Empagliflozin improves left ventricular ejection fraction and end systolic volume in patients with type 2 diabetes mellitus and coronary artery disease: a post-hoc analysis of EMPA-CARD trial.

Background: Sodium glucose co-transporter2 (SGLT2) inhibitors have exhibited cardioprotective properties in diabetes patients. The aim of this study was to investigate the effect of Empagliflozin on changes in echocardiographic parameters. Methods: This was a post hoc analysis of the EMPA-CARD trial which was a multicenter, triple-blind randomized controlled trial. Type 2 diabetes mellitus patients with concomitant history of coronary artery disease were randomized on a 1:1 ratio into two groups receiving either 10 mg/day Empagliflozin or placebo. Patients with a history of heart failure (NYHA class 3-4) and ejection fraction (EF) < 40% were excluded. Trans-thoracic echocardiography was performed at baseline and at 26 weeks of intervention. Results: A total of 69 (Empagliflozin = 39 and placebo = 30) patients underwent echocardiography. Significant changes were observed for left ventricular ejection fraction [standard error (SE) = 0.76; beta (95% correlation interval (CrI)] = -5.558 (-7.25; -4.18) and left ventricular end-systolic volume (SE = 1.38; beta (95% CrI) = 3.915 (1.2; 0.66). Other echocardiographic parameters relating to right ventricular or atrial function did not change significantly. Conclusion: Empagliflozin can have cardioprotective benefits in subjects without HF. Further studies are required to determine the effect of Empagliflozin in non-HF patients. Trial registration: The original EMPA-CARD study has been registered in Iranian Registry of Clinical Trials. www.IRCT.ir, Identifier: IRCT20190412043247N2. Registration Date: 6/13/2020. Registration timing: prospective.

Potential role of resveratrol in prevention and therapy of diabetic complications: a critical review.

Background: Diabetes mellitus (DM) is a category of metabolic conditions affecting about 5% of people worldwide. High mortality associated with DM is mostly due to its severe clinical complications, including diabetic nephropathy, retinopathy, neuropathy, and cardiomyopathy. Resveratrol (RSV) is a natural, biologically active polyphenol known to have various health-promoting effects in animal models and humans. Objective: In this review, we have reviewed the preventive and therapeutic role of RSV on diabetes complications with emphasis on its molecular mechanisms of action. Methods: To prepare this review, all the basic and clinical available literatures regarding this topic were gathered through electronic databases, including PubMed, Web of Science, Scopus, and Google Scholar. Therefore, we summarized previous studies that have evaluated the effects of RSV on diabetic complications and their mechanisms. Only English language studies published up to January 2023 were included in this review. Results: RSV improves glucose homeostasis, decreases insulin resistance, induces autophagy, regulates lipid metabolism, protects pancreatic ß-cells, ameliorates metabolic disorders, and increases the GLUT4 expression. These effects induced by RSV are strongly associated with ability of this polyphenol agent to elevation expression/activity of AMP-activated protein kinase and Sirtuin 1 in various organs of diabetic subjects, which leads to prevention and therapy of diabetic complications. In addition, antioxidant and anti-inflammatory properties of RSV were reported to be involved in its action in diabetic complications, such as retinopathy and nephropathy. Conclusion: RSV is a promising compound for improving diabetic complications. However, the exact antidiabetic mechanisms of RSV need to be further investigated.

Association of maternal exposure to endocrine disruptor chemicals with cardio-metabolic risk factors in children during childhood: a systematic review and meta-analysis of cohort studies.

BACKGROUND: In the present systematic review and meta-analysis, the association of maternal exposure to the endocrine disrupting chemicals (EDCs) with cardio-metabolic risk factors in children during childhood for the first time. METHOD: The PubMed, Scopus, EMBASE, and Web of Science databases were systematically searched, up to Feb 2023. In total 30 cohort studies had our inclusion criteria. A random-effects model was used for the variables that had considerable heterogeneity between studies. The Newcastle-Ottawa Scale (NOS) tool was used to classify the quality score of studies. All statistical analyses were conducted using Stata 14 and P-value < 0.05 considered as a significant level. RESULTS: In the meta-analysis, maternal exposure to the EDCs was weakly associated with higher SBP (Fisher_Z: 0.06, CI: 0.04, 0.08), BMI (Fisher_Z: 0.07, CI: 0.06, 0.08), and WC (Fisher_Z: 0.06, CI: 0.03, 0.08) z-scores in children. A significant linear association was found between maternal exposure to the bisphenol-A and pesticides with BMI and WC z-score in children (p < 0.001). Subgroup analysis showed significant linear association of BPA and pesticides, in the urine samples of mothers at the first trimester of pregnancy, with BMI and WC z-score in children from 2-8 years (p < 0.05). CONCLUSION: Prenatal exposure to the EDCs in the uterine period could increase the risk of obesity in children. Maternal exposure to bisphenol-A and pesticides showed the strongest association with the obesity, especially visceral form, in the next generation.

