Moderate UV Exposure Enhances Learning and Memory by Promoting a Novel Glutamate Biosynthetic Pathway in the Brain.

Sunlight exposure is known to affect mood, learning, and cognition. However, the molecular and cellular mechanisms remain elusive. Here, we show that moderate UV exposure elevated blood urocanic acid (UCA), which then crossed the blood-brain barrier. Single-cell mass spectrometry and isotopic labeling revealed a novel intra-neuronal metabolic pathway converting UCA to glutamate (GLU) after UV exposure. This UV-triggered GLU synthesis promoted its packaging into synaptic vesicles and its release at glutamatergic terminals in the motor cortex and hippocampus. Related behaviors, like rotarod learning and object recognition memory, were enhanced after UV exposure. All UV-induced metabolic, electrophysiological, and behavioral effects could be reproduced by the intravenous injection of UCA and diminished by the application of inhibitor or short hairpin RNA (shRNA) against urocanase, an enzyme critical for the conversion of UCA to GLU. These findings reveal a new GLU biosynthetic pathway, which could contribute to some of the sunlight-induced neurobehavioral changes.

Hemodialysis and risk of acute pancreatitis: A systematic review and meta-analysis.

BACKGROUND: Epidemiological evidence indicates that hemodialysis may be a risk factor for acute pancreatitis. This meta-analysis was conducted with the aim of summarizing all available data and examining the present evidence. AIM: To quantify the association between hemodialysis and the incidence of acute pancreatitis. METHODS: This meta-analysis included studies on the incidence of acute pancreatitis in patients with hemodialysis. We summarized the incidence of acute pancreatitis in hemodialysis patients, and compared the incidence of acute pancreatitis in hemodialysis patients with that in non-hemodialysis individuals. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. RESULTS: A total of 5 observational studies with 1059384 individuals were identified for the meta-analysis. Meta-analysis of these observational studies showed that the pooled prevalence of acute pancreatitis in hemodialysis patients was 1.1% (95% CI: 0.2%-2.3%). In addition, we found that hemodialysis was associated with an increased risk of acute pancreatitis (relative risk = 6.96; 95% CI 3.71-13.06). CONCLUSION: This meta-analysis confirmed that hemodialysis is associated with an increased risk of acute pancreatitis. More fundamental research should be carried out to elucidate the biological mechanisms.

Prevalence of Helicobacter pylori babA, oipA, sabA, and homB genes in isolates from Chinese patients with different gastroduodenal diseases.

Disease outcome is associated with virulence factors of Helicobacter pylori (H. pylori), which are partially attributed to the outer membrane protein (OMP). This study aimed to investigate the correlation between the four OMP genes (babA, oipA, sabA, and homB) and gastroduodenal diseases. One hundred and seventy-seven H. pylori strains were isolated from Chinese patients with different gastroduodenal diseases (49 chronic gastritis, 19 gastric ulcer, 33 gastric cancer, and 76 duodenal ulcer), 94 of which contained pathological information (41 superficial gastritis, 24 intestinal hyperplasia, and 29 gastric adenocarcinoma). The full-length amplification of babA, oipA, sabA, and homB genes was acquired and sequenced. Then, the genetic polymorphism was analyzed to compare with the reference strains from the GenBank database. Functional status and cluster analysis were also performed to evaluate the impact of genetic polymorphism on disease outcome. The prevalence of babA, oipA, sabA, and homB genes were 91.5%, 100%, 94.0%, and 95.5%, respectively. The four OMP genes were characterized by genetic polymorphism and in the status of positive selection (Ka/Ks> 1). The proportion of strains with functional status on for oipA and sabA gene was 100% and 76.2%, respectively. The sequences of four OMP genes were mainly clustered together with the East Asian references. The four OMP genes were not different in patients with gastroduodenal diseases and pathologic changes (P > 0.05). H. pylori babA, oipA, sabA, and homB genes were common in the Chinese populations, but did not seem to be involved in the development of gastroduodenal diseases.

Outer inflammatory protein of Helicobacter pylori impacts IL-8 expression, adherence, cell apoptosis and cell cycle of gastric cells independent of its copy number.

