Berberine decreases S100B generation to regulate gut vascular barrier permeability in mice with burn injury.

Context: Berberine (BBR) can regulate enteric glial cells (EGCs) and the gut vascular barrier (GVB).Objective: To explore whether BBR regulates GVB permeability via the S100B pathway.Materials and methods: GVB hyperpermeability in C57BL/6J mice was induced by burns or S100B enema. BBR (25 or 50 mg/kg/d, 3 d) was gavaged preburn. S100B monoclonal antibody (S100BmAb) was i.v. injected postburn. Mouse intestinal microvascular endothelial cells (MIMECs) were treated with S100B, S100B plus BBR, or Z-IETD-FMK. GVB permeability was assayed by FITC-dextran, S100B by ELISA, caspase-8, ß-catenin, occludin and PV-1 by immunoblot.Results: Burns elevated S100B in serum and in colonic mucosa to a peak (147.00 ± 4.95 ng/mL and 160.30 ± 8.50 ng/mg, respectively) at 36 h postburn, but BBR decreased burns-induced S100B in serum (126.20 ± 6.30 or 90.60 ± 3.78 ng/mL) and in mucosa (125.80 ± 12.40 or 91.20 ± 8.54 ng/mg). Burns raised GVB permeability (serum FITC-dextran 111.40 ± 8.56 pg/mL) at 48 h postburn, but BBR reduced GVB permeability (serum FITC-dextran 89.20 ± 6.98 or 68.60 ± 5.50 ng/mL). S100B enema (1 µM) aggravated burns-raised GVB permeability (142.80 ± 8.07 pg/mL) and PV-1, but the effect of S100B was antagonized by BBR. Z-IETD-FMK (5 µM) increased S100B-induced permeability to FITC-dextran (205.80 ± 9.70 to 263.80 ± 11.04 AUs) while reducing ß-catenin in MIMECs. BBR (5 µM) reduced S100B-induced permeability (104.20 ± 9.65 AUs) and increased caspase-8, ß-catenin and occludin.Discussion and conclusion: BBR decreases burns-induced GVB hyperpermeability via modulating S100B/caspase-8/ß-catenin pathway and may involve EGCs.

Conv-TabNet: an efficient adaptive color correction network for smartphone-based urine component analysis.

The camera function of a smartphone can be used to quantitatively detect urine parameters anytime, anywhere. However, the color captured by different cameras in different environments is different. A method for color correction is proposed for a urine test strip image collected using a smartphone. In this method, the color correction model is based on the color information of the urine test strip, as well as the ambient light and camera parameters. Conv-TabNet, which can focus on each feature parameter, was designed to correct the color of the color blocks of the urine test strip. The color correction experiment was carried out in eight light sources on four mobile phones. The experimental results show that the mean absolute error of the new method is as low as 2.8±1.8, and the CIEDE2000 color difference is 1.5±1.5. The corrected color is almost consistent with the standard color by visual evaluation. This method can provide a technology for the quantitative detection of urine test strips anytime and anywhere.

Apoptosis-Related Gene-Mediated Cell Death Pattern Induces Immunosuppression and Immunotherapy Resistance in Gastric Cancer.

Background: Apoptosis is a type of cell death, which can produce abundant mediators to modify the tumor microenvironment. However, relationships between apoptosis, immunosuppression, and immunotherapy resistance of gastric cancer (GC) remain unclear. Methods: Gene expression data and matching clinical information were extracted from TCGA-STAD, GSE84437, GSE34942, GSE15459, GSE57303, ACRG/GSE62254, GSE29272, GSE26253, and IMvigor210 datasets. A consensus clustering analysis based on six apoptosis-related genes (ARGs) was performed to determine the molecular subtypes, and then an apoptosisScore was constructed based on differentially expressed and prognostic genes between molecular subtypes. Estimate R package was utilized to calculate the tumor microenvironment condition. Kaplan-Meier analysis and ROC curves were performed to further confirm the apoptosisScore efficacy. Results: Based on six ARGs, two molecular subgroups with significantly distinct survival and immune cell infiltration were identified. Then, an apoptosisScore was built to quantify the apoptosis index of each GC patient. Next, we investigated the correlations between the clinical characteristics and apoptosisScore using logistic regression. Multivariate Cox analysis shows that low apoptosisScore was an independent predictor of poor overall survival in TCGA and ACRG datasets, and was associated with the higher pathological stage. Meanwhile, low apoptosisScore was associated with higher immune cell, higher ESTIMATEScore, higher immuneScore, higher stromalScore, higher immune checkpoint, and lower tumorpurity, which was consistent with the "immunity tidal model theory". Importantly, low apoptosisScore was sensitive to immunotherapy. In addition, GSEA indicated that several gene ontology and Kyoto Encyclopedia of Genes and Genomes items associated with apoptosis, several immune-related pathways, and JAK-STAT signal pathway were considerably enriched in the low apoptosisScore phenotype pathway. Conclusion: Our findings propose that low apoptosisScore is a prognostic biomarker, correlated with immune infiltrates, and sensitivity to immunotherapy in GC.

Berberine reduces gut-vascular barrier permeability via modulation of ApoM/S1P pathway in a model of polymicrobial sepsis.

AIMS: The hyperpermeability of gut-vascular barrier (GVB) plays a role in gut-derived sepsis. The goal of this study was to evaluate if berberine might improve hepatic apolipoprotein M (ApoM) generation and raise plasma ApoM level to protect the compromised GVB. MATERIALS AND METHODS: The compromised GVB was induced by sepsis. Hepatic ApoM mRNA and phosphoenolpyruvate carboxykinase (PEPCK) mRNA and plasma ApoM level were assayed by qRT-PCR and ELISA, respectively. The permeability of intestinal capillary in vivo and of rat intestinal microvascular endothelial cells (RIMECs) in vitro was assayed by FITC-dextran. The blood glucose was detected by a glucometer. Plasma insulin, TNF-α and IL-1ß were assayed by ELISA. The plasmalemma vesicle-associated protein-1 (PV1), ß-catenin and occludin in RIMECs were assayed by Western blot. KEY FINDINGS: Sepsis decreased hepatic ApoM mRNA and plasma ApoM level, but raised hepatic PEPCK mRNA and plasma glucose, insulin, TNF-α, and IL-1ß levels. The increased vascular endothelial permeability was abrogated by recombinant rat ApoM in vivo or ApoM-bound S1P in vitro. ApoM-bound S1P decreased PV1 but increased occludin and ß-catenin expression in LPS-treated RIMECs. Berberine in a dose-dependent manner raised hepatic ApoM mRNA and plasma ApoM level, but decreased septic hyperglycemia, insulin resistance and plasma TNF-α and IL-1ß levels. Berberine reduced sepsis-induced PEPCK and TLR4 mRNA overexpression in the liver. SIGNIFICANCE: This study demonstrated berberine inhibited TLR4-mediated hyperglycemia, insulin resistance and proinflammatory molecule production, thereby increasing ApoM gene expression and plasma ApoM. Berberine protected the damaged GVB via modulation of ApoM/S1P pathway.