Oligodendroglial fatty acid metabolism as a central nervous system energy reserve.

Brain function requires a constant supply of glucose. However, the brain has no known energy stores, except for glycogen granules in astrocytes. In the present study, we report that continuous oligodendroglial lipid metabolism provides an energy reserve in white matter tracts. In the isolated optic nerve from young adult mice of both sexes, oligodendrocytes survive glucose deprivation better than astrocytes. Under low glucose, both axonal ATP levels and action potentials become dependent on fatty acid ß-oxidation. Importantly, ongoing oligodendroglial lipid degradation feeds rapidly into white matter energy metabolism. Although not supporting high-frequency spiking, fatty acid ß-oxidation in mitochondria and oligodendroglial peroxisomes protects axons from conduction blocks when glucose is limiting. Disruption of the glucose transporter GLUT1 expression in oligodendrocytes of adult mice perturbs myelin homeostasis in vivo and causes gradual demyelination without behavioral signs. This further suggests that the imbalance of myelin synthesis and degradation can underlie myelin thinning in aging and disease.

Validity and reliability of Persian version of Low Physical Activity Questionnaire (LoPAQ).

BACKGROUND: The Low Physical Activity Questionnaire (LoPAQ) was specifically developed to measure the low activity level observed in extremely inactive hemodialysis (HD) patients. This study aims to evaluate reliability and validity of Persian version of the LoPAQ. METHODS: This study was a cross sectional study, conducted in three HD centers in Iran. The LoPAQ was translated into Persian. After cultural adaptions, it was filled out by 120 HD patiens. Convergent validity, was evaluated by calculating the correlations among the Persian version of the LoPAQ and Persian version of the Community Healthy Adults Model Program for Seniors (CHAMPS) questionnaire, physical function scale of the SF-36 and physical function (Short Physical Performance Battery (SPPB) test) using Spearman's correlation coefficients. The test-retest reliability was analyzed using the intraclass correlation coefficient (ICC). RESULTS: In total, 109 patients completed all of the questionnaires, took part in physical performance tests and had valid data. Their mean age was 64 ± 11 years, with a dialysis history of 31 ± 10 months. For total calories, there was a strong correlation between the Persian version of the LoPAQ and CHAMPS-measured physical activity (rho = 0.85, p < 0.001). In addition, the higher physical activity level reported by Persian version of the LoPAQ was also correlated with better self-reported physical function (rho = 0.7, p < 0.001) and better physical performance (rho = 0.67, p < 0.001). The ICC ranged from 0.65 to 0.78, indicating strong reliability. CONCLUSION: The assessment of the validity and reliability of the Persian version of the questionnaire confirmed its suitability for evaluating the level of physical activity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05930964, Registered on 05/07/2023. Registered trial name: Validity and Reliability of Persian Version of Low Physical Activity Questionnaire (LoPAQ).

Regulatory Non-coding RNAs Involved in Oxidative Stress and Neuroinflammation: An Intriguing Crosstalk in Parkinson's Disease.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the accumulation of α-synuclein and the degeneration of dopaminergic neurons in the substantia nigra. Although the molecular bases for PD development are not fully recognized, extensive evidence has suggested that the development of PD is strongly associated with neuroinflammation. It is noteworthy that while neuroinflammation might not be a primary factor in all patients with PD, it seems to be a driving force for disease progression, and therefore, exploring the role of pathways involved in neuroinflammation is of great importance. Besides, the importance of non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and competing endogenous RNAs (ceRNAs), has been widely studied with a focus on the pathogenesis of PD. However, there is no comprehensive review regarding the role of neuroinflammation-related ncRNAs as prospective biomarkers and therapeutic targets involved in the pathogenesis of PD, even though the number of studies connecting ncRNAs to neuroinflammatory pathways and oxidative stress has markedly increased in the last few years. Hence, the present narrative review intended to describe the crosstalk between regulatory ncRNAs and neuroinflammatory targets with respect to PD to find and propose novel combining biomarkers or therapeutic targets in clinical settings.

