Gegen Qinlian Decoction Ameliorates Hepatic Insulin Resistance by Silent Information Regulator1 (SIRT1)-Dependent Deacetylation of Forkhead Box O1 (FOXO1).

BACKGROUND Gegen qinlian decoction (GGQLD) is a form of traditional Chinese medicine used for hundreds of years for its efficacy in treating diabetes. However, the mechanisms underlying the therapeutic effects of GGQLD on diabetes are still not clear. We aimed to evaluate the effect of GGQLD on hepatic insulin resistance (IR) through silent information regulator1 (SIRT1)/forkhead box O1 (FOXO1) in an IR mouse model. MATERIAL AND METHODS A high-fat diet (HFD) mouse model was established and GGQLD was administrated by oral gavage. Metabolic parameters were detected, including body weights, triglyceride, fasting glucose, fasting insulin and HOMA-IR index, glucose intolerance, and insulin resistance. HE-stained sections were used to observe the histopathology of liver tissue. For in vitro study, GGQLD-medicated serum was used to treat palmitic acid-stimulated HepG2 cells. The glycogen synthesis and downstream SIRT1/FOXO1 signaling pathways were examined. Specific siRNAs were used to knock down SIRT1 in HepG2 cells. RESULTS GGQLD administration significantly decreased body weights, triglyceride level, fasting glucose level, fasting insulin level, and HOMA-IR index, and improved IR in HFD mice. GGQLD enhanced SIRT1 expression and suppressed the expression of Ac-FOXO1 in liver tissues. Further, GGQLD-medicated serum promoted SIRT1 upregulation and suppressed Ac-FOXO1 levels in palmitate-stimulated HepG2 cells. GGQLD-medicated serum also increased the protein expression of PPARγ and reduced the expression of FABP4 in palmitate-stimulated HepG2 cells. CONCLUSIONS We found that GGQLD alleviates insulin resistance through SIRT1-dependent deacetylation of FOXO1.

Bu-shen-zhu-yun decoction inhibits granulosa cell apoptosis in rat polycystic ovary syndrome through estrogen receptor α-mediated PI3K/AKT/mTOR pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Bu-shen-zhu-yun decoction (BSZYD) is a traditional chinese herbal prescription is widely used in the treatment of infertility. AIM OF THE STUDY: We aimed to elucidate the impact of a traditional herbal prescription BSZYD on polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: The candidate active compounds in BSZYD and their putative targets were investigated by bioinformatics analysis. A deydroepiandrosterone (DHEA)-induced PCOS rat model was then constructed using female Sprague-Dawley (SD) rats. Serum hormone levels were measured by enzyme-linked immunosorbent assay (ELISA). Pathological changes in ovarian tissues were analyzed with hematoxylin and eosin (H&E) staining. The expressions of estrogen receptor α (ER α)-mediated PI3K/AKT/mTOR pathway were measured by immunofluorescence and western blotting. RESULTS: Bioinformatics analysis showed that the putative targets of active compound candidates in BSZYD were enriched in PI3K/AKT and estrogen signaling pathways related to regulating ovarian ovulation. Animal experiments showed that BSZYD significantly alleviated pathological changes in the ovary, altered hormone levels of serum and reduced apoptosis rate of granulosa cells. In addition, BSZYD treatment notably upregulated the expressions of proteins in ER α-mediated PI3K/AKT/mTOR pathway and downregulated apoptosis-related proteins in PCOS rats. CONCLUSION: BSZYD can restore ovary lesions and ameliorate apoptosis through ER α-mediated PI3K/AKT/mTOR pathway, which might partly contribute to the treatment of PCOS.

Berberine Ameliorates Hepatic Insulin Resistance by Regulating microRNA-146b/SIRT1 Pathway.

