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Background: Oxidative stress has been shown to be an important factor, which plays a significant role in the pathogenesis of neurodegenerative disorders. Heat Shock Protein-27 (HSP-27) has been implicated in antioxidant responses against oxidative stress. Trehalose is a natural disaccharide widely used in a variety of food products with demonstrated protective effects against several neurodegenerative diseases. This study investigated the effects of trehalose on antioxidant responses, and the gene expressions for HSP-27 and caspase-3 against hydrogen peroxide (H2O2) induced oxidative injury in PC-12 cell line. Methods: The PC-12 cells were treated with various concentrations of H2O2 and trehalose for 24hr. The cell viability was assessed, using MTT and Lactate Dehydrogenase (LDH) release assays. Moreover, the activity of Catalase (CAT) and Glutathione Peroxidase (GPx) enzymes, and the Malondialdehyde (MDA) levels were determined. In addition, the levels of HSP-27 and caspase-3 gene expressions were measured. Results: The results indicated that the pretreatment with trehalose increased cell survival against the H2O2-induced oxidative injury. Furthermore, trehalose elevated the CAT and GPx activities and reduced MDA levels compared to that of control group (P˂0.05). Moreover, trehalose upregulated the HSP-27 gene expression, while reducing the expression of caspase-3 gene compared to that of the untreated cells (P˂0.05). All of these biochemical changes were found to be dose-dependent for trehalose. Conclusion: Based on the study findings, trehalose had the capacity to attenuate the oxidative stress and cell injury. Therefore, trehalose may be suggested as a therapeutic agent to treat neurodegenerative disorders caused by oxidative stress damages.

Multiple sclerosis (MS) is a chronic disorder characterized by reactive gliosis, inflammation, and demyelination. Microglia plays a crucial role in the pathogenesis of MS and has the dynamic plasticity to polarize between pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes. Metformin, a glucose-lowering drug, attenuates inflammatory responses by activating adenosine monophosphate protein kinase (AMPK) which suppresses nuclear factor kappa B (NF-κB). In this study, we indirectly investigated whether metformin therapy would regulate microglia activity in the cuprizone (CPZ)-induced demyelination mouse model of MS via measuring the markers associated with pro- and anti-inflammatory microglia. Evaluation of myelin by luxol fast blue staining revealed that metformin treatment (CPZ + Met) diminished demyelination, in comparison to CPZ mice. In addition, metformin therapy significantly alleviated reactive microgliosis and astrogliosis in the corpus callosum, as measured by Iba-1 and GFAP staining. Moreover, metformin treatment significantly downregulated the expression of pro-inflammatory associated genes (iNOS, H2-Aa, and TNF-α) in the corpus callosum, whereas expression of anti-inflammatory markers (Arg1, Mrc1, and IL10) was not promoted, compared to CPZ mice. Furthermore, protein levels of iNOS (pro-inflammatory marker) were significantly decreased in the metformin group, while those of Trem2 (anti-inflammatory marker) were increased. In addition, metformin significantly increased AMPK activation in CPZ mice. Finally, metformin administration significantly reduced the activation level of NF-κB in CPZ mice. In summary, our data revealed that metformin attenuated pro-inflammatory microglia markers through suppressing NF-κB activity. The positive effects of metformin on microglia and remyelination suggest that it could be used as a promising candidate to lessen the incidence of inflammatory neurodegenerative diseases such as MS.

