Arctigenin prevents the progression of osteoarthritis by targeting PI3K/Akt/NF-κB axis: In vitro and in vivo studies.

Osteoarthritis (OA), which is principally featured by progressive joint metabolic imbalance and subsequent degeneration of articular cartilage, is a common chronic joint disease. Arctigenin (ATG), a dietary phyto-oestrogen, has been described to have potent anti-inflammatory effects. Nevertheless, its protective effects on OA have not been clearly established. The target of our following study is to evaluate the protective effects of ATG on IL-1ß-induced human OA chondrocytes and mouse OA model. Our results revealed that the ATG pre-treatment effectively decreases the level of pro-inflammatory mediators, such as prostaglandin E2 (PGE2), nitrous oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), IL-6 and tumour necrosis factor alpha (TNF-α) in IL-1ß-induced human chondrocytes. In addition, ATG protects against the degradation of extracellular matrix (ECM) under the stimulation of IL-1ß and the possible mechanism might be connected with the inactivation of phosphatidylinositol-3-kinase (PI3K)/Akt/nuclear factor-kappa B (NF-κB) axis. Furthermore, a powerful binding capacity between ATG and PI3K was also uncovered in our molecular docking research. Meanwhile, ATG may act as a protector on the mouse OA model. Collectively, all these findings suggest that ATG could be utilized as a promising therapeutic agent for the treatment of OA.

Adrenocorticotropic hormone application lowered aldosterone/cortisol value on dominant side without superior surgical outcomes during adrenal venous sampling.

Adrenal venous sampling (AVS) is thought to be the gold standard for primary aldosteronism (PA) subtype discrimination, during which the application of adrenocorticotropic hormone (ACTH) arouses heated debate. We aimed to identify the effect of ACTH on AVS and surgical outcomes. After propensity score matching (PSM), a total of 220 patients diagnosed with PA and completed AVS were included (110 without ACTH stimulation and 110 with ACTH stimulation). According to AVS results, surgeries were conducted in appropriate patients. ACTH stimulation significantly increased almost all selectivity index (SI) in both left adrenal vein (LAV) and right adrenal vein (RAV). We discovered that aldosterone/cortisol (A/C) value on dominant side significantly reduced after ACTH stimulation, with a reduction in lateralization index (LI) observed. Finally, 39 patients in unstimulated group and 32 patients in stimulated group completed surgery and enough follow-up. The comparison between surgical outcomes with and without ACTH stimulation was analyzed and the difference was not significant (p = .464). In conclusion, ACTH application significantly lowered A/C value instead of the relative aldosterone secretion index (RASI) value on dominant side, which did not yield superior surgical outcomes and might render confusing AVS interpretation.

An Appraisal of the Role of Previously Reported Risk Factors in the Age at Menopause Using Mendelian Randomization.

OBJECTIVE: Menopause at a young age is associated with many health problems in women, including osteoporosis, depressive symptoms, coronary disease, and stroke. Many traditional observational studies have reported some potential risk factors for early menopause but have drawn different conclusions. This inconsistency can be attributed mainly to unmodified confounding factors. Identifying the factors causally associated with age at menopause is important for early intervention in women with abnormal menopause timing, and for improving the quality of life for postmenopausal women. This study aims to appraise whether the previously reported risk factors are causally associated with early age at natural menopause (ANM) susceptibility. METHODS: We used Mendelian randomization, a statistical method wherein genetic variants are used to determine whether an observational association between a risk factor and an outcome is consistent with a causal effect. RESULTS: Women with earlier age at menarche (ß = 0.34, se = 0.16, p = 0.035), lower education level (ß = 1.19, se = 0.41, p = 0.004) and higher body mass index (ß = -0.05, se = 0.02, p = 0.027) had greater risk for early ANM. The causal link between early age at menarche and early ANM was replicated using ReproGen consortium data (ß = 0.23, se = 0.07, p = 0.001). However, a current smoking habit, one of previously reported risk factors, was less likely to be correlated causally with early ANM, suggesting that previous observational studies may not have sufficiently adjusted for confounders. CONCLUSION: Our results help to identify the risk factors of ANM via a genetics approach and future research into the biological mechanism could further help with targeted prevention for early menopause.

The protective effect of sophocarpine in osteoarthritis: An in vitro and in vivo study.

BACKGROUND: Osteoarthritis (OA) is a type of degenerative joint disease affecting millions of individuals worldwide. However, there are currently no great inflammatory treatments available for it. Sophocarpine (SPC), one of the key bioactive compounds derived from Sophora flavescens, has shown remarkable anti-inflammatory effects. METHODS: In this study, we evaluated the effect of SPC on preventing the progression of OA and investigated its molecular target involved. In brief, rat chondrocytes were pretreated with SPC and subsequently stimulated with IL-1ß. We found that SPC reduced the production of pro-inflammatory cytokines, such as nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6). SPC also inhibited the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) at both the gene and protein level. Moreover, SPC promoted the expression of anabolic factors Sox-9 and aggrecan, while inhibiting the expression of catabolic factors, such as matrix metalloproteinases 13 (MMP-13) and thrombospondin motifs 5 (ADAMTS-5) in rat chondrocytes. Mechanistically, we found that SPC inhibited nuclear factor kappa B (NF-κB) via the phosphatidylinositol 3 kinase (PI3K)/AKT pathway. The beneficial effects of SPC were also observed in vivo using a rat OA model. CONCLUSIONS: Our findings indicate that SPC may be a potential novel therapeutic in the treatment of OA.

Sauchinone inhibits IL-1ß induced catabolism and hypertrophy in mouse chondrocytes to attenuate osteoarthritis via Nrf2/HO-1 and NF-κB pathways.

BACKGROUND: Osteoarthritis (OA) is a common degenerative joint disease for which currently no anti-inflammatory therapy is available. Sauchinone (SAU), a key bioactive compound derived from Saururus chinensis, which has shown remarkable anti-inflammatory effects. METHODS: To evaluate the effect of SAU on OA progression, mouse chondrocytes were pretreated with SAU and subsequently stimulated with interleukin (IL)-1ß. We found that SAU reduced the production of pro-inflammatory cytokines, such as nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α), and IL-6. SAU also inhibited the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) at both the gene and protein level. Moreover, SAU promoted the expression of aggrecan, while inhibiting the expression of catabolic factors, such as matrix metalloproteinases (MMPs) and thrombospondin motifs 5 (ADAMTS-5) in mouse chondrocytes. Col X, vascular endothelial growth factor-A (VEGF)-A, and Runx2, major markers of hypertrophic chondrocytes, were markedly elevated following IL-1ß stimulation, and were reduced by SAU treatment while having the opposite effect on Col II. Mechanistically, we found that SAU inhibited nuclear factor kappa B (NF-κB) and activated the Nrf2/HO-1 pathway. The beneficial effects of SAU were also observed in vivo using a mouse OA model. CONCLUSIONS: Our findings indicate that SAU may be a potential novel therapeutic for the treatment of OA.