OBJECTIVE: Hepatic insulin resistance is a major initiating factor for type 2 diabetes mellitus. In previous study, Gegen Qinlian Decoction containing berberine could enhance hepatic insulin sensitivity by SIRT1-dependent deacetylation of FOXO1. However, it is not clear whether berberine also can improve hepatic insulin sensitivity by SIRT1/FOXO1 pathway. This study aimed to evaluate the efficacy of berberine for improving hepatic insulin resistance and the possible molecular mechanisms involved. METHODS: In vitro, HepG2 cells were induced with palmitic acid, and glycogen synthesis was examined. In vivo, a high-fat diet (HFD)-fed mouse model was established, and metabolic parameters were assessed. The expressions of miR-146b and sirtuin 1 (SIRT1) in liver were also examined. The relationship between miR-146b and SIRT1 was examined by the dual-luciferase reporter gene assay. RESULTS: Serum biochemical parameters, such as glucose and HOMA-IR index, were increased in HFD mice; miR-146b and SIRT1 were abnormally expressed in HFD mice and palmitic acid-treated HepG2 cells. Interestingly, berberine reduced body weight and caused a significant improvement in glucose tolerance and HOMA-IR index without altering food intake in mice. Overexpression of miR-146b abolished the protective effect of berberine on palmitic acid-induced impaired glycogen synthesis in HepG2 cells. Luciferase assay showed that miR-146b directly targeted SIRT1. CONCLUSION: The present findings suggest that berberine could attenuate hepatic insulin resistance through the miR-146b/SIRT1 pathway, which may represent a potential therapeutic target for the prevention and treatment of metabolic diseases, particularly diabetes.

Comparative assessment of functional properties, free and bound phenolic profile, antioxidant activity, and in vitro bioaccessibility of rye bran and its insoluble dietary fiber.

In cereals, 95% of dietary fiber is associated with phenolic compounds. The present study examined the functional properties, phenolic composition, antioxidant activity, and in vitro bioaccessibility of phenolics and flavonoids present in rye bran (RB) and its insoluble dietary fiber (IDF). Compared to RB, higher functional properties (WHC, WRC, and OHC) were represented by IDF due to its porous structure. The IDF contained lower free but higher bound phenolics and flavonoids content as compared to RB, whereas highest total phenolics (556.6 mg GAE/100 g) and flavonoids (378.3 mg RE/100 g) content were observed in IDF. Results had identified significant differences (p < .05) in phenolic acids composition between RB and IDF determined by HPLC-MS and the total phenolic acids were higher in IDF. The antioxidant capacity of IDF was higher than RB in DPPH, FRAP, ABTS, and reducing power assay. However, the in vitro phenolics and flavonoids bioaccessibility of IDF was much lower because of its high content of bound phenolics and flavonoids. PRACTICAL APPLICATIONS: A successful comparative study between RB and its IDF has been conducted in this research work that edifies the health benefits associated with the phytochemicals linked with RB and IDF. The present study also carries rich information regarding the cereal chemistry of RB that truly facilitates the food developers to specifically focus on the bioaccessibility of phenolic compounds present in IDF and RB. The findings about the functional properties and antioxidant capacities of RB and its IDF can also open new research horizons when dealing with food product development tasks, specifically related to therapeutic and medically tailored meals for the targeted customers.

Clinical value of early laparoscopic therapy in the management of tubo-ovarian or pelvic abscess.

Broad-spectrum antibiotics are the conservative treatment for tubo-ovarian abscess (TOA) or pelvic abscess, but the failure rate of antibiotic therapy remains higher in patients with a larger abscess. The present study aimed to evaluate the clinical value of early laparoscopic therapy in the management of TOA or pelvic abscess. A total of 100 patients were enrolled and their medical records were retrospectively analyzed after excluding 6 patients with malignant diseases. Based on the treatment they had received, the patients were divided into a conservative treatment group (n=41) and an early laparoscopic treatment group (n=53). In the conservative treatment group, 21 patients (51.2%) finally received laparoscopic exploration (late laparoscopic treatment group), and 20 patients (48.8%) achieved a success of antibiotic therapy (successful antibiotic therapy group). The cut-off value of abscess size for predicting antibiotic treatment failure was determined using receiver operating characteristic curve analysis. Multivariate logistic regression analyses were used to explore the association between the clinical variables and antibiotic therapy failure in conservative treatment group. The durations of elevated temperature >38.0°C and hospitalization were significantly longer in the conservative treatment group than those in the early laparoscopic treatment group (all P<0.001). The patients in the late laparoscopic treatment group had a larger abscess size than those in the successful antibiotic therapy group (6.2±1.8 cm vs. 4.8±1.4 cm, P=0.008). An abscess diameter of 5.5 cm was obtained as the cut-off of antibiotic failure, and the sensitivity and specificity were 81.0 and 85.0%, respectively. An abscess diameter of ≥5.5 cm was independently associated with antibiotic failure (odds ratio=5.724; 95%CI: 2.025-16.182; P=0.001). In conclusion, early laparoscopic treatment was associated with a better clinical prognosis than conservative treatment and late laparoscopic therapy for TOA or pelvic abscess patients.

