Ricekrabbe3774

Small noncoding microRNA (miRNA) have regulatory functions in polycystic ovary syndrome (PCOS) that differ to those in women without PCOS. However, little is known about miRNA expression in women with PCOS who are not insulin resistant (IR).

Circulating miRNAs were measured using quantitative polymerase chain reaction (qPCR) in 24 non-obese BMI and age matched women with PCOS and 24 control women. A miRNA data set was used to determine miRNA levels.

Women with PCOS showed a higher free androgen index (FAI) and anti-mullerian hormone (AMH) but IR did not differ. Four miRNAs (miR-1260a, miR-18b-5p, miR-424-5p, and miR let-7b-3p) differed between control and PCOS women that passed the false discovery rate (FDR) out of a total of 177 circulating miRNAs that were detected. MiRNA let-7b-3p correlated with AMH in PCOS (p < 0.05). When the groups were combined, miR-1260a correlated with FAI and let-7b-3p correlated with body mass index (BMI) (p < 0.05). There was no correlation to androgen levels. Ingenuity pathway analysis showed that nine of the top 10 miRNAs reported were associated with inflammatory pathways.

When IR did not differ between PCOS and control women, only four miRNA differed significantly suggesting that IR may be a driver for many of the miRNA changes reported. Let-7b-3p was related to AMH in PCOS, and to BMI as a group, whilst miR-1260a correlated with FAI. Androgen levels, however, had no effect upon circulating miRNA profiles. The expressed miRNAs were associated with the inflammatory pathway involving TNF and IL6.

When IR did not differ between PCOS and control women, only four miRNA differed significantly suggesting that IR may be a driver for many of the miRNA changes reported. Let-7b-3p was related to AMH in PCOS, and to BMI as a group, whilst miR-1260a correlated with FAI. Androgen levels, however, had no effect upon circulating miRNA profiles. The expressed miRNAs were associated with the inflammatory pathway involving TNF and IL6.The traditional Chinese medicine has long been used in the treatment of diabetes, one major disease threatening the public health. It has been reported that artemether exerts antidiabetic effects on type 2 diabetes in db/db mice, however the underlying mechanisms remain unknown. In the present study, we show that artemether regulates expression of related enzymes participating in the glucose and lipid metabolism in the liver of db/db mice, which could at least partly explain the improved glucose and lipid metabolism in artemether-treated mice. Additionally, artemether also regulates expression of glycogen synthesis related enzymes in the skeletal muscle of db/db mice, supporting its promotive role in glycogen synthesis. Mechanistically, artemether activates AMPK pathway as well as PI3K/Akt pathway in the liver and skeletal muscle of db/db mice, suggesting that these two signaling pathways are both involved in the antidiabetic effects of artemether on type 2 diabetes in db/db mice. In conclusion, our study connects the antidiabetic effects of artemether to the regulation of metabolic enzymes and signaling pathways, and also provides molecular basis for the potential application of artemether in treating type 2 diabetes.Background The fibroblast growth factors (FGF) 19 subfamily, also referred to as endocrine FGFs, includes FGF19, FGF21, and FGF23 are metabolic hormones involved in the regulation of glucose and lipid metabolism. Fetuin-A is a hepatokine involved in the regulation of beta-cell function and insulin resistance. Endocrine FGFs and fetuin-A are dysregulated in metabolic disorders including obesity, type 2 diabetes, non-alcoholic fatty liver disease and polycystic ovary syndrome (PCOS). Our study was designed to examine the response of endocrine FGFs and fetuin-A to an acute intralipid, insulin infusion and exercise in PCOS and healthy women. Subjects and Measurements Ten healthy and 11 PCOS subjects underwent 5-h saline infusions with a hyperinsulinemic-euglycemic clamp (HIEC) performed during the final 2 h. One week later, intralipid infusions were undertaken with a HIEC performed during the final 2 h. After an 8 week of exercise intervention the saline, intralipid, and HIEC were repeated. Plasma levels of endocrine FGFs and fetuin-A were measured. Results Baseline fetuin-A was higher in PCOS women but FGF19, FGF21, and FGF23 did not differ and were unaffected by exercise. Insulin administration elevated FGF21 in control and PCOS, suppressed FGF19 in controls, and had no effects on FGF23 and fetuin-A. Intralipid infusion suppressed FGF19 and increased FGF21. Insulin with intralipid synergistically increased FGF21 and did not have effects on lipid-mediated suppression of FGF19 in both groups. https://www.selleckchem.com/products/bay1251152.html Conclusion Our study provides evidence for insulin and lipid regulation of endocrine FGFs in healthy and PCOS women, suggesting that FGF family members play a role in lipid and glucose metabolism. Clinical Trial Registration www.isrctn.org, Identifier ISRCTN42448814.Background Oral squamous cell carcinoma (OSCC) that comprises about 90% of all oral cancer cases is associated with poor prognosis due to its highly metastatic nature. The majority of OSCC treatment options are related detrimental side-effects. Hypothesis/Purpose The present study aimed at deciphering the effects of a bioactive phytochemical, sodium danshensu, on human oral cancer cell metastasis. Methods and Results The treatment of FaDu and Ca9-22 cells with different doses of sodium danshensu (25, 50, and 100 μM) caused a significant reduction in cellular motility, migration, and invasion, as compared to the untreated cells. This effect was associated with a reduced expression of MMP-2, vimentin and N-cadherin, together with an enhanced expression of E-cadherin and ZO-1. Further investigation on the molecular mechanism revealed that treatment with sodium danshensu caused significant reduction in p38 phosphorylation; however, phosphorylation of ERK1/2 significantly decreased only in FaDu cells, whereas p-JNK1/2 did not show any alteration. A combination of p38 and JNK1/2 inhibitors with sodium danshensu also reduced the migration in the FaDu and Ca9-22 cell lines. Conclusion Collectively, the present study findings reveal that sodium danshensu execute anti-metastatic effect by suppressing p38 phosphorylation in human oral cancer. The study identifies sodium danshensu as a potential natural anticancer agent that can be used therapeutically to manage highly metastatic OSCC.

