[Vitamin D3 alleviates the gastritis that associated with Helicobacter pylori infection in mice with hypercholesterolemia by enhancing the activity of vitamin D receptors in the liver tissue and blocking the signaling pathway of JAK/STAT3].

Objective To investigate whether vitamin D3 (VD3) can alleviate Helicobacter pylori (Hp) infection by reducing blood lipids and inhibiting the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling pathway. Methods High-cholesterol mouse model and Hp infected mouse model were established. Each was treated with VD3 via oral administration for 8 weeks. Real-time quantitative PCR was used to detect the expression of vitamin D receptor (VDR), insulin-induced gene 2 (Insig-2), and gastrin mRNA. Western blot analysis was used to examine the expression of JAK, STAT3, and cyclooxygenase-2 (COX2) proteins in gastric tissues. Biochemical analyses were performed to measure serum cholesterol levels, and ELISA was utilized to evaluate serum gastrin, interleukin 6 (IL-6), and IL-8 levels, along with histopathological examination of liver and gastric tissues using HE staining. Results After oral administration of VD3, the levels of VDR and Insig-2 in mouse liver tissue significantly increased in the high cholesterol group and the high cholesterol combined with Hp infection group. And the expression of serum gastrin decreased. The expression of JAK, STAT3 in gastric tissues reduced, as did the expression of COX2. Serum cholesterol levels decreased, with no significant changes in IL-6 levels, but a reduction in IL-8 levels. Compared to the control group, the high cholesterol combined with Hp infection group showed reduced hepatic ballooning degeneration and alleviated gastric tissue inflammation. In addition, inflammation in gastric tissue was also reduced in the cholesterol group and the Hp infection group. Conclusion VD3 alleviates gastritis by enhancing the activity of VDR in liver tissues, blocking the JAK/STAT3 signaling pathway, and inhibiting the expression of inflammatory factors.

Inhibition of lincRNA-Cox2 alleviates apoptosis and inflammatory injury of lipopolysaccharide-stimulated human bronchial epithelial cells via the Nrf2/HO-1 axis.

This study mainly explored the role and mechanism of lincRNA-Cox2 in inflammatory injury of human bronchial epithelial cells. BEAS-2B cells were stimulated with lipopolysaccharide to establish an in vitro inflammatory injury model. Real-time polymerase chain reaction was used to detect lincRNA-Cox2 expression in LPS-stimulated BEAS-2B. Cell viability and apoptosis of cells were assessed using CCK-8 and Annexin V-PI double staining. The contents of inflammatory factors were determined by enzyme-linked immunosorbent assay kits. The protein levels of nuclear factor erythrocyte 2-related factor 2 and haem oxygenase 1 protein levels were measured by Western blot. The results showed that lincRNA-Cox2 was upregulated in LPS-stimulated BEAS-2B cells. lincRNA-Cox2 knockdown inhibited apoptosis and the release of tumour necrosis factor alpha, interleukin 1beta (IL-1ß), IL-4, IL-5, and IL-13 in BEAS-2B cells. lincRNA-Cox2 overexpression had the opposite effect. lincRNA-Cox2 knockdown also inhibited LPS-induced oxidative damage in BEAS-2B cells. Further mechanistic studies showed that inhibition of lincRNA-Cox2 upregulated the levels of Nrf2 and HO-1, and si-Nrf2 reversed the effects of si-lincRNA-Cox2. In conclusion, lincRNA-Cox2 knockdown inhibited BEAS-2B apoptosis and the level of inflammatory factors by activating the Nrf2/HO-1 pathway.

Silencing of FSTL1 Alleviated LPS-Induced Inflammatory Damage and Oxidative Damage in Human Bronchial Epithelial Cells via BMP4/KLF4 Axis.

INTRODUCTION: Childhood asthma is a common chronic inflammatory lung disease in children, among which airway inflammation is the main driving factor of asthma symptoms. Follistatin-like protein 1 (FSTL1) is involved in multiple inflammatory processes, but its role in airway inflammation has not been fully elucidated. METHODS: We used lipopolysaccharide (LPS) to stimulate human primary bronchial epithelial (BEAS-2B) cells to establish an in vitro airway inflammation model. The expression of FSTL1 was detected by qPCR. Cell Counting Kit-8 and Annexin V-PI double staining was used to analyze the viability and apoptosis of BEAS-2B. The content of IL-6, IL-8 and TNF-α was determined by ELISA kit. Western blot was used to detect the protein expression level of the bone morphogenetic protein 4 (BMP4) and KLF4. The levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and malondialdehyde were measured to assess oxidative stress. RESULTS: The mRNA expression of FSTL1 was significantly increased in LPS-treated BEAS-2B cells. Silencing of FSTL1 inhibited the release of IL-6, IL-8, TNF-α, and cell apoptosis as well as enhanced the activities of SOD, CAT, and GSH-Px. Silencing of FSTL1 reversed the inflammatory state of cells by upregulating BMP4 and increasing the expression level of KLF4. CONCLUSION: Silencing of FSTL1 reduced LPS-induced BEAS-2B cell damage by regulating the BMP4/KLF4 axis. FSTL1 may be a potential target for the treatment of asthma.