Principal component analysis of adipose tissue gene expression of lipogenic and adipogenic factors in obesity.

OBJECTIVE: A better understanding of mechanisms regulating lipogenesis and adipogenesis is needed to overcome the obesity pandemic. We aimed to study the relationship of the transcript levels of peroxisome proliferator activator receptor γ (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBP-α), liver X receptor (LXR), sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) from obese and normal-weight women with a variety of anthropometric indices, metabolic and biochemical parameters, and insulin resistance. METHODS: Real-time PCR was done to evaluate the transcript levels of the above-mentioned genes in VAT and SAT from all participants. RESULTS: Using principal component analysis (PCA) results, two significant principal components were identified for adipogenic and lipogenic genes in SAT (SPC1 and SPC2) and VAT (VPC1 and VPC2). SPC1 was characterized by relatively high transcript levels of SREBP1c, PPARγ, FAS, and ACC. However, the second pattern (SPC2) was associated with C/EBPα and LXR α mRNA expression. VPC1 was characterized by transcript levels of SREBP1c, FAS, and ACC. However, the VPC2 was characterized by transcript levels of C/EBPα, LXR α, and PPARγ. Pearson's correlation analysis showed that unlike SPC2, which disclosed an inverse correlation with body mass index, waist and hip circumference, waist to height ratio, visceral adiposity index, HOMA-IR, conicity index, lipid accumulation product, and weight-adjusted waist index, the VPC1 was positively correlated with above-mentioned obesity indices. CONCLUSION: This study provided valuable data on multiple patterns for adipogenic and lipogenic genes in adipose tissues in association with a variety of anthropometric indices in obese subjects predicting adipose tissue dysfunction and lipid accumulation.

A novel approach to type 3 diabetes mechanism: The interplay between noncoding RNAs and insulin signaling pathway in Alzheimer's disease.

Today, growing evidence indicates that patients with type 2 diabetes (T2D) are at a higher risk of developing Alzheimer's disease (AD). Indeed, AD as one of the main causes of dementia in people aged more than 65 years can be aggravated by insulin resistance (IR) and other metabolic risk factors related to T2D which are also linked to the function of the brain. Remarkably, a new term called "type 3 diabetes" has been suggested for those people who are diagnosed with AD while also showing the symptoms of IR and T2D. In this regard, the role of genetic and epigenetic changes associated with AD has been confirmed by many studies. On the other hand, it should be noted that the insulin signaling pathway is highly regulated by various mechanisms, including epigenetic factors. Among these, the role of noncoding RNAs (ncRNAs), including microRNAs and long noncoding RNAs has been comprehensively studied with respect to the pathology of AD and the most well-known underlying mechanisms. Nevertheless, the number of studies exploring the association between ncRNAs and the downstream targets of the insulin signaling pathway in the development of AD has notably increased in recent years. With this in view, the present study aimed to review the interplay between different ncRNAs and the insulin signaling pathway targets in the pathogenesis of AD to find a new approach in the field of combining biomarkers or therapeutic targets for this disease.

Evidence for the effect of soluble uric acid in augmenting endoplasmic reticulum stress markers in human peripheral blood mononuclear cells