Outer inflammatory protein (OipA) is an important virulence factor of Helicobacter pylori (H. pylori), but the correlation between oipA copy number and its virulence remains unknown. The study was designed to investigate whether the duplicate oipA gene loci showed more virulent than one oipA gene in vitro. H. pylori strain CCS9803 (China Chongqing Strain 9803) that carries duplicate oipA loci was used to construct one or two oipA knockout mutant strain, which was further verified by qPCR and western blot. Gastric epithelial cells AGS and GES-1 were infected with wild-type (WT) or oipA mutants for 6 or 24 h. The expression levels of IL-8, bacterial adhesion, cell apoptosis and cell cycle were performed to analyze the function of oipA. The WT and oipA mutant strains induce significantly higher mRNA and protein levels of IL-8 than the uninfected group (P < 0.05), but only oipA2 mutants induced significantly decreased expression levels than the WT-infected group (P < 0.05). Adherence to gastric cells was significantly decreased by inactivated two oipA loci (P < 0.05). The WT strain caused a significant rising proportion of early apoptosis cell, which had dropped after duplicate oipA genes were both knockout (P < 0.05). WT and oipA1 mutants failed to affect cell cycle; however, the oipA2 mutants increased M phase and reduced S phase when compared to the uninfected group. In conclusion, our study demonstrated that oipA impacts IL-8 expression, adherence, cell apoptosis and cell cycle of gastric cells independent of its gene copy number.

Sequential versus concomitant therapy for treatment of Helicobacter pylori infection: an updated systematic review and meta-analysis.

BACKGROUND: Sequential and concomitant therapies are two innovative therapies for Helicobacter pylori (H. pylori) eradication. However, the comparative efficacy and safety of these treatments are controversial. Therefore, we aimed to conduct an updated systematic review and meta-analysis of studies that compared these two treatments. METHODS: A search of PubMed, Embase, the Cochrane Library, and Web of Science was carried out. Randomized controlled trials (RCTs) that compared sequential with concomitant therapies were selected for meta-analysis. RESULTS: Twenty RCTs were included in the analysis. The eradication rate of 10-day sequential therapy was superior to that of 5-day concomitant therapy (82.09 versus 77.79%, relative risk (RR) 1.052 (95% confidence interval (CI) 1.004-1.103), P = 0.035)), similar to that of 7-day concomitant therapy (82.40 versus 86.99%, RR 0.959 (95% CI 0.874-1.053), P = 0.382), and inferior to that of 10-day concomitant therapy (78.39 versus 83.32%, RR 0.945 (95% CI 0.907-0.984, P = 0.006); the occurrence of diarrhea was higher in 10-day concomitant therapy than that in 10-day sequential therapy. Compared with the eradication rate of sequential therapy, that of concomitant therapy was higher in metronidazole-resistant strains (RR 0.912 (95% CI 0.844-0.986, P = 0.020)) and strains resistant to metronidazole and clarithromycin (RR 0.542 (95% CI 0.308-0.956, P = 0.035)). CONCLUSION: The efficacy of concomitant therapy was duration dependent, and 10-day concomitant therapy was superior to 10-day sequential therapy. Compared to sequential therapy, concomitant therapy was more efficacious for metronidazole-resistant strains and metronidazole plus clarithromycin-resistant strains. However, diarrhea was more frequent with concomitant therapy than with sequential therapy.

Diagnostic Performance of Contrast-Enhanced Ultrasound in Testicular Space-Occupying Lesions: A Systematic Review and Meta-analysis.

