Hyperhomocysteinaemia Promotes Doxorubicin-Induced Cardiotoxicity in Mice.

Doxorubicin, a widely used chemotherapeutic drug in clinical oncology, causes a series of cardiac side effects referred to as doxorubicin-induced cardiotoxicity. Hyperhomocysteinaemia is an independent risk factor for multiple cardiovascular diseases. However, whether hyperhomocysteinaemia contributes to doxorubicin-induced cardiotoxicity is currently unknown. In this study, we explored the pathogenic effects of hyperhomocysteinaemia induced by dietary methionine supplementation (2% wt/wt in rodent chow) in a mouse model of doxorubicin-induced cardiotoxicity. Our data showed that methionine supplementation doubled serum homocysteine levels, inducing mild hyperhomocysteinaemia. Doxorubicin at a cumulative dosage of 25 mg/kg body weight led to significant weight loss and severe cardiac dysfunction, which were further exacerbated by methionine-induced mild hyperhomocysteinaemia. Doxorubicin-induced cardiac atrophy, cytoplasmic vacuolisation, myofibrillar disarray and loss, as well as cardiac fibrosis, were also exacerbated by methionine-induced mild hyperhomocysteinaemia. Additional folic acid supplementation (0.006% wt/wt) prevented methionine-induced hyperhomocysteinaemia and inhibited hyperhomocysteinaemia-aggravated cardiac dysfunction and cardiomyopathy. In particular, hyperhomocysteinaemia increased both serum and cardiac oxidative stress, which could all be inhibited by folic acid supplementation. Therefore, we demonstrated for the first time that hyperhomocysteinaemia could exacerbate doxorubicin-induced cardiotoxicity in mice, and the pathogenic effects of hyperhomocysteinaemia might at least partially correlate with increased oxidative stress and could be prevented by folic acid supplementation. Our study provides preliminary experimental evidence for the assessment of hyperhomocysteinaemia as a potential risk factor for chemotherapy-induced cardiotoxicity in cancer patients.

Hyperhomocysteinemia Promotes Cardiac Hypertrophy in Hypertension.

Hyperhomocysteinemia (HHcy) is positively linked with several cardiovascular diseases; however, its role and underlying mechanisms in pathological cardiac hypertrophy are still unclear. Here, we focused on the effects and underlying mechanisms of HHcy in hypertensive cardiac hypertrophy, one of the most common and typical types of pathological cardiac hypertrophy. By a retrospective analysis of the association between HHcy and cardiac hypertrophy in a hypertensive cohort, we found that the prevalence of HHcy was higher in patients with hypertrophy and significantly associated with the presence of cardiac hypertrophy after adjusting for other conventional risk factors. In mice, HHcy induced by a methionine (2% wt/wt) diet feeding significantly promoted cardiac hypertrophy as well as cardiac inflammation and fibrosis induced by 3-week angiotensin ІІ (AngІІ) infusion (1000 ng/kg/min), while folic acid (0.006% wt/wt) supplement corrected HHcy and attenuated AngII-stimulated cardiac phenotypes. Mechanistic studies further showed that homocysteine (Hcy) exacerbated AngII-stimulated expression of Calcineurin and nuclear factor of activated T cells (NFAT), which could be attenuated by folic acid both in mice and in neonatal rat cardiomyocytes. Moreover, treatment with cyclosporin A, an inhibitor of Calcineurin, blocked Hcy-stimulated Calcineurin-NFAT signaling and hypertrophy in neonatal rat cardiomyocytes. In conclusion, our study indicates that HHcy promotes cardiac hypertrophy in hypertension, and Calcineurin-NFAT pathway might be involved in the pro-hypertrophic effect of Hcy.

Association between dietary selenium intake and the prevalence of osteoporosis: a cross-sectional study.

OBJECTIVE: To examine the correlation between dietary selenium (Se) intake and the prevalence of osteoporosis (OP) in the general middle-aged and older population in China. METHODS: Data for analyses were collected from a population based cross-sectional study performed at the Xiangya Hospital Health Management Centre. Dietary Se intake was evaluated using a validated semi-quantitative food frequency questionnaire. OP was diagnosed on the basis of bone mineral density scans using a compact radiographic absorptiometry system. The correlation between dietary Se intake and the prevalence of OP was primarily examined by multivariable logistic regression. RESULTS: This cross-sectional study included a total of 6267 subjects (mean age: 52.2 ± 7.4 years; 42% women), and the prevalence of OP among the included subjects was 9.6% (2.3% in men and 19.7% in women). Compared with the lowest quartile, the energy intake, age, gender and body mass index (BMI)-adjusted odds ratios of OP were 0.72 (95% confidence interval [CI] 0.55-0.94), 0.72 (95% CI 0.51-1.01) and 0.47 (95% CI 0.31-0.73) for the second, third and fourth quartiles of dietary Se intake, respectively (P for trend = 0.001). The results remained consistent in male and female subjects. Adjustment for additional potential confounders (i.e., smoking status, drinking status, physical activity level, nutritional supplements, diabetes, hypertension, fibre intake, and calcium intake) did not cause substantial changes to the results. CONCLUSIONS: In the middle-aged and older humans, participants with lower levels of dietary Se intake have a higher prevalence of OP in a dose-response manner.

Efficacy and safety of the pulsed electromagnetic field in osteoarthritis: a meta-analysis.

OBJECTIVE: To investigate the efficacy and safety of the pulsed electromagnetic field (PEMF) therapy in treating osteoarthritis (OA). DESIGN: Meta-analysis. DATA SOURCES: PubMed, Embase, the Cochrane Library and Web of Science were searched through 13 October 2017. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials compared the efficacy of PEMF therapy with sham control in patients with OA. DATA EXTRACTION AND SYNTHESIS: Pain, function, adverse effects and characteristics of participants were extracted. RevMan V.5.2 was used to perform statistical analyses. RESULTS: Twelve trials were included, among which ten trials involved knee OA, two involved cervical OA and one involved hand OA. The PEMF group showed more significant pain alleviation than the sham group in knee OA (standardised mean differences (SMD)=-0.54, 95% CI -1.04 to -0.04, p=0.03) and hand OA (SMD=-2.85, 95% CI -3.65 to -2.04, p<0.00001), but not in cervical OA. Similarly, comparing with the sham-control treatment, significant function improvement was observed in the PEMF group in both knee and hand OA patients (SMD=-0.34, 95% CI -0.53 to -0.14, p=0.0006, and SMD=-1.49, 95% CI -2.12 to -0.86, p<0.00001, respectively), but not in patients with cervical OA. Sensitivity analyses suggested that the exposure duration <=30 min per session exhibited better effects compared with the exposure duration >30 min per session. Three trials reported adverse events, and the combined results showed that there was no significant difference between PEMF and the sham group. CONCLUSIONS: PEMF could alleviate pain and improve physical function for patients with knee and hand OA, but not for patients with cervical OA. Meanwhile, a short PEMF treatment duration (within 30 min) may achieve more favourable efficacy. However, given the limited number of study available in hand and cervical OA, the implication of this conclusion should be cautious for hand and cervical OA.