MicroRNAs in thyroid cancer with focus on medullary thyroid carcinoma:potential therapeutic targets and diagnostic/prognostic markers and web based tools

This review aimed to describe the inculpation of microRNAs(miRNAs)in thyroid cancer(TC)and its subtypes,mainly medullary thyroid carcinoma(MTC),and to outline web-based tools and databases for bioinformatics analysis of miRNAs in TC.Additionally,the capacity of miRNAs to serve as therapeutic targets and biomarkers in TC management will be discussed.This review is based on a literature search of relevant articles on the role of miRNAs in TC and its subtypes,mainly MTC.Additionally,web-based tools and databases for bioinformatics analysis of miRNAs in TC were identified and described.MiRNAs can perform as oncomiRs or antioncoges,relying on the target mRNAs they regulate.MiRNA replacement therapy using miRNA mimics or antimiRs that aim to suppress the function of certain miRNAs can be applied to correct miRNAs aberrantly expressed in diseases,particularly in cancer.MiRNAs are involved in the modulation of fundamental pathways related to cancer,resembling cell cycle checkpoints and DNA repair pathways.MiRNAs are also rather stable and can reliably be detected in different types of biological materials,rendering them favorable diagnosis and prognosis biomarkers as well.MiRNAs have emerged as promising tools for evaluating medical outcomes in TC and as possible therapeutic targets.The contribution of miRNAs in thyroid cancer,particularly MTC,is an active area of research,and the utility of web applications and databases for the biological data analysis of miRNAs in TC is becoming increasingly important.

Prevalence of Anemia in Patients with Diabetes Mellitus:A Systematic Review and Meta-Analysis

Objective Anemia is a common public health concern in patients with type 2 diabetes worldwide.This study aimed to identify the prevalence of anemia among patients with diabetes.Methods Electronic databases,including PubMed,Scopus,Web of Sciences,and Google Scholar,were searched systematically for studies published between 2010 and 2021.After removing duplicates and inappropriate reports,the remaining manuscripts were reviewed and appraised using theNewcastleOttawa Scale(NOS)tool.A random-effects model was used to calculate the pooled estimates of the extracted data using Stata version 17.Heterogeneity of the studies was assessed using the Q statistic.Results A total of 51 articles containing information on 26,485 patients with diabetes were included in this study.The articles were mainly from Asia(58.82%)and Africa(35.29%).The overall prevalence of anemia was 35.45%(95%CI:30.30–40.76),with no evidence of heterogeneity by sex.Among the two continents with the highest number of studies,the prevalence of anemia in patients with diabetes was significantly higher in Asia[40.02;95%CI:32.72–47.54]compared to Africa[28.46;95%CI:21.90–35.50](P for heterogeneity=0.029).Moreover,there has been an increasing trend in the prevalence of anemia in patients with diabetes over time,from[15.28;95%CI:9.83–22.21]in 2012 to[40.70;95%CI:10.21–75.93]in 2022.Conclusion Globally,approximately 4 in 10 patients with diabetes suffer from anemia.Therefore,routine anemia screening and control programs every 3 months might be useful in improving the quality of life of these patients.

Functional foods-based diet as a novel dietary approach for management of type 2 diabetes and its complications: A review

Type 2 diabetes is a complicated metabolic disorder with both short- and long-term undesirable complications. In recent years, there has been growing evidence that functional foods and their bioactive compounds, due to their biological properties, may be used as complementary treatment for type 2 diabetes mellitus. In this review, we have highlighted various functional foods as missing part of medical nutrition therapy in diabetic patients. Several in vitro, animal models and some human studies, have demonstrated that functional foods and nutraceuticals may improve postprandial hyperglycemia and adipose tissue metabolism modulatecarbohydrate and lipid metabolism. Functional foods may also improve dyslipidemia and insulin resistance, and attenuate oxidative stress and inflammatory processes and subsequently could prevent the development of long-term diabetes complications including cardiovascular disease, neuropathy, nephropathy and retinopathy. In conclusion available data indicate that a functional foods-based diet may be a novel and comprehensive dietary approach for management of type 2 diabetes.

