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Lipids and insulin regulate mitochondrial-derived peptide (MOTS-c) in PCOS and healthy subjects.

Polycystic ovarian syndrome (PCOS) is a heterogeneous endocrine disorder associated with mitochondrial dysfunction and insulin resistance (IR). MOTS-c, a mitochondrial peptide, promotes insulin sensitivity (IS) through activating AKT and AMPK-dependent pathways. The current study was designed to examine the response of MOTS-c to lipids (intralipid) followed by insulin in PCOS and healthy subjects.

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Effect of AMPK/Akt/mTOR pathway on cytokine-induced killer cells immunotherapy on colorectal cancer cells.

To investigate the effect of cytokine-induced killer cells (CIKs) immunotherapy on colorectal cancer cells and the possible mechanisms using co-culture model of CIKs and human colorectal cancer cells.

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1,25(OH)D Activates Autophagy to Protect against Oxidative Damage of INS-1 Pancreatic Beta Cells.

Diabetes mellitus is a serious disease endangering human health worldwide. Vitamin D (Vit D) is a well-characterized regulator of calcium-phosphorus metabolism that also exerts other biological effects extending far beyond mineral homeostasis. Some epidemiological studies have suggested that Vit D has a role in defense against diabetes, although the mechanism remains unclear. Autophagy, an intracellular catabolic process, is necessary to maintain the normal structure and function of host cells. In our previous study, we found that Vit D could induce autophagy of pancreatic beta cells and prevent insulitis, although the underlying mechanisms remain to be fully elucidated. In this study, the protective effect of 1,25(OH)D, the physiologically active metabolite of Vit D, against streptozotocin-induced cytotoxicity in rat insulinoma cell line (INS-1) cells was explored. Cell viability and insulin secretion of INS-1 cells in response to different treatments were measured with a cell counting kit and enzyme-linked immune absorbent assay (ELISA), respectively. In addition, malondialdehyde (MDA) content and total antioxidant capacity (T-AOC) were measured by ELISA. RT-PCR and Western blot analyses were used to detect autophagy levels, reactive oxygen species (ROS) was assessed by fluorescence microscope, ultrastructure analysis was performed using transmission electron microscopy. The results demonstrated that 1,25(OH)D could increase cell viability and insulin secretion of INS-1 cells, and protected cells from oxidative damage induced by streptozotocin (STZ) through autophagy activation. These findings shed light on mechanisms underlying the ameliorative effects of Vit D on diabetes mellitus.

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Adiponectin: A Predictor for Breast Cancer Survival?

Breast cancers in women with low serum adiponectin levels have been reported to show phenotypes that are more aggressive. In 2008, we investigated the relationship between serum adiponectin levels and breast cancer in our case-controlled study involving 83 patients, in which serum adiponectin levels were measured preoperatively. In this study, we aimed to investigate the relationship between serum adiponectin levels and breast cancer-specific survival among these 83 patients.

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Rapid transport of insulin to the brain following intranasal administration in rats.

We previously reported that intranasal insulin protects substantia nigra dopaminergic neurons against 6-hydroxydopamine neurotoxicity in rats. This study aimed to assess insulin pharmacokinetics in the rat brain following intranasal application. Recombinant human insulin (rh-Ins) or phosphate buffer solution was administered to both nostrils of rats. Animals were sacrificed at 15 minutes, 1, 2, and 6 hours to determine insulin levels in different brain regions by an ultrasensitive, human-specific enzyme-linked immunosorbent assay kit. For fluorescence tracing study, rats were administered with intranasal florescence-tagged insulin (Alex546-Ins), and brains were fixed at 10 and 30 minutes to prepare sagittal sections. rh-Ins was detected in all brain regions examined except the cerebral cortex. The highest levels were detected in the brainstem, followed by the cerebellum, substantia nigra/ventral tegmental area, olfactory bulb, striatum, hippocampus, and thalamus/hypothalamus. Insulin levels reached a peak at 15 minutes and then declined gradually overtime, but remained significantly higher than baseline levels at 6 hours in most regions. Consistently, widespread Alex546-Ins-binding cells were detected in the brain at 10 and 30 minutes, with the olfactory bulb and brainstem showing the highest while the cerebral cortex showing lowest fluorescence signals. Double-immunostaining showed that Alex546-Ins-bindings were primarily co-localized with neuronal nuclei-positive neurons. In the subtantia nigra, phospho-Akt was found to be activated in a subset of Alex546-Ins and tyrosine hydroxylase double-labeled cells, suggesting activation of the Akt/PI3K pathway in these dopaminergic neurons. Data from this study suggest that intranasal insulin could effectively reach deep brain structures including the nigrostriatal pathways, where it binds to dopaminergic neurons and activates intracellular cell survival signaling. This study was approved by the Institutional Animal Care Committee at the University of Mississippi Medical Center (protocol 1333A) on June 29, 2015.

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[ANTHROPOMETRIC CHARACTERISTICS AND PARAMETERS OF LIPID-CARBOHYDRATE METABOLISM IN PATIENTS WITH NONALCOHOLIC FATTY LIVER DISEASE AND HYPERTENSION DEPENDING ON THE DEGREE OF HEPATIC STEATOSIS].

