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Background: Circular RNAs (circRNAs), as covalently closed single-stranded noncoding RNA molecules, have been recently identified to involve in several biological processes, principally through targeting microRNAs. Among various neurodegenerative diseases (NDs), accumulating evidence has proposed key roles for circRNAs in the pathogenesis of Alzheimer’s disease (AD); although the exact relationship between these RNA molecules and AD progression is not clear, they have been believed to mostly act as miRNA sponges or gene transcription modulators through the correlating with multiple proteins, involved in the accumulation of Amyloid β (Aβ) peptides, as well as tau protein, as AD’s pathological hallmark. More interestingly, circRNAs have also been reported to play diagnostic and therapeutic roles during the AD progression. Objective: The literature review indicated that circRNAs could essentially contribute to the onset and development of AD. Thus, in the current review, the circRNAs’ biogenesis and functions are addressed at first, and then the interplay between particular circRNAs and AD is comprehensively discussed. Eventually, the diagnostic and therapeutic significance of these noncoding RNAs is briefly highlighted. Results: A large number of circRNAs are expressed in the brain. Thereby, these RNA molecules are noticed as potential regulators of neural functions in healthy circumstances, as well as in neurological disorders. Moreover, circRNAs have also been reported to have potential diagnostic and therapeutic capacities in relation to AD, the most prevalent ND. Conclusion: CircRNAs have been shown to act as sponges for miRNAs, thereby regulating the function of related miRNAs, including oxidative stress, reduction of neuroinflammation, and the formation and metabolism of Aβ, all of which developed in AD. CircRNAs have also been proposed as biomarkers that have potential diagnostic capacities in AD. Despite these characteristics, the use of circRNAs as therapeutic targets and promising diagnostic biomarkers will require further investigation and characterization of the function of these RNA molecules in AD.

Background: Diabetic nephropathy (DN), as a severe complication of diabetes mellitus (DM), is a crucial menace for human health and survival and remarkably elevates the healthcare systems’ costs. Therefore, it is worth noting to identify novel preventive and therapeutic strategies to alleviate the disease conditions. Resveratrol, as a well-defined anti-diabetic/ antioxidant agent has capabilities to counteract diabetic complications. It has been predicted that resveratrol will be a fantastic natural polyphenol for diabetes therapy in the next few years. Objective: Accordingly, the current review aims to depict the role of resveratrol in the regulation of different signaling pathways that are involved in the reactive oxygen species (ROS) production, inflammatory processes, autophagy, and mitochondrial dysfunction, as critical contributors to DN pathophysiology. Results: The pathogenesis of DN can be multifactorial; hyperglycemia is one of the prominent risk factors of DN development that is closely related to oxidative stress. Resveratrol, as a well-defined polyphenol, has various biological and medicinal properties, including anti-diabetic, anti-inflammatory, and anti-oxidative effects. Conclusion: Resveratrol prevents kidney damages that are caused by oxidative stress, enhances antioxidant capacity, and attenuates the inflammatory and fibrotic responses. For this reason, resveratrol is considered an interesting target in DN research due to its therapeutic possibilities during diabetic disorders and renal protection.

Polyphenols are abundant in regular diets and possess antioxidant, anti-inflammatory, anti-cancer, neuroprotective, and cardioprotective effects. Regarding the inadequacy of the current treatments in preventing cardiac remodeling following cardiovascular diseases, attention has been focused on improving cardiac function with potential alternatives such as polyphenols. The following online databases were searched for relevant orginial published from 2000 to 2023: EMBASE, MEDLINE, and Web of Science databases. The search strategy aimed to assess the effects of polyphenols on heart failure and keywords were “heart failure” and “polyphenols” and “cardiac hypertrophy” and “molecular mechanisms”. Our results indicated polyphenols are repeatedly indicated to regulate various heart failure-related vital molecules and signaling pathways, such as inactivating fibrotic and hypertrophic factors, preventing mitochondrial dysfunction and free radical production, the underlying causes of apoptosis, and also improving lipid profile and cellular metabolism. In the current study, we aimed to review the most recent literature and investigations on the underlying mechanism of actions of different polyphenols subclasses in cardiac hypertrophy and heart failure to provide deep insight into novel mechanistic treatments and direct future studies in this context. Moreover, due to polyphenols' low bioavailability from conventional oral and intravenous administration routes, in this study, we have also investigated the currently accessible nano-drug delivery methods to optimize the treatment outcomes by providing sufficient drug delivery, targeted therapy, and less off-target effects, as desired by precision medicine standards.

