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Introduction Chronic hyperglycemia activates the inflammatory pathways and oxidative stress mechanisms with consequent damage to nerve tissue and retina. The Keap1‐Nrf2 pathway acts as one of the most important antioxidant pathways of the organism. Variants of Keap1 could affect susceptibility to diabetes and its complications. Methods In a case‐control study, 400 individuals included type 2 diabetes mellitus (T2DM) patients without complication, with neuropathy, with retinopathy, and healthy individuals were investigated. The levels of glutathione (GSH), glutathione peroxidase (GPx), malondialdehyde (MDA), and total antioxidant capacity (TAC) were measured using chemical methods. Using the PCR‐RFLP method, the Keap1 (rs11085735) variants were identified. Results Neuropathic patients had significantly lower levels of GSH, GPx, and TAC and higher levels of total oxidative status (TOS), MDA, and oxidative stress index (OSI) compared to T2DM patients without complication and controls. Lower levels of GSH and GPx and a higher level of MDA were observed in patients with retinopathy compared with controls. Obesity was associated with significantly lower GPx activity and higher TOS. A significantly higher Keap1 AA genotype was found in patients with neuropathy than T2DM without complication and controls. The presence of Keap1 AA genotype correlated with lower GPx activity compared to CC genotype. Conclusions Our study suggests the role of reduced antioxidant system and Keap1 variants in the pathogenesis of T2DM and its complications of neuropathy and retinopathy and also obesity in enhanced oxidative stress. Monitoring oxidative stress parameters in diabetic patients, especially those with complication and their treatment with antioxidants is suggested., Studying 400 T2DM patients without complication indicated: In T2DM patients without complication, the GPx and TAC levels decreased and the MDA level elevated. T2DM with neuropathy had lower levels of GSH, GPx, and TAC and higher levels of TOS, MDA, and OSI and a higher frequency of Keap1 AA genotype. T2DM with retinopathy had lower levels of GSH and GPx and a higher level of MDA. Obesity‐enhanced oxidative stress was associated with lower GPx activity and higher TOS and Keap1 AA genotype correlated with lower GPx activity. Reduced antioxidant system and Keap1 variants are involved in the pathogenesis of T2DM and its complications of neuropathy and retinopathy.

Background Menopausal symptoms have remarkable negative effects on women’s quality of life, justifying the need to assess various therapeutic options. This research aimed to determine the effectiveness of Vitex agnus-castus extracts in alleviating menopausal symptoms in comparison with that of placebo. Methods This study was a randomized controlled double-blind clinical trial with a study group of 52 women referred to a clinic in Kermanshah in 2017. The participants were randomly divided into two groups: Vitex group (26 subjects) and placebo group (26 subjects). Menopausal symptoms were assessed using the Greene Scale before and 8 weeks after the intervention. Results After the intervention, the mean scores for total menopausal disorder, anxiety, and vasomotor dysfunction were significantly lower in the Vitex group than in the placebo group (P0.05). Conclusion Administration of Vitex agnus-castus extracts as a phytoestrogenic medicine can alleviate menopausal symptoms in women.

OBJECTIVES: Diabetic neuropathy (DNP) is a widespread and debilitating complication with complex pathophysiology that is caused by neuronal dysfunction in diabetic patients. Conventional therapeutics for DNP are quite challenging due to their serious adverse effects. Hence, there is a need to investigate novel effective and safe options. The novelty of the present study was to provide available therapeutic approaches, emerging molecular mechanisms, signaling pathways and future directions of DNP as well as polyphenols’ effect, which accordingly, give new insights for paving the way for novel treatments in DNP. EVIDENCE ACQUISITION: A comprehensive review was done in electronic databases including Medline, PubMed, Web of Science, Scopus, national database (Irandoc and SID), and related articles regarding metabolic pathways on the pathogenesis of DNP as well as the polyphenols’ effect. The keywords “diabetic neuropathy” and “diabetes mellitus” in the title/abstract and “polyphenol” in the whole text were used. Data were collected from inception until May 2019. RESULTS: DNP complications is mostly related to a poor glycemic control and metabolic imbalances mainly inflammation and oxidative stress. Several signaling and molecular pathways play key roles in the pathogenesis and progression of DNP. Among natural entities, polyphenols are suggested as multi-target alternatives affecting most of these pathogenesis mechanisms in DNP. CONCLUSION: The findings revealed novel pathogenicity signaling pathways of DNP and affirmed the auspicious role of polyphenols to tackle these destructive pathways in order to prevent, manage, and treat various diseases. [Figure: see text]