Is there any correlation between vitamin D insufficiency and diabetic retinopathy?

AIM: To determine a relation between vitamin D level,which is an inhibitor of angiogenesis, and diabetic retinopathy and its risk factorsMETHODS: In a clinic-based cross sectional study two hundred and thirty-five type 2 diabetic patients older than 20 y were selected. Patients were classified according to ophthalmologic examination as following:no diabetic retinopathy(NDR)(n =153), non-proliferative diabetic retinopathy(NPDR)(n =64) and proliferative diabetic retinopathy(PDR)(n =18). Study subjects were tested for fasting blood glucose, glycated hemoglobin A1C(Hb A1C), lipid profile, microalbuminuria, Hs CRP,IGF1, insulin(in patients without history of insulin taking)and 25 hydroxy vitamin D [25(OH) D] levels. Vitamin D insufficiency was defined according to 25(OH) D level less than 30 ng/m L. The relationship between diabetic retinopathy and serum 25(OH) D insufficiency was evaluated.RESULTS: The prevalence of diabetic retinopathy was34.8% in our patients. Long duration of diabetes,hypertension, poor glycemic control, diabetic nephropathy, hyperinsulinemia and insulin resistance were risk factors for diabetic retinopathy but 25(OH) D level was not significant different between NDR, NPDR and PDR groups. Correlation between 25(OH) D level and other known risk factors of diabetic retinopathy was not significant.CONCLUSION: This study did not find any association between diabetic retinopathy and its severity and vitamin D insufficiency. Vitamin D insufficiency is not related to risk factors of diabetic retinopathy.

Nitrate-nitrite-nitrosamines exposure and the risk of type 1 diabetes: A review of current data

The potential toxic effects of nitrate-nitrite-nitrosamine on pancreatic β cell have remained a controversial issue over the past two decades. In this study, we reviewed epidemiological studies investigated the associations between nitrate-nitrite-nitrosamines exposure, from both diet and drinking water to ascertain whether these compounds may contribute to development of type 1 diabetes. To identify relevant studies, a systematic search strategy of Pub Med, Scopus, and Science Direct was conducted using queries including the key words "nitrate", "nitrite", "nitrosamine" with "type 1 diabetes" or "insulin dependent diabetes mellitus". All searches were limited to studies published in English. Ecologic surveys, case-control and cohort studies have indicated conflicting results in relation to nitrate-nitrite exposure from drinking water and the risk of type 1 diabetes. A null, sometimes even negative association has been mainly reported in regions with a mean nitrate levels < 25 mg/L in drinking water, while increased risk of type 1 diabetes was observed in those with a maximum nitrate levels > 40-80 mg/L. Limited data are available regarding the potential diabetogenic effect of nitrite from drinking water, although there is evidence indicating dietary nitrite could be a risk factor for development of type 1 diabetes, an effect however that seems to be significant in a higher range of acceptable limit for nitrate/nitrite. Current data regarding dietary exposure of nitrosamine and development of type 1 diabetes is also inconsistent. Considering to an increasing trend of type 1 diabetes mellitus(T1DM) along with an elevated nitrate-nitrite exposure, additional research is critical to clarify potential harmful effects of nitrate-nitritenitrosamine exposure on β-cell autoimmunity and the risk of T1DM.

Elevated serum nitric oxide and hydrogen peroxide levels as potential valuable predictors of herpes zoster

Objective:To evaluate the biomarkers of oxidative stress in herpes zoster patients compared with control subjects.Methods:This study compared the nitric oxide(NO),hydrogen peroxide(H2 O2),malon dialdehyde,uric acid,and bilirubin levels between 43 herpes zoster patients and 47 age-matched control subjects.The area under the curve of the receiver operating characteristic curve was performed to evaluate the final logistic regression model.Results:The significant differences were observed in the serum levels of NO,H2 O2,and malondialdehyde between the case and the control groups(P<0.001).However,no statistical differences were found in both uricacid and bilirubin levels between the groups.Additionally,the raised oxidant biomarkers were strongly associated with increased disease severity(P<0.001).Multiple logistic regression analysis with the highest area under the curve[0.98(95%CI 0.95-1.00)]and the minimum number of variables showed that high levels of NO(OR 1.24;95%CI 1.06-1.46;P=0.008)and H2 O2(OR 1.25;95%CI 1.09-1.43;P=0.001)were associated with herpes zoster.Conclusions:High levels of NO and H2 O2 were observed in patients with herpes zoster.Increased NO and H2 O2 levels might be associated with herpes zoster,which needs to be confirmed by further studies.