The Effect of Magnesium Supplementation on Insulin Resistance and Metabolic Profiles in Women with Polycystic Ovary Syndrome: a Randomized Clinical Trial.

Due to the definitive known effect of magnesium on insulin resistance and the fact that insulin resistance is a main etiology in polycystic ovary syndrome (PCOS), it is assumed the use of magnesium supplements can improve insulin resistance, lipid profiles, and glucose and thus may also play a role in improving the clinical condition of patients with PCOS. We aimed to assess the effects of magnesium supplements on anthropometric, clinical, and metabolic parameters in women suffering from PCOS. This triple-blind randomized clinical trial study was conducted on women aged 15-35 years with PCOS. The patients were randomly assigned to receive a magnesium oxide supplement (250 mg/day for 2 months) or a placebo. The study parameters were evaluated and compared between two groups before as well as 2 months and 5 months after the initial assessment. In total, 40 cases (20 in each group) were recruited in the study. A significant reduction in the serum insulin level (P-value = 0.036) and insulin resistance (p-value = 0.032) was observed in the case group. Prescribing magnesium supplements could also lead to lowering total cholesterol, low-density lipoprotein, and fasting blood sugar along with increasing the level of high-density lipoprotein. We could not find any significant difference in anthropometric parameters as well as the mean systolic and diastolic blood pressures before and after intervention between the two groups. Although the rate of oligomenorrhea significantly decreased in the two study groups, it was no different across the two groups before and also after the intervention. The use of magnesium supplements in patients with PCO, regardless of the etiology or progression of the disease, can greatly improve the metabolic status of these patients by improving insulin resistance and modulating the level of lipid profile.

Correlation of Dietary Macro- and Micro-Mineral Intake with Seminal Plasma Quality/Quantity and Oxidant/Antioxidant Status in Infertile Compared to the Normal Men: a Case-Control Study.

Male infertility is a global public health issue, but studies on the correlation between the dietary components and sperm quality showed inconclusive results due to the heterogeneous population with different dietary habits and environmental stimuli. Herein, the correlation of dietary macro- and micro-mineral intake was evaluated with quality/quantity and oxidant/antioxidant status of seminal fluid in infertile compared to the healthy men. One hundred twenty men attending to the infertility clinic of Ayatollah Mousavi Hospital in Zanjan City were enrolled. Seminal fluid was extracted, and groups were categorized into the infertile (non-standard) and normal (standard) groups based on the WHO, 2020 criteria. Food frequency questionnaire was completed. Seminal malondialdehyde (MDA) and total antioxidant capacity (TAC) were measured by ELISA kit based on the manufacture's instruction. An independent sample t-test was used to determine differences between the two groups, and linear regression model was used to determine the effect of each dietary macro/micro mineral intake on these parameters. Adjusting for all parameters, dietary selenium increased 3.7-folds the seminal TAC level (p=0.04) and decreased sperm with non-progressive motility by 2.4-folds (p=0.04). Higher manganese intake increased the sperm count by 7.8-folds (p=0.005). Dietary copper decreased sperm vitality and increased sperm with slow motility (OR= -1.7, 95% CI= -59.8, -9.9; p=0.007). Dietary zinc (OR=1.24, p=0.01) and iron (OR=1.5, p=0.02) showed a positive effect on sperm vitality. None of macro and micro minerals showed a significant effect on the seminal MDA level. Daily intake of adequate amounts of micro and macro minerals improves sperm quality and increases the antioxidant capacity of the seminal fluid; however, copper showed a negative correlation that must be evaluated in future studies.

Empagliflozin improves high-sensitive cardiac troponin-I and high-density lipoprotein cholesterol in patients with type 2 diabetes mellitus and coronary artery disease: a post-hoc analysis of EMPA-CARD Trial.

