Bone morphogenetic protein 4 is involved in cadmium-associated bone damage.

Cadmium (Cd) is a well-characterized bone toxic agent and can induce bone damage via inhibiting osteogenic differentiation. Bone morphogenetic protein (BMP)/SMAD signaling pathway can mediate osteogenic differentiation, but the association between Cd and BMP/SMAD signaling pathway is yet to be illuminated. To understand what elements of BMPs and SMADs are affected by Cd to influence osteogenic differentiation and if BMPs can be the biomarkers of which Cd-induced osteoporosis, human bone marrow mesenchymal stem cells (hBMSCs) were treated with cadmium chloride (CdCl2) in vitro to detect the expression of BMPs and SMADs, and 134 subjects were enrolled to explore if the BMPs can be potential biomarkers of Cd-associated bone damage. Our results showed that Cd exposure significantly promoted the adipogenic differentiation of hBMSCs and inhibited its osteogenic differentiation by inhibiting the expression of BMP-2/4, SMAD4, and p-SMAD1/5/9 complex. And mediation analyses yielded that BMP-4 mediated 39.32% (95% confidence interval 7.47, 85.00) of the total association between the Cd and the risk of Cd-associated bone damage. Moreover, during differentiation, BMP-4 had the potential to enhance mineralization compared with CdCl2 only group. These results reveal that BMP-4 can be a diagnostic biomarker and therapeutic target for Cd-associated bone damage.

An aqueous extract of Prunella vulgaris L. inhibits the growth of papillary thyroid carcinoma by inducing autophagy in vivo and in vitro.

The continued global rise in papillary thyroid carcinoma (PTC) combined with potential adverse effects of regular treatments calls for an alternative therapy. Prunella vulgaris L. (PV) is commonly used as a herbal remedy for thyroid diseases in China, but its influence on PTC is unclear. This study investigated the effect of PV aqueous extract on PTC and its underlying mechanism using a mouse xenograft model and the human PTC cell line K1. PV suppressed tumor growth in PTC-bearing mice at 0.05 and 0.1 g/kg bw, accompanied by improvements in autophagy-related protein expressions in xenografts. In K1 cells, PV inhibited cell growth and induced autophagic flux, manifesting as changes in autophagy-related proteins, the presence of autophagosomes, and a further increase in LC3-II by co-incubation with bafilomycin A1. Autophagy inhibitor 3-methyladenine ameliorated the autophagic cell death caused by PV. The mammalian target of rapamycin (mTOR) activator MHY1485 blocked the antiproliferative activity of PV by regulating mTOR, unc-51-like autophagy activating kinase 1 (ULK1), autophagosomes formation, and autophagy-related proteins. The adenosine monophosphate-activated protein kinase (AMPK) inhibitor compound C attenuated PV-induced inhibition of mTOR. Our results suggest that PV inhibits the growth of PTC in vivo and in vitro via autophagy, which is associated with the AMPK/mTOR/ULK1 pathway. Thus, PV has the potential to function as a therapeutic agent against PTC.

[Knowledge, attitudes, and practices related to COVID-19 pandemic among residents in Hubei and Henan Provinces].

OBJECTIVE: To survey the residents for their understanding of Coronavirus Disease 2019 (COVID-19)-related knowledge, attitude and practices (KAP) in two hard hit provinces of China to facilitate the governmental decisions on strategies against the disease. METHODS: We invited the participants from Hubei and Henan Provinces of China for an internetbased survey starting from 12:00 on February 21, 2020 to 12:00 on February 23. The survey included the general conditions, KAP of COVID-19, psychological status and living conditions of the residents. RESULTS: The effective response rate of the questionnaire was 98.9%. The mean (P25, P75) age of the participants was 19 (16, 40) years, and 54.3% of them were students. Social media were the most important source of information concerning the pandemic of the respondents. The respondents had a high awareness of person-to-person transmission of the virus through the respiratory tract or droplets but showed a relatively low level of awareness of the population susceptible to COVID-19 and its specific symptoms. The results of multivariate analysis showed that women, undergraduate students (including college students) and higher degree holders had better knowledge of COVID-19 (P < 0.05); the proportion of respondents who expressed to have different levels of psychological stressed such as worry, anxiety and panic reached 77.2%; 16.7% of the responders considered psychological interventions necessary for their psychological conditions; 63.6% of the respondents confessed a bias against the people returning from Hubei and Henan provinces, while 22.4% worried that they might be biased because of their residence in Hubei and Henan. The rate of personal protective equipment shortage was as high as 69.4%; the rates of the responders who would "covering the mouth and nose when coughing or sneezing", "properly use masks in accordance with regulations", "maintain proper hand hygiene ", "avoid gatherings with relatives and friends" and "refrain from going to public places" were 92.4%, 95.9%, 93.5%, 88.8% and 93.1%, respectively. Women and groups with good knowledge of the disease reported better protective behaviors against the diseases (P < 0.05). CONCLUSIONS: The residents in Hubei and Henan Provinces have generally good KAP related to COVID-19, and the online platforms plays a positive role to in circulating epidemic-related information. It is essential to further increase the supply of the protective materials and pay more attention to the mental health of the residents during the pandemic, and psychological counseling and psychological protection should be provided if necessary.

MircoRNA-143-3p regulating ARL6 is involved in the cadmium-induced inhibition of osteogenic differentiation in human bone marrow mesenchymal stem cells.

Cadmium, which is extensively distributed in the environment, accumulates in organisms through the trophic chain. Although cadmium can cause bone injury, its role in osteogenesis of human bone marrow mesenchymal stem cells (hBMSCs) remains unclear. The present study investigated the effect of cadmium chloride (CdCl2) on osteogenesis of hBMSCs and the underlying mechanism. CdCl2 dose-dependently reduced the viability of hBMSCs. Concentrations of CdCl2 (2.5 and 5.0 µM) increased miR-143-3p levels; decreased levels of adenosine diphosphate-ribosylation factor-like protein 6 (ARL6); inhibited Wnt family member 3A (Wnt3a), ß-catenin, lymphoid enhancer factor (LEF1), and T-cell factor 1 (TCF1); and suppressed osteogenesis of hBMSCs. Inhibition of miR-143-3p or overexpression of ARL6 with lentivirus blocked these CdCl2-induced changes. Luciferase reporter assays confirmed that miR-143-3p binds to the 3'-UTR regions of ARL6 mRNA. Reduced-expression of miR-143-3p enhanced the CdCl2-induced suppression of the osteogenesis of hBMSCs and inhibition of the Wnt/ß-catenin pathway, effects that were reversed by down-regulated expression of ARL6. Thus, miR-143-3p targets ARL6 to down-regulate the Wnt/ß-catenin pathway, which is involved in the suppression of osteogenic differentiation of hBMSCs. The results provide new directions for clinical treatment of bone diseases resulting from cadmium toxicity.