Age-related estrogen deficiency leads to accelerated bone resorption. There is evidence that, through selective estrogen receptor modulation, isoflavones may exert beneficial effects against estrogen-deficient bone loss. Isoflavone aglycones show higher bioavailability than their glycosidic counterparts and thus may have greater potency. To summarize evidence, we executed a systematic review and meta-analysis examining isoflavone therapies and bone mineral density (BMD) loss in peri- and postmenopausal women. We systematically searched EMBASE and PubMed for randomized controlled trials (RCTs) evaluating isoflavone therapies for treating BMD loss at the lumbar spine and femoral neck in estrogen-deficient women. Separate meta-analyses were carried out with the use of random-effects models for the lumbar spine and femoral neck for all studies providing isoflavones as aglycones. Twenty-six RCTs ( = 2652) were included in the meta-analysis. At the lumbar spine, isoflavone treatment was associated with a significantly ( < 0.00001) higher weighted mean difference (WMD) of BMD change of 0.01 (95% CI: 0.01, 0.02) than the control. For the femoral neck (18 RCTs, = 1604), isoflavone treatment showed a significantly ( < 0.01) higher WMD of BMD change of 0.01 (95% CI: 0.00, 0.02) compared with the control. When isolating studies that provide isoflavone aglycones in their treatment arm, the average effect was further significantly increased at the spine (5 RCTs, = 682) to 0.04 ( < 0.00001; 95% CI: 0.02, 0.05) and femoral neck (4 RCTs, = 524) to 0.03 ( < 0.05; 95% CI: 0.00, 0.06) compared with the control. This protective effect against bone loss disappeared when only studies with formulations comprising predominantly isoflavone glycosides were included. Isoflavone treatments exert a moderately beneficial effect against estrogen-deficient bone loss in women. The effect appears dependent on whether isoflavone treatments are in aglycone form; we conclude that beneficial effects against bone loss may be enhanced for isoflavone aglycones.

BackgroundCerebral ischemia-reperfusion (CI/R) injury is a more serious brain injury caused by the recovery of blood supply after cerebral ischemia for a certain period of time. Rutaecarpine (Rut) is an alkaloid isolated from Evodia officinalis with various biological activities. Previous studies have shown that Rut has a certain protective effect on ischemic brain injury, but the specific molecular mechanism is still unknown.MethodsIn this study, a rat model of CI/R was established to explore the effects and potential molecular mechanisms of Rut on CI/R injury in rats.ResultsThe results showed that Rut alleviated neuronal injury induced by CI/R in a dose-dependent manner. Besides, Rut inhibited neuronal apoptosis by inhibiting the activation of caspase 3 and the expression of Bax. In addition, Rut alleviated the inflammatory response and oxidative stress caused by CI/R through inhibiting the production of pro-inflammatory factors (IL-6 and IL-1β), lactate dehydrogenase (LDH), malondialdehyde (MDA) and ROS, and increased the levels of anti-inflammatory factors (IL-4 and IL-10) and superoxide dismutase (SOD). Biochemically, Western blot analyses showed that Rut inhibited the phosphorylation of ERK1/2 and promoted the expression of nuclear factor-erythroid 2 related factor 2 (Nrf2) pathway-related proteins (Nrf2, heme oxygenase 1 (HO-1) and NAD (P) H-quinone oxidoreductase 1) in a dose-dependent manner. These results show that Rut may alleviate brain injury induced by CI/R by regulating the expression of ERK1/2 and the activation of Nrf2/HO-1 pathway.ConclusionIn conclusion, these results suggest that Rut may be used as an effective therapeutic agent for damage caused by CI/R.