Background: Empagliflozin is a sodium glucose cotransporter-2 (SGLT2) inhibitor that has been suggested to improve cardiac function and vascular recovery. The risk of coronary artery diseases is much higher in diabetic patients and is associated with greater morbidity and mortality. High-sensitivity cardiac troponin-I (hs-cTnI) is an important prognostic biomarker in cardiac diseases. Therefore, this study aimed to investigate the effect of empagliflozin compared to placebo on changes in hs-cTnI and lipid profile after 26 weeks of treatment. Methods: This was an ancillary study in a randomized trial of patients with concomitant type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) (The EMPA-CARD study). Patients who were already on standard anti-diabetic/anti-ischemic medications were randomized to receive either placebo or empagliflozin 10 mg/daily. Serum hs-cTnI and lipid profile were measured at baseline and after 26 weeks. Results: Of the 95 randomized patients, hs-cTnI and lipid profile were measured for a total of 77 patients. No significant difference was observed regarding the baseline characteristics between the two arms. Compared to placebo, empagliflozin significantly reduced hs-cTnI after 26 weeks (mean difference (MD) of -13.242, 95%CI: -14.151 to -12.333, p < 0.001). In the empagliflozin group, non-significant reductions in total cholesterol, LDL-C, and triglyceride have resulted; however, there was an increase in HDL-C level (MD = 2.40,95%CI:0.16-4.60, p < 0.04). Conclusion: Empagliflozin compared to placebo was superior in reducing circulating hs-cTnI that may indicate improvements in cardiomyocytes function in patients with T2DM and CAD. Moreover, empagliflozin had a modest impact on the serum lipid profile biomarkers. Trial registration: The original EMPA-CARD study has been registered in Iranian Registry of Clinical Trials. www.IRCT.ir, Identifier: IRCT20190412043247N2. Registration Date: 6/13/2020. Registration timing: prospective.

A low-carb diet increases fecal short-chain fatty acids in feces of obese women following a weight-loss program: randomized feeding trial.

To compare fecal level of short-chain fatty acid (SCFA) and some serum inflammatory markers between the low-carbohydrate (LCD) and the habitual (HD) diet, subjects were enrolled from our previous study on the effect of LCD vs. HD on gut microbiota in obese women following an energy-restricted diet. Serum interleukin-6 (IL-6) significantly increased in the HD group (p < 0.001). Adjusted for the baseline parameters, fecal level of butyric, propionic, and acetic acid were significantly different between the LCD and HD groups (p < 0.001, p = 0.02, and p < 0.001, respectively). Increase in serum insulin level correlated with decrease in fecal propionic acid by 5.3-folds (95% CI = - 2.7, - 0.15, p = 0.04). Increase in serum high sensitive C-reactive protein (hs-CRP) correlated with decrease in the percentage of fecal butyric acid by 25% (p = 0.04). Serum fasting blood sugar (FBS) and insulin showed a significant effect on fecal acetic acid (p = 0.009 and p = 0.01, respectively). Elevated serum FBS and insulin correlated with increase in fecal acetic acid by 2.8 and 8.9-folds (95%CI = 0.34, 1.9 and 1.2, 9.2), respectively. The LCD increased fecal SCFAs and a significant correlation was seen between serum IL-6 and fecal propionic acid level. More studies are needed to reach a concise correlation. Trial registration number: The trial was registered in Iranian ClinicalTrials.gov IRCT20200929048876N3.

Age-related histopathological and biochemical testicular damages were ameliorated by vitamin C administration / Los daños testiculares histopatológicos y bioquímicos relacionados con la edad mejoraron con la administración de vitamina C

Introduction and objectives: Aging is an irreversible process associated with decreased biological functions that can lead to the reduction of reproductive organs capacities in males and females. Paternal age is a significant predictor of offspring health and development. So, the aim of this study was to evaluate the effects of vitamin C on histopathological and biochemical testicular changes following aging process with a focus on stereological methods. Material and methods: For this study, 48 adult male NMRI mice were divided into two control and experimental groups. Mice in experimental group were supplemented with vitamin C (150mg/kg) including 24-h interval by oral gavage for 33 weeks. Same regime was performed for animals in control group except that vitamin C was replaced by water. Then, right testes were extracted for stereological and left testes were used for molecular analyses on weeks 8, 12, and 33. (AU)

