Vitamin D supplementation in the treatment of polycystic ovary syndrome: A meta-analysis of randomized controlled trials.

Background: Vitamin D level is closely associated with the development of polycystic ovary syndrome (PCOS). We aimed to systematically evaluate the effects of vitamin D supplementation on patients with PCOS, to provide reliable evidence to the clinical treatment of PCOS. Methods: We searched PubMed, Medline, EMbase, Cochrane Library, Web of Science, WanFang, China national knowledge infrastructure(CNKI) and Weipu databases for randomized controlled trials (RCTs) on vitamin D supplementation for the treatment of PCOS. Two reviewers independently screened literature, extracted data and evaluated the risk of bias of included RCTs. RevMan 5.3 software was used for meta-analysis. Results: 13 RCTs with 840 PCOS patients were included finally. Meta-analyses indicated that vitamin D supplementation increase the serum vitamin D level[mean difference(MD) = 17.81, 95% confidence interval(CI) (10.65, 24.97)] and endometrial thickness [MD = 1.78, 95%CI (0.49, 3.06), P = 0.007], reduce the serum hs-CRP [MD = -0.54, 95%CI (-1.00, -0.08)], parathyroid hormone[MD = -14.76, 95%CI (-28.32, -1.19)], total cholesterol[MD = -12.00, 95%CI (-18.36, -5.56)] and total testosterone level [MD = -0.17, 95%CI (-0.29, -0.05)] (all p < 0.05). No significant differences in the SHBG level [MD = 1.33, 95%CI (-2.70, 5.36)] and mF-G score [MD = 0.04, 95%CI (-0.79, 0.86)] between vitamin D and control group were found (all p > 0.05). Egger's tests showed that there were no publication biases in every synthesized result (all P > 0.05). Conclusion: Vitamin D may be helpful to improve the endocrine and metabolism-related indexes in patients with PCOS. More high-quality studies with larger sample size are warranted to further evaluate the role of vitamin D supplementation in patients with PCOS.

Preventive and reparative functions of host-associated probiotics against soybean meal induced growth, immune suppression and gut injury in Japanese seabass (Lateolabraxjaponicus).

A 56-day feeding trial was conducted to examine the preventive and reparative functions of host-associated probiotics against high soybean meal (SM)-induced negative effects in Japanese seabass (Lateolabrax japonicus). Fish continuously fed low SM (containing 16% SM) and high SM (containing 40% SM) diets were named as positive (PC) and negative (C) control, respectively. Preventive functions of probiotics were evaluated by continuously feeding diets LF3 (Lactococcus petauri LF3 supplemented in high SM diet, group PLF3) and LF4 (Bacillus siamensis LF4 supplemented in high SM diet, group PLF4), while reparative functions were estimated by feeding the high SM diet during 0-28 days, then feeding diets LF3 (group RLF3) and LF4 (group RLF4) until day 56. Compared with the group PC, suppressed growth and immunity, and damaged intestinal health were observed in the group C on days 28 and 56. Fish in groups PLF3 and PLF4, rather than in groups RLF3 and RLF4, showed higher growth compared with the group C and displayed similar immune status to the group PC, indicating that the initial and continued application of probiotic LF3 and LF4 can efficiently improve high SM induced growth and immune deficiency in Japanese seabass, but probiotics had limited reparative benefits when they were administrated at the middle of the feeding trial (28 d). Furthermore, probiotics showed good preventive functions and limited reparative functions on gut health via improving intestinal morphology and inflammation markers, for example, decreasing diamine oxidase activity and d-lactate content, while up-regulating anti-inflammatory TGF-ß1 expression and down-regulating pro-inflammatory TNF-α, IL-1ß, and IL-8 expressions. Moreover, dietary supplementation of probiotics (especially on day 56) could effectively shape the gut microbiota, such as significantly decreasing abundances of opportunistic pathogens (phylum Actinobacteria, genera Pseudomonas and Moheibacter on day 28, phylum Proteobacteria, genus Plesiomonas on day 56), significantly increasing gut microbial diversity and abundances of possible beneficial bacteria (phylum Bacteroidetes and genus Lactobacillus on day 28, phyla Firmicutes, Bacteroidetes and Cyanobacteria, genera Bacillus, Lactobacillus and Bacteroides on day 56). In conclusion, we evidenced for the first time that host-associated L. petauri LF3 and B. siamensis LF4 can provide effectively preventive and certain reparative functions against high SM-induced adverse effects in L. japonicus.

Study on inhibition of Britannin on triple-negative breast carcinoma through degrading ZEB1 proteins.

