Plumbagin induces apoptosis, cell cycle arrest, and inhibits protein synthesis in LoVo colon cancer cells: A proteomic analysis.

Extracted from the roots of Plumbago zeylanica L., plumbagin is a natural naphthoquinone with potential as an anticancer compound. However, no studies have investigated its impact on LoVo (colon cancer) cells, and the specific mechanisms by which plumbagin exerts its anticancer effects remain to be established. The anticancer potential of plumbagin against LoVo cells was evaluated using a battery of assays, including MTT assay, clone formation assay, transwell chamber invasion assay, and wound-curing assay. Cell cycle analysis and cell apoptosis analysis were conducted to break down the anticancer impact of plumbagin on LoVo cells. A label-free proteomics technology was employed to investigate alterations in protein expression in LoVo cells treated with plumbagin. Our investigation indicated that plumbagin markedly inhibited the LoVo cells proliferation, and induced the apoptosis in LoVo cells, simultaneously induced G0/G1 phase cell cycle arrest. The LC-MS/MS proteomics assay revealed 78 proteins that were differentially expressed upon treatment with plumbagin. Bioinformatics and functional analyses indicated that these proteins were predominantly involved in protein synthesis and translation. Our findings revealed that multiple mechanisms are involved in the anticancer activity of plumbagin against LoVo cells, resulting in decreased cell viability. Proteomic analysis suggests that plumbagin may impede protein synthesis by reducing the expression of eukaryotic initiation factors. Our findings demonstrate that plumbagin exerts its anticancer activity against LoVo cells through multiple mechanisms, including inhibition of cell proliferation, induction of apoptosis, cell cycle arrest, and disruption of protein synthesis. These results provide new insights into the therapeutic potential of plumbagin for colon cancer treatment.

Efficacy and safety of IL inhibitors, TNF-α inhibitors, and JAK inhibitors in patients with ankylosing spondylitis: a systematic review and Bayesian network meta-analysis.

Background: Biologics and Janus kinase (JAK) inhibitors are commonly used to improve ankylosing spondylitis (AS) symptoms if conventional treatments are ineffective or unsuitable. This systematic review aimed to compare the therapeutic effects and safety of JAK inhibitors, tumor necrosis factor-alpha (TNF-α) inhibitors, and interleukin (IL) inhibitors in patients with AS. Methods: We retrieved literature from various databases including Web of Science, Cochrane, Embase, PubMed, China National Knowledge Infrastructure, Weipu Journal Database, SinoMed, and WanFang Data up to February 1, 2023, and evaluated the quality of the included RCTs using the Cochrane risk-of-bias tool. R 4.1.3, STATA 15.1 were employed for network meta-analyses. Results: We identified 48 eligible articles including 8,937 patients. Ten articles were rated as "low risk", 5 as "high risk", and the others as "some concerns". In terms of efficacy, IL-17, IL-6, and JAK inhibitors were compared with TNF-α inhibitors in ASAS20 (RR =0.81, 95% CI: 0.66-0.98; RR =0.57, 95% CI: 0.35-0.95; RR =0.77, 95% CI: 0.60-0.99). IL-6 inhibitors were compared with TNF-α inhibitors in ASAS5/6 (RR =0.39, 95% CI: 0.16-0.98). IL-23, JAK inhibitors were compared with TNF-α inhibitors in BASDAI50 (RR =0.35, 95% CI: 0.20-0.60; RR =0.70, 95% CI: 0.49-0.98). IL-17 inhibitors were compared with IL-23 and IL-6 inhibitors in BASFI (MD =-1.05, 95% CI: -1.65--0.51; MD =-1.46, 95% CI: -2.02--0.97). In terms of safety, IL-6 inhibitors were compared with JAK, TNF-α inhibitors in AEs (RR =1.38, 95% CI: 1.06-1.88; RR =1.30, 95% CI: 1.01-1.70). Conclusions: TNF-α inhibitors are significantly superior to both IL and JAK inhibitors, and may be the preferable option to deal with the rapid progression of AS and severe functional limitations. IL-17 inhibitors may better improve the BASDAI50 response compared with JAK, IL-23, and TNF-α inhibitors. The efficacy and safety of IL-6 inhibitors are inferior to other types of drugs, indicating the low efficacy and high risk of IL-6 inhibitors.

Regulatory Role of miRNAs and lncRNAs in Gout.