Breast cancer (BC) is the most common malignancy among women worldwide. Like many other cancers, BC therapy is challenging and sometimes frustrating. In spite of the various therapeutic modalities applied to treat the cancer, drug resistance, also known as, chemoresistance, is very common in almost all BCs. Undesirably, a breast tumor might be resistant to different curative approaches (e.g., chemo- and immunotherapy) at the same period of time. Exosomes, as double membrane-bound extracellular vesicles 1) secreted from different cell species, can considerably transfer cell products and components through the bloodstream. In this context, non-coding RNAs (ncRNAs), including miRNAs, long ncRNAs (lncRNAs), and circular RNAs (circRNAs), are a chief group of exosomal constituents with amazing abilities to regulate the underlying pathogenic mechanisms of BC, such as cell proliferation, angiogenesis, invasion, metastasis, migration, and particularly drug resistance. Thereby, exosomal ncRNAs can be considered potential mediators of BC progression and drug resistance. Moreover, as the corresponding exosomal ncRNAs circulate in the bloodstream and are found in different body fluids, they can serve as foremost prognostic/diagnostic biomarkers. The current study aims to comprehensively review the most recent findings on BC-related molecular mechanisms and signaling pathways affected by exosomal miRNAs, lncRNAs, and circRNAs, with a focus on drug resistance. Also, the potential of the same exosomal ncRNAs in the diagnosis and prognosis of BC will be discussed in detail.

Abstract: Heart failure (HF) is a public health issue that imposes high costs on healthcare systems. Despite the significant advances in therapies and prevention of HF, it remains a leading cause of morbidity and mortality worldwide. The current clinical diagnostic or prognostic biomarkers, as well as therapeutic strategies, have some limitations. Genetic and epigenetic factors have been identified to be central to the pathogenesis of HF. Therefore, they might provide promising novel diagnostic and therapeutic approaches for HF. Long non-coding RNAs (lncRNAs) belong to a group of RNAs that are produced by RNA polymerase II. These molecules play an important role in the functioning of different cell biological processes, such as transcription and regulation of gene expression. LncRNAs can affect different signaling pathways by targeting biological molecules or a variety of different cellular mechanisms. The alteration in their expression has been reported in different types of cardiovascular diseases, including HF, supporting the theory that they are important in the development and progression of heart diseases. Therefore, these molecules can be introduced as diagnostic, prognostic, and therapeutic biomarkers in HF. In this review, we summarize different lncRNAs as diagnostic, prognostic, and therapeutic biomarkers in HF. Moreover, we highlight various molecular mechanisms dysregulated by different lncRNAs in HF.

Some risk causes may be associated with the severity of COVID-19. The central host-pathogen factors might affect infection are human receptor angiotensin-converting enzyme 2 (ACE2), trans-membrane protease serine 2 (TMPRSS2), and SARS-CoV-2 surface spike (S)-protein. The main purpose of this study was to determine the differences in the expression the metalloproteinases-2 (MMP-2), MMP-9, ACE2, and TMPRSS2 genes and their correlation with lymphopenia in the mild and severe types of the COVID-19 patients. Eighty-eight patients, aged 36 to 60 years old with the mild (n=44) and severe (n=44) types of COVID-19 were enrolled. Total RNA was isolated from the peripheral blood mononuclear cells (PBMCs). The changes of MMP-2, MMP-9, ACE2 and TMPRSS2 gene expression in PBMCs from mild and severe COVID-19 patients were examined by the real time-quantitative polymerase chain reaction (RT-qPCR) assay and, compared between the groups. Data were collected from May 2021 to March 2022. The mean age of the patients in both groups was 48 (interquartile range, 36–60), and there were no appreciable differences in age or gender distribution between the two groups. The present study showed that a significant increase in the expression of ACE2, TMPRSS2, MMP-2, and MMP-9 genes in the severe type of the COVID-19 patients compared, to the mild type of the COVID-19 patients. Overall, it suggests the expression levels of these genes on the PBMC surface in the immune system are susceptible to infection by SARS-COV-2 and therefore could potentially predict the patients’ outcome.