Brown adipose tissue (BAT) is present in humans and rodents, and contributes to energy expenditure by converting energy stored in lipids and glucose into heat. Beta adrenergic receptor (β-AR) agonists have been proposed as pharmacological tools to activate BAT, but they lack selectivity for this tissue. This study aimed to investigate the possibility to apply electrical neurostimulation as a novel approach to activate BAT by promoting the sympathetic outflow towards BAT.

Male C57BL/6J mice were treated with either unilateral electrical neurostimulation of interscapular BAT or with the β3-AR agonist CL316,243. Thermogenesis, nutrient uptake by BAT and downstream signaling of adrenergic receptors in BAT were examined.

Electrical neurostimulation and β3-AR agonism acutely increased heat production by BAT, as evidenced by an increase in local temperature in BAT, without influencing the core body temperature. Both treatments acutely increased tyrosine hydroxylase content in the nerve terminals thereby confirming enhanced sympathetic activity. In addition, we identified increased phosphorylation of hormone-sensitive lipase coinciding with reduced intracellular lipids in BAT, without affecting acute nutrient uptake from plasma. The increased BAT temperature as induced by electrical neurostimulation was reversed by β3-AR antagonism.

Electrical neurostimulation acutely promotes thermogenesis in BAT as dependent on β3-AR signaling. We anticipate that electrical neurostimulation may be further developed as a novel strategy to activate BAT and thereby combat (cardio)metabolic diseases.

Electrical neurostimulation acutely promotes thermogenesis in BAT as dependent on β3-AR signaling. We anticipate that electrical neurostimulation may be further developed as a novel strategy to activate BAT and thereby combat (cardio)metabolic diseases.Epidemiologic analyses have shed light on an association between type 2 diabetes (T2D) and pancreatic ductal adenocarcinoma (PDAC). Recent data also suggest a potential relationship between T2D and insulinoma. Under rare circumstances, type 1 diabetes (T1D) can also be implicated in tumorigenesis. The biological mechanisms underlying such relationships are extremely complex. Some genetic factors contributing to the development of T2D are shared with pancreatic exocrine and endocrine tumors. link2 Obesity and overweight can also contribute to the initiation and severity of T2D, while aging may influence both endocrine and exocrine tumors. Finally, pharmacological treatments of T2D may have an impact on PDAC. On the other hand, some treatments for insulinoma can trigger diabetes. In the present minireview, we discuss the cellular and molecular mechanisms that could explain these interactions. This analysis may help to define new potential therapeutic strategies.Objective To demonstrate the association between pre-pregnancy maternal overweight, obesity, and perinatal outcomes of singletons conceived by assisted reproductive technology (ART). Design Retrospective cohort study from 2006 to 2015 data from a single ART center. Setting Assisted Reproduction Center, Northwest Women's and Children's Hospital, Xi'an, Northwestern China. Patients We included 7,818 women undergoing ART and their singleton infants. Interventions None. link3 Main Outcome Measure The primary outcome measures were preterm birth (PTB), macrosomia, low birth weight, small for gestational age, and large for gestational age (LGA). Results We experienced an increase in the risk of PTB, macrosomia, and LGA in overweight and obese groups compared with that in normal-weight groups [PTB overweight vs. normal weight odds ratio [OR] = 1.44, 95% CI 1.18-1.75; obesity vs. normal weight OR = 1.53, 95% CI 1.04-2.25; macrosomia overweight vs. normal weight OR = 1.78, 95% CI 1.48-2.14; obesity vs. normal weight OR = 2.16, 95% CI 1.52-3.06; LGA overweight vs. normal weight OR = 1.63, 95% CI 1.39-1.90; obesity vs. normal weight OR = 2.11, 95% CI 1.57-2.83]. We observed a significant interaction between maternal BMI and fresh/frozen embryo transfer on PTB and LGA (P = 0.030; P = 0.030). Fresh embryo transfer significantly increased the effect of maternal BMI on LGA (fresh OR = 1.14, 95% CI 1.10-1.18; frozen OR = 1.09, 95% CI 1.04-1.13), and frozen embryo transfer increased the effect of maternal BMI on PTB (fresh OR = 1.03, 95% CI 0.99-1.08; frozen OR = 1.09, 95% CI 1.04-1.15). Conclusions Pre-pregnancy maternal overweight and obesity were associated with higher risks of PTB, macrosomia, and LGA in ART-conceived singletons. These associations were affected by the timing of embryo transfer (fresh/frozen embryo transfer). Therefore, we recommend women before ART to maintain a normal BMI for the prevention of adverse perinatal outcomes.