A study on the significance of serine hydroxymethyl transferase expression and its role in bladder cancer.

Bladder cancer (BLCA) is a common malignant tumor in urinary system all over the world. However, due to its high recurrence rate and complex causes, clinicians often have limited options for surgical and drug treatments. Recent researchs on the molecular mechanism of BLCA have reveals its biological progress and potential for early diagnosis. Serine hydroxymethyltransferase 1/2 (SHMT1/2) is a crucial enzyme in the one-carbon metabolism of tumor cells, and the expression levels of these isozymes have been found to be associated with the biological progression of various malignant tumors. However, the impact of SHMT1/2 on the biological progression of bladder cancer and its molecular regulation mechanism remain unclear. In this research utilizes BLCA clinical sample data, the TCGA database, and in vitro cell experiments to predict the expression levels of SHMT1/2 in BLCA. The findings indicate that SHMT1 remained unchanged, while SHMT2 expression is increased in BLCA, which was related to poor prognosis. Additionally, SHMT2 affects the growth, migration, and apoptosis of bladder cancer cells in vitro. It also influences the expression levels of E-cadherin and N-cadherin, ultimately impacting the malignant biological progression of bladder tumors. These results establish a correlation between SHMT2 and the malignant biological progression of BLCA, providing a theoretical basis for the early diagnosis and treatment of bladder cancer.

Identification of key pathways and mRNAs in interstitial cystitis/bladder pain syndrome treatment with quercetin through bioinformatics analysis of mRNA-sequence data.

BACKGROUND: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition with painful bladder. At present, the pathogenesis of IC/BPS is still unknown. Quercetin (QCT) is a kind of natural flavonoid with wide sources and multiple biological activities. The purpose of this study was to explore the effects of QCT on mRNA expression and related regulatory signal pathways in IC model rats. METHODS: LL-37 was used to induce the IC/BPS model rats. 20 mg/kg QCT was injected intraperitoneally into IC/BPS rats. ELISA, HE, Masson and TB staining were used to evaluate the level of inflammation and pathology. The concentration of QCT in rats was detected by HPLC. The mRNA sequencing was used to detect the differentially expressed (DE) mRNA in each group. The over-expression experiment of Lpl was carried out in IC/BPS model rats. RESULTS: QCT treatment significantly decreased the level of MPO, IL-1ß, IL-6 and TNF-α induced by LL-37 in rats, and alleviated bladder injury and mast cell degranulation. There were significant differences in mRNA sequencing data between groups, and the hub gene Lpl were screened by Cytohubba. The expression of Lpl was downregulated in IC/BPS rats. QCT intervention promoted Lpl expression. Overexpression of Lpl reduced the bladder injury induced by LL-37, increased GAG level and decreased the expression of MPO, IL-1ß, IL-6 and TNF-α. CONCLUSION: In this study, we provided the DE mRNA in IC/BPS rats treated with QCT, the signaling pathways for DE enrichment, screened out the hub genes, and revealed that Lpl overexpression alleviated IC/BPS model rats.

Promoting the proliferation of osteoarthritis chondrocytes by resolvin D1 regulating the NLRP3/caspase-1 signaling pathway.

Osteoarthritis (OA) is a degenerative joint disease commonly found in middle-aged and older people. Chondrocytes are the only cells in joint cartilage that are difficult to heal after pyroptosis, and they will aggravate the wear and tear of joint cartilage and affect the progression of OA. Pyroptosis is a novel form of programmed cell death, and the classical pyroptosis pathway is a programmed cell death pattern mediated by inflammatory cysteine protease-1. Activation of NLRP3 leads to activation and cleavage of caspase-1 precursors, which in turn leads to activation and cleavage of GSDMD proteins and the release of proinflammatory factors. Resolvin D1 (RvD1) is a specialized pro-resolving mediator (SPM) derived from omega-3 unsaturated fatty acids that reduces inflammation and catabolic responses in OA chondrocytes. However, it is unclear whether RvD1 promotes OA chondrocyte proliferation and thus joint cartilage repair. Our results show that RvD1 regulates the NLRP3/caspase-1 signaling pathway by inhibiting the expression of caspase-1, promoting the proliferation of OA chondrocytes, promoting the repair of articular cartilage in rats and delaying the progression of osteoarthritis.

Identifying the shared genes and KEGG pathways of Resolvin D1-targeted network and osteoarthritis using bioinformatics.

Osteoarthritis (OA) is a common chronic degenerative disease characterized by the loss of articular cartilage, which causes loss of joint function and reduce quality of life. Resolvin D1 (RvD1) has shown interesting anti-inflammatory effects; however, the mechanism of action of RvD1 in OA remains unclear. The aim of this study was to investigate the potential mechanism of RvD1 in OA by bioinformatics and partial in vitro mechanisms. Here, 106 shared differentially expressed genes (DEGs) were identified based on the GSE82107, GSE55235, GSE55457 dataset; 700 DEGs were identified based on GSE169077. Enrichment analyses of these genes were then successively conducted. RvD1-targeted genes and KEGG pathways are identified by STITCH. 27 shared KEGG pathways were identified among RvD1-targeted pathways and OA. Furthermore, cell apoptosis assay, western blotting, real-time fluorescent quantitative PCR (qRT-PCR), enzyme linked immunosorbent assay (ELISA) were used to confirm the expression levels of the key genes of shared Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways between RvD1-targeted and OA in IL-1ß treated rat knee chondrocytes. The results showed that RvD1-targeted pathways and the expression of nuclear p65, p53, and p-JNK were inhibited in the RvD1 group compared with the IL-1ß group. Thus, the findings indicate that RvD1 may inhibit the development of OA through NF/kB, p53, MAPK/JNK, PI3K-AKT signaling pathways, and act as a treatment for OA.

Resolvin D1 inhibits the proliferation of osteoarthritis fibroblast-like synoviocytes through the Hippo-YAP signaling pathway.

OBJECTIVE: Osteoarthritis (OA) is a disease characterized by cartilage degradation and structural destruction. Resolvin D1 (RvD1), a specialized proresolving mediator (SPM) derived from omega-3 fatty acids, has been preliminarily proven to show anti-inflammatory and antiapoptotic effects in OA. However, the mechanisms of RvD1 in osteoarthritis fibroblast-like synoviocytes (OA-FLSs) need to be clarified. METHODS: Synovial and fibroblast-like synoviocytes were obtained from OA patients and healthy individuals. MTT and EdU assays were performed to determine cell cytotoxicity and proliferation. The protein expression levels of cyclin D1, cyclin B1, PCNA, p53, MMP-13, YAP, p-YAP, and LATS1 were detected by western blot analysis. The release levels of IL-1ß were detected by ELISA. The cell cycle was assessed by flow cytometry. Immunofluorescence was used to detect the levels of YAP in OA-FLSs. RESULTS: RvD1 inhibited OA-FLS proliferation and reduced MMP-13 and IL-1ß secretion in the concentrations of 20 nM and 200 nM. Furthermore, RvD1 induced G2 cell cycle arrest in OA-FLSs via the Hippo-YAP signaling pathway and promoted YAP phosphorylation. However, RvD1 had no effects on normal FLSs. CONCLUSIONS: RvD1 inhibits OA-FLS proliferation by promoting YAP phosphorylation and protects chondrocytes by inhibiting the secretion of MMP-13 and IL-1ß, providing an experimental basis for RvD1 treatment of OA.