Introducción y objetivos: El envejecimiento es un proceso irreversible asociado a una disminución de las funciones biológicas que puede conducir a la reducción de la capacidad de los órganos reproductivos en hombres y mujeres. La edad paterna es un predictor significativo de la salud y el desarrollo de la descendencia. Por lo tanto, el objetivo de este estudio fue evaluar los efectos de la vitamina C sobre los cambios testiculares histopatológicos y bioquímicos posteriores al proceso de envejecimiento con un enfoque en los métodos estereológicos.Material y métodos: Para este estudio, 48 ratones NMRI machos adultos se dividieron en dos grupos de control y experimentales. Los ratones del grupo experimental se suplementaron con vitamina C (150mg/kg), incluido un intervalo de 24 horas mediante sonda oral durante 33 semanas. Se realizó el mismo régimen para los animales del grupo de control, excepto que se reemplazó la vitamina C por agua. Luego, se extrajeron los testículos derechos para estereología y los testículos izquierdos se utilizaron para análisis moleculares en las semanas 8, 12 y 33. (AU)

A Deletion in Duchenne Muscular Dystrophy Gene Found Through Whole Exome Sequencing in Iran.

Duchenne muscular dystrophy (DMD) is a severe progressive X-linked neuromuscular illness that affects movement through mutations in dystrophin gene. The mutation leads to insufficient, lack of, or dysfunction of dystrophin. The cause of DMD was determined in an Iranian family. Exome sequencing was carried out along with a complete physical examination of the family. In silico methods were applied to find the alteration in the protein structure. The homozygous variant in DMD gene (NM-004006.2) was defined as c.2732-2733delTT (p.Phe911CysfsX8) in exon 21. In addition, phylogenetic conservation study of the human dystrophin protein sequence revealed that phenylalanine 911 is one of the evolutionarily conserved amino acids. In conclusion, our study indicated a new deletion in the DMD gene in the affected family. This deletion with an X-linked inheritance pattern is new in Iran. These findings could facilitate genetic counseling for this family and other patients in the future.

Age-related histopathological and biochemical testicular damages were ameliorated by vitamin C administration.

INTRODUCTION AND OBJECTIVES: Aging is an irreversible process associated with decreased biological functions that can lead to the reduction of reproductive organs capacities in males and females. Paternal age is a significant predictor of offspring health and development. So, the aim of this study was to evaluate the effects of vitamin C on histopathological and biochemical testicular changes following aging process with a focus on stereological methods. MATERIAL AND METHODS: For this study, 48 adult male NMRI mice were divided into two control and experimental groups. Mice in experimental group were supplemented with vitamin C (150mg/kg) including 24-h interval by oral gavage for 33 weeks. Same regime was performed for animals in control group except that vitamin C was replaced by water. Then, right testes were extracted for stereological and left testes were used for molecular analyses on weeks 8, 12, and 33. RESULTS: Our findings showed low semen quality, decreased level of serum Luteinizing hormone (LH), Follicle-stimulating hormone (FSH), and testosterone along with increased reactive oxygen species (ROS) production and higher apoptotic gene expression following aging. Stereological studies showed that the volume of testes, the length of seminiferous tubules, and the number of spermatogenic and none-spermatogenic cells decreased significantly during aging. Also, vitamin C consumption for 33 weeks significantly improved biochemical and histological indices. The impact of aging on male reproduction seems to be inevitable worldwide. Therefore, the use of protective and preventive remedies conserving male fecundity is very important and based on our results, vitamin C is a beneficial candidate for improving age-related testicular changes due to aging process.

The effect of EMPAgliflozin on markers of inflammation in patients with concomitant type 2 diabetes mellitus and Coronary ARtery Disease: the EMPA-CARD randomized controlled trial.