Comparison of therapeutic effects of topical azithromycin solution and systemic doxycycline on posterior blepharitis

AIM：To compare the effect of azithromycin drop and doxycyciine capsule on treatment of posterior blepharitis.METHODS：Fifty patients（100 eyes） with moderate posterior blepharitis,randomly divided into two therapeutic groups;all the patients got warm eyelid compress and massage three times a day for 3wk.In addition the first group got azithromycin 1% drop,twice daily for 1wk and then one drop daily for 2wk.The second group got oral doxycyciine 100 mg daily for 3wk.At the end of the research,patients＇ signs and symptoms were compared together.ANOVA,Chi-square and MannWhitney tests were used for statistical analysis.RESULTS：Topical therapy with azithromycin and oral therapy with doxycyciine relieved signs and symptoms after 3wk.There were no significant differences between symptoms healing rate and foreign body sensation healing in these two groups（P〉0.05）.However,azithromycin drop was more effective in reduction of eye redness and doxycyciine was more effective in meibomian glands plugging healing and reducing the corneal staining.CONCLUSION：Topical azithromycin could have similar effects as oral doxycyciine on posterior blepharitis in improving subjective symptoms.However,doxycyciine can reduce objective signs such as ocular surface staining and meibomian gland plugging more than azithromycin.

Severe unilateral congenital ptosis with poor levator function:tarsoconjunctival mullerectomy plus levator resection vs frontalis sling procedure

AIM:To compare frontalis sling and tarsoconjunctival mullerectomy plus levator resection(TCMLR)in subjects with severe unilateral congenital ptosis with poor levator function(LF).METHODS:A prospective non-randomized nonblinded single center clinical trial.Fifty patients with severe unilateral congenital ptosis with poor LF were recruited.The frontalis sling and TCMLR were performed and the functional,cosmetic outcomes,complications,and success rate were evaluated at 1,3,and 6mo postoperatively.The t-test,Chi-square,Fishers exact,and nonparametric MannWhitney tests were used by SPSS software.RESULTS:Frontalis sling and TCMLR procedures were performed on 26 and 24 patients respectively.The mean age was 10.97±10.67y.LF was significantly better in the TCMLR group at months 1,3,and 6(P=0.002).Lagophthalmos was more common in the TCMLR group(no significant difference).At month 3,mild punctate epithelial erosions were observed more in the frontalis sling group(P=0.002).Significant complete success rate of 1st and 6th month for the frontalis sling vs TCMLR groups were 50%vs 20.8%(P=0.02),and 38.4%vs 50%(P=0.03)respectively.CONCLUSION:Complete success rate of TCMLR is higher in long-term follow-up in contrast with the frontalis sling in the short-term.Transient complications are more detected in mid-term follow-ups in both groups.

Transition Logic Regression Method to Identify Interactions in Binary Longitudinal Data

Logic regression is an adaptive regression method which searches for Boolean (logic) combinations of binary variables that best explain the variability in the outcome, and thus, it reveals interaction effects which are associated with the response. In this study, we extended logic regression to longitudinal data with binary response and proposed “Transition Logic Regression Method” to find interactions related to response. In this method, interaction effects over time were found by Annealing Algorithm with AIC (Akaike Information Criterion) as the score function of the model. Also, first and second orders Markov dependence were allowed to capture the correlation among successive observations of the same individual in longitudinal binary response. Performance of the method was evaluated with simulation study in various conditions. Proposed method was used to find interactions of SNPs and other risk factors related to low HDL over time in data of 329 participants of longitudinal TLGS study.