There is evidence regarding the association of hyperuricemia with inflammatory disorders. Hence, it has been of particular interest to dissect the exact role of alteration in uric acid (UA) levels in the context of inflammation. Recently, the endoplasmic reticulum (ER) stress pathway has come into the forefront as a possible mechanism linking hyperuricemia to inflammation. Here, we intended to examine the role of UA in the presence or absence of a second stimulus, LPS, in human peripheral blood mononuclear cells (PBMCs), and analyzed ROS production as well as expression of ER stress markers: GRP78 and CHOP, and inflammatory cytokines.PBMCs were isolated using Ficoll gradient centrifugation from healthy volunteers. Cell viability was measured by MTT assay. PBMCs were treated with an increasing concentration of soluble UA (0, 5, 12, and 20 mg/dl) for 20 h, followed by the addition of 100 ng/mL of LPS or vehicle for another 4 h. Real time-PCR was performed to investigate the mRNA expression of GRP78, CHOP, TNF-α, IL-1β, and IL-6, and western blot was used to investigate the protein levels of GRP78 and CHOP. Moreover, ELISA was used to evaluate the protein levels of TNF-α, IL-1β, and IL-6. Finally, intracellular ROS production was determined using fluorescent probes (DCFH-DA).High concentrations of UA either alone or combined with LPS increased the protein levels of GRP78 and CHOP. On the other hand, LPS alone increased the protein levels of GRP78 and CHOP. However, there was no significant difference between the mRNA expression of GRP78, CHOP, TNF-α, IL-1β, and IL-6 when PBMCs were treated with UA. High concentrations of UA augmented LPS-stimulated IL-1β transcript and protein levels as well as TNF-α protein levels in PBMC culture. Moreover, high concentrations of UA along with LPS significantly increased intracellular ROS production. (AU)

Evidence for the effect of soluble uric acid in augmenting endoplasmic reticulum stress markers in human peripheral blood mononuclear cells.

There is evidence regarding the association of hyperuricemia with inflammatory disorders. Hence, it has been of particular interest to dissect the exact role of alteration in uric acid (UA) levels in the context of inflammation. Recently, the endoplasmic reticulum (ER) stress pathway has come into the forefront as a possible mechanism linking hyperuricemia to inflammation. Here, we intended to examine the role of UA in the presence or absence of a second stimulus, LPS, in human peripheral blood mononuclear cells (PBMCs), and analyzed ROS production as well as expression of ER stress markers: GRP78 and CHOP, and inflammatory cytokines.PBMCs were isolated using Ficoll gradient centrifugation from healthy volunteers. Cell viability was measured by MTT assay. PBMCs were treated with an increasing concentration of soluble UA (0, 5, 12, and 20 mg/dl) for 20 h, followed by the addition of 100 ng/mL of LPS or vehicle for another 4 h. Real time-PCR was performed to investigate the mRNA expression of GRP78, CHOP, TNF-α, IL-1ß, and IL-6, and western blot was used to investigate the protein levels of GRP78 and CHOP. Moreover, ELISA was used to evaluate the protein levels of TNF-α, IL-1ß, and IL-6. Finally, intracellular ROS production was determined using fluorescent probes (DCFH-DA).High concentrations of UA either alone or combined with LPS increased the protein levels of GRP78 and CHOP. On the other hand, LPS alone increased the protein levels of GRP78 and CHOP. However, there was no significant difference between the mRNA expression of GRP78, CHOP, TNF-α, IL-1ß, and IL-6 when PBMCs were treated with UA. High concentrations of UA augmented LPS-stimulated IL-1ß transcript and protein levels as well as TNF-α protein levels in PBMC culture. Moreover, high concentrations of UA along with LPS significantly increased intracellular ROS production.It seems that a high concentration of UA not only induces the protein levels of ER stress markers in PBMCs but also augments the impact of LPS on the levels of pro-inflammatory markers and ROS production.

Low level of adiponectin predicts the development of Nonalcoholic fatty liver disease: is it irrespective to visceral adiposity index, visceral adipose tissue thickness and other obesity indices?

We aimed to study the correlation of adiponectin level with insulin resistance (IR), carotid intima-media thickness (cIMT), and various obesity indices especially visceral adipose tissue (VAT) thickness, and visceral adiposity index (VAI), in patients with NAFLD (n = 41), T2D (n = 22), NAFLD + T2D (n = 41), and healthy subjects (n = 20). Results showed the median level of adiponectin in patients with NAFLD (2.97 µg/mL) and ones with NAFLD + T2D (3.21 µg/mL) is significantly lower rather than in controls (4.39 µg/mL). Moreover, VAI is the only predictor for adiponectin concentration in the combination of patient groups and also in all participants independent of IR and other obesity indices. Adiponectin level had also a positive correlation with cIMT and IR in NAFLD patients. Interestingly, lower level of adiponectin was associated with the presence of T2D, NAFLD, and NAFLD + T2D independent of IR and obesity indices. Collectively, it seems that VAI reflecting visceral adipose tissue function is a possible predictor of adiponectin level.