PURPOSE: Contrast-enhanced ultrasound (CEUS) has been increasingly used for the diagnostic identification of neoplasms due to its ability to visualize the microvascularization of lesions. In the study of testicular abnormalities, the appropriate use of CEUS can improve the diagnostic accuracy of conventional gray-scale ultrasound and color Doppler ultrasound (CDUS). The purpose of this study is to comprehensively evaluate the diagnostic performance of CEUS in testicular space-occupying lesions. METHODS: A comprehensive search of PubMed, Embase, Cochrane Library, and Web of Science databases was conducted from the inception of each database to November 16, 2022 for relevant studies. The required data were extracted, and the methodological quality of the studies was assessed using the QUADAS-2 tool. The diagnostic value of CEUS was assessed by calculating the combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio, and a summary receiver operating characteristic (SROC) curve was used to conduct this meta-analysis. RESULTS: A total of six studies with 354 testicular space-occupying lesions were included in the analysis. The results showed that CEUS could provide additional useful information for the diagnosis of testicular space-occupying lesions, with a sensitivity of 0.92 (95% CI:0.82, 0.97), specificity of 0.91 (95% CI:0.80, 0.96), diagnostic odds ratio of 114 (95% CI:25, 528), respectively, and an overall diagnostic accuracy expressed as area under the SROC curve (AUC) of 0.97 (95% CI:0.95-0.98). Significant heterogeneity was seen in the sensitivity with I2 = 82.53% (95% CI:69.44-95.61). Subgroup analysis revealed that the proportion of infertile patients selected may be the source of heterogeneity. CONCLUSION: CEUS can be used to diagnose testicular space-occupying lesions more accurately and improve diagnostic accuracy when the conventional US cannot accurately differentiate the type of lesion. In particular, CEUS should be recommended for the identification of microscopic lesions so that physicians can provide patients with more appropriate interventions to avoid unnecessary orchiectomy.

Effect of exogenous galectin-9, a natural TIM-3 ligand, on the severity of TNBS- and DSS-induced colitis in mice.

Inflammatory bowel disease (IBD) have a complex pathogenesis that is yet to be completely understood. However, a strong correlation between Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling and IBD has been observed. T-cell immunoglobulin and mucin domain-containing-3 (Tim-3) has been reported to regulate TLR4/NF-κB by interacting with Galectin-9 (Gal-9), and recombinant Gal-9 can activate Tim-3; however, its potential properties in IBD and the underlying mechanism remain unclear. This study aimed to determine how Gal-9 affects experimental colitis in mice. Dextran sodium sulfate (DSS) and 2,4,6-trinitrobenzene sulfonic acid (TNBS) were used to establish colitis in mice, and the severity of the illness was assessed based on body weight, colon length, and histology. Therefore, we explored the effects of Gal-9 treatment on colitis. Furthermore, we analyzed the effect of Gal-9 on the expression of Tim-3 and TLR4/NF-κB pathway in colonic tissues and the serum levels of interferon-gamma (IFN-γ), interleukin (IL)-1ß, and IL-6. Tim-3 expression in the colon was notably decreased in mice with TNBS-induced colitis, whereas TLR4/NF-kB expression was significantly increased. Intraperitoneal injection of Gal-9 dramatically decreased the disease activity index and attenuated the level of intestinal mucosal inflammation in TNBS-induced colitis mice (p < 0.05). Intraperitoneal administration of Gal-9 significantly increased Tim-3 expression in the colon and decreased the serum concentrations of IFN-γ, IL-1ß, and IL-6. Additionally, Gal-9 treatment significantly downregulated the expression of TLR4 signaling pathway-related proteins. In contrast, Gal-9 did not reduce the severity of DSS-induced colitis. In summary, exogenous Gal-9 increased Tim-3 expression, inhibited the TLR4/NF-κB pathway, and alleviated TNBS-induced colitis in mice but not DSS-induced colitis in mice, revealing its potential therapeutic ramifications for IBD.

Identification and Validation of Immune Cells and Hub Genes in Gastric Cancer Microenvironment.

Gastric cancer (GC) is the most common malignant tumor in the digestive system, traditional radiotherapy and chemotherapy are not effective for some patients. The research progress of immunotherapy seems to provide a new way for treatment. However, it is still urgent to predict immunotherapy biomarkers and determine novel therapeutic targets. In this study, the gene expression profiles and clinical data of 407 stomach adenocarcinoma (STAD) patients were downloaded from The Cancer Genome Atlas (TCGA) portal, and the abundance ratio of immune cells in each sample was obtained via the "Cell Type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT)" algorithm. Five immune cells were obtained as a result of abundance comparison, and 295 immune-related genes were obtained through differential gene analysis. Enrichment, protein interaction, and module analysis were performed on these genes. We identified five immune cells associated with infiltration and 20 hub genes, of which five genes were correlated with overall survival. Finally, we used Real-time PCR (RT-PCR) to detect the expression differences of the five hub genes in 18 pairs of GC and adjacent tissues. This research not only provides cellular and gene targets for immunotherapy of GC but also provides new ideas for researchers to explore immunotherapy for various tumors.