Systemic inflammation and oxidative burden in patients with type 2 diabetes mellitus (T2DM) causes deleterious cardiovascular outcomes. We sought to investigate the clinical antioxidative and anti-inflammatory effects of empagliflozin. Platelet function, oxidant and antioxidant biomarkers and pro-inflammatory agents at baseline and at 26 weeks were measured. A total of 95 patients (41.05% male, mean age 62.85 ± 7.91 years, mean HbA1c 7.89 ± 0.96%) with concomitant T2DM and coronary artery disease (CAD) were randomized (1:1) to receive empagliflozin (10 mg/daily) or placebo. Patients treated with empagliflozin had lower levels of interleukin 6 (IL-6) (adjusted difference (adiff): - 1.06 pg/mL, 95% CI - 1.80; - 0.32, P = 0.006), interleukin 1ß (IL-1ß) and high-sensitive C-reactive protein (Hs-CRP) (adiff: - 4.58 pg/mL and - 2.86 mg/L; P = 0.32 and 0.003, respectively) compared to placebo. There were elevations in super oxidase dismutase (SOD) activity, glutathione (GSHr), and total antioxidant capacity (TAC) with empagliflozin (adiff: 3.7 U/mL, 0.57 muM, and 124.08 mmol/L, 95% CI 1.36; 6.05, 0.19; 0.95, and 47.98; 200.18, P = 0.002, 0.004, and 0.002, respectively). While reactive oxygen species (ROS) improved significantly (adiff: - 342.51, 95% CI - 474.23; - 210.79, P < 0.001), the changes in catalase activity (CAT), malondialdehyde (MDA), or protein carbonyl groups (PCG) were not significant. Moreover, the P-selectin antigen expression on platelet surface was significantly reduced (adiff: - 8.81, 95% CI - 14.87; - 2.75, P = 0.005). Markers of glycemic status (fasting blood glucose, HbA1c, and HOMA-IR (homeostatic model assessment for insulin resistance) significantly improved (P < 0.001). Among patients with T2DM and CAD, 6-month treatment with empagliflozin can mitigate inflammation, platelet activity and oxidative stress and is associated with clinical cardiovascular benefits.Trial Registration Iranian Registry of Clinical Trials. www.IRCT.ir , Identifier: IRCT20190412043247N2. Registration Date: 6/13/2020. Registration timing: prospective.

Vitamin D role in hepatitis B: focus on immune system and genetics mechanism.

According to the World Health Organization (WHO) report, viral hepatitis has been a problem in human society. Vitamins play a significant role in preventing the hepatocarcinoma and liver cirrhosis. In this report, we will first focus on the vitamin D function in the immune system reactions, and then investigate its role in the viral infections and the signaling pathway of hepatitis B virus. The existence of the cytochrome P450 (CYP) 27B1 enzyme, which is involved in vitamin D synthesis in immune system cells, has drawn researchers ' attention to the field of immune system. Toll like receptor (TLR) play a significant role in the immune system, and are one of the primary receptors of the innate immune system. In addition, the synthesis of inflammatory cytokines, such as Interferon γ (IFNγ) and Interleukin-2 (IL-2) is one of the key roles of T helper type 1 (Th1) cells; these cells can suppress two cited cytokines via vitamin D. In the chronic phase of hepatitis B, Cytotoxic T lymphocytes (CTLs) cells have weaker performance than the acute phase of the disease. The association between vitamin D physiologies with viral infections is also confirmed by genetic studies, carried out on genetic variations of vitamin D receptor (VDR) R-encoding disease susceptibility gene. Vitamin D affects different phases of the disease. Therefore, further experiments in this area are proposed.

Protective effects of curcumin on ischemia/reperfusion injury.

Ischemia/reperfusion (I/R) injury is a term used to describe phenomena connected to the dysfunction of various tissue damage due to reperfusion after ischemic injury. While I/R may result in systemic inflammatory response syndrome or multiple organ dysfunction syndrome, there is still a long way to improve therapeutic outcomes. A number of cellular metabolic and ultrastructural alterations occur by prolonged ischemia. Ischemia increases the expression of proinflammatory gene products and bioactive substances within the endothelium, such as cytokines, leukocytes, and adhesion molecules, even as suppressing the expression of other "protective" gene products and substances, such as thrombomodulin and constitutive nitric oxide synthase (e.g., prostacyclin, nitric oxide [NO]). Curcumin is the primary phenolic pigment derived from turmeric, the powdered rhizome of Curcuma longa. Numerous studies have shown that curcumin has strong antiinflammatory and antioxidant characteristics. It also prevents lipid peroxidation and scavenges free radicals like superoxide anion, singlet oxygen, NO, and hydroxyl. In our study, we highlight the mechanisms of protective effects of curcumin against I/R injury in various organs.

Effect of lifestyle modification for two years on obesity and metabolic syndrome components in elementary students: A community- based trial.