Diabetes mellitus is an associated risk factor for coronary artery disease (CAD). There is a growing interest in myocardial infarction (MI) to better understand the relationship between hyperglycemia and CVD. Glycated hemoglobin (HbA1c) is the standard measure for assessing glucose regulation in diabetes mellitus and an indicator of potential cardiovascular risk and exposure to glucose concentrations over a duration of approximately 3 months. Glycated albumin (GA) may be useful for evaluating hyperglycemia in settings in which HbA1c screening is problematic or inaccessible. Another indicator that has been considered recently is the GA/HbA1c ratio. The goal of this study was to investigate the relationship between GA/HbA1c and the presence of MI and identify the sugar fluctuations as a suitable indicator for early screening and prevention of MI. This was a case-control study of diabetic patients with MI and patients with type 2 diabetes with no history of heart problems. Each group consisted of 117 participants (117 cases and 117 controls), and the total number of participants was 234. The data collection tools included laboratory tests and a demographic questionnaire. Each patient was assigned to either the case or the control group in a simple and convenient way and the relationship between MI and the GA/HbA1c ratio was investigated. The findings of this study indicated that the ratio of glycated albumin to glycated hemoglobin was higher in the case group with MI than the control group (p = 0.001). To achieve the objectives of the study, descriptive statistics and the Mann-Whitney test were used to analyze the data. This study revealed the relationship between MI and the GA/HbA1c ratio. It can be said that prior to the occurrence of MI, blood glucose levels are a good indicator of recent glucose fluctuations, as well as the prediction and occurrence of MI. Therefore, the improved control of blood sugar and avoidance of high fluctuation may prevent MI from occurring.

Aging is associated with an increase in oxidative stress, which damages organs such as the kidney. Trehalose has abundant beneficial activities including antioxidative effects. This study aimed to investigate the effects of trehalose on several antioxidant parameters of the aged kidney. Wistar rats were divided into three groups: young (4 months), aged (24 months), and aged-trehalose. The third group was treated with 2% trehalose for one month. The expression of target genes and enzyme activities in the kidney of the animals were evaluated by quantitative polymerase chain reaction (qPCR) and enzyme colorimetric procedures, respectively. Protein levels of NFE2L2 showed a 50% reduction in aged rats compared to young rats (P0.001), which was restored by trehalose intervention. In addition, the activity and mRNA levels of catalase (CAT) increased in aged rats while treatment with trehalose reversed this trend. On the other hand, superoxide dismutase (SOD) activity was reduced in the kidneys of aged rats but was not affected by trehalose intervention .It is concluded that trehalose supplementation alleviates the antioxidant system impairments in the kidneys of aged rats. However, further investigations are needed to thoroughly describe the antioxidative impacts of trehalose on the kidneys during aging.

Polycystic ovarian syndrome (PCOS) is a common poignant endocrine disorder affecting women, posing a close association with metabolic syndrome and obesity. Existing literature characterizes PCOS with deranged levels of several adipokines and myokines. CTRP15 is a paralogue of adiponectin, mainly expressed by skeletal muscles, and plays a key role in insulin, glucose, and lipid metabolism. In the current study, we aim to determine the circulating levels of CTRP15 and evaluate its association with cardiometabolic and inflammatory parameters in PCOS women. This case-control study included 120 PCOS patients (60 Recurrent pregnancy loss (RPL) and 60 infertile (inf) PCOS) and 60 healthy non-PCOS controls. Serum levels of hs-CRP were measured by commercial kits, while serum levels of adiponectin and CTRP15 were determined using the ELISA technique. Serum levels of CTRP15 were significantly elevated in PCOS-RPL and PCOS-inf subgroups when compared to controls (94.80 ± 27.08 and 87.77 ± 25.48 vs. 54.78 ± 15.45, both P < 0.001). Moreover, serum adiponectin was considerably lower in the PCOS group and subgroups (P < 0.001), while serum hs-CRP, fasting insulin, HOMA-IR, and free testosterone were significantly higher when compared to the non-PCOS group (P < 0.05). Furthermore, CTRP15 closely associated with FSH, HOMA-IR, hs-CRP, and BMI. These results highlight a possible involvement of CTRP15 in the pathogenesis of PCOS. The elevated levels of CTRP15 might be a compensatory mechanism for the metabolic dysregulations (excess adiposity, insulin resistance, metaflammation) associated with the syndrome. Nevertheless, future studies are necessary to unravel the underlying mechanism.