Background: Aging is associated with variations in hypothalamic-pituitary-gonadal (HPG) axis hormones. However, it is not clear how aging changes these hormones. This study examined the natural alterations in the HPG axis in aging men and women in China. Methods: Data were obtained from our cross-sectional study (SPECT-China) in 16 areas of three provinces in East China between February and June 2014. There were 6,825 subjects selected, including 2,908 men and 3,917 women aged 25-93 years who had no diseases affecting HPG hormones and did not take exogenous supplements. Total testosterone (TT), estradiol (E2), free testosterone, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were measured. Results: In men, the ranges of the 10-90th percentiles for each hormone were as follows: TT, 9.9-23.4 nmol/l; SHBG, 20.6-79.54 nmol/l; E2, 34.84-187 pmol/l. TT values were higher in men aged 25-30 years than in those aged 31-35 years and began to increase progressively at the age of 41-50 years until men reached their eighties. The unadjusted annual age trend (β) was 0.079 nmol/l/year (p < 0.001). A linear regression analysis, after full adjustment for demographic variables, metabolic factors, other hormones, lifestyle and co-morbidities, showed that higher TT levels were still associated with aging (p < 0.05). However, the ratio of TT to LH decreased with age (β = -0.272/year, p < 0.001). E2 and SHBG increased with age (β = 1.774 pmol/l/year and 1.118 nmol/l/year, respectively, p < 0.001). In women, the 10-90th percentile range of E2 was 32.79-565.8 pmol/l. E2 began to decrease at the age of 46-50 years, declined sharply at the age of 51-55 years (β = -5.73 pmol/l/year, p < 0.001) and then stabilized at a low concentration after the age of 55 years. The 10-90th percentile ranges of LH and FSH in men were 2.4-9.2 and 3.4-15.5 IU/l, and in women they were 3-36.6 and 4-89.28 IU/l, respectively. FSH increased by 7.11% per annum in men and by 12.76% per annum in women, but LH increased by only approximately 4.00% per annum in both sexes. Conclusions: The influence of aging on the HPG axis is sex dependent. The pattern of age-related TT was different in Chinese Han men when compared with previous studies in Western populations. TT values increased in aging men, so it is not suitable to estimate the life quality of older Chinese men just based on TT.

Background: PXR (Pregnane X Receptor) and CAR (Constitutive Androstane Receptor) are termed as xenobiotic receptors, which are known as core factors in regulation of the transcription of metabolic enzymes and drug transporters. However, accumulating evidence has shown that PXR and CAR exert their effects on energy metabolism through the regulation of gluconeogenesis, lipogenesis and β-oxidation. Therefore, in this review, we are trying to summary recent advances to show how xenobiotic receptors regulate energy metabolism. Methods: A structured search of databases has been performed by using focused review topics. According to conceptual framework, the main idea of research literature was summarized and presented. Results: For introduction of each receptor, the general introduction and the critical functions in hepatic glucose and lipid metabolism have been included. Recent important studies have shown that CAR acts as a negative regulator of lipogenesis, gluconeogenesis and β -oxidation. PXR activation induces lipogenesis, inhibits gluconeogenesis and inhabits β-oxidation. Conclusion: In this review, the importance of xenobiotic receptors in hepatic glucose and lipid metabolism has been confirmed. Therefore, PXR and CAR may become new therapeutic targets for metabolic syndrome, including obesity and diabetes. However, further research is required to promote the clinical application of this new energy metabolism function of xenobiotic receptors.

Parkinson's disease (PD) is a neurodegenerative disease which results in damage in neuronal cells. Insulin-like growth factor (IGF)-1 was previously reported to play a role of neuroprotection in some diseases. Nitric oxide (NO) can also regulate neuronal cells. However, the mechanisms underlying IGF-1 and NO in PD still need to be elucidated. In present study, we explored the interaction between IGF-1 and inducible Nitric-Oxide Synthase (iNOS) in PD progression. We firstly constructed PD models by methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or MPP + treatment. Then RT-qPCR revealed that IGF-1 expression was downregulated while iNOS expression was upregulated in MPTP model. Moreover, IGF-1 elevation or iNOS depletion enhanced cell viability and blocked cell apoptosis. Rescue assay disclosed iNOS overexpression reversed the effect on viability and apoptosis mediated by IGF-1 upregulation. Furthermore, IGF-1 was identified to positively regulate miR-302b-5p which could target iNOS. MiR-302b-5p could abolish the inhibitory function IGF-1 exerted on cell apoptosis and iNOS could counteract miR-302b-5p upregulation-triggered inhibition on cell apoptosis as well. Besides, we observed the deficiency of miR-302b-5p improved the lesioned neurobehavior of MPTP-treated mice. To sum up, present study proved that miR-302b-5p enhanced the neuroprotective effect of IGF-1 in MPTP-induced PD by regulating iNOS, recommending a novel therapeutic target for PD treatment. Significance of the study: In this study, we mainly explored that IGF-1 was decreased while iNOS was boosted in MPTP-induced PD mice model; IGF-1 suppressed while iNOS promoted MPP +-induced toxicity and apoptosis in SH-SY5Y cells; miR-302b-5p ehanhced the neuroprotective effect of IGF-1 via targeting Inos; deficiency of miR-302b-5p improved the lesioned neurobehavior of MPTP-treated mice.