Metabolic syndrome is a common metabolic disorder which has become a public health challenge worldwide. There has been growing interest in medications including natural products as complementary or alternative choices for common chemical therapeutics regarding their limited side effects and ease of access. Nanosizing these compounds may help to increase their solubility, bioavailability, and promisingly enhance their efficacy. This study, for the first time, provides a comprehensive overview of the application of natural-products-based nanoformulations in the management of metabolic syndrome. Different phytochemicals including curcumin, berberine, Capsicum oleoresin, naringenin, emodin, gymnemic acid, resveratrol, quercetin, scutellarin, stevioside, silybin, baicalin, and others have been nanosized hitherto, and their nanosizing method and effect in treatment and alleviating metabolic syndrome have been reviewed and discussed in this study. It has been discovered that there are several pathways or molecular targets relevant to metabolic disorders which are affected by these compounds. Various natural-based nanoformulations have shown promising effect in treatment of metabolic syndrome, and therefore can be considered as future candidates instead of or in conjunction with pharmaceutical drugs if they pass clinical trials successfully.

Chemotherapy, as one of the main approaches of cancer treatment, is accompanied with several adverse effects, including chemotherapy-induced peripheral neuropathy (CIPN). Since current methods to control the condition are not completely effective, new treatment options should be introduced. Medicinal plants can be suitable candidates to be assessed regarding their effects in CIPN. Current paper reviews the available preclinical and clinical studies on the efficacy of herbal medicines in CIPN.Electronic databases including PubMed, Scopus, and Cochrane library were searched with the keywords "neuropathy" in the title/abstract and "plant", "extract", or "herb" in the whole text. Data were collected from inception until April 2018.Plants such as chamomile (Matricaria chamomilla L.), sage (Salvia officinalis L.), cinnamon (Cinnamomum cassia (L.) D. Don), and sweet flag (Acorus calamus L.) as well as phytochemicals like matrine, curcumin, and thioctic acid have demonstrated beneficial effects in animal models of CIPN via prevention of axonal degeneration, decrease in total calcium level, improvement of endogenous antioxidant defense mechanisms such as superoxide dismutase and reduced glutathione, and regulation of neural cell apoptosis, nuclear factor-ĸB, cyclooxygenase-2, and nitric oxide signaling. Also, five clinical trials have evaluated the effect of herbal products in patients with CIPN.There are currently limited clinical evidence on medicinal plants for CIPN which shows the necessity of future mechanistic studies, as well as well-designed clinical trial for further confirmation of the safety and efficacy of herbal medicines in CIPN. Graphical abstract Schematic mechanisms of medicinal plants to prevent chemotherapy-induced neuropathy: NO: nitric oxide, TNF: tumor necrosis factor, PG: prostaglandin, NF-ĸB: nuclear factor kappa B, LPO: lipid peroxidation, ROS: reactive oxygen species, COX: cyclooxygenase, IL: interleukin, ERK: extracellular signal-related kinase, X: inhibition, ↓: induction.

Polycystic ovary syndrome (PCOS) is known as the most common endocrine and metabolic disorder in the reproductive-age women. Due to the effects of PCOS on the physical and mental health, the investigation of the factors affecting the development of PCOS is crucial. Hexose-6-phosphate dehydrogenase (H6PD) is a microsomal enzyme that catalyzes the first two reactions of the oxidative chain of the pentose phosphate pathway. The present study examined the polymorphisms of the H6PD gene (R453Q and D151A) in PCOS patients of Iranian Kurdish women.br /Materials and Methods: In this case-control study, a total, of 200 female volunteers in two equal groups participated in our study. The PCOS patients were selected based on the Rotterdam diagnostic criteria. The association of H6PD gene polymorphisms, D151A and R453Q, with the development of PCOS were investigated. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for genotyping. Statistical analysis was applied by the SPSS (version 16) software.br /Results: Statistically significant lower frequencies of AA+AG genotype (37% vs. 55%, P=0.01) and A allele (22.5%br /vs. 34%, P=0.01) of R453Q were observed in the patients compared to the controls. In the case of D151A, no significantbr /differences were observed in the frequency of genotypes and alleles between the two groups.The findings of this study suggest that variants of H6PD R453Q affect the risk of PCOS.