Background: Lifestyle modifications, especially improving nutritional patterns and increasing physical activity are the most important factors in preventing obesity and metabolic syndrome in children and adolescents. For this purpose, the following interventional study was designed to investigate the effects of educational programs for students, as well as the changes in diet and physical activity on obesity and components of the metabolic syndrome. Methods: This study is part of an interventional research project (elementary school) conducted on all students of Sama schools in Zanjan and Abhar in three levels;elementary, middle and high school, including 1000 individuals in Zanjan (intervention group) and 1000 individuals (control group) in Abhar in 2011. Interventions were based on educating students, teachers and parents, changes in food services and physical activity. We primarily measured anthropometric indices, fasting blood sugar, lipid profiles and blood pressure and completed standard nutrition and physical activity questionnaires. Also, blood insulin levels were randomly measured in a number of students. Data analysis was done by SPSS software Version 16.0. Results: Overall, 589 individuals (252 males, 337 females) entered the case group and 803 individuals (344 males, 459 females) entered the control group. After two years of intervention, the mean waist circumference (63.8±10.9) and diastolic BP (63.8±10.4) were significantly lower, however, the mean systolic BP (10.1.0±12.5), food score (25.0±5.0) and drinking score (12.1±2.3) were higher in the intervention group (p<0.001). Comparing the components of metabolic syndrome between the second year and at the time of recruitment within the intervention group, showed that although the number of overweight/obese individuals, individuals with hypertriglyceridemia and high LDL increased, while those with abdominal obesity, high BP, hyperglycemia, and insulin resistance decreased (p<0.001). On the other hand, in the control group, the number of individuals with high BP increased significantly. Conclusion: The prevalence of abdominal obesity and hypertension, which are the two major components of metabolic syndrome, are much higher in our study than the other regions of the country. However, interventions for modification of diet and increasing physical activity, are effective in lowering of their prevalence.

Effect of Atkins versus a low-fat diet on gut microbiota, and cardiometabolic markers in obese women following an energy-restricted diet: Randomized, crossover trial.

BACKGROUND AND AIMS: There is controversy about effects of the Atkins diet on cardiometabolic markers in previous studies. No study compared effects of Atkins versus a low-fat diet on gut microbiota in obese women during a weight-loss program up to date. METHODS AND RESULTS: A 6-week, randomized, crossover trial was conducted. Twenty-four healthy women with obesity (BMI≥30 kg/m2) were randomly assigned to receive the Atkins (55%, 25%, and 20% of total daily calories from fat, protein, and carbohydrates), or low-fat (20%, 15%, and 65% of total daily calories from fat, protein, and carbohydrates) diets while following a weight-loss program. Vegetable oils were used as the main source of dietary fat. Dietary groups were switched after two weeks of washout period with a weight maintenance low-fat diet. The effects of the two diets did not differ for the most endpoints. However, Gut Actinobacteria residency and serum total antioxidant capacity significantly increased in the Akins diet group compared with the low-fat one (p = 0.02 and p = 0.04). Adjusting for all parameters, gut Actinobacteria residency 1.48- and 2.5-folds decreased the serum LDL.C/HDL.C ratio and non-HDL.C levels (95%CI: 3.1, -0.22; p = 0.03 and -0.07, -0.002; p = 0.04), respectively. Decrease in gut Proteobacteria residency showed a significant reduction in serum total oxidant status (95%CI: 7.4, -0.07; p = 0.04). CONCLUSIONS: The Atkins diet, based on vegetable oils, alters gut microbiota composition, atherogenic and antioxidant parameters. REGISTRATION NUMBER FOR CLINICAL TRIAL: IRCT20200929048876N3.

Short-Term Adverse Pregnancy Outcomes in Women with Subclinical Hypothyroidism: A Comparative Approach of Iranian and American Guidelines.

Introduction: Subclinical hypothyroidism during pregnancy can be associated with numerous adverse outcomes. The purpose of this study was to compare short-term adverse pregnancy outcomes in treated versus nontreated patients who fall within the numerical range of thyroid-stimulating hormone (TSH) between the Iranian and American reference ranges. Materials and Methods: Eighty pregnant women with a known level of antithyroid peroxidase (anti-TPO) and TSH levels of 2.5-3.9 mIu/L in the first trimester and 3-4.1 mIu/L in the second and third trimesters were enrolled in the study and randomly assigned into two groups including 41 patients in the intervention group and 39 in the control group. The intervention group was treated with levothyroxine at least 50 µg/day and the control group received no treatment. The data were analyzed by SPSS software version 23. Results: The only significant findings were a correlation between pregnancy loss frequency (p - 0.011) and/or increased TSH level in the follow-up period (p = 0.008) with anti-TPO antibody positivity. Forty-four percent of mothers with positive anti-TPO Ab needed treatment initiation with levothyroxine, based on Iranian guidelines, due to increased TSH level during the follow-up period. Conclusion: Untreated pregnant women with subclinical hypothyroidism, who were placed in the intermediate range of TSH, recommended by Iranian and American guidelines, did not show any significant difference in short-term adverse pregnancy outcomes compared to the treated patients. Positive anti-TPO Ab may play a role in the development of short-term complications in mothers with subclinical hypothyroidism or it may increase the likelihood of an increase in TSH level during pregnancy.

