Genetic causality and site-specific relationship between sarcopenia and osteoarthritis: a bidirectional Mendelian randomization study.

Background: Previous studies demonstrated a controversial relationship between sarcopenia (SP) and osteoarthritis (OA) and their genetic causality is unclear. Thus, we conducted a Mendelian randomization (MR) analysis to evaluate the possible causal association between sarcopenia-related traits (appendicular lean mass (ALM), grip strength, usual walking pace) and OA. Method: We used pooled genetic data from the UK Biobank for ALM(n = 450,243), left-hand grip strength (n = 461,026), right-hand grip strength (n = 461,089) and usual walking pace (n = 459,915). Moreover, summary statistics for OA were obtained from the latest study conducted by the Genetics of Osteoarthritis Consortium, including all OA (n = 826,690), hand OA (n = 303,7782), hip OA (n = 353,388) and knee OA (n = 396,054). The primary method for estimating causal effects was the inverse-variance weighted (IVW) method, with the utilizing of false discovery rate adjusted p values (P FDR). Additional MR methods such as MR-Egger regression, MR pleiotropy residual sum and outlier (MR-PRESSO), weighted median were employed as supplementary analyses. Results: We discovered ALM (odds ratio (OR) = 1.103, 95% confidence interval (CI) = 1.052-1.156, P FDR = 2.87E-04), hand grip strength (left, IVW OR = 0.823, 95% CI = 0.712 to 0.952, P FDR = 0.020; right, OR = 0.826, 95% CI = 0.718 to 0.950, P FDR = 0.020), and usual walking pace (OR = 0.339, 95% CI = 0.204 to 0.564, P FDR = 2.38E-04) were causally associated with OA risk. In the reverse MR analysis, we identified a causal effect of OA on ALM (ß = -0.258, 95% CI = -0.369 to 0.146, P FDR = 0.6.07E-06), grip strength (left, ß = -0.064, 95% CI = -0.104 to 0.024, P FDR = 0.002; right, ß = -0.055, 95% CI = -0.095 to 0.014, P FDR = 0.008), and usual walking pace (ß = -0.104, 95% CI = -0.147 to 0.061, P FDR = 1.61E-05). Conclusion: This present study suggests an obvious causality of SP on OA, with condition exhibiting site-specific effects, while evidence was also provided for the causal effect of OA on SP.

Metformin Attenuates Silica-Induced Pulmonary Fibrosis by Activating Autophagy via the AMPK-mTOR Signaling Pathway.

Long-term exposure to crystalline silica particles leads to silicosis characterized by persistent inflammation and progressive fibrosis in the lung. So far, there is no specific treatment to cure the disease other than supportive care. In this study, we examined the effects of metformin, a prescribed drug for type || diabetes on silicosis and explored the possible mechanisms in an established rat silicosis model in vivo, and an in vitro co-cultured model containing human macrophages cells (THP-1) and human bronchial epithelial cells (HBEC). Our results showed that metformin significantly alleviated the inflammation and fibrosis of lung tissues of rats exposed to silica particles. Metformin significantly reduced silica particle-induced inflammatory cytokines including transforming growth factor-ß1 (TGF-ß1), tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in rat lung tissue and HBEC culture supernatant. The protein levels of Vimentin and α-smooth muscle actin (α-SMA) were significantly decreased by metfomin while expression level of E-cadherin (E-Cad) increased. Besides, metformin increased the expression levels of phosphorylated adenosine 5'-monophosphate (AMP)-activated protein kinase (p-AMPK), microtubule-associated protein (MAP) light chain 3B (LC3B) and Beclin1 proteins, and reduced levels of phosphorylated mammalian target of rapamycin (p-mTOR) and p62 proteins in vivo and in vitro. These results suggest that metformin could inhibit silica-induced pulmonary fibrosis by activating autophagy through the AMPK-mTOR pathway.

[Experimental study on the therapeutic effect of C-phycocyanin against pulmonary fibrosis induced by paraquat in rats].

