Reproductive factors and risk of Parkinson's disease in women: A meta-analysis of observational studies.

Evidence on the relationship between reproductive factors, use of oral contraceptives (OCs) and the incidence of Parkinson's disease (PD) remain inconclusive. The aim of this meta-analysis is to evaluate whether relevant reproductive factors including age at menarche, age at menopause, fertile lifespan, parity, type of menopause (surgical versus natural), and use of OCs are associated with risk of PD in women via random-effects model. PubMed and EMBASE database were used to search for case-control or cohort studies published before February17, 2017. 6 case-control and 5 cohort studies were included in the meta-analysis. The pooled relative risks (RRs) of PD risk were 1.00 (95% CI: 0.79-1.28) for use of OCs (ever versus never), 1.03 (95% CI: 0.84-1.26) for age at menarche, 0.98 (95% CI: 0.75-1.29) for age at menopause, 0.98(95% CI: 0.77-1.25) for fertile lifespan, 0.99(95% CI:0.0.79-1.25) for parity, 0.93 (95% CI:0.68-1.29) for type of menopause (surgical versus natural). In the subgroup analysis stratified by study design, age, caffeine intake and smoking, an inverse association was found between surgical menopause and risk of PD for those adjusting for caffeine intake (RR: 0.67, 95% CI: 0.45-0.99) and smoking (RR: 0.77, 95% CI: 0.63-0.94); while a positive association was found between surgical menopause and PD risk for those not adjusting for smoking (RR: 1.91, 95% CI: 1.29-2.83). In conclusion, our meta-analysis provided little epidemiological support for the role of reproductive factors in the incidence of PD. Whether surgical menopause is inversely associated with the risk of PD requires further explorations.

Rosmarinic acid suppresses adipogenesis, lipolysis in 3T3-L1 adipocytes, lipopolysaccharide-stimulated tumor necrosis factor-α secretion in macrophages, and inflammatory mediators in 3T3-L1 adipocytes.

Background: Rosmarinic acid (RA) is a natural phenol carboxylic acid with many promising biological effects. It may be a suitable candidate for improving obesity-related adipose tissue dysfunction. Objective: We aimed to investigate the therapeutic use of RA as an anti-obesity agent by measuring its effects on adipogenesis, lipolysis, and messenger RNA (mRNA) expression of major adipokines in 3T3-L1 adipocytes; and its effects on lipopolysaccharide (LPS)-induced tumor necrosis factor-α (TNF-α) secretion in macrophages and inflammatory mediators in 3T3-L1 adipocytes incubated with macrophage-conditioned medium (MCM). Methods: 3T3-L1 preadipocytes were used to explore how RA affects adipogenesis, as well as the involvement of phosphorylated extracellular signal-regulated kinase-1/2 (p-ERK1/2) and mothers against decapentaplegic homolog 3 (p-Smad3). 3T3-L1 preadipocytes were also differentiated into mature adipocytes to explore how RA affects basal and isoproterenol- and forskolin-stimulated lipolysis; and how RA affects key adipokines' mRNA expression. RAW 264.7 macrophages were stimulated with LPS in the absence or presence of RA to explore RA's effects on TNF-α secretion. MCM was collected and 3T3-L1 adipocytes were incubated with MCM to explore RA's effects on interleukin-6 (IL-6), IL-1ß, monocyte chemoattractant protein-1 (MCP-1), and RANTES mRNA expression. Results: During the preadipocyte differentiation process, RA suppressed peroxisome proliferator-activated receptor-γ and CCAAT/enhancer binding protein-α, and activated p-ERK1/2 and p-Smad3; inhibition of adipogenesis by RA was partially restored following treatment with p-ERK1/2 and p-Smad3 inhibitors. In mature adipocytes, RA inhibited basal lipolysis; phosphodiesterase-3 inhibitor reversed this. RA also inhibited isoproterenol- and forskolin-stimulated glycerol and free fatty acid release, and the phosphorylation of hormone-sensitive lipase and perilipin. RA had no effects on leptin, adiponectin, resistin, or visfatin mRNA expression. RA suppressed TNF-α mRNA expression and secretion in LPS-stimulated RAW 264.7 macrophages; and reduced LPS-MCM-induced IL-6, IL-1ß, MCP-1, and RANTES mRNA expression in 3T3-L1 adipocytes. Conclusions: RA exerts inhibitory effects on adipogenesis, lipolysis, and inflammation. RA could be a promising natural product for improving adipose mobilization in obesity.

The combination of 1α,25dihydroxyvitaminD3 with resveratrol improves neuronal degeneration by regulating endoplasmic reticulum stress, insulin signaling and inhibiting tau hyperphosphorylation in SH-SY5Y cells.

Endoplasmic reticulum (ER) stress is a critical factor involved in the pathogenesis of Alzheimer's disease (AD). Vitamin D and resveratrol are two nutritional factors that have reported neuroprotective effects, and findings from cellular models suggest that resveratrol could potentiate vitamin D's effects. We aimed to determine the effects of vitamin D & resveratrol on ER stress mediated neurodegeneration and whether synergistic effects existed. Tunicamycin and Aß25-35 was utilized to induce ER stress in SH-SY5Y cells, cells were then incubated with vitamin D and resveratrol. The combination of vitamin D & resveratrol completely reversed tunicamycin and Aß25-35 induced cytotoxicity in SH-SY5Y cells, as well as elevation in ER stress markers (i.e.GRP78, p-eIF2α and CHOP), insulin signaling disruption (i.e. elevation in p-IRS-1serine307 and reduction in p-Akt serine473) and tau phosphorylation (i.e. reduction in p-GSK3ß serine9, and elevation in p-Tau serine396 &404). Further studies are required to clarify whether the observed synergistic effects in the present study would also existed in vivo, this will lay scientific foundation whether the combination of vitamin D with resveratrol might be an effective maneuver in the treatment of AD in human subjects.