Increased IGFBP7 Expression Correlates with Poor Prognosis and Immune Infiltration in Gastric Cancer.

Background: Insulin-like growth factor binding protein-7 (IGFBP7) contributes to multiple biological processes in various tumors. However, the role of IGFBP7 in gastric cancer (GC) is still undetermined. The study aims to explore the role of IGFBP7 in GC via an integrated bioinformatics analysis. Methods: IGFBP7 expression levels in GC and its normal gastric tissues were analyzed using multiple databases, including the Tumor Immune Estimation Resource (TIMER), Oncomine, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, as well as by our clinical gastric specimens. The methylation analysis was conducted with MEXPRESS, UALCAN and Xena online tools. The survival analysis was conducted using the Kaplan-Meier Plotter and Gene Expression Profiling Interactive Analysis (GEPIA) databases. Coexpressed genes of IGFBP7 were selected with the cBioPortal tool and enrichment analysis was conducted with the clusterProfiler package in R software. Gene set enrichment analysis (GSEA) was performed to explore the IGFBP7-related biological processes involved in GC. Correlations between IGFBP7 and immune cell infiltrates were analyzed using the TIMER database. Results: IGFBP7 expression was significantly upregulated in GC and correlated with stage, grade, tumor status and Helicobacter pylori infection. High IGFBP7 expression and low IGFBP7 methylation levels were significantly associated with short survival of patients with GC. Univariate and multivariate analyses revealed that IGFBP7 was an independent risk factor for GC. The coexpressed genes LHFPL6, SEPTIN4, HSPB2, LAYN and GGT5 predicted unfavorable outcomes of GC. Enrichment analysis showed that the coexpressed genes were involved in extracellular matrix (ECM)-related processes. GSEA indicated that IGFBP7 was positively related to ECM and inflammation-related pathways. TIMER analysis indicated that the mRNA level of IGFBP7 was strongly correlated with genes related to various infiltrating immune cells in GC, especially with gene markers of tumor associated macrophages (TAMs). Conclusions: Increased IGFBP7 expression correlates with poor prognosis and immune cell infiltration in GC, which might be a potential biomarker for the diagnosis of GC.

Weighted correlation network analysis identifies FN1, COL1A1 and SERPINE1 associated with the progression and prognosis of gastric cancer.

BACKGROUND: Gastric cancer (GC) is one of the most deadliest tumours worldwide, and its prognosis remains poor. OBJECTIVE: This study aims to identify and validate hub genes associated with the progression and prognosis of GC by constructing a weighted correlation network. METHODS: The gene co-expression network was constructed by the WGCNA package based on GC samples and clinical data from the TCGA database. The module of interest that was highly related to clinical traits, including stage, grade and overall survival (OS), was identified. GO and KEGG pathway enrichment analyses were performed using the clusterprofiler package in R. Cytoscape software was used to identify the 10 hub genes. Differential expression and survival analyses were performed on GEPIA web resources and verified by four GEO datasets and our clinical gastric specimens. The receiver operating characteristic (ROC) curves of hub genes were plotted using the pROC package in R. The potential pathogenic mechanisms of hub genes were analysed using gene set enrichment analysis (GSEA) software. RESULTS: A total of ten modules were detected, and the magenta module was identified as highly related to OS, stage and grade. Enrichment analysis of magenta module indicated that ECM-receptor interaction, focal adhesion, PI3K-Akt pathway, proteoglycans in cancer were significantly enriched. The PPI network identified ten hub genes, namely COL1A1, COL1A2, FN1, POSTN, THBS2, COL11A1, SPP1, MMP13, COMP, and SERPINE1. Three hub genes (FN1, COL1A1 and SERPINE1) were finally identified to be associated with carcinogenicity and poor prognosis of GC, and all were independent risk factors for GC. The area under the curve (AUC) values of FN1, COL1A1 and SERPINE1 for the prediction of GC were 0.702, 0.917 and 0.812, respectively. GSEA showed that three hub genes share 15 common upregulated biological pathways, including hypoxia, epithelial mesenchymal transition, angiogenesis, and apoptosis. CONCLUSION: We identified FN1, COL1A1 and SERPINE1 as being associated with the progression and poor prognosis of GC.