Combined chemotherapy is a treatment method based on the simultaneous use of two or more therapeutic agents; it is frequently necessary to produce a more effective treatment for cancer patients. Such combined treatments often improve the outcomes over that of the monotherapy approach, as the drugs synergistically target critical cell signaling pathways or work independently at different oncostatic sites. A better prognosis has been reported in patients treated with combination therapy than in patients treated with single drug chemotherapy. In recent decades, 5-fluorouracil (5-FU) has become one of the most widely used chemotherapy agents in cancer treatment. This medication, which is soluble in water, is used as the first line of anti-neoplastic agent in the treatment of several cancer types including breast, head and neck, stomach and colon cancer. Within the last three decades, many studies have investigated melatonin as an anti-cancer agent; this molecule exhibits various functions in controlling the behavior of cancer cells, such as inhibiting cell growth, inducing apoptosis, and inhibiting invasion. The aim of this review is to comprehensively evaluate the role of melatonin as a complementary agent with 5-FU-based chemotherapy for cancers. Additionally, we identify the potential common signaling pathways by which melatonin and 5-FU interact to enhance the efficacy of the combined therapy. Graphic abstract

Abstract: Polycystic ovary syndrome (PCOS) is a prevalent endocrine/metabolic disorder in women of reproductive age. PCOS is characterized by hyperandrogenism, polycystic ovary morphology, and ovulatory dysfunction/anovulation. It involves multiple effects in patients, including granulosa/theca cell hyperplasia, menstrual disturbances, infertility, acne, obesity, insulin resistance, and cardiovascular disorders. Biochemical analyses and the results of RNA sequencing studies in recent years have shown a type of non-coding RNAs as a splicing product known as circular RNAs (circRNAs). Several biological functions have been identified in relation to circRNAs, including a role in miRNA sponge, protein sequestration, increased parental gene expression, and translation leading to polypeptides. These circular molecules are more plentiful and specialized than other types of RNAs. For this reason, they are referred to as potential biomarkers in different diseases. Evidence suggests that circRNAs may have regulatory potentials through different signaling pathways, such as the miRNA network. Probably most experts in the field of obstetricians are not aware of circRNAs as a useful biomarker. Therefore, this review focused on the researches that have been done on the involvement of circRNAs in PCOS and summarized recent supportive evidence, and evaluated the circRNA association and mechanisms involved in PCOS.

Abstract: Gliomas are the most common malignant cancers of the brain that have unregulated proliferation and are known as highly invasive tumors. Hence, their relapse rate is high, and the prognosis is low. Despite remarkable advances in neuroimaging, neurosurgery, and radiation therapy, they, especially glioblastoma, are highly resistant to treatments, including radiotherapy, surgery, and temozolomide chemotherapy. The average survival rate for patients with malignant glioma is still less than two years. Accordingly, the search for new treatment options has recently become an urgent need. Today, a number of nutraceuticals have been considered because of their special role in inhibiting the angiogenic process, metastasis, and apoptosis, resulting in the inhibition of tumor growth, including glioma. Nutraceuticals can disrupt cancer cells by affecting different pathways. In fact, these compounds can reduce the growth of cancer cells, inhibit their proliferation and angiogenesis, as well as induce apoptosis in these cells and play an important role in various stages of treatment. One of the key targets of nutraceuticals may be to regulate cellular signaling pathways, such as PI3K/Akt/mTORC1, JAK/STAT, and GSK-3, or to exert their effects through other mechanisms, such as cytokine receptors and inflammatory pathways, reactive oxygen species, and miRNAs. This review refers to the results of recent studies and target molecules as well as signaling pathways affected by some nutraceuticals in glioma cells. These studies indicated that clinical trials are imminent and new approaches can be beneficial for patients.