Magnesium isoglycyrrhizinate ameliorates liver fibrosis and hepatic stellate cell activation by regulating ferroptosis signaling pathway.

Ferroptosis is recently reported as a new mode of regulated cell death. It is triggered by disturbed redox homeostasis, overloaded iron and increased lipid peroxidation. Howerver, the role of ferroptosis in hepatic fibrosis remains obscure. In the current study, we attempted to investigate the effect of Magnesium isoglycyrrhizinate (MgIG) on ferroptosis in liver fibrosis, and to further clarify the possible mechanisms. Our data showed that MgIG treatment markedly attenuated liver injury and reduced fibrotic scar formation in the rat model of liver fibrosis. Moreover, experiments in vitro also confirmed that MgIG treatment significantly decreased expression of hepatic stellate cell (HSC) activation markers. Interestingly, HSCs treated by MgIG presented morphological features of ferroptosis. Furthermore, MgIG treatment remarkably induced HSC ferroptosis by promoting the accumulation of iron and lipid peroxides, whereas inhibition of ferroptosis by specific inhibitor ferrostatin-1 (Fer-1) completely abolished MgIG-induced anti-fibrosis effect. More importantly, our results determined that heme oxygenase-1 (HO-1) was in the upstream position of MgIG-induced HSC ferroptosis. Conversely, HO-1 knockdown by siRNA evidently blocked MgIG-induced HSC ferroptosis and in turn exacerbated liver fibrosis. Overall, our research revealed that HO-1 mediated HSC ferroptosis was necessary for MgIG to ameliorate CCl4-induced hepatic fibrosis.

Efficacy of Metformin for Benign Thyroid Nodules in Subjects With Insulin Resistance: A Systematic Review and Meta-Analysis.

Background: To evaluate the effect of metformin therapy on decreasing benign thyroid nodule volume in subjects with insulin resistance (IR). Method: Randomized controlled trials (RCTs) and self-controlled trials for the meta-analysis published, before January 31, 2018 were selected from the PubMed, Cochrane Library, Embase, Web of Science, Chinese Biomedical Literature Database, National Knowledge Infrastructure, WANFANG and VIP Database. Pooled standard mean difference with 95% confidence interval was estimated by fixed- or random-effects model depending on heterogeneity. The risk of bias using the Cochrane Collaboration's tool was used to assess the quality of the RCTs contained. The quality of self-controlled studies was evaluated using the Methodological index for non-randomized studies (MINORS) method. Results: 7 studies (3 RCTs and 4 prospective self-controlled studies) with 240 patients were considered to be appropriate for the meta-analysis. The results of the meta-analysis indicated that the volume of thyroid nodule decreased significantly after metformin therapy (SMD -0.62, 95% CI -0.98 ~ -0.27). 6 studies reported the changes of the level of TSH. TSH levels decreased significantly after metformin therapy (SMD -0.27, 95% CI -0.47 ~ -0.07). The pooled data indicated an increase in FT3 level, and an unchanged FT4 level after metformin therapy (FT3, SMD 0.25, 95% CI 0.05 ~ 0.45; FT4, SMD -0.07, 95% CI -0.27 ~ 0.13). HOMA-IR levels decreased significantly after metformin therapy based on the pooled results of 3 RCTs and 3 prospective self-controlled studies (SMD -1.08, 95% CI -1.69 ~ -0.47). Conclusion: The meta-analysis demonstrated that metformin was safe and useful in shrinking benign thyroid nodules volume, improving thyroid function and IR. A large number of high-quality prospective studies still need to be carried out.

