Ju Liu’s research while affiliated with China Academy of Traditional Chinese Medicine and other places

Background Reflux esophagitis (RE) is a disease in which inflammation of the esophageal mucosa owing to the reflux of gastric contents into the esophagus results in cytokine damage. Britannilactone 1-O-acetate (Brt) has anti-inflammatory effects, significantly inhibiting the activation of the NLRP3 inflammasome, leading to a decrease in inflammatory factors including IL-1 β, IL-6, and TNF-α. However, the mechanism underlying its protective effect against RE-induced esophageal injury remains unclear. In the present study, we investigated the protective mechanism of TRIM31 against NLRP3 ubiquitination-induced RE both in vivo and in vitro. Methods A model of RE was established in vivo in rats by the method of “4.2 mm pyloric clamp + 2/3 fundoplication”. In vitro, the mod was constructed by using HET-1A (esophageal epithelial cells) and exposing the cells to acid, bile salts, and acidic bile salts. The 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay was used to screen the concentration of administered drugs, and the viability of HET-1A cells in each group. HE staining was used to assess the degree of pathological damage in esophageal tissues. Toluidine blue staining was used to detect whether the protective function of the esophageal epithelial barrier was damaged and restored. The enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of IL-1 β, IL-6, and TNF-α factors in serum. Immunohistochemistry (IHC) was used to detect the expression level of NLRP3 in esophageal tissues. The molecular docking and Co-immunoprecipitation assay (Co-IP assay) were used to detect the TRIM31 interacts with NLRP3. Western blotting detected the Claudin-4, Claudin-5, The G-protein-coupled receptor calcium-sensitive receptor (CaSR), NLRP3, TRIM31, ASC, C-Caspase1, and Caspase1 protein expression levels. Results Brt could alleviate RE inflammatory responses by modulating serum levels of IL-1 β, IL-6, and TNF-α. It also activated the expression of NLRP3, ASC, Caspase 1, and C-Caspase-1 in HET-1A cells. Brt also attenuated TRIM31/NLRP3-induced pathological injury in rats with RE through a molecular mechanism consistent with the in vitro results. Conclusions Brt promotes the ubiquitination of NLRP3 through TRIM31 and attenuates esophageal epithelial damage induced by RE caused by acidic bile salt exposure. This study provides valuable insights into the mechanism of action of Brt in the treatment of RE and highlights its promising application in the prevention of NLRP3 inflammatory vesicle-associated inflammatory pathological injury. Graphical Abstract Supplementary Information The online version contains supplementary material available at 10.1186/s13020-024-00986-y.

The stomach is a crucial digestive organ in the human body, highly susceptible to inflammation or pathogen invasion, which can lead to various gastric diseases, including gastric cancer. Toll-like receptors (TLRs) are the first line of defense against pathogen invasion. TLR4, a member of the TLRs family, recognizes pathogen and danger-related molecular patterns to induce inflammatory responses. Helicobacter pylori (H. pylori) is a significant factor in gastric health, and TLR4 recognizes H. pylori -LPS to trigger an inflammatory response. Downstream TLR4 signaling generates proinflammatory cytokines that initiate inflammation in the gastric mucosa. In addition, TLR4 gene polymorphisms can increase health risks. This study aims to investigate the contribution of TLR4 to the inflammatory response in gastric diseases and the relation between TLR4 and H. pylori, TLR4 gene polymorphisms, and how TLR4 affects gastric diseases’ possible pathways to provide further insight for future prevention and clinical treatment strategies.

Background: Reflux esophagitis (RE) is a clinically common digestive disease, and the main pathological manifestation of RE is esophageal mucosa inflammatory damage. Xuanfu Daizhe (XFDZ) decoction is a traditional Chinese herbal compound that is famous for RE treatment, but the pharmacological and molecular mechanism of XFDZ remains largely unknown. Methods: The active ingredients of XFDZ were detected using the ultra-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS). The rat model of RE was established with pylorus clamp and 2/3 fundus of stomach ligated. XFDZ (8.55 g/kg) and Omeprazole + Mosapride (1.35 g/kg) were orally administered for 14 days. Pathology of esophageal mucosal inflammation was evaluated under microscopy by hematoxylin-eosin (HE) staining. In vitro, by inducing cellular inflammatory response with glycocholic and taurocholic acid mixture (PH 4.7 acid medium added 500 μmol/L concentration of mixed bile acids) in human esophageal epithelial cells(HEEC). The mitochondrial membrane potential was detected using JC-1 fluorescence mitochondrial imaging. The mtDNA copy number was determined via quantitative real-time polymerase chain reaction (qRT-PCR). Fluorescent probe DCFH-DA was used to detect ROS. The relative fluorescence expression of NLRP3 inflammasome was determined by high-intension cell imaging and quantitative fluorescence techniques. ELISA was used to detect and quantify inflammatory cytokines related to the NLRP3 inflammasome. Western blot analysis was performed to investigate proteins that are associated with the NLRP3 inflammasome. Results: Twenty chemical components such as alkaloids and flavonoids were identified in the analysis of XFDZ, which may be the material basis for XFDZ to exert its effect. XFDZ can significantly reduce the contents of Caspase-1, IL-1β and IL-18 in serum of rats, and down-regulate the protein expression levels of NLRP3, Caspase-1, IL-1β and IL-18 in esophageal tissue. The simulated reflux could decrease the membrane potential, increase the ROS production, decrease the relative expression of mtDNA and activate the NLRP3/Caspase-1 signaling pathway in vitro. XFDZ had no obvious protective effect on the membrane potential and mtDNA, but could inhibit ROS production and the activation of NLRP3/Caspase-1 signaling pathway. Conclusion: We concluded that XFDZ could reduce the inflammatory damage in RE by inhibiting NLRP3/Caspase-1 signaling pathway both in vitroand in vivo, indicating the capability of XFDZ as a promising drug for the treatment of RE.

The study aimed to explore the reliability and validity of the Sub-Health Measurement Scale version 1.0 (SHMS v1.0) for the assessment of the suboptimal health status (SHS) of Tianjin residents. This was a cross-sectional study that surveyed 2640 urban residents in Tianjin from June 2016 to January 2018. Demographic and clinical characteristics were collected. Each subject completed the SHMS v1.0 and Short Form-36 (SF-36) scale assessments. The retest coefficient was 0.675. The overall Cronbach's α coefficient was 0.921. The correlation between SHMS v1.0 and SF-36 was 0.781 (P < .01). The SHS frequency increased with age, from 62.4% in participants ≤25 years of age to 72.8% in those ≥ 56 years of age. The multivariable analysis showed that female sex (P < .001), age >25 years old (P = .009), bachelor degree or above (P < .001), obesity (P < .0), regular smoking (P = .043), frequent drinking (P = .045), sleep time < 6 hours (P = .006), working time >10 hours (P < .001), physical exercise <5 times/mo (P < .001), and adverse events >9 (P < .001) were associated with SHS. The prevalence of SHS is high among urban residents in Tianjin.