BICC1 as a novel prognostic biomarker in gastric cancer correlating with immune infiltrates.

AIM: BicC family RNA-binding protein 1 (BICC1) codes an RNA-binding protein that regulates gene expression and modulates cell proliferation and apoptosis. We aim at investigating the role of BICC1 in gastric carcinogenesis. METHODS: BICC1 mRNA expression in gastric cancer (GC) was examined using the Tumor Immune Estimation Resource (TIMER), The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Correlations between BICC1 expression and clinicopathological parameters were analyzed. The Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan-Meier plotter databases were used to examine the clinical prognostic significance of BICC1 in GC. Signaling pathways related to BICC1 expression were identified by gene set enrichment analysis (GSEA). TIMER and CIBERSORT were used to analyze the correlations among BICC1, BICC1-coexpressed genes and tumor-infiltrating immune cells. RESULTS: BICC1 was highly expressed in GC and significantly correlated with grade (P = 0.002), TNM stage (P = 0.033), invasion depth (P = 0.001) and vital status (P = 0.009) of GC patients. High BICC1 expression correlated with poor overall survival. The GSEA results showed that cell adhesion-, tumor- and immune- related pathways were significantly enriched in samples with high BICC1 expression. BICC1 and its coexpressed genes were positively related to tumor-infiltrating immune cells and were strongly correlated with tumor-infiltrating macrophages (all r ≥ 0.582, P < 0.0001). The CIBERSORT database revealed that BICC1 correlated with M2 macrophages (P < 0.0001), regulatory T cells (P < 0.0001), resting mast cells (P < 0.0001), activated memory CD4+ T cells (P = 0.002), resting NK cells (P = 0.002), activated dendritic cells (P = 0.002), and follicular helper T cells (P = 0.016). The results from TIMER database confirmed that BICC1 is closely associated with the markers of M2 macrophages and tumor-associated macrophages (all r ≥ 0.5, P < 0.0001). CONCLUSION: BICC1 may be a potential prognostic biomarker in GC and correlates with immune infiltrates.

Genotype profiles of Helicobacter pylori from gastric biopsies and strains with antimicrobial-induced resistance.

BACKGROUND AND AIMS: The genotypic method could significantly shorten the time needed to obtain antibiotic susceptibility data for Helicobacter pylori. The aim of this study was to explore the profile of H. pylori from gastric biopsies and strains with antibiotic-induced resistance. METHODS: A total of 124 gastric biopsies were used to perform gene sequencing and to perform bacterial culture and susceptibility testing. Seven susceptible strains were selected to develop resistance to clarithromycin, levofloxacin, and metronidazole. Four susceptible strains were selected to transfer candidate mutations. The genotype profiles of these groups were analyzed by sequencing analysis. The antibiotic susceptibility of these strains was detected using the E-test method. RESULTS: Phenotypic resistance to clarithromycin, levofloxacin, and metronidazole was observed in 35.5%, 40.0%, and 79.8% strains, respectively. Point mutations in 23 S rRNA, gyrA, and rdxA genes were observed in 39.5%, 38.7%, and 86.3% of gastric biopsies, respectively. The A2143G mutation in the 23S rRNA occurs in most clarithromycin-resistant samples. The A2142C point mutation showed a higher efficacy than A2142G and A2143G for inducing clarithromycin resistance. The D91N and N87K mutations in gyrA occurs in most levofloxacin-resistant samples, and double point mutations showed a higher efficacy than single mutations for inducing levofloxacin resistance. Phenotypic resistance and mutations in rdxA lacked consistency. CONCLUSION: Genotype-based gastric biopsy analysis was reliable for determining clarithromycin and levofloxacin resistance. A2143G in 23S rRNA and N87K/D91N in the gyrA gene occurred in most resistant strains. Mutations in the rdxA gene were not good indicators of metronidazole resistance.