The emerging role of noncoding RNAs in neuroinflammation: Implications in pathogenesis and therapeutic approaches.

Noncoding RNAs (ncRNAs) are important regulators of gene expression in different cell processes. Due to their ability in monitoring neural development genes, these transcripts confer neurons with the potential to exert broad control over the expression of genes for performing neurobiological functions. Although the change of ncRNA expression in different neurodegenerative diseases has been reviewed elsewhere, only recent evidence drove our attention to unravel the involvement of these molecules in neuroinflammation within these devastating disorders. Remarkably, the interactions between ncRNAs and inflammatory pathways are not fully recognized. Therefore, this review has focused on the interplay between diverse inflammatory pathways and the related ncRNAs, including microRNAs, long noncoding RNAs, and competing endogenous RNAs in Alzheimer's disease, Parkinson's diseases, amyotrophic lateral sclerosis, epilepsy, multiple sclerosis, Huntington's disease, and prion diseases. Providing novel insights in the field of combining biomarkers is a critical step for using them as diagnostic tools and therapeutic targets in clinical settings.

Nutrient patterns and their relation to obesity and metabolic syndrome in Iranian overweight and obese adult women.

PURPOSE: Nutrient patterns have been associated with an increased risk for chronic disease. Evidence to confirm a direct relationship between nutrient patterns and obesity and metabolic syndrome (MetS) throughout population-based differences including cultural contexts add complexity is not well established yet. The aim of this study is to investigate the association between nutrient patterns and MetS among overweight and obese Iranian women. METHODS: Three hundred and sixty obese and overweight women (25 < BMI < 40) were included in this cross-sectional analysis. Dietary intake of 19 nutrients was evaluated by a semi-quantitative standard food frequency questionnaire (FFQ). MetS was determined by abdominal obesity > 88 (cm) in females, Triglycerides ≥ 150 (mg/dL), dyslipidemia (HDL < 50 mg/dL), systolic blood pressure > 130/85 (millimeters), and glucose > 100 (mg/dL). Body composition was assessed by a multi-frequency bioelectrical impedance analyzer, InBody 770 scanner. Principle components analysis was applied and four nutrient patterns were identified as following: Pattern 1 (thiamin, iron, carbohydrate, zinc, niacin, protein, magnesium, phosphorus, riboflavin), represented the carbo-vitamin group. Lipid group was showed in pattern 2 (PUFAs, MUFA, vitamin E, trans fatty acids, and Pattern 3 (beta-carotene, vitamin K, vitamin A, vitamin C) represented the anti-oxidant group, finally Pattern 4 was the indicator of the milk group (vitamin D, calcium). RESULTS: A significant positive association was observed between the anti-oxidant group and obesity (OR 1.40; 95% CI 1.09-1.8; P = 0.01). No relationship between other nutrient pattern and MetS was observed. CONCLUSIONS: The nutrient patterns that are highly loading of beta-carotene, vitamin K, vitamin A, and vitamin C in nutrient patterns may be associated to higher risk of obesity in overweight and obese Iranian women. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

The possible mediatory role of adipokines in the association between low carbohydrate diet and depressive symptoms among overweight and obese women.

