Diosbulbin B (DIOB), a furanoid, is a major constituent of herbal medicine Dioscorea bulbifera L. Exposure to DIOB caused liver injury in humans and experimental animals. The mechanisms of DIOB-induced hepatotoxicities remain unknown. The present study demonstrated that DIOB induced hepatotoxicities in a time- and dose-dependent manner in mice. H&E stained histopathologic image showed the occurrence of necrosis in the liver obtained from the mice treated with DIOB at dose of 200 mg/kg. Pretreatment with KTC protected the animals from hepatotoxicities and hepatic GSH depletion induced by DIOB, increased area under the concentration-time curve of blood DIOB, decreased urinary excretion of GSH conjugates derived from DIOB, and increased urinary excretion of parent drug. Pretreatment with BSO exacerbated DIOB-induced hepatotoxicities. In order to define the role of furan moiety in DIOB-induced liver toxicities, we replaced the furan of DIOB with a tetrahydrofuran group by chemical hydrogenation of the furan ring of DIOB. No liver injury was observed in the animals given the same doses of tetrahydro-DIOB. The furan moiety was essential for DIOB-induced hepatotoxicities. The results implicate the cis-enedial reactive metabolite of DIOB was responsible for the observed toxicities. The observed modest depletion of hepatic GSH in DIOB-treated animals suggests the actions of one or more reactive metabolites, and the hepatic injury observed could be due at least in part to reactions of these metabolites with crucial biomolecules. Cytochrome P450 3A enzymes are implicated in DIOB-induced hepatotoxicities by catalyzing the formation of the reactive metabolite of DIOB.

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The present study aimed to determine the effect of microRNA (miR)‑210 on osteoarthritis (OA). The expression levels of miR‑210, type I and X collagen (COL1A1 and COL10A1) and matrix metallopeptidase 13 (MMP13) in OA and normal chondrocytes were determined using reverse transcription‑quantitative polymerase chain reaction analysis. The OA chondrocytes were transfected with an miRNA precursor for miR‑210 or a negative control. After 3, 7, 14 and 21 days, the expression levels of miR‑210 were examined, the proliferation of the OA chondrocytes were determined using an XTT assay and the protein levels of Ki67 and HIF‑3α were analyzed by Western blotting. After 21 days, the mRNA and protein levels of COL1A1, COL10A1 and MMP13 were analyzed. Th present study demonstrated that the expression levels of miR‑210 and COL1A1 were lower, and the expression levels of COL10A1 and MMP13 were higher in the OA chondrocytes, compared with the levels of expression in the normal chondrocytes. Overexpression of miR‑210 significantly promoted the proliferation of OA chondrocytes and induced the protein expression of Ki67. In addition, miR‑210 overexpression markedly increased the expression of COL1A1 expression, but decreased the expression levels of COL10A1 and MMP13. A luciferase reporter assay confirmed the direct interaction between miR‑210 and hypoxia‑inducible factor (HIF)‑3α. miR‑210 did not alter the mRNA expression of HIF‑3α, however, it suppressed the protein expression of HIF‑3α. Additionally, HIF‑3α knockdown significantly promoted OA chondrocyte proliferation and increased the mRNA levels of COL1A1, whereas it decreased the mRNA levels of COL10A1 and MMP13. The results of the present study suggested that miR‑210 may be a negative regulator of the progression of OA, which increases chondrocyte proliferation and prompts extracellular matrix deposition by directly targeting HIF‑3α.

Background: Adalimumab, golimumab, infliximab, certolizumab, and etanercept are five anti-tumor necrosis factor (anti-TNF) medicines that have been approved for use in rheumatology. Apart from their well-established therapeutic usefulness, -it is unclear to what extent -they are linked to an increased risk of various side effects. The present meta-analysis was carried out to assess the risk of infection and other side effects after anti-TNF- α for the treatment of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.Methods: We searched PubMed, Cinahl (via Ebsco), Scopus, and Web of Sciences databases for trials comparing anti-TNF medications to placebo or no therapy in adult patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis from August 2006 to August 2020. A total of 23 articles were used for meta-analysis. The Cochrane Collaboration’s risk of bias tool was used to assess the methodological quality of the included studies. In addition, a random-effects model was used to calculate the pooled odds ratio, and Forest plots were constructed to determine the risk of infections and cancer following the use of anti-TNF treatment.Results: Treatment with anti-TNFα agents resulted in an increase in the risk of serious infections (OR: 1.72, 95% CI: 1.56–1.90, p < 0.00001) and an increase in cancer risk (OR: 1.36, 95% CI: 1.20–1.53, p < 0.00001) whereas the risk of developing tuberculosis was not significantly different with anti-TNFα agents versus those without treatment with anti-TNFα agents (OR: 2.55, 95% CI: 0.40–16.23, p = 0.32) although the number of studies is limited to make a definitive conclusion. The risk of bias of the included studies was unclear to high across most domains, and there was evidence of publication bias for most outcomes.Conclusion: The present meta-analysis suggests an increased risk of infectious adverse events, including overall adverse events and cancer following anti-TNFα treatment, whereas the risk of tuberculosis was not significantly different. Although anti-TNF agents have shown promise to treat inflammatory conditions, their use should be balanced by the risk-benefit ratio as suggested by the meta-analysis.