the global population, mainly target immune cells and inflammatory cytokines with a success rate of less than 40%.

Eupatilin attenuates the senescence of nucleus pulposus cells and mitigates intervertebral disc degeneration inhibition of the MAPK/NF-κB signaling pathway.

Intervertebral disc degeneration (IDD) is the main cause of low back pain. An increasing number of studies have suggested that inflammatory response or the senescence of nucleus pulposus (NP) cells is strongly associated with the progress of IDD. Eupatilin, the main flavonoid extracted from , was reported to be associated with the inhibition of the intracellular inflammatory response and the senescence of cells.

Scutellarin ameliorates osteoarthritis by protecting chondrocytes and subchondral bone microstructure by inactivating NF-κB/MAPK signal transduction.

Osteoarthritis (OA), a chronic degenerative disease, is a major cause of pain, disability, and reduced quality of life among the elderly worldwide. The key to treating it is early prevention and effective intervention. The anti-inflammatory effects of scutellarin (SCU), a flavonoid derived from Erigeron breviscapus, have been increasingly reported.

Oral zero-valent-molybdenum nanodots for inflammatory bowel disease therapy.

Inflammatory bowel disease (IBD) affects millions of people each year. The overproduction of reactive oxygen species (ROS) plays a critical role in the progress of IBD and will be a potential therapeutic target. Here, we synthesize a kind of oral zero-valent-molybdenum nanodots (ZVMNs) for the treatment of IBD by scavenging ROS.

Vps33B controls Treg cell suppressive function through inhibiting lysosomal nutrient sensing complex-mediated mTORC1 activation.

The suppressive function of regulatory T (Treg) cells is tightly controlled by nutrient-fueled mechanistic target of rapamycin complex 1 (mTORC1) activation, yet its dynamics and negative regulation remain unclear. Here we show that Treg-specific depletion of vacuolar protein sorting 33B (Vps33B) in mice results in defective Treg cell suppressive function and acquisition of effector phenotype, which in turn leads to disturbed T cell homeostasis and boosted antitumor immunity. Mechanistically, Vps33B binds with lysosomal nutrient-sensing complex (LYNUS) and promotes late endosome and lysosome fusion and clearance of the LYNUS-containing late endosome/lysosome, and therefore suppresses mTORC1 activation.

Patients with Primary and Secondary Bile Duct Stones Harbor Distinct Biliary Microbial Composition and Metabolic Potential.

Introduction: Cholelithiasis has a high incidence worldwide and limited treatment options due to its poorly understood pathogenesis. Furthermore, the role of biliary microbiota in cholelithiasis remains understudied. To address these questions, we performed microbial sequencing from biliary samples from primary bile duct stone (PBDS) and secondary bile duct stone (SBDS) patients.

Balancing Microthrombosis and Inflammation via Injectable Protein Hydrogel for Inflammatory Bowel Disease.

Emerging evidence indicates that a vicious cycle between inflammation and microthrombosis catalyzes the pathogenesis of inflammatory bowel disease (IBD). Over-stimulated inflammation triggers a coagulation cascade and leads to microthrombosis, which further complicates the injury through tissue hypoxia and ischemia. Herein, an injectable protein hydrogel with anti-thrombosis and anti-inflammation competency is developed to impede this cycle, cross-linked by silver ion mediated metal-ligand coordination and electronic interaction with sulfhydryl functionalized bovine serum albumin and heparin, respectively.

Single-cell and spatial analysis reveal interaction of FAP fibroblasts and SPP1 macrophages in colorectal cancer.

Colorectal cancer (CRC) is among the most common malignancies with limited treatments other than surgery. The tumor microenvironment (TME) profiling enables the discovery of potential therapeutic targets. Here, we profile 54,103 cells from tumor and adjacent tissues to characterize cellular composition and elucidate the potential origin and regulation of tumor-enriched cell types in CRC.