BACKGROUND: Previous studies showed the possible association between obesity, dietary pattern, and depressive symptoms. Due to the lack of enough data to confirm the association of obesity and depression in the Middle East, here, we aimed to explore the possible mediatory role of adipokines Galectin-3, transforming growth factor-beta (TGF-ß), and endothelial plasminogen activator inhibitor (PAI-1) in the association between low carbohydrate diet (LCD) and depressive symptoms. METHODS: A total of 256 women aged 17-56 years old were grouped based on their LCD score. Depression anxiety stress scales-21 (DASS-21) self-administered questionnaire was used to evaluate the three negative emotional states of stress, depressive symptoms, and anxiety. Body composition and dietary intake were assessed. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum levels of Galectin-3, TGF-ß, and PAI-1. RESULTS: No significant difference was observed regarding Galectin-3, TGF-ß, and PAI-1 levels between the groups with dissimilar adherence to LCD or the groups with different levels of depressive symptoms (P>0.05). However, there was a negative association between LCD score as a covariant and depressive symptoms as an independent variable (P = 0.02) and remarkably, a regression model linear analysis using Galectin-3, TGF-ß, and PAI-1 as confounding variables indicated the mediatory role of these adipokines in this association (P>0.05). In other words, adipokines eliminated the significance of the relationship between adherence to LCD and depressive symptoms. CONCLUSION: It seems that higher adherence to LCD is probably associated with a lower prevalence of depressive symptoms in obese adults through the mediatory role of adipokines.

Iran diabetes research study; knowledge discovery in diagnosis: a scoping review.

INTRODUCTION: The rising prevalence of diabetes shows high health and socio-economic burdens. Therefore, the development and evaluation of new diagnostic methods may improve the detection of disease and its complications in the early stages. This study aimed to analyze the scope of the studies related to diabetes diagnosis. MATERIAL AND METHOD: Publications from January 2015 until December 2019 (5 years) were searched with keywords of (diabetes OR diabetic) AND (Iran) in Scopus and PubMed databases. All data were reviewed by two reviewers and the included publications were categorized based on the subjects, study design, and publication year. RESULTS: Based on the selected criteria, 103 articles were included. The highest number of publications was observed in 2019. The trend of publication was slightly increased during the study period (2015-2019). Case-control and cross-sectional studies were the most common type of study design used in the included documents. Publications in the field of diagnostic models, biomarkers, and biosensors from 2015 to 2019 showed an increasing trend compared to others subjects. DISCUSSION AND CONCLUSION: Studies about proper diabetes diagnostic procedures such as new diagnostic techniques, using diagnostic models, and evaluation of new diagnostic biomarkers in Iran are remarkably increased. However, more original and review studies are needed to improve scientific methods in the field of early detection of diabetes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-021-00843-x.

Overview of biological effects of Quercetin on ovary.

Over the last few decades, using natural products has been increased to treat different diseases. Today, great attention has been pointed toward the usage of natural products such as flavonoids, especially Quercetin (QUR), in the treatment of diseases. QUR as a natural antioxidant has been traditionally used to prevent or treat a variety of diseases such as cancer, cardiovascular disease, polycystic ovary syndrome (PCOS), obesity, chronic inflammation, and reproductive system dysfunction. Several studies demonstrated that QUR acts as an anti-inflammatory, anti-apoptotic, antioxidant, and anticancer agent. With this in view, in this study, we intended to describe an overview of the biological effects of QUR on the ovary. QUR improves the quality of oocytes and embryos. It affects the proliferation and apoptosis and decreases the oxidative stress in granulosa cells (GCs). Furthermore, QUR can be used as a complementary and alternative therapy in ovarian cancer and it has beneficial effects in the treatment of PCOS patients. It seems that QUR as a supplementary factor has different activities for the treatment of different disorders and it also has bidirectional activities. However, further investigations are needed for understanding the efficacy of QUR in the treatment and improvement of gynecological patients.

Competing Endogenous RNAs (CeRNAs): Novel Network in Neurological Disorders.