OBJECTIVE: To investigate the therapeutic effect of C-phycocyanin (C-PC) from Spirulina platensis on paraquat (PQ)-induced pulmonary fibrosis in rats. METHODS: A total of 90 healthy Wistar rats were randomly and equally divided into normal control group, model group (PQ group), and C-PC treatment group (C-PC group). Each rat in the PQ group and C-PC group were orally administered with a single dose of PQ (50 mg/kg) to establish a rat model of PQ poisoning. Then, the rats in the normal control group and PQ group were orally given saline solution (1 ml/100 g) every day, and the rats in the C-PC group were orally given C-PC (50 mg/kg) every day. Six rats were randomly selected from each group on days 1, 3, 7, 14, and 28. The inferior lobe of each rat's right lung was homogenized for the measurement of hydroxyproline (HYP) and maleic dialdehyde (MDA) levels and superoxide dismutase (SOD) activity. Parts of each rat's left lung were subject to HE staining and Masson staining for pathological observation, and the expression of transforming growth factor-ß(1) (TGF-ß(1)), nuclear factor-kappa B p65 (NF-κB p65), and tumor necrosis factor-α (TNF-α) in lung tissue was measured by immunohistochemistry. RESULTS: The HYP levels on days 1, 3, 7, 14, and 28 and MDA levels on days 14 and 28 were significantly lower in the C-PC group than in the PQ group (P < 0.05, P < 0.01). The SOD activity was significantly higher in the C-PC group than in the PQ group on days 1, 7, 14, and 28 (P < 0.05, P < 0.01). The protein content of TGF-ß(1) and the activities of NF-κB p65 and TNF-α in the PQ group and C-PC group were significantly higher than those in the normal control group, while the indices in the C-PC group were significantly lower than those in the PQ group (P < 0.05, P < 0.01). The pathological observation showed that C-PC could alleviate pulmonary alveolitis and fibrosis in rats with PQ poisoning. CONCLUSION: C-PC can significantly inhibit PQ-induced pulmonary alveolitis and fibrosis in rats.

[The occupational and procreation health of immigrant female workers in electron factory].

OBJECTIVE: To explore the occupational and reproductive health problems of migrant female workers in electron factory. METHODS: A total number of 2000 female migrant workers were randomly sampled from three electronic factories for the study. All were investigated by questionnaire and data were input to EpiData 3.0 data base, SPSS17.0 statistical software and analyzed by Chi-square test. RESULTS: 1971 complete questionnaires were received, the recovery rate reached over 98.6%. The average age of interviewees is (21.1 ± 3.9) years. Junior employee between 16 and 18 years accounted for 19.04%. The average working age was (1.1 ± 2.2) years and about 90% were single including 0.11% of them were divorced. The main occupational hazards were: sodium hydroxide, sodium carbonate, formaldehyde, hydrochloric acid, stannic anhydride, benzene analogues, n-hexane methanol, glycol isopropanol, sulphuric acid, nitric oxide, noise, ultraviolet radiation, etc. Workplace monitoring indicated that benzene and noise levels and ultraviolet radiation were over the national OEL at fewer worksites. More than 50% female workers worked over 8 hours per day and 83% of them worked 22 days per month. The ergonomic problems: 63.86% of them worked with tedious repetitiveness and monotonous job task. About 42% of them need to be continuously with standing posture. As a consequence, there were 30% workers complain about LBP, 21% had experienced work injury; 15% ∼ 18% had some non-specific discomfort, such as insomnia, dysacusis, dizzy and headache. The incidence rate of reproductive system such as abnormal menstrual cycle (5.71%), dysmenorrhea (25.11%), congestion (8.91%), etc. The first four reproductive system disease were pelvic inflammation, adnexitis, cervical erosion, and vaginitis. There are significant differences between continuous and temporary standing work, and repeated and unrepeated job action in terms of dysmenorrheal and congestion related-discomfort(P < 0.05). CONCLUSION: There are many occupational hazards in electronic industry. And there is somewhat a serious occupational and reproductive health problems among female migrant workers, that seem to be a matter of great concern.

[Carbendazim affects testicular development and spermatogenic function in rats].

OBJECTIVE: To explore the effects of carbendazim on the testicular development and spermatogenic function of male rats and its action mechanism. METHODS: Forty clean-grade impubic male Wistar rats were equally randomized into a low-dose, a medium-dose, a high-dose and a control group, treated respectively with carbendazim at 20, 100 and 200 mg/kg (bw) and Tween-80 solution, all by oral gavage once a day for 80 days. After treatment, the rats were weighed, their testes and epididymides immediately excised, their morphological changes observed and the weights of the right testis and epididymis obtained. Sperm motility and counts in the left cauda epididymis were determined. Histopathological changes, cell apoptosis and the expression of Bcl-2/Bax in the testis were detected by HE staining, TUNEL and immunohistochemical SABC method. RESULTS: The medium- and high-dose groups showed obviously atrophic testes and epididymides, marked histopathological abnormality of the testis, reduced weight of the right testis and epididymis, and decreased sperm motility and counts in the left cauda epididymis (P < 0.01). With the increasing dose of carbendazim, the apoptosis rate and Bax expression were significantly raised, while the expression of Bcl-2 significantly decreased (P < 0.05, P < 0.01). CONCLUSION: Carbendazim affects the testicular development and spermatogenic function of male rats, and the mechanism may involve cell apoptosis induced by down-regulation of Bcl-2 and up-regulation of Bax.