Increasing evidence suggests that apelin and ghrelin may participate in atherogenesis. We sought to investigate whether the serum levels of apelin and ghrelin are significantly different in patients with coronary artery disease (CAD) compared to patients with nonsignificant coronary stenosis and determine the correlation between these adipokines and the severity of coronary stenosis. The study population included 31 stable CAD patients, 38 unstable CAD patients, and 39 non-CAD subjects. Serum levels of apelin and ghrelin, fasting blood glucose, lipid parameters, hs-CRP and hematological indices were determined in all groups using routine standard laboratory procedures. Serum apelin levels were significantly lower in patient with unstable CAD (0.354 ± 0.063 ng/mL) compared to stable CAD patients (0.401 ± 0.045 ng/mL, p = 0.003) and non-CAD subjects (0.415 ± 0.055 ng/mL, p

Abstract: The increasing number of cases of diabetes mellitus (DM) and related diseases has become a global health concern. In this context, controlling blood glucose levels is critical to prevent and/or slow down the development of diabetes-related complications. Incretins, as gutderived hormones that trigger the post-meal secretion of insulin, are a well-known family of blood glucose modulators. Currently, incretin medications, including glucagon-like peptide-1 receptor agonist (GLP-1RA) and dipeptidyl peptidase-4 (DPP-4) inhibitors, are extensively used to treat patients with type 2 diabetes mellitus (T2D). Several experimental and clinical studies illustrate that these metabolic hormones exert their antidiabetic effects through multiple molecular mechanisms. Accordingly, the current review aims to investigate key mechanisms and signaling pathways, such as the cAMP/PKA, Nrf2, PI3K/Akt, and AMPK pathways, associated with the antidiabetic effects of incretins. It also summarizes the outcomes of a group of clinical trials evaluating the incretins’ antidiabetic potential in diabetic patients.

Gliomas are the most lethal primary brain tumors in adults. These highly invasive tumors have poor 5-year survival for patients. Gliomas are principally characterized by rapid diffusion as well as high levels of cellular heterogeneity. However, to date, the exact pathogenic mechanisms, contributing to gliomas remain ambiguous. MicroRNAs (miRNAs), as small noncoding RNAs of about 20 nucleotides in length, are known as chief modulators of different biological processes at both transcriptional and posttranscriptional levels. More recently, it has been revealed that these noncoding RNA molecules have essential roles in tumorigenesis and progression of multiple cancers, including gliomas. Interestingly, miRNAs are able to modulate diverse cancer-related processes such as cell proliferation and apoptosis, invasion and migration, differentiation and stemness, angiogenesis, and drug resistance; thus, impaired miRNAs may result in deterioration of gliomas. Additionally, miRNAs can be secreted into cerebrospinal fluid (CSF), as well as the bloodstream, and transported between normal and tumor cells freely or by exosomes, converting them into potential diagnostic and/or prognostic biomarkers for gliomas. They would also be great therapeutic agents, especially if they could cross the blood–brain barrier (BBB). Accordingly, in the current review, the contribution of miRNAs to glioma pathogenesis is first discussed, then their glioma-related diagnostic/prognostic and therapeutic potential is highlighted briefly.

Glioblastoma multiforme (GBM), as a deadly and almost incurable brain cancer, is the most invasive form of CNS tumors that affects both children and adult population. It accounts for approximately half of all primary brain tumors. Despite the remarkable advances in neurosurgery, radiotherapy, and chemotherapeutic approaches, cell heterogeneity and numerous genetic alterations in cell cycle control, cell growth, apoptosis, and cell invasion, result in an undesirable resistance to therapeutic strategies; thereby, the median survival duration for GBM patients is unfortunately still less than two years. Identifying new therapeutics and employing the combination therapies may be considered as wonderful strategies against the GBM. In this regard, circular RNAs (circRNAs), as tumor inhibiting and/or stimulating RNA molecules, can regulate the cancer-developing processes, including cell proliferation, cell apoptosis, invasion, and chemoresistance. Hereupon, these molecules have been introduced as potentially effective therapeutic targets to defeat GBM. The current study aims to investigate the fundamental molecular and cellular mechanisms in association with circRNAs involved in GBM pathogenesis. Among multiple mechanisms, the PI3K/Akt/mTOR, Wnt/β-catenin, and MAPK signaling, angiogenic processes, and metastatic pathways will be thoroughly discussed to provide a comprehensive understanding of the role of circRNAs in pathophysiology of GBM. Video Abstract Supplementary Information The online version contains supplementary material available at 10.1186/s12964-021-00809-9.