Neurological disorders (NDs) comprise a broad range of diseases affecting both central and peripheral nervous systems. These complex multifactorial diseases have a high rate of mortality all over the world, particularly in aged people. Today, new evidence drove our attention to the notable role of noncoding RNAs (ncRNAs) in the progression of NDs. Remarkably, recent studies showed that there are close communication networks among RNA transcripts such as mRNAs, long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and pseudogenes for regulating each other's expression through competing for shared sequences in microRNAs (miRs). This concept is a new area of ongoing research recognized as competing endogenous RNA (ceRNA) hypothesis. CeRNAs are novel regulatory molecules in a wide range of biological stages and pathological contexts. Indeed, the disruption of ceRNA networks (ceRNETs) may affect neural development genes and induce neuropathological changes leading to the development of NDs. Because of this, identifying the correlation of ceRNETs with NDs will open a new window for expanding our knowledge about this field of science, as well as creating novel roads for developing specific diagnostic biomarkers for NDs management. Owing to these unique features, exploring the exact role of ceRNAs is a hot topic in NDs investigations. Hence, in this review, we will summarize the evidence supporting ceRNETs in the regulation of NDs-related gene expression.

The genetic factors associated with Wnt signaling pathway in colorectal cancer.

Colorectal cancer (CRC) is a common cancer with poor prognosis and high mortality. There is growing information about the factors involved in the pathogenesis of CRC. However, the knowledge of the predisposing factors is limited. The development of CRC is strongly associated with the Wingless/Integrated (Wnt) signaling pathway. This pathway comprises several major target proteins, including LRP5/6, GSK3ß, adenomatous polyposis coli (APC), axis inhibition protein (Axin), and ß-catenin. Genetic variations in these components of the Wnt signaling pathway may lead to the activation of ß-catenin, potentially increasing the proliferation of colorectal cells. Because of the potentially important role of the Wnt signaling pathway in CRC, we aimed to review the involvement of different mutations in the main downstream proteins of this pathway, including LRP5/6, APC, GSK3ß, Axin, and ß-catenin. Determination of the genetic risk factors involved in the progression of CRC may lead to novel approaches for the early diagnosis of CRC and the identification of potential therapeutic targets in the treatment of CRC.

Adipose tissue gene expression of long non-coding RNAs; MALAT1, TUG1 in obesity: is it associated with metabolic profile and lipid homeostasis-related genes expression?

BACKGROUND: Recent studies point toward the possible regulatory roles of two lncRNAs; metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and taurine upregulated gene 1 (TUG1) in the pathogenesis of obesity-related disorders and regulation of lipogenesis and adipogenesis. In an attempt to understand the molecules involved in human obesity pathogenesis, we aimed to evaluate the expression of MALAT1 and TUG1 in visceral adipose tissues (VAT) and subcutaneous adipose tissues (SAT) of obese women, as compared to normal-weight women. The mRNA expression of possible target genes including peroxisome proliferator-activated receptor gamma (PPARγ), PPARγ coactivator-1 alpha (PGC1α), sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) which are involved in adipogenesis and lipogenesis were also examined. METHODS: This study was conducted on 20 obese [body mass index (BMI) ≥ 30 kg/m 2] female participants and 19 normal-weight (BMI < 25 kg/m 2) female participants. Real-time PCR was performed to investigate the mRNA expression of the above-mentioned genes in VAT and SAT from all participants. RESULTS: The results showed lower mRNA levels of TUG1 in both the VAT and SAT of obese women, compared to normal-weight women. Furthermore, TUG1 expression in SAT positively correlated with BMI, waist circumference (WC), hip circumference, HOMA-IR, and insulin levels, eGFR value, creatinine levels, and hs-CRP in all participants independent of age and HOMA-IR. However, VAT mRNA expression of TUG1 had a positive correlation with obesity indices and HOMA-IR and insulin levels in the whole population. Moreover, SAT mRNA level of TUG1 was positively correlated with SAT gene expression of PGC1α, SREBP-1c, FAS, and ACC independent of age and HOMA-IR. Although mRNA expression of MALAT1 did not differ between two groups for any tissue, it was positively correlated with SAT mRNA levels of SREBP-1c, PPARγ, and their targets; FAS and ACC, as well as with VAT mRNA levels of PGC1α. CONCLUSIONS: It seems likely that TUG1 with distinct expression pattern in VAT and SAT are involved in the regulation of lipogenic and adipogenic genes and obesity-related parameters. However, more studies are necessary to establish this concept.