This article is a Letter to the Editor and does not include an Abstract.

Inflammatory bowel diseases (IBD), which is classified into Crohn's disease and ulcerative colitis, are among chronic gastrointestinal diseases with unknown pathogenesis. Diverse strategies have been applied for the treatment of this chronic disease. However, selective and site-specific routes of drug delivery to the inflamed location of the colon remain of high importance. Consequently, the application and effects of natural products in the form of nanoformulation and stimuli responsive nanoparticles as a novel strategy for the treatment of IBD are discussed in this review article. This approach may potentially overcome some complications that are associated with conventional means of colon drug delivery. Meanwhile, in vitro and in vivo studies pave the way for understanding of the mechanism that lies behind this chronic relapsing disease and potentially more effective treatment. Graphical abstract ᅟ.

Inflammatory bowel disease (IBD) is a chronic idiopathic inflammatory disorder. A wealth of data pointed out that various aspects of chronic inflammation may be affected by several specific dietary factors. This paper calls attention to anthocyanins enriched plant food and anthocyanin dietary supplements, whose role in the management of IBD and its associated oncogenesis deems crucial. Area covered: We updated the most relevant dietary anthocyanins with potential anti-colitis and preventive effect on inflammatory associated colorectal cancer based on the recent animal and human researches along with revealing the major cellular and molecular mechanisms of action. Mounting evidence reported that anthocyanins enriched plant foods perform their protective role on IBD and inflammatory-induced colorectal cancer via different cellular transduction signaling pathways, including inflammatory transcription factors, SAPK/JNK and p38 MAPK cascade, JAK/STAT signaling, NF-kB/pERK/MAPK, Wnt signaling pathway, Nrf2 cytoprotective pathway as well as AMPK pathway and autophagy. Expert commentary: Combination of anthocyanins enriched dietary supplements with existing medications can provide new therapeutic options for IBD patients. Further, well-designed randomized control trials (RCTs) are essential to evaluate the role of anthocyanins enriched medicinal foods as well as isolated anthocyanin components as promising preventive and therapeutic dietary agents for IBD and its associated oncogenesis.

Background Polycystic ovary syndrome (PCOS) is the known endocrinopathy disorder in the reproductive phase of women’s life. More than half of the women with PCOS suffer from obesity which impacts the ovarian functions by leptin levels. Here the R223Q and P1019P polymorphisms of leptin receptor (LEPR) gene were examined in PCOS patients of Kurdish women from west of Iran. Materials and Methods In this case-control study, one hundred women with PCOS and 100 healthy women bearing similar age range were selected based on Rotterdam diagnostic criteria. Polymerase chain reaction-restriction frag- ment length polymorphism (PCR-RFLP) method was used to genotype polymorphisms LEPR (R223Q and P1019P), by respectively the BsaWI and NcoI restriction enzymes. Pearson’s chi-square (χ2) test was used to analyze the vari- ation in genetic distributions and unconditional logistic regression model was used to calculate the odds ratio (OR; 95% CI). Results Genotype frequencies of the R223Q and P1019P polymorphisms showed significant difference between the patients with PCOS compared to the controls. G allele (R223Q) reduced the risk of PCOS about 0.49-fold (P