Seasonal influenza represents a huge health burden, resulting in significant mortality and morbidity. Following the 2009 H1N1 pandemic, focus has been directed on the burden of influenza globally. Country and regional disease burden estimates play important roles in helping inform decisions on national influenza intervention programmes. Despite improvements in influenza surveillance following the 2009 pandemic, many opportunities remain unexplored in the Eastern Mediterranean and North African (EMNA) region, which has a high prevalence of patients with chronic disease and thus a population at high risk of influenza complications. We conducted a systematic literature review of Embase, Medline, Scopus and the Cochrane Database of Systematic Reviews from 1 January 1998 to 31 January 2020 covering the EMNA region with the aim to describe the epidemiology of influenza in the region and assess the influenza epidemiological surveillance research landscape. Relevant data on study characteristics, population, clinical/virology characteristics and epidemiology were extracted and summarised descriptively. Of the 112 studies identified for inclusion, 90 were conducted in the Eastern Mediterranean region, 19 in North Africa and three across the EMNA region. Data were reported on 314,058 laboratory-confirmed influenza cases, 96 of which were derived from surveillance systems. Amongst the surveillance studies, the percentage of positive cases reported ranged from 1% to 100%. The predominantly identified influenza strain was strain A; H1N1 was the most prominent circulating subtype. Typing was performed in approximately 75% and subtyping in 50% of studies, respectively. Data on those considered most at risk for influenza complications were collected in 21% of studies, highlighting a regional gap for these data. Our review reveals existing gaps in regional estimates of influenza health and economic burden, hospitalisation rates and duration, and highlights the need for robust and high-quality epidemiology data to help inform public health interventions. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-021-00534-3.

Diabetic nephropathy (DN), also known as diabetic kidney disease (DKD), is a drastic renal complication of type 1 and type 2 diabetes mellitus (DM). Poorly controlled DM over the years, may disrupt kidneys' blood vessels, leading to the hypertension (HTN) and DN onset. During DN, kidneys' waste filtering ability becomes disturbed. Being on a healthy lifestyle and controlling both DM and HTN are now the best proceedings to prevent or at least delay DN occurrence. Unfortunately, about one-fourth of diabetic individuals eventually experience the corresponding renal failure, and thus it is critical to discover effective diagnostic biomarkers and therapeutic strategies to combat DN. In the past few years, circular RNAs (circRNAs), as covalently closed endogenous non-coding RNAs (ncRNAs), are believed to affect DN pathogenesis in a positive manner. CircRNAs are able to impact different cellular processes and signaling pathways by targeting biological molecules or various molecular mechanisms. Still, as a key regulatory axis, circRNAs can select miRNAs as their molecular targets, in which they are considered as miRNA sponges. In this way, circRNA-induced suppression of particular miRNAs may prevent from DN progression or promotes the DN elimination. Since the expression of circRNAs has also been reported to be increased in DN-associated cells and tissues, they can be employed as either diagnostic biomarkers or therapeutic targets.

The aim of this study was to evaluate the effect of the co-administration of carnitine and chromium on mental health, hormonal, inflammatory and genetic parameters in women with PCOS.This randomized, double-blinded, placebo-controlled clinical trial was conducted on 54 subjects, aged 18-40 years old. Subjects were randomly allocated to take either 1000 mg/d carnitine plus 200 µg/d chromium as chromium picolinate (n = 26) or placebo (n = 27) for 12 weeks.Carnitine and chromium co-supplementation, compared with the placebo, significantly improved beck depression inventory (β - 0.84; 95% CI, -1.51, -0.17; p = 0.01), general health questionnaire scores (β - 1.13; 95% CI, -2.13, -0.14; p = 0.02) and depression anxiety and stress scale scores (β - 0.96; 95% CI, -0.78, -0.14; p = 0.02). Participants who received carnitine plus chromium supplements had significantly lower total testosterone (β - 0.15 ng/mL; 95% CI, -0.24, -0.06; p = 0.002), hirsutism (β - 0.48; 95% CI, -0.91, -0.06; p = 0.02), high-sensitivity C-reactive protein (hs-CRP) (β - 1.02 mg/L; 95% CI, -1.79, -0.25; p = 0.01), and malondialdehyde (MDA) levels (β - 0.38 µmol/L; 95% CI, -0.56, -0.20; p 0.001), and higher total antioxidant capacity (TAC) levels (β 107.18 mmol/L; 95% CI, 44.24, 170.12; p = 0.001) compared with the placebo. Moreover, carnitine and chromium co-supplementation upregulated gene expression of interleukin-6 (IL-6) (p = 0.02) and tumor necrosis factor alpha (TNF-α) (p = 0.02) compared with the placebo.Overall, the co-administration of carnitine and chromium for 12 weeks to women with PCOS had beneficial effects on mental health parameters, serum total testosterone, mF-G scores, hs-CRP, TAC and MDA levels, and gene expression of IL-6 and TNF-α.

