Co-exposure to molybdenum and cadmium evokes necroptosis and decreases apoptosis in duck myocardium.

Superfluous molybdenum (Mo) and cadmium (Cd) in the environment are detrimental to organisms through their accumulation. The NF-κB/TNF-α axis plays a vital part in regulating necroptosis and apoptosis. However, the impacts of Mo and/or Cd on myocardium injury in ducks and the function of NF-κB/TNF-α axis are not clear in the process. In this research, ducks exposed to different dosages of Mo and/or Cd were applied as the study object. The findings substantiated that the accumulation of Mo and/or Cd caused elements imbalance and necroptosis in myocardial tissue. As p-NF-κB/TNF-α expression up-regulated, RIPK1/RIPK3/p-MLKL expression significantly increased in all treatment groups, while the expression of c-caspase-8/3 markedly decreased. Moreover, apoptosis rate obviously decreased in Cd treated groups and clearly elevated in Mo group. Mitochondria-mediated apoptosis was activated by excessive Mo and inhibited by Mo + Cd, but Cd exposure alone had little effect on it. Collectively, our research confirmed that Mo and/or Cd evoked necroptosis via NF-κB/TNF-α axis, and decreased death receptor-mediated apoptosis in duck myocardium, the impacts of Mo and/or Cd on mitochondrial-mediated apoptosis were different. These results are significant for studying toxicology of Mo and/or Cd and preserving the ecosystem.

Yoda1 Enhanced Low-Magnitude High-Frequency Vibration on Osteocytes in Regulation of MDA-MB-231 Breast Cancer Cell Migration.

Low-magnitude (≤1 g) high-frequency (≥30 Hz) (LMHF) vibration has been shown to enhance bone mineral density. However, its regulation in breast cancer bone metastasis remains controversial for breast cancer patients and elder populations. Yoda1, an activator of the mechanosensitive Piezo1 channel, could potentially intensify the effect of LMHF vibration by enhancing the mechanoresponse of osteocytes, the major mechanosensory bone cells with high expression of Piezo1. In this study, we treated osteocytes with mono- (Yoda1 only or vibration only) or combined treatment (Yoda1 and LMHF vibration) and examined the further regulation of osteoclasts and breast cancer cells through the conditioned medium. Moreover, we studied the effects of combined treatment on breast cancer cells in regulation of osteocytes. Combined treatment on osteocytes showed beneficial effects, including increasing the nuclear translocation of Yes-associated protein (YAP) in osteocytes (488.0%, p < 0.0001), suppressing osteoclastogenesis (34.3%, p = 0.004), and further reducing migration of MDA-MB-231 (15.1%, p = 0.02) but not Py8119 breast cancer cells (4.2%, p = 0.66). Finally, MDA-MB-231 breast cancer cells subjected to the combined treatment decreased the percentage of apoptotic osteocytes (34.5%, p = 0.04) but did not affect the intracellular calcium influx. This study showed the potential of stimulating Piezo1 in enhancing the mechanoresponse of osteocytes to LMHF vibration and further suppressing breast cancer migration via osteoclasts.

Aluminum (Al) causes a delayed suppression of nucleotide excision repair (NER) capacity in zebrafish (Danio rerio) embryos via disturbance of DNA lesion detection.

Aluminum (Al) is extensively used for making cooking utensils and its presence in the aquatic environment may occur through acid mine drainage and wastewater discharge. Al is known to induce genotoxicity in human cells, rodents, and fish. Nucleotide excision repair (NER) eliminates helix-twisting DNA lesions such as UV-induced dipyrimidine photoproducts. Because our earlier investigation revealed the operation of NER in zebrafish (Danio rerio) embryos, this study explored if inhibition of NER could be a mechanism of Al-induced genotoxicity using zebrafish embryo as a model system. An acute fish embryo toxicity test indicated that Al (as aluminum sulfate) at 2-15 mg/L were nonlethal to zebrafish embryos, yet exposure of embryos at 1 h post fertilization (hpf) to Al at 10-15 mg/L for 71 h significantly repressed their NER capacity monitored by a transcription-based DNA repair assay. Band shift analysis indicated a higher sensitivity of (6-4) photoproduct (6-4PP) than cyclobutane pyrimidine dimer (CPD) detecting activities to Al, reflecting the preferential influence of Al on the detection of strongly distorted DNA lesions. Time-course experiments showed a delayed response of NER to Al as repair machinery was unaffected by Al at 15 mg/L following a 35-h exposure, while Al treatment for the same period obviously inhibited 6-4PP binding activities although the gene expression of damage recognition factors remained active. Inhibition of 6-4PP detection blocked downstream lesion incision/excision detected by a terminal deoxy transferase-mediated end labeling assay. As the disturbance of damage sensing preceded that of the overall repair process, Al exposure was believed to downregulate NER capacity by inhibiting the activities of lesion detection proteins. Our results revealed the ability of Al to enhance its genotoxicity by suppressing NER capacity.