Sleep disturbances have been shown to be associated with adverse health outcomes including diabetes mellitus (DM), hypertension, and obesity. However, little is known about the relationship between sleep duration and diabetes complications. The present cross-sectional study aimed to examine the association between sleep duration and nephropathy in a population of type 2 DM patients. Diabetic patients aged ≥ 18 years who visited two outpatient clinics in Kermanshah from February 2014 to February 2015 entered the study. Demographic, anthropometric, and biochemical data, as well as information on sleep duration of participants within the past 4 weeks, were collected by an interviewer. Patients with estimated glomerular filtration rate (eGFR) ≤ 60 ml/24 h were excluded from the study. Proteinuria was defined as excretion of more than 150 mg protein in 24-h urine. Differences in urine protein and related variables were examined between four sleep duration groups (≤ 5, 6, 7, and ≥ 8 h). Linear and logistic regression analyses were employed to assess the association between sleep duration and diabetic nephropathy. Four hundred thirty-two patients (63.8% female) with a mean age of 54.68 ± 9.98 years were analyzed. There were statistically significant differences in age, body mass index, waist circumference, DM duration, HbA1C, total cholesterol, HDL cholesterol, triglyceride, uric acid, and urine protein between sleep duration groups. While adjusted linear regression showed no association between sleep duration and urine protein (p = 0.300), multivariable logistic regression revealed male gender, increased HbA1C, shorter sleep duration, increased DM duration, lower eGFR, higher DBP, decreased HDL-C, and higher uric acid levels to be statistically associated with proteinuria. Short sleep duration is adversely associated with proteinuria in type 2 DM patients with normal and near-normal kidney function.

Glycoproteins are organic compounds formed from proteins and carbohydrates, which are found in many parts of the living systems including the cell membranes. Furthermore, impaired metabolism of glycoprotein components plays the main role in the pathogenesis of diabetes mellitus. The aim of this study is to investigate the influence of glycoprotein levels in the treatment of diabetes mellitus.All relevant papers in the English language were compiled by searching electronic databases, including Scopus, PubMed and Cochrane library. The keywords of glycoprotein, diabetes mellitus, glycan, glycosylation, and inhibitor were searched until January 2019.Glycoproteins are pivotal elements in the regulation of cell proliferation, growth, maturation and signaling pathways. Moreover, they are involved in drug binding, drug transportation, efflux of chemicals and stability of therapeutic proteins. These functions, structure, composition, linkages, biosynthesis, significance and biological effects are discussed as related to their use as a therapeutic strategy for the treatment of diabetes mellitus and its complications.The findings revealed several chemical and natural compounds have significant beneficial effects on glycoprotein metabolism. The comprehension of glycoprotein structure and functions are very essential and inevitable to enhance the knowledge of glycoengineering for glycoprotein-based therapeutics as may be required for the treatment of diabetes mellitus and its associated complications. Graphical abstract.

McCune-Albright syndrome (MAS) is a uncommon disease caused by a mutation in the GNAS1 gene and is associated with exposure to dysplasia of polypropylene fibers (PFD), Cafe-au-lait spots and hyperfunctioning endocrinopathies mostly including hyperthyroidism and precocious puberty (PP). The present article describes an eight-year-old boy presenting to a physician for the first time at the age of four owing to recurrent pathological fractures of the femur as well as hyperthyroidism, which was found in physical examinations to be associated with several nodules in the thyroid.

We summarized 16 controlled studies and evaluated the correlation of resveratrol supplementation with metabolic parameters such as the body weight, waist circumference (WC), systolic blood pressure (sbp), HDL, total cholesterol, triglyceride and glucose levels. This meta-analysis was carried out to determine the association between the resveratrol intake with metabolic parameters in metabolic syndrome patients. PubMed, Scopus, Cochrane and Google Scholar were searched from inception to December 2018 using relevant keywords. All articles were independently reviewed by two authors using predetermined selection criteria. We have selected the studies that investigated the effects of resveratrol on metabolic parameters. Of 16 studies, 10 were performed on human subjects, and in 6 studies animal models were used. Standard mean difference (SMD) with 95% confidence interval were determined using Der Simonian and Laird random-effects modeling, when there was a significant heterogeneity between studies. Funnel plot and Egger's test were conducted to examine the risk of publication bias. Pooled effect sizes in human studies indicated a significant impact of resveratrol supplementation on glucose level [-1.73 (-2.99, -0.47); p = 0.007)] and WC [-1.73 (-2.79, -0.67); p = 0.001] compared with the control group. Also combining the results of studies on rat samples (n = 6), indicated significant effect of resveratrol on decreasing weight [-22.95 (-44.74, -1.17); p = 0.04], TGs [-6.76 (-11.10, -2.42); p = 0.001], sbp [-7.30 (-12.48, -2.13); p = 0.006], and it can influence significantly on increasing HDL level (4.75 (1.87, 7.63); p = 0.001). However, resveratrol was not significantly effective on total cholesterol in both samples. The results of subgroup analysis of human studies showed that resveratrol has significant effect on metabolic parameters (glucose level and WC) at the dosage of > 500 mg and with long-term interventions ≥ 10 weeks. Administration of resveratrol can meaningfully reduce the BW, WC, TGs, and glucose level, also it can increase HDL, but not total cholesterol.