The current systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to summarize the effect of vitamin D supplementation on biomarkers of inflammation and oxidative stress among women with polycystic ovary syndrome (PCOS). Cochrane library, Embase, PubMed, and Web of Science database were searched to identify related randomized-controlled articles (RCTs) published up to November 2017. Two researchers assessed study eligibility, extracted data, and evaluated risk of bias of included RCTs, independently. To check heterogeneity Q-test and I2 statistics were used. Data were pooled by using the random-effect model and standardized mean difference (SMD) was considered as summary effect size. Seven RCTs were included into our meta-analysis. The findings showed that vitamin D supplementation in women with PCOS significantly decreased high-sensitivity C-reactive protein (hs-CRP) (SMD −1.03; 95% CI, −1.58, −0.49; p

This study was carried out to investigate the effects of chromium intake on glycemic control, markers of cardio-metabolic risk, and oxidative stress in infertile polycystic ovary syndrome (PCOS) women candidate for in vitro fertilization (IVF). This randomized double-blind, placebo-controlled trial was done among 40 subjects with infertile PCOS candidate for IVF, aged 18–40 years old. Individuals were randomly allocated into two groups to take either 200 μg/day of chromium (n = 20) or placebo (n = 20) for 8 weeks. Biochemical parameters were assessed at baseline and at end-of-trial. Compared with the placebo, taking chromium supplements led to significant reductions in fasting plasma glucose (− 2.3 ± 5.7 vs. + 0.9 ± 3.1 mg/dL, P = 0.03), insulin levels (− 1.4 ± 2.1 vs. + 0.4 ± 1.7 μIU/mL, P = 0.004), homeostatic model of assessment for insulin resistance (− 0.3 ± 0.5 vs. + 0.1 ± 0.4, P = 0.005), and a significant increase in quantitative insulin sensitivity check index (+ 0.004 ± 0.008 vs. − 0.001 ± 0.008, P = 0.03). In addition, chromium supplementation significantly decreased serum triglycerides (− 19.2 ± 33.8 vs. + 8.3 ± 21.7 mg/dL, P = 0.004), VLDL- (− 3.8 ± 6.8 vs. + 1.7 ± 4.3 mg/dL, P = 0.004) and total cholesterol concentrations (− 15.3 ± 26.2 vs. − 0.6 ± 15.9 mg/dL, P = 0.03) compared with the placebo. Additionally, taking chromium supplements was associated with a significant increase in plasma total antioxidant capacity (+ 153.9 ± 46.1 vs. − 7.8 ± 43.9 mmol/L, P

This study was carried out to evaluate the effects of probiotics administration on the metabolic and genetic profiles in patients with diabetic nephropathy (DN). This was a randomized, placebo-controlled clinical trial with homeostasis model of assessment-estimated insulin resistance (HOMA-IR) as the primary and other metabolic profiles, and biomarkers of inflammation and oxidative stress as the secondary outcomes. This randomized, double-blind, placebo-controlled clinical trial was performed on 60 patients with DN. The patients were randomly assigned into two groups to receive either 8 × 109 CFU day-1 probiotic supplements or placebo (n = 30 in each group) for 12 weeks. Fasting blood was collected at the baseline and end of intervention to measure glycemic control, lipid profiles, biomarkers of inflammation and oxidative stress. Multiple linear regression models were used to assess the treatment effects on the outcomes adjusting for confounding variables. Probiotics supplementation, compared with the placebo, resulted in a significant reduction in fasting plasma glucose (P = 0.01), serum insulin concentrations (P = 0.01) and HOMA-IR (P = 0.007), and a significant increase in the quantitative insulin sensitivity check index (P = 0.04). Additionally, compared with the placebo, probiotic intake resulted in a significant reduction in triglycerides (P = 0.001) and total-/HDL-cholesterol ratio (P < 0.001), and a significant increase in HDL-cholesterol levels (P < 0.001). Supplementation with probiotics, compared with the placebo, was associated with a significant reduction in high-sensitivity C-reactive protein (P = 0.001), malondialdehyde (P < 0.001) and advanced glycation end products (P < 0.001), and a significant elevation in plasma total glutathione (P < 0.001). Overall, our study indicated that probiotics supplementation had beneficial effects on glycemic control and markers of cardio-metabolic risk.