Prospective study of total and various types of vegetables and the risk of metabolic syndrome among children and adolescents

BACKGROUND Data available on the association between consumption of various types of vegetables and metabolic syndrome (MetS) remain inconsistent. AIM To investigate the association between the intake of various types of vegetables and MetS among children and adolescents and MetS. METHODS The Tehran Lipid and Glucose Study cohort included 424 children and adolescents initially free of MetS. At the 3.6 year follow-up, 47 new cases of MetS were identified. A 168-item semi-quantitative food-frequency questionnaire was used to collect information about total and various types of vegetables consumed, including allium-, green leafy-, fruity-, root-, stalk-, starchy-, potatoes, and cabbage. MetS was defined according to the Cook et al[32] criteria. RESULTS The median (interquartile range) of total vegetable consumption was 217 (146- 344) g/d. After adjustment for demographic characteristics and dietary intake, higher total-(≥ 350 g/d) and higher allium vegetable consumption (≥ 30 g/d) in the fourth quartile were significantly and inversely associated with risk of MetS compared to the first quartile. Consumption of green leafy vegetables in the third (21.4-38.3 g/d) versus the first quartile (≤ 13.5 g/d) demonstrated a significant inverse association with lower risk of MetS in children and adolescents;associations for other types of vegetables consumed were not significant. CONCLUSION Consumption of vegetables, especially allium and green leafy vegetables, in sufficient amounts may be beneficial in reducing the risk of MetS among children and adolescents.

Clinico-epidemiological factors of health related quality of life among people with type 2 diabetes

AIM To investigate the quality of life(QOL) and its clinical and epidemiological correlates among people with type 2 diabetes.METHODS This cross-sectional study was conducted in Tabriz, Northwest of Iran, including a total of 394 people with type 2 diabetes using convenient sampling method from November 2014 to March 2015. General information including demographic, socioeconomic status and lifestyle factors were collected by trained interviewers. Clinical information was retrieved from clinic's record and QOL was assessed using the 26-item WHOQOL-BRIFE questionnaire. Univariate and multivariate linear regression were performed to assess the related factors and QOL dimensions. RESULTS The mean of overall health related QOL was 52.11 ± 11.53 and the maximum and minimum dimensions wererespectively seen in psychological(60.38 ± 14.54) and social(38.32 ± 16.94) dimensions. The results of multiple linear regression showed a significant overall relationship between HRQOL and age(b =-1.48%, 95%CI:-0.03 and-2.93) level of education(b = 4.12%, 95%CI: 2.73 and 5.5), number of comorbidities(b =-2.41%, 95%CI:-3.89 and-9.41), and level of income(b = 1.98, 95%CI: 0.05 and 3.9), functional limitation(b =-3.59, 95%CI:-2.26 and-4.92) and psychological distress(b =-2.02%, 95%CI:-2.83 and-1.21). Level of education, functional limitation, psychological distress were associated with the score of physical, mental and environmental dimensions, and number of comorbidities was associated with the score of physical and mental dimensions. CONCLUSION Based on our findings, lifestyle modification and increasing facilities of clinics providing service can be effective steps to improve the QOL among people with type 2 diabetes.