The spring-like effect of microRNA-31 in balancing inflammatory and regenerative responses in colitis.

Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders caused by the disruption of immune tolerance to the gut microbiota. MicroRNA-31 (MIR31) has been proven to be up-regulated in intestinal tissues from patients with IBDs and colitis-associated neoplasias. While the functional role of MIR31 in colitis and related diseases remain elusive. Combining mathematical modeling and experimental analysis, we systematically explored the regulatory mechanism of MIR31 in inflammatory and epithelial regeneration responses in colitis. Level of MIR31 presents an "adaptation" behavior in dextran sulfate sodium (DSS)-induced colitis, and the similar behavior is also observed for the key cytokines of p65 and STAT3. Simulation analysis predicts MIR31 suppresses the activation of p65 and STAT3 but accelerates the recovery of epithelia in colitis, which are validated by our experimental observations. Further analysis reveals that the number of proliferative epithelial cells, which characterizes the inflammatory process and the recovery of epithelia in colitis, is mainly determined by the inhibition of MIR31 on IL17RA. MIR31 promotes epithelial regeneration in low levels of DSS-induced colitis but inhibits inflammation with high DSS levels, which is dominated by the competition for MIR31 to either inhibit inflammation or promote epithelial regeneration by binding to different targets. The binding probability determines the functional transformation of MIR31, but the functional strength is determined by MIR31 levels. Thus, the role of MIR31 in the inflammatory response can be described as the "spring-like effect," where DSS, MIR31 action strength, and proliferative epithelial cell number are regarded as external force, intrinsic spring force, and spring length, respectively. Overall, our study uncovers the vital roles of MIR31 in balancing inflammation and the recovery of epithelia in colitis, providing potential clues for the development of therapeutic targets in drug design.

Psychometric Properties of the Modified Personal Diabetes Questionnaire Among Chinese Patients With Type 2 Diabetes.

This study examined the psychometric properties of the Chinese version of the Personal Diabetes Questionnaire (C-PDQ). The PDQ was translated into Chinese using a forward and backward translation approach. After being reviewed by an expert panel, the C-PDQ was administered to a convenience sample of 346 adults with Type 2 diabetes. The Chinese version of the Summary of Diabetes Self-Care Activities (C-SDSCA) was also administered. The results of the exploratory factor analysis revealed a one-factor structure for the Diet Knowledge, Decision-Making, and Eating Problems subscales and a two-factor structure for the barriers-related subscales. The criterion and convergent validity were supported by significant correlations of the subscales of the C-PDQ with the glycated hemoglobin values and the parallel subscales in the C-SDSCA, respectively. The C-PDQ subscales also showed acceptable internal consistency (α = .61-.89) and excellent test-retest reliability (intraclass correlation coefficients: .73-.96). The results provide preliminary support for the reliability and validity of the C-PDQ. This comprehensive, patient-centered instrument could be useful to identify the needs, concerns, and priorities of Chinese patients with type 2 diabetes.

[Clinical study of yishen jianpi yangxue tongli therapy in treating polycystic ovary syndrome].

OBJECTIVE: To observe the effect of Yishen Jianpi Yangxue Tongli Therapy (YJYTT) in treating polycystic ovary syndrome (PCOS) and to explore the therapeutic mechanism of YJYTT. METHODS: One hundred and seven PCOS patients with syndrome differentiation of TCM as Pi-Shen Yang deficiency were randomly divided into two groups, the treated group (n = 76) was treated with Chinese herbal medicine, while the control group (n = 31) was treated by clomiphen. The therapeutic effect in both groups and the change of body mass index (BMI), Ferriman-Gallway (F-G) score, serum sex hormones and serum oral glucose tolerance test (OGTT) before and after treatment were observed. RESULTS: The comparison of total effective rate between two groups was insignificantly different, but the pregnancy rate of the treated group (65.7%) was markedly higher than that of control group (25.0%, P < 0.01). Also, significant difference was shown in the aspect of BMI, F-G score, serum testosterone (T), luteinizing hormone (LH) and OGTT, etc. between the two groups (P < 0.05). CONCLUSION: The YJYTT could markedly improve the clinical symptoms and pregnancy rate of PCOS patients, particularly showing good effect to the clomiphen resistant patients. The mechanism possibly was due to its regulation on hypothalamus-pituitary-ovarium axis and reducing the insulin resistance.