To evaluate salivary factors in type 2 diabetes melliuts patients.The case-control study was conducted from June to November 2016 at Kermanshah University of Medical Sciences, Kermanshah, Iran, and comprised patients with type 2 diabetes mellitus and healthy controls matched in terms of age and gender. Unstimulated saliva samples were collected in the morning after an overnight fast of 8-12 hours. The samples were centrifuged at 1500 rpm for 5 minutes, and every isolated transparent liquid was immediately frozen at a temperature of -45ºC in a tube. The test sample was later aspirated, and readings were taken. The data was analyzed using SPSS 16..Of the 200 subjects, 100(50%) were diabetic patients and 100(50%) were healthy controls. The two groups were matched with regard to age, gender, diabetes duration, serum glucose, and glycated haemoglobin (p0.05 each). In terms of laboratory variables, there were significant differences between the groups related to urea, phosphorus, pH, and glucose (p0.05 each). Urea and glucose levels were higher in the patient group than the controls (p0.05 each). Also, calcium and total protein levels were higher in male patients compared to female patients (p0.0 5 each) .Salivary pH, urea, calcium, phosphorus, glucose, and total protein levels could be bio chemical parameters for screening, diagnosis and monitoring of diabetes .

Acne vulgaris (AV) is a common skin disease that causes physical and psychological problems for the affected individual. In addition to systemic changes in hormone levels, overproduction of local steroids, especially androgens are associated with AV. Cytochrome (CYP) 19 is involved in the synthesis of estrogens. The aim of the present study was to investigate the influence of CYP19A

Background and aims: Diabetes mellitus is a chronic heterogenic disease characterized by the deregulation of the metabolism of insulin and glucose. The aim of this review has been to evaluate the e...

Flavonoids comprise a group of natural polyphenols consisting of more than 5,000 subtypes mostly existing in fruits and vegetables. Flavonoids consumption could potentially attenuate the incidence and recurrence risk of colorectal cancers through their antiperoxidative, antioxidant, and anti-inflammatory effects. In addition, these compounds regulate the mitochondrial function, balance the bacterial flora and promote the apoptosis process in cancerous cells. However, some previous data failed to show the effectiveness of flavonoids in reducing the risk of colorectal cancer. In this study, we have reviewed the efficacy of different flavonoids subtypes on the risk of colon cancer and molecular mechanisms involved in this process in both clinical and animal studies. In addition, we tried to elucidate the potential synergy between these compounds and current colorectal cancer treatments.