Acetylation and insulin resistance: a focus on metabolic and mitogenic cascades of insulin signaling.

Insulin resistance is associated with an increased risk of several metabolic disorders including type 2 diabetes, hypertension and cardiovascular diseases. Advances over the last decade have expanded our understanding of the molecular mechanisms underlying insulin resistance; however, many details of the mechanisms causing insulin resistance remain unknown. Recently, attention has shifted toward the role of epigenetics in insulin resistance. In this regard, acetylation of the histone tails has been widely investigated for its role in influencing both metabolic and mitogenic cascades of insulin signaling. More specifically, histone acetyltransferases and histone deacetylases, as major modulators of chromatin accessibility and gene expression, have been studied to determine a possible interconnectivity between the special effects of lysine acetylation status and tyrosine phosphorylation networks on the target proteins of downstream pathways involved in both metabolic and mitogenic cascades of insulin signaling. There is accumulating evidence for the post-translational modification effects of IGFR, InsR, IRS1/2, PI3K, Akt, GLUT4, FoxO, PGC-1α, PPAR, AMPK and MAPKs on insulin resistance and glucose homeostasis. In this paper, we review the importance of acetylation of these factors in the regulation of insulin signaling and glucose metabolism, with a primary focus on the target proteins of downstream signaling of insulin. We also provide an update on the interplay between epigenetic modification and the cellular genome in the context of insulin signaling and describe the possible effect of the environment on this epigenetic regulation.

The role of microRNAs in the regulation of insulin signaling pathway with respect to metabolic and mitogenic cascades: A review.

Insulin resistance (IR) is a shared pathological condition among type 2 diabetes, obesity, cardiovascular disease, and other metabolic disorders. It is growing significantly all over the world and consequently, a substantial effort is needed for developing the potential novel diagnostics and therapeutics. An insulin signaling pathway is tightly modulated by different mechanisms including the epigenetic modifications. Today, a deal of great attention has been shifted towards the regulatory role of noncoding RNAs on target proteins of the insulin signaling pathway. Noncoding RNAs are a major area of the epigenetics which control gene expression at the posttranscriptional levels and include a large class of microRNAs (miRNAs). With this in view, many studies have implicated the mediatory effects of miRNAs on the downstream metabolic and mitogenic proteins of the insulin signaling pathway. Since providing new biomarkers for the early diagnosis of IR and related metabolic traits are very significant, we intended to review the possible role of miRNAs in the regulation of the insulin signaling pathway, with a primary focus on the downstream target proteins of the metabolic and mitogenic cascades.

Circulating exosomal miRNAs in cardiovascular disease pathogenesis: New emerging hopes.

Cardiovascular diseases (CVDs) are one of the leading causes of morbidity and mortality. Standard therapies have failed to significantly increase patients' survival. Moreover, the majority of conventional screening procedures are ineffective for the diagnosis of CVDs at early stages. Accumulating evidence suggests that numerous cell types release a class of nano-sized vesicles named exosomes into the extracellular space. Exosomes are widely distributed in various body fluids and contain a number of diverse biomolecules such as proteins, lipids, and both mRNA and noncoding RNAs which reflect host-cell molecular architecture. MicroRNAs (miRNAs), which can be found in exosomes, could be taken up by both neighboring and distal cells. Not only has recent evidence indicated the regulatory role of exosomal miRNAs in the pathogenesis of CVD, but it has also been shown that differential expression of exosomal miRNAs in CVDs has made them promising biomarkers for early detection of CVDs. Owing to these remarkable features, exosomal miRNAs have emerged as hot spots in research. This review summarizes the role of exosomal miRNAs in the pathogenesis of CVDs and discusses their potential application in the clinical setting as both therapeutic and diagnostic tools.