Background: Insulin resistance has a key role in the pathophysiology of polycystic ovary syndrome (PCOS). Previous investigations have informed that some lipid ratios could be a simple clinical indicator of insulin resistance (IR) in some disorders and ethnicities. We aimed to examine the correlation between triglyceride to HDL-cholesterol (TG/HDL-C), total cholesterol to HDL-cholesterol (TC/HDL-C) and fasting triglyceride-glucose (TyG) indices with IR (as measured by homeostasis model assessment of IR [HOMA-IR], quantitative insulin sensitivity check index [QUICKI] and fasting glucose to insulin ratio [FGIR]), and determine a good clinical predictor for IR in Iranian PCOS woman. Methods: We evaluated 305 PCOS women. After physical evaluations, biochemical parameters were measured using commercial kits and TG/HDL-C, TC/HDL-C and TyG indices were calculated using formula. Fasting insulin level measured using ELISA technique. IR was defined as a HOMA-IR value ≥2.63, FG-IRResults: The insulin-resistance and insulin-sensitive groups, which established by HOMA-IR, FG-IR and QUICKI values, were different in terms of TG/HDL-C, TC/HDL-C and TyG indices. These indices were associated with IR after adjusting for age and BMI. The under ROC curves (AUC) of TyG, TG/HDL-C and TC/HDL-C for predicting HOMA-IR index were 0.639, 0.619 and 0.623 respectively which were significant, with a p-value 0.012, 0.033 and 0.027, respectively. The AUC of TC/HDL-C (0.614) was significant (p-value 0.04) for predicting FG-IR.Conclusion: Our findings demonstrated that the elevated TyG, TG/HDL-C and TC/HDL-C were significantly associated with IR and could be utilized as indicators of IR among PCOS women in Iran.

Resveratrol was reported to inhibit inflammatory responses; however, the role of this polyphenol in obesity-induced skeletal muscle inflammation remains unknown. Mice fed a high fat diet (HFD) were treated with resveratrol for 16 weeks. Resveratrol treatment decreased macrophage infiltration into skeletal muscle of HFD-fed mice. Resveratrol also led to the polarization of macrophages to the M2 direction, as well as decreasing the expression of a number of M1 pro-inflammatory cytokines [tumor necrosis factor α (TNF-α), interleukin 1 β (IL-1β) and interleukin 6 (IL-6)]. In addition, increased infiltration of regulatory T cells (Treg cells) was found following resveratrol treatment in skeletal muscle of mice. Decreased intramyocellular lipid deposition was associated with reduced expression levels of toll-like receptors 2 (TLR2) and TLR4 in resveratrol treated mice. We also found that diminished inflammation in skeletal muscle following resveratrol treatment was accompanied by increasing phosphorylation of 5’-adenosine monophosphate-activated protein kinase (AMPK) and decreasing phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK). Taken together, these findings suggest that resveratrol ameliorates inflammation in skeletal muscle of HFD-induced model of obesity. Therefore, resveratrol might represent a potential treatment for attenuation of inflammation in skeletal muscle tissue.

It is indicated that malvidin has anti-inflammatory and antioxidant effects on various cells, although the function of malvidin in preventing inflammatory reactions caused by lipopolysaccharide (LPS) in peripheral blood mononuclear cells (PBMCs) is still not known. The objective of this study was to examine the impact of malvidin on inflammatory responses and oxidative stress in PBMCs as caused by LPS. The present findings showed that LPS significantly increased the expression of IL-6, TNF-α, IL-1β, and COX-2 mRNA and protein release from PBMCs 22 hr after treatments. It was also revealed that increased levels in cytokine expression coincided with increased phosphorylation of JNK, P65-NF-κB, and IKKα/IKKβ. Also, the expression of IL-6, TNF-α, IL-1β, and COX-2 mRNA induced by LPS as well as secretion of protein in PBMC has been significantly decreased by pretreatment of malvidin. Importantly, pretreatment of the cells with malvidin completely abrogated the phosphorylation of P65-NF-κB, JNK, and IKKα/IKKβ in LPS treated cells. Malvidin protection against LPS-induced inflammation was coupled with a decline in the levels of nitric oxide metabolite and malondialdehyde, along with an increase in the ferric reducing antioxidant power, total thiol activity, and also superoxide dismutase and glutathione peroxidase activity. In accordance with this finding, malvidin may represent a promising therapeutic agent for the prevention of inflammation in PBMCs.