Oxidative stress has been considered a key causing factor of liver damage induced by a variety of agents, including alcohol, drugs, viral infections, environmental pollutants and dietary components, which in turn results in progression of liver injury, non-alcoholic steatohepatitis, non-alcoholic liver disease, liver fibrosis and cirrhosis. During the past 30 years and even after the major progress in the liver disease management, millions of people worldwide still suffer from an acute or chronic liver condition. Curcumin is one of the most commonly used indigenous molecules endowed by various shielding functionalities that protects the liver. The aim of the present study is to comprehensively review pharmacological effects and molecular mechanisms, as well as clinical evidence, of curcumin as a lead compound in the prevention and treatment of oxidative associated liver diseases. For this purpose, electronic databases including “Scopus,” “PubMed,” “Science Direct” and “Cochrane library” were extensively searched with the keywords “curcumin or curcuminoids” and “hepatoprotective or hepatotoxicity or liver” along with “oxidative or oxidant.” Results showed that curcumin exerts remarkable protective and therapeutic effects of oxidative associated liver diseases through various cellular and molecular mechanisms. Those mechanisms include suppressing the proinflammatory cytokines, lipid perodixation products, PI3K/Akt and hepatic stellate cells activation, as well as ameliorating cellular responses to oxidative stress such as the expression of Nrf2, SOD, CAT, GSH, GPx and GR. Taking together, curcumin itself acts as a free radical scavenger over the activity of different kinds of ROS via its phenolic, β-diketone and methoxy group. Further clinical studies are still needed in order to recognize the structure-activity relationships and molecular mechanisms of curcumin in oxidative associated liver diseases.

Background Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease mainly caused by high-fat diets and sudden feed changes, vitamin and energy deficiency, and inflammatory processes. Fatty liver leads to cirrhosis, hepatocellular carcinoma as well as liver failure. Lifestyle-modifying such as weight loss and a healthy diet have an inverse correlation with the risk of fatty liver. The promising effect of a diet rich in vegetables and fruits against fatty liver has been evidenced by several empirical studies focused on flavonoids. Among naturally occurring flavonoids, naringenin is one of the most important flavonoids which can be isolated from some edible fruits, especially citrus species. Methods In the present review, we discuss the effects of naringenin and its nano-formulations against fatty liver disease and the proposed molecular mechanism of action. A large number of studies attributed to naringenin anti-inflammatory, antioxidant and insulin-like actions, as well as different types of effects on sex hormone metabolism and lipid metabolism. Naringenin-loaded nanoparticles have been used to solve the limited stability, solubility, bioavailability and pharmacological activity of naringenin and, consequently, to improve its therapeutic effects. Results and discussion Naringenin exerts diverse biological actions including the decrease of biomarkers of lipid peroxidation and protein carbonylation, increase of antioxidant defenses, scavenging of reactive oxygen species and modulation of signaling pathways related to fatty acid metabolism which can favor the oxidation of fatty acid, lower lipid accumulation in the liver and thereby prevent fatty liver.

Background: Studies demonstrated controversial results on subclinical hypothyroidism (SCH) regarding lipid profile alteration with or without Levothyroxine treatment. The purpose of this study is to investigate the effects of Levothyroxine on serum lipids in SCH. Materials and Methods: One hundred patients with SCH referred to Taleghani hospital in Kermanshah were recruited and randomly assigned into the intervention or the control group. Patients in intervention group received Levothyroxine 50-75 micrograms for three months. Patients in control group received the same placebo with the same dose and duration. Lipid profile was measured before and after the trial and the changes were compared between groups. (IRCT code: 138903244179N1). Results: Triglyceride, Total Cholesterol, LDL, HDL and Lipoprotein-A were measured before and after treatment. None of the factors showed significant difference either between or within groups, before and after the treatment (P

The corresponding author, Mohammad Hosein Farzaei, affiliation is Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran. The correct spelling of the 7th author surname is Iranpanah.

Cyclosporine is the main immunosuppressive drug used for renal transplant reci-pients in order to prevent transplant rejection. Although the drug has increased the survival of patients and grafted organ, it has some side effects independent of its effect on the immune system. This study was done to evaluate the effect of cyclosporine on serum Mg level and its metabolic side effects in renal allograft patients. 157 (62 female and 95 male) renal transplant recipients treated with cyclosporine to prevent transplant rejection were included in the study. Clinical and biochemical data along with cyclosporine levels was documented. Mean serum Mg level was 196 ± 0.31 mg/dL and mean serum cyclosporine level was 371 ± 192 µg/dL. Hypomagnesemia was detected in 16 (10.2%) with a negative significant correlation with cyclosporine levels, serum creatinine, plasma LDL, fasting Blood sugar and uric acid. In conclusion according to the results of this study there is a significant correlation between cyclosporine and hypomagnesemia. Therefore, routine measurement of serum Mg and its treatment seems necessary to prevent its complications.