BACKGROUND: Triple-negative breast carcinomas (TNBCs) are a breast carcinoma with the most aggressive form, which is demonstrated as enhanced invasion and recurrence. Britannin is extracted mainly from the traditional Chinese herb Inula japonica Thunb, and few studies have focused on its effect on TNBC. Moreover, there is still no report concerning the role of Britannin in degrading the transcripts of Zinc finger E-box-binding homeobox 1 (ZEB1) proteins. PURPOSE: To explore the potential effect of Britannin on invasion and stemness of TNBCs and its underlying mechanism. METHODS: Cellular activity was measured using MTT, and cell cycle was measured using flow cytometry (FCM). The effect of Britannin on the migrating and invading abilities of MDA-MB-231 and 4T1 cells were measured using the wound healing and transwell assays. The sizes and number of breast carcinoma cells were measured by tumor formation assay and in vitro limiting-dilution assay. CD44 expression in tumor spheroids was tested by immunofluorescence assay. Nextly, the expressions of epithelial-mesenchymal transition (EMT) markers and ZEB1 protein expressional level were detected by western blot . ZEB1 mRNA expressional level was analyzed using RT-qPCR. Drug affinity-responsive target stability (DARTS) method was used to detect the binding activity between Britannin and ZEB1. Co-immunoprecipitation (Co-IP) analysis was applied to test the ubiquitination of ZEB1. The mouse models for experimental lung metastasis of 4T1 cells were established to detect the anti-metastasis effect of Britannin in vivo, and the expressional levels of EMT markers in lung metastases were detected by immunohistochemistry. RESULTS: Britannin could inhibit cell growth and G2/M arrest in TNBC cells. Britannin could inhibit the migrating and invading ability without inducing severe apoptosis of MDA-MB-231 and 4T1 cells. Meanwhile, Britannin reduced the size and number of spheroids formed in these two cells, and decreased the expressional level of stem cells biomarker CD44 in tumor spheroids. Mechanism research showed that Britannin specifically bound to ZEB1 and induced its ubiquitination in MDA-MB-231 cells. Afterwards, Britannin disturbed protein stability and promoted ZEB1 protein degradation. Importantly, Britannin could not inhibit cell invasion and spheroid formation after ZEB1 expression was knocked down. Finally, Britannin inhibition of 4T1 cell metastasis was confirmed through establishing mouse models for the experimental lung metastasis. It was proved that both Britannin and paclitaxel could decrease the lung metastases, and Britannin could also down-regulate the protein expressional levels of ZEB1, MMP9 and CD44. CONCLUSION: This study reveals that Britannin suppresses the invasion and metastasis of TNBC cells through degrading ZEB1, which suggests that Britannin can be used to prevent tumor metastasis and recurrence via degrading ZEB1proteins.

Modification of lysine deacetylation regulates curcumol-induced necroptosis through autophagy in hepatic stellate cells.

The excessive deposition of extracellular matrix (ECM) is the main characteristic of liver fibrosis, and hepatic stellate cells (HSCs) are the main source of ECM. The removal of activated HSCs has a reversal effect on liver fibrosis. Western blot and MTT analysis indicated that curcumol could relieve hepatic fibrosis by promoting HSCs receptor-interacting protein kinase 1/3 (RIP1/RIP3)-dependent necroptosis. Importantly, autophagy flow was monitored by constructing the mRFP-GFP-LC3 plasmid, and it was found that curcumol cleared activated HSCs in a necroptosis manner that was dependent on autophagy. Our study suggested that the activation of necrosome formed by RIP1 and RIP3 depended on Atg5, and that autophagosomes were also necessary for curcumol-induced necroptosis. Furthermore, microscale thermophoresis and co-immunoprecipitation assay results proved that curcumol could target Sirt1 to regulate autophagy by reducing the acetylation level of Atg5. The HSCs-specific silencing of Sirt1 exacerbated CCl4 -induced liver fibrosis in mice. The deacetylation of Atg5 not only accelerated the accumulation of autophagosomes but also enhanced the interaction between Atg5 and RIP1/RIP3 to induce necroptosis. Overall, our study indicated that curcumol could activate Sirt1 to promote Atg5 deacetylation and enhanced its protein-protein interaction function, thereby inducing autophagy and promoting the necroptosis of HSCs to reduce liver fibrosis.

[Clinical evaluation of the antioxidant activity of astragalus in women with gestational diabetes].

OBJECTIVE: To evaluate the antioxidant activity of astragalus and its therapeutic effect on gestational diabetes. METHODS: Eighty-four pregnant women with gestational diabetes were divided into insulin and insulin plus astragalus groups after regular dietary control and insulin treatment to maintain stable blood glucose level. The 43 patients in insulin group received insulin injection, whereas the 41 patients in the other group received treatment with both insulin and astragalus. The SOD activity, MDA level, blood lipids and renal function were determined in both groups after the treatments. RESULTS: The patients with both insulin and astragalus treatments showed significantly increased serum SOD activity and decreased MDA level, renal function and blood lipids in comparison with those with exclusive insulin treatment. CONCLUSION: Astragalus can effectively control blood glucose, reduce the free radicals, and promote the antioxidative activity, and may play a role in the prevention and treatment of gestational diabetes.