Pleomorphic hyalinizing angiectatic tumor (PHAT) is a rare, slow-growing mass, which is locally aggressive and classified as tumors of borderline malignancy. In this study, we report a case of subcutaneous ankle mass in 43-year-old female since 2 years ago with a pathological diagnosis of PHAT, characterized by clusters of ectatic, fibrin-lined, and thin-walled vessels which are surrounded by a spindled or pleomorphic neoplastic stroma.

Autophagy is a cellular process activated in response to various stresses such as starvation, hypoxia, and oxidative stress. Autophagy was reported to modulate the inflammatory pathways. However, whether autophagy is involved in regulation of palmitate-induced inflammation of skeletal muscle C2C12 cells is still unknown. The present study aimed to investigate the autophagic pathway in C2C12 cells treated with 0.5 mM palmitate. The results showed that the protein levels of LC3BII and P62 were increased in C2C12 cells after 12 h palmitate treatment. Besides, inhibition of autophagy by chloroquine or 3-methyladenin and its activation by rapamycin were associated with elevated mRNA and protein levels of IL-6 and TNF-α inflammatory cytokines in C2C12 cells. To study the mechanism by which autophagy impairment leads to activation of inflammatory responses, reactive oxygen species (ROS) levels in palmitate-treated cells were measured. The results showed that while palmitate stimulates ROS production, pretreatment of the cells with N-acetyl cysteine (NAC), a ROS scavenger, reduced inflammatory responses and also improved LC3-BII and P62 protein in the C2C12 cells exposed to palmitate. These findings suggest that palmitate-induced defect of autophagic flux leads to elevated inflammatory cytokine expression in the skeletal muscle cells by regulating the oxidative stress process.

Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of insulin signaling which is overexpressed in the liver of diabetic animals. The aims of this study were to generate liver-specific PTP1B knockout mice using a PTP1B-short hairpin RNA (shRNA) plasmid and to investi- gate the effect of PTP1B inhibition on plasma glucose levels in streptozotocin-induced diabetic mice. We first validated the hydrodynamic tail vein injection in mice using a vector carrying the luciferase gene. Expression of the PTP1B gene was quantified by real-time PCR. The level of phosphorylated Akt was examined by western blot analysis. The injection of the plasmid containing firefly luciferase revealed that the highest transfer of the vector into the liver was obtained 24 h after the injection of 20 µg plasmid. The injection of PTP1B-shRNA, but not the scrambled shRNA plasmid, resulted in a reduction in PTP1B expression levels by up to 84% in the liver of the diabetic mice. Plasma glucose levels following the injection of PTP1B-shRNA remained significantly lower in the diabetic mice for 5 days. In addition, mice receiving PTP1B-shRNA in the basal and insulin-stimulated states had higher levels of Akt phosphorylation in the liver cells compared with mice that were injected with the scrambled sequence (35 and 60%, respectively; p

To develop a convenient animal model of T2D by pretreatment with low-dose 10% w/v fructose (FRC) solution followed by the injection of low doses of streptozotocin (STZ) in Wistar rats. For this 8-week experimental study; rats were first fed a standard chow ad-libitum diet and either tap water (n=40) or 10% w/v FRC solution (n=40) for 4 weeks. Next, rats in each category were randomly allocated to 4 subgroups (n=10 each) of low-dose STZ (25,35, and 45 mg/kg). The final mean fasting blood sugar (FBG) of FRC+STZ45 (197±55.87 mg/dl) were significantly higher than that of the STZ45 (P=0.015) and FRC (P=0.019) groups. FRC+STZ45 showed the highest insulin resistance demonstrated by insulin tolerance test [area under the curve (AUC) of insulin tolerance test; P