The prognostic value of gender in gastric gastrointestinal stromal tumors: a propensity score matching analysis.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) of the stomach are the most common GISTs. The risk, incidence, and outcome of cancer are different between the sexes. Whether gender is related to the prognosis of gastric stromal tumors is unclear. Therefore, this study aims to explore the relationship between gender and gastric GIST prognosis. METHODS: Data from gastric GIST patients were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was performed to reduce confounding factors, and the clinicopathological features and prognosis of GIST patients were comprehensively evaluated. RESULTS: There were 512 male patients and 538 female patients with gastric GIST. The gender of gastric GIST patients was associated with marital status, surgical treatment, tumor size, and mitotic index (P < 0.05). The Kaplan-Meier analysis and log-rank test revealed that male patients had a higher mortality rate than female patients (P = 0.0024). After matching all the potential confounding factors, the survival of the female gastric GIST patients was better than that of the male gastric GIST patients (P = 0.042). Cox regression analysis revealed that gender was an independent risk factor for overall survival. The risk of death was higher for males than for females (HR 1.677, 95% CI 1.150-2.444, P = 0.007). CONCLUSION: Gender could be a prognostic factor for gastric GIST survival, and male patients had a higher risk of death.

In-vitro characterisation of a novel antimicrobial agent, TNP-2092, against Helicobacter pylori clinical isolates.

BACKGROUND AND OBJECTIVES: TNP-2092 is a novel dual-action lead compound consisting of rifamycin SV and 4H-4-oxo-quinolizine pharmacophores, with a broad spectrum of antibacterial activities. This compound is currently in the early stage of clinical development for Helicobacter pylori infection. The aim of the present study was to determine the antibacterial activity of TNP-2092 against H. pylori isolated from primary patients. METHODS: A total of 100 H. pylori clinical isolates from primary patients were selected. The minimum inhibitory concentrations (MICs) for clarithromycin, levofloxacin, rifampin and TNP-2092 were determined using an agar dilution method. A time-kill study was performed with different concentrations of TNP-2092 relevant to MIC against H. pylori ATCC strain 43504 for up to 24 hours. The time-kill study with drug concentrations of 0-4 × MIC was also used to determine the antibacterial activity of TNP-2092 against H. pylori under different pH conditions (pH 4-7). RESULTS: The primary resistance percentages to clarithromycin, levofloxacin, rifampin and TNP-2092 were 13, 18, 1 and 1%, respectively. TNP-2092 killing kinetics were both concentration and time dependent. The effectiveness of TNP-2092 against H. pylori was gradually reduced with a decrease in pH. CONCLUSIONS: TNP-2092 is highly active against H. pylori and against strains resistant to clarithromycin or levofloxacin. Its antibacterial activity is both concentration- and time-dependent .The antibacterial activity of TNP-2092 appears to be pH-dependent and is more active under neutral pH. TNP-2092 represents a promising new therapy for the treatment of H. pylori infection in primary patients.

The sinomenine enteric-coated microspheres suppressed the TLR/NF-κB signaling in DSS-induced experimental colitis.

Sinomenine is a pure alkaloid with immunosuppressive effects that is extracted from the Chinese medicinal plant Sinomenium acutum. We studied the therapeutic effects of sinomenine on inflammatory bowel disease. In this study, we randomly divided mice into the following ten groups: Control group; DSS-induced colitis group; Salicylazosulfapyridine (SASP)-treated group; Chitosan-treated group; low-, medium-, and high-dose sinomenine-treated and sinomenine enteric-coated microspheres-treated groups. We recorded changes in colon length, disease activity index (DAI), and colon pathology, measured TLR4, MyD88, SIGIRR, NF-κB p65 protein levels and inflammatory serum cytokine levels. Except for the Control group, the weight of mice in each group decreased, the DAI of the DSS-induced colitis group was significantly higher than the other groups, and the DAIs of the sinomenine- and sinomenine enteric-coated microspheres-treated groups were significantly lower than that of the SASP-treated group. TLR4, MyD88, NF-κB p65 and proinflammatory cytokine expressions decreased dose dependently in the sinomenine and sinomenine enteric-coated microspheres-treated groups and were generally lower in the sinomenine enteric-coated microspheres groups. However, SIGIRR and anti-inflammatory IL-10 expressions exhibited the opposite pattern. Based on the superior therapeutic effect, sinomenine enteric-coated microspheres might regulate TLR/NF-κB signaling and would be beneficial for an effective and safe therapy of inflammatory bowel disease.