Prevalence of Hypogonadotropic Hypogonadism in Type 2 Diabetes Male Patients

Background: Erectile dysfunction is common in patients with diabetes mellitus. In addition, reduced testosterone itself is considered as a risk factor for diabetes;therefore hypogonadism was studied in diabetes. Objective: This study was done to determine the prevalence of hypo- and hypergonadotropic hypogonadism in the type 2 diabetes male patients in Mashhad in north-east of Iran. Methods: This study was done on type 2 diabetic men aged 40 - 60 years in the endocrine clinic, Endocrinology Research Center, Mashhad University of Medical Sciences, Iran. Fasting blood samples were collected at 8 am for measurement of fasting blood sugar (FBS), HbA1C, total serum testosterone, FSH, Sex Hormone Binding Globulin (SHBG), LH, prolactin, thyroxin-stimulating hormone (TSH), and immediately was sent to laboratory. Results: Out of total 96 type 2 diabetic males (mean age of 51.4 ± 11.26 years, range of 40 - 60 years), 11 (12.94%) patients were excluded because of inadequate samples, insufficient information and fulfillment of the exclusion criteria of the study. Hypogonadism based on Testosterone, Calculated free testosterone (CFT), and boiavailable testosterone (BT) were observed in 10 (11.8%), 31 (36.6%), and 30 (35.3%) of the patients, respectively. Libido was decreased in 55 (64.7%) of the patients. Based on the obtained SHBG values there were 7 (8.2%), 52 (61.2%), and 26 (30.6%) cases of low, normal and high values, respectively. According to TSH observed values there were 6 (7.1%) patients and 1 case of sub-clinical hypothyroidism and hyperthyroidism, respectively, and the rest 78 (91.8%) cases were euthyroid. Prolactin level was normal in all cases. Conclusion: Hypogonadotropic hypogonadism is common in type 2 diabetic men, and whether its treatment is useful for erectile dysfunction or not, needed additional investigation.

Analysis of the glucokinase gene in Iranian families with maturity onset diabetes of the young

Non insulin dependent diabetes mellitus (NIDDM) as a most common form of diabetes is a major public health problem;there is a subgroup of NIDDM patients who develop the disease at an early age and show a dominant mode of inheritance. This type is nominates Maturity onset diabetes of the young (MODY). The prevalence of MODY is difficult to access, and patients with MODY genes mutations are often identified during routine screening for other purposes. MODY2 was linked to glucokinase gene (GCK) mutations, and accounted for 8% to 56% of MODY, with the highest prevalence found in the southern Europe. The aim of this study was to examine the prevalence and nature of mutations in GCK gene in Iranian paients. We have screened GCK mutations by polymerase chain reaction (PCR);single stranded conformation polymorphism (SSCP) technique in 12 Iranian families with clinical diagnosis of MODY, included 30 patients (8 males and 22 females) and their 21 family members. PCR products with abnormal mobility in denaturing gradient gel electrophoresis (DGGE) were directly sequenced. We identified 6 novel mutations in GCK gene in Iranian families (corresponding to 36.6% prevalence). Our findings and the last study on MODY1 highlight that in addition to GCK, other MODY genes such as MODY3 and MODYX may play a significant role in diabetes characterized by monogenic autosomal dominant transmission. There is an important point that the genetic recognation can be used to pre-symptomatically identify family members at risk for developing MODY.

Comparison of the effects of acute and chronic psychological stress on metabolic features in rats

This study was aimed to compare the effects of acute and chronic psychological stress on metabolic factors. Forty-two male Wistar rats were divided into control and stressed groups. Stress was applied by a communication box acutely (1 d) and chronically (15 and 30 d). Blood sampling was carried out by retro-orbital-puncture method. The plasma levels of glucose, cholesterol, triglyceride, insulin, and corticosterone were measured. In addition, feed and water intake, latency to eat and drink, adrenal and body weights were determined. Acute and chronic psychological stress did not significantly change basal plasma corticosterone levels. However, immediately (1 min) after acute exposure to stress, plasma corticosterone level increased compared to that before stress exposure. Acute stress increased plasma insulin levels significantly. Fifteen days of stress exposure resulted in plasma glucose increase. Chronic stress significantly increased feed intake, latency to eat, and adrenal weight compared to acute stress. The body weights of both control and stressed groups increased markedly during the experiment. Homeostasis model assessment of insulin resistance (HOMA-IR) index did not change significantly in the stressed group. In conclusion, application of acute and chronic psychological stress leads to different metabolic and/or behavioral changes but the metabolic changes resulting from acute exposure to stress seem to be more pronounced.

Diet quality and nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease(NAFLD)is the most common cause of chronic liver disease and comprises a wide range of clinical symptoms from nonalcoholic fatty liver to nonalcoholic steatohepatitis(NASH),advanced fibrosis,and cirrhosis(1).Obesity is the major risk factor of NAFLD and its main treatment is lifestyle modifications,including weight management,dietary changes and physical activity(2).