Magnesium is known to exert several beneficial effects, including antiglycemic and antilipidemic properties. The aim of this study was to evaluate the effects of magnesium supplementation on gene expression related to insulin and lipid metabolism in women with gestational diabetes (GDM) who were not on oral hypoglycemic agents. This randomized double-blind, placebo-controlled trial was conducted among 40 patients diagnosed with GDM, aged 18-40 years. Participants were randomly allocated into two groups to take either 250 mg/day of magnesium supplements in the form of magnesium oxide (n = 20) or placebo (n = 20) for 6 weeks. Gene expression related to insulin and lipid metabolism was assessed in peripheral blood mononuclear cells (PBMCs) of women with GDM using RT-PCR method. Compared with the placebo, magnesium supplementation to women with GDM resulted in a significant decrease in levels of fasting plasma glucose (FPG) (-9.7 ± 5.6 vs. -0.1 ± 8.5 mg/dL, P

This study was carried out to evaluate the effects of probiotic supplementation on genetic and metabolic profiles in patients with gestational diabetes mellitus (GDM) who were not on oral hypoglycemic agents. This randomized, double-blind, placebo-controlled clinical trial was conducted in 48 patients with GDM. Participants were randomly divided into two groups to intake either probiotic capsule containing Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, Lactobacillus fermentum (2 × 109 CFU/g each) (n = 24) or placebo (n = 24) for 6 weeks. Probiotic intake upregulated peroxisome proliferator-activated receptor gamma (P = 0.01), transforming growth factor beta (P = 0.002) and vascular endothelial growth factor (P = 0.006), and downregulated gene expression of tumor necrosis factor alpha (P = 0.03) in peripheral blood mononuclear cells of subjects with GDM. In addition, probiotic supplementation significantly decreased fasting plasma glucose (β, − 3.43 mg/dL; 95% CI, − 6.48, − 0.38; P = 0.02), serum insulin levels (β, − 2.29 μIU/mL; 95% CI, − 3.60, − 0.99; P = 0.001), and insulin resistance (β, − 0.67; 95% CI, − 1.05, − 0.29; P = 0.001) and significantly increased insulin sensitivity (β, 0.009; 95% CI, 0.004, 0.01; P = 0.001) compared with the placebo. Additionally, consuming probiotic significantly decreased triglycerides (P = 0.02), VLDL-cholesterol (P = 0.02), and total-/HDL-cholesterol ratio (P = 0.006) and significantly increased HDL-cholesterol levels (P = 0.03) compared with the placebo. Finally, probiotic administration led to a significant reduction in plasma malondialdehyde (P

MicroRNAs (miRNAs) have recently become well-known efficacious biomarkers for the diagnosis of diabetic nephropathy (DN). MiRNAs, short noncoding RNAs, are posttranscriptional regulators of gene expression, which regulate several biological cell functions, including insulin production and secretion, as well as insulin resistance in tissues. Today, the focus of the medical world is centered on the role of miRNAs as mediators for different diseases, such as DN and end-stage renal diseases (ESRD). MiRNAs are stable and detectable in human biological fluids, so their detection for early diagnosis of different diseases is highly sensitive and specific. Previous reports have shown that the alteration of miRNA profiles significantly correlates with specific stages of DN, kidney fibrosis, and renal dysfunction. This review was aimed at assessing the pathway of different miRNA expressions responsible for insulin secretion disorder and DN progression.