Objective: To explore the regulatory functions of ceRNA networks in the nosogenesis of gout and search for potential therapeutic targets. Methods: We searched the GEO database and downloaded the lncRNA microarray chipset GSE160170. This matrix series was analyzed to yield differentially expressed lncRNAs and mRNAs. Then, the correlations between lncRNAs and miRNAs were obtained by comparing the highly conserved miRNA families. The predicted miRNA-regulating mRNAs were matched to the differentially expressed mRNAs from the chipset analyses to obtain miRNA-mRNA interactions. Next, we used the Cytoscape software to model ceRNA networks and the STRING database to determine their protein-protein interactions. The R software was used to algorithmically screen the functional pathways of key PPI modules in the ceRNA networks. Results: A total of 354 lncRNAs (140 downregulated and 214 upregulated) and 693 mRNAs (399 downregulated and 294 upregulated) were differentially expressed between the gout group and the healthy group. The ceRNA network of differentially expressed lncRNAs contained 86 lncRNAs (35 downregulated and 51 upregulated), 29 miRNAs, and 57 mRNAs. The processes identified in the GO enrichment analysis included gene transcription, RNA polymerase II transcription, and the regulation of cell growth and apoptosis. The pathways identified in the KEGG enrichment analysis included IL-17, TNF, and MAPK signaling. Nine lncRNAs (AC104024, AC084082, AC083843, FAM182A, AC022819, FAM215B, AP000525, TTTY10, and ZNF346-IT1), eleven miRNAs (hsa-miR-1297, hsa-miR-17-5p, hsa-miR-429, hsa-miR-139-5p, hsa-miR-449c-5p, hsa-miR-125a-5p, hsa-miR-125b-5p, hsa-miR-23b-3p, hsa-miR-217, hsa-miR-363-3p, and hsa-miR-20b-5p), and nine mRNAs (JUN, CASP2, PMAIP1, FOS, TNFAIP3, MAP3K8, BTG2, NR4A2, and DUSP2) were identified in the exploration of the key modules. Conclusion: Characterization of ceRNA networks could be a promising approach for better understanding the pathogenesis of gout, with the TTTY10/hsa-miR-139-5p/AP-1 axis likely to be of clinical significance.

Serum homocysteine levels and their association with clinical characteristics of inflammatory arthritis.

OBJECTIVE: The aim of our study was to explore the serum levels of homocysteine (Hcy) and its association with clinical characteristics in patients with different types of inflammatory arthritis. METHODS: A total of 242 patients diagnosed with inflammatory arthritis (which included rheumatoid arthritis (RA), ankylosing spondylitis (AS), and gout), 49 with osteoarthritis (OA), and 36 with hyperuricaemia (HUA) and 81 healthy controls (HCs) were enrolled for comparisons. RESULTS: The serum Hcy levels of patients with RA, AS, and OA were comparable with those of the HC group (P > 0.05). However, the serum level of Hcy was significantly higher in patients with gout than in HCs (18.75 ± 9.98 vs. 14.20 ± 6.22 µmol/L, P = 0.007). In addition, we found that the serum Hcy level was much higher in RA patients who received methotrexate (MTX) therapy without folic acid supplementation than in those who received MTX with folic acid supplementation (13.39 ± 4.80 vs. 9.41 ± 2.04 µmol/L, P = 0.001). Furthermore, there was a positive correlation between uric acid and Hcy in patients without uric acid-lowering treatment (r = 0.537, P = 0.002), but the correlation was eliminated after adjusting uric acid-lowering treatment (r = 0.139, P = 0.393). Finally, consistent with the above findings, hyperhomocysteinaemia (HHcy) was more common in gout patients (P < 0.05). CONCLUSION: Screening for HHcy in patients with gout and RA, especially RA patients treated with MTX, might be necessary, and patients with HHcy might benefit from earlier supplementation with folic acid. Key Points • Serum homocysteine (Hcy) was elevated and the rate of hyperhomocysteinaemia (HHcy) was significantly higher in gout. • Rheumatoid arthritis (RA) patients who received methotrexate (MTX) treatment without folic acid supplementation showed higher serum Hcy than those who received MTX treatment with folic acid supplementation. • The serum Hcy level was positively correlated with age in only RA patients. • Serum Hcy was correlated with uric acid in gout patients, but the correlation was eliminated after adjusting uric acid-lowering treatment.