Ubiquitin-specific protease 47 regulates intestinal inflammation through deubiquitination of TRAF6 in epithelial cells.

Deubiquitinates (DUBs) alter the stabilities, localizations or activities of substrates by removing their ubiquitin conjugates, which are closely related to the development of inflammatory response. Here, we show that ubiquitin-specific protease 47 (USP47) prevents inflammation development in inflammatory bowel disease (IBD). Compared with wild-type mice, Usp47 knockout mice are more susceptible to dextran sodium sulfate (DSS)-induced acute and chronic colitis with higher inflammatory cytokines expression and severe intestinal tissue damage.

SENP7 senses oxidative stress to sustain metabolic fitness and antitumor functions of CD8+ T cells.

The functional integrity of CD8+ T cells is tightly coupled to metabolic reprogramming, but how oxidative stress directs CD8+ T cell metabolic fitness in the tumor microenvironment (TME) remains elusive. Here, we report that SUMO-specific protease 7 (SENP7) senses oxidative stress to maintain the CD8+ T cell metabolic state and antitumor functions. SENP7-deficient CD8+ T cells exhibited decreased glycolysis and oxidative phosphorylation, resulting in attenuated proliferation in vitro and dampened antitumor functions in vivo.

Second-line sunitinib for Chinese patients with advanced gastrointestinal stromal tumor: 37.5 mg schedule outperformed 50 mg schedule in adherence and prognosis.

Background: Sunitinib is widely accepted as a second-line treatment for advanced gastrointestinal stromal tumor (GIST). This study aimed to evaluate patients' adherence to sunitinib treatment and optimize the dosing schedule for Chinese patients.

Methods: The present study analyzed medical data of patients with advanced GIST treated in Shanghai Ruijin Hospital and Shaoxin Shangyu People's Hospital.

Prevalence of Sarcopenia and Its Effect on Postoperative Complications in Patients with Crohn's Disease.

Background And Aims: Sarcopenia is a prognostic factor of outcomes for various diseases, but reports on sarcopenia in patients with Crohn's disease (CD) are few. We aim to determine the prevalence of sarcopenia and assess the role of sarcopenia in postoperative complications in patients with CD at a tertiary referral center.

Methods: Patients who underwent intestinal surgery for CD from January 2013 to October 2019 were retrospectively enrolled.

CD177 modulates the function and homeostasis of tumor-infiltrating regulatory T cells.

Regulatory T (Treg) cells are one of the major immunosuppressive cell types in cancer and a potential target for immunotherapy, but targeting tumor-infiltrating (TI) Treg cells has been challenging. Here, using single-cell RNA sequencing of immune cells from renal clear cell carcinoma (ccRCC) patients, we identify two distinct transcriptional fates for TI Treg cells, Fate-1 and Fate-2. The Fate-1 signature is associated with a poorer prognosis in ccRCC and several other solid cancers.

Single-cell transcriptomic landscape reveals tumor specific innate lymphoid cells associated with colorectal cancer progression.

Innate lymphoid cells (ILCs) are tissue-resident lymphocytes differing from conventional T lymphocytes in having no antigen-specific receptors. ILCs include natural killer (NK) cells, helper-like ILC1s, ILC2s, and ILC3s, and lymphoid tissue-inducer (LTi) cells. Tumor ILCs are frequently found in various cancers, but their roles in cancer immunity and immunotherapy remain largely unclear.

ZFP91 disturbs metabolic fitness and antitumor activity of tumor-infiltrating T cells.

Proper metabolic activities facilitate T cell expansion and antitumor function; however, the mechanisms underlying disruption of the T cell metabolic program and function in the tumor microenvironment (TME) remain elusive. Here, we show a zinc finger protein 91-governed (ZFP91-governed) mechanism that disrupts the metabolic pathway and antitumor activity of tumor-infiltrating T cells. Single-cell RNA-Seq revealed that impairments in T cell proliferation and activation correlated with ZFP91 in tissue samples from patients with colorectal cancer.