Association between DNA methylation of SORL1 5'-flanking region and mild cognitive impairment in type 2 diabetes mellitus.

OBJECTIVES: In the present study, we examined whether DNA methylation of the sortilin-related receptor 1 (SORL1) 5'-flanking region is associated with the manifestation and clinical presentation of mild cognitive impairment in type 2 diabetes mellitus (T2DM). METHODS: Of 84 diabetic patients with mild cognitive impairment (MCI group), 78 diabetic patients without mild cognitive impairment (NMCI group) and 80 age-matched normal controls (NC group), the DNA methylation of the SORL1 5'-flanking region was completely analyzed. The SORL1 methylation ratios of the above three groups were compared statistically. Next, we investigated the correlation between the DNA methylation status and the clinical presentation of diabetes with or without cognitive impairment (MCI and NMCI groups). RESULTS: The methylation ratio (86.9%) of MCI patients was significantly higher than that in the NMCI patients (35.9%, P<0.05) and in the NC group (11.3%, P<0.05). Moreover, the diabetic patients with methylation alleles had greater ages, longer diabetes duration, lower MOCA scores and higher plasma amyloid Aß 1-42 levels than those with unmethylation alleles (P<0.05). CONCLUSION: These results suggested that the DNA methylation of the SORL1 5'-flanking region may significantly influence the manifestation of mild cognitive impairment in T2DM, and might be associated with its neurocognitive presentation.

A study on the correlation between MTHFR promoter methylation and diabetic nephropathy.

OBJECTIVE: In order to observe the relationship between MTHFR promoter and DN, the determinations on MTHFR promoter methylation level and expression of HCY from DN patients have been carried out. METHODS: According to the Diabetes diagnosis and classification standard from WHO in 1999, 85 patients with DM diagnosed by Endocrinology and 30 healthy participants from our medical examination center were chosen as control specimen to study in this paper. All this specimen were divided into A, B, C and D four groups , which are corresponding simple diabetes mellitus group (SDM), early diabetic nephropathy group (EDN), clinical diabetic nephropathy group (CDN) and normal control group. And then, all common materials and clinical experiments data have been collected respectively. (1) Extracted the peripheral blood DNA of each group and determinate the methylation status of MTHFR gene promoter by PCR (MSP). (2) Determinated the serum HCY protein expression of each group. RESULTS: (1) The MTHFR promoter methylation of SDM and diabetic nephropathy group are wear off comparied with normal control group. And MTHFR promoter was in demethylation state in normal control group, a slightly weak in SDN, a obviously weak in early diabetic nephropathy group; the MTHFR promoter was in methylation state in clinical diabetic nephropathy group. (2) The HCY protein of simple diabetes mellitus group, early diabetic nephropathy group and clinical diabetic nephropathy group are Pitch with normal control group. HCY protein level of each group are as 7.41±1.61 umol/L, 10.34±2.89 umol/L, 10.95±5.89 umol/L and 13.03±6.14 umol/L corresponding normal control group, simple diabetes mellitus group, early diabetic nephropathy group and clinical diabetic nephropathy group. And there is no statistical significance about the differences among four groups. CONCLUSION: The demethylation state of MTHFR promoter was obviously weaker in clinical diabetic nephropathy group than in SDM. The level of serum HCY was obviously higher in clinical diabetic nephropathy group than in SDM. It suggested that MTHFR promoter demethylation may be involoed in the pathogenesis of DN.

[One case of overseas imported quartan malaria].

A case of overseas imported quartan malaria was reported in Weihai City. The patient worked in Africa for many years, had no blood transfusion history, and had not been to malaria endemic regions of China. In approximately half a month after returning from Africa, the patient appeared suspected malaria symptoms, such as irregular fever, sweating, and headache. The patient was diagnosed as quartan malaria by a blood test in basic hospital, reviewed with a microscope by Weihai Centre for Disease Control and Prevention, and checked through the microscopic examination of malaria diagnosis and reference laboratory and PCR amplification by Shandong Institute of Parasitic Diseases. The patient was cured after the treatment with chloroquine/ primaquine for 8 days, and did not recur in the 3-month following up.