Objective This study was conducted to evaluate the effects of omega-3 fatty acids and vitamin E co-supplementation on gene expression related to inflammation, insulin and lipid in subjects with Parkinson's disease (PD). Patients and methods This randomized, double-blind, placebo-controlled clinical trial was performed in 40 subjects with PD. Participants were randomly allocated into two groups to take either 1000 mg/day of omega-3 fatty acids from flaxseed oil plus 400 IU/day of vitamin E supplements or placebo (n = 20 each group) for 12 weeks. Gene expression related to inflammation, insulin and lipid were quantified in peripheral blood mononuclear cells (PBMC) of PD patients with RT-PCR method. Results After the 12-week intervention, compared with the placebo, omega-3 fatty acids and vitamin E co-supplementation downregulated gene expression of tumor necrosis factor alpha (TNF-α) (P = 0.002) in PBMC of subjects with PD. In addition, omega-3 fatty acids and vitamin E co-supplementation upregulated peroxisome proliferator-activated receptor gamma (PPAR-γ) (P = 0.03), and downregulated oxidized low-density lipoprotein receptor (LDLR) (P = 0.002) in PBMC of subjects with PD compared with the placebo. We did not observe any significant effect of omega-3 fatty acids and vitamin E co-supplementation on gene expression of interleukin-1 (IL-1) and IL-8 in PBMC of patients with PD. Conclusions Overall, omega-3 fatty acids and vitamin E co-supplementation for 12 weeks in PD patients significantly improved gene expression of TNF-α, PPAR-γ and LDLR, but did not affect IL-1 and IL-8.

The investigation was done to assess the impacts of probiotic supplementation on movement and metabolic parameters in individuals with Parkinson's disease (PD).The study is randomized, double-blind, placebo-controlled clinical trial, which was done in sixty people with PD. Individuals were randomly divided into two groups in order to take either 8 × 10Compared with the placebo, consuming probiotic decreased MDS-UPDRS (-4.8 ± 12.5 vs. +3.8 ± 13.0, P = 0.01). Probiotic supplementation also reduced high-sensitivity C-reactive protein (-1.6 ± 2.5 vs. +0.1 ± 0.3 mg/L, P 0.001) and malondialdehyde (-0.2 ± 0.3 vs. +0.1 ± 0.3 μmol/L, P = 0.006), and enhanced glutathione levels (+40.1 ± 81.5 vs. -12.1 ± 41.7 μmol/L, P = 0.03) in comparison with the placebo. Additionally, probiotic consumption resulted in a statistically significant reduction in insulin levels (-2.1 ± 3.4 vs. +1.5 ± 5.1 μIU/mL, P = 0.002) and insulin resistance (-0.5 ± 0.9 vs. +0.4 ± 1.2, P = 0.002), and a statistically significant rise in insulin sensitivity (+0.01 ± 0.02 vs. -0.006 ± 0.02, P = 0.01) in comparison with the placebo. Probiotic intake had no any significant impact on other metabolic profiles.Our study evidenced that 12 weeks of probiotic consumption by individuals with PD had useful impacts on MDS-UPDRS and few metabolic profiles. Registered under ClinicalTrials.gov Identifier no. http://www.irct.ir: IRCT2017082434497N4.

Objective/background Over-the-counter availability of antibiotics together with poor access to diagnostics is recognised to promote antimicrobial resistance (AMR) including generation of drug-resistant tuberculosis (DR-TB). In accordance with the End TB Strategy target of ending TB epidemic by 2030, efforts to control DR-TB are ongoing in Eastern Mediterranean Region (EMR) countries, a number of which have well-established facilities for diagnostics, disease care and prevention as well as surveillance. These could serve as models for AMR control. The United Nation’s historic 2016 declaration recognises AMR as a threat to health, food production and development, and emphasises the need for global action. In view of this declaration, establishment of collaboration between the DR-TB and AMR activities would be mutually beneficial and lead to strengthening of both programs. Methods Available information on TB control and AMR programs in EMR was reviewed. To assist with policy and planning strategies for promoting collaboration between AMR and TB, control activities were explored. Results Review of available information suggests gaps in TB care in many countries in EMR, most of which are linked to limited access to resources. At the same time, the fledgling AMR programs have a lot to learn from the experiences, successes and challenges faced by TB control efforts. A logic model is presented to enhance interprogram collaboration. Conclusions Given the global commitment and potential availability of resources towards controlling AMR, collaboration between the two programs is discussed towards a more efficient use of resources in the region.