The aim of the study was to establish the relationship between anthropometric characteristics, lipid-carbohydrate metabolism parameters, endothelial lipase (EL) levels of blood serum depending on the degree of liver steatosis in patients with non-alcoholic fatty liver disease and hypertension. 60 patients with NAFLD on the background of hypertension and overweight were examined. The examined patients were divided into three groups: with hypertension without increasing the NAFLD liver fat score (group 1, n = 16), with steatosis on the background of hypertension (group 2, n = 20), with steatosis with hypertension and with laboratory signs of steatohepatitis (group 3, n = 24). All patients were divided with accordance of age and sex. The contol group consisted of 20 healthy individuals. To identify liver steatosis, NAFLD liver fat score was used according to the formula: NAFLD liver fat score = - 2.89 + 1.18 × Metabolic syndrome (yes = 1/no = 0) + 0.45 × type 2 DM (yes = 2/no = 0) + 0.15 × insulin (mU /L) + 0.04 × AST (U/L) - 0.94 × AST/ALT. The concentration of EL serum was determined by ELISA method using Aviscera Bioscience INC reagents kit (USA). The study revealed a significant difference in groups of surrogate coefficient hepatic steatosis (NAFLD liver fat score), which also takes into account the sensitivity to insulin, significantly (SS effect 27,39; MS effect 13,69; F = 6,73; p = 0,002) increases from group to group with steatosis to steatohepatitis. In patients with steatohepatitis, the expression of abdominal fatty deposits is greater than in those who have steatosis. Thus, simultaneously with increasing BMI and abdominal fat deposition, significantly increases the concentration of triglycerides, LDL, and VLDL. The concentration of EL, which is involved in the metabolism of HDL, is lowest in patients of the control group (does not exceed 10 mmol / l) and increases progressively with steatosis with hypertension and with steatohepatitis compared with those suffering from hypertension without steatosis. In addition, an increase in EL is associated with the presence of metabolic disorders, which, in aggregate, makes it possible to attribute it to independent markers of the atherosclerotic process and cardiovascular risk.

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Methylation and Acetylation Enhanced the Antidiabetic Activity of Some Selected Flavonoids: In Vitro, Molecular Modelling and Structure Activity Relationship-Based Study.

Flavonoids have been reported to exert antihyperglycemic effects and have potential to enhance the current therapy options against type 2 diabetes mellitus. However, the structure activity relationships (SAR) studies of flavonoids against this disease have not been thoroughly comprehended. Hence, in the present study, 14 structurally related flavonoids viz. wogonin, techtochrysin, norwogonin, isoscutellarein, hypolaetin, kaempferol, quercetin, methyl ether of wogonin, acetate of wogonin, acetate of norwogonin, 8-hydroxy-7-methoxyflavone, chrysin, (+)-catechin and (-)-epicatechin were taken into account for in vitro antidiabetic evaluation. Cell viability of RIN-5F pancreatic cells and 3T3-L1 pre-adipocyte cells was initially tested, then an insulin secretion assay of RIN-5F as well as adipogenesis and glucose uptake measurements of adipocyte were investigated. Subsequently, protein expressions study through adipokines measurement (leptin, adiponectin, TNF-α, RBP-4) via enzyme-linked immunosorbent assay (ELISA) kit, Western blotting analysis against GLUT4 and C/EBP-α as well as molecular docking against GLUT1 were analyzed. The results from cell culture antidiabetic assays (insulin secretion, adipogenesis, and glucose uptake), protein expressions and molecular docking pointed that the methoxy group at position C-8 is responsible for antidiabetic property of selected flavonoids via glucose uptake mechanism indicated by up regulation of GLUT4 and C/EBP-α expressions. The mechanism could be enhanced by the addition of an acetate group at C-5 and C-7 of the flavone skeleton.

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Association of serum total bilirubin and plasma 8-OHdG in HIV/AIDS patients.

Oxidative stress is a major contributor in the pathogenesis of insulin resistance (IR) and DNA damage in HIV/AIDS patients. Bilirubin has been shown to have antioxidant effects. In this case-control study, 600 subjects were included. We determined serum total bilirubin and IR in all subjects. We measured 8-hydroxy-2-deoxyguanosine with 8-hydroxy-2-deoxyguanosine enzyme-linked immunosorbent assay kit. IR and oxidative DNA damage were significantly higher in HIV-positive patients with second-line antiretroviral therapy (ART) and first-line ART than ART-naive patients. However, average serum total bilirubin was higher in ART-naive patients than the HIV-positive patients with second-line ART and first-line ART. In a logistic regression analysis, serum total bilirubin was negatively associated with the IR [odds ratio (OR): 0.0127, 95% confidence interval (CI): 0.023-0.070,  = 0.0000] and DNA damage (OR: 0.525, 95% CI: 0.351-0.783,  = 0.0016). We found that prevalence of IR and DNA damage was less in ART-naive patients compared with ART first-line and ART second-line HIV-positive patients. Larger studies are warranted to determine the molecular mechanisms involved in the negative association of serum bilirubin and DNA damage in ART naive patients.

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Effect of Dandelion Extracts on the Proliferation of Ovarian Granulosa Cells and Expression of Hormone Receptors.

In the current society, infertility related to age has become a social problem. The in vitro fertilization (IVF) success rate in women with poor ovarian response (POR) is very low. Dandelion extract T-1 (DE-T1) is an effective component of the extract from the leaves and stems of Taraxacum officinale, which is one of the medicines used in some patients with POR, but its molecular mechanism remains unclear.

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Hesperidin inhibits insulin-induced phosphoinositide 3-kinase/Akt activation in human pre-B cell line NALM-6.

It has been shown that hesperidin induces apoptosis in NALM-6 cells through inhibition of nuclear factor-kappa B (NF-κB) activation.

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