Serum cortisol concentration and COVID-19 severity: a systematic review and meta-analysis.

The novel COVID-19 outbreak is a major health threat to human beings with multiorgan injuries. However, its endocrine system manifestations are much less studied. In this study, we aimed to reassess the available findings on the association between cortisol level and severity of COVID-19 infection. We conducted a systematic search on Medline/PubMed, Scopus, Web of Science, and Cochrane Library databases. To pool data, a random-effects model was performed depending on the heterogeneity among studies. Sensitivity analysis was also carried out by removing each study systematically. In addition, subgroup and meta-regression analyses were performed depending on the presence of the variables of sex and age. Subsequently, 11 studies (5 observational studies and 6 case reports) were included in the meta-analysis. Pooled analysis on the observational studies showed significantly higher levels of cortisol in patients with severe COVID-19 in comparison with those with mild-to-moderate COVID-19 (standardized mean difference: 1.48 µg/dL; 95% CI (0.51 to 2.46); p=0.003). Assessment of the results of case reports revealed that the patients with severe COVID-19 demonstrated higher cortisol levels than the patients with mild-to-moderate COVID-19. No publication bias was observed using the Begg's (p=0.08) and Egger's tests (p=0.09). Meta-regression illustrated a significant correlation between cortisol levels with sex. The serum cortisol level seems to be higher in patients with severe COVID-19 infection. This finding could be helpful to detect patients with poor prognosis at early stages of the disease, although age and sex may modify this level.

Synthesis of a green bigel using cottonseed oil/cannabis oil/alginate/ferula gum for quercetin release: Synergistic effects for treating infertility in rats.

Although therapeutic effect of quercetin (Quer) was reported on non-alcoholic fatty liver disease (NAFLD), destructive effects have been shown on male fertility due to its pro-oxidative properties. On the other hand, NAFLD impairs germ cells to produce sperm and leads to male infertility. Herein, a biocompatible and green bigel was designed for Quer delivery to prevent infertility induced by NAFLD as the increasing complications. Bigels were prepared using cottonseed oil/cannabis oil/alginate/ferula gum and optimized by the mixture design method. NAFLD was induced by 58% of dietary calorie as lard and 42 g/l fructose for 16 weeks in Sprague-Dawley rats. So on animals received 2 mg/kg Quer loaded on bigels, free bigels, or free Quer for 45 days as daily gavage. Semen was analyzed, followed by the assessment of DNA integrity. Count, motility, and normal morphology reached the healthy control group at the bigel-Quer-treated one. Moreover, all of these parameters were significantly higher in the bigel-Quer group than the Quer and bigel, alone. The percent of sperms with head and tail abnormality decreased considerably in the bigel-Quer group compared with the Quer, free bigel, and NAFLD groups. Serum testosterone levels significantly increased and reached the healthy control group in the bigel-Quer group. DNA fragmentation of sperm significantly decreased in the bigel-Quer group (p < 0.05). The bigel showed synergistic effects with Quer for treating infertility in rats with NAFLD.

COVID-19: Virology, biology and novel laboratory diagnosis.

BACKGROUND: At the end of December 2019, a novel coronavirus tentatively named SARS-CoV-2 in Wuhan, a central city in China, was announced by the World Health Organization. SARS-CoV-2 is an RNA virus that has become a major public health concern after the outbreak of the Middle East Respiratory Syndrome-CoV (MERS-CoV) and Severe Acute Respiratory Syndrome-CoV (SARS-CoV) in 2002 and 2012, respectively. As of 29 October 2020, the total number of COVID-19 cases had reached over 44 million worldwide, with more than 1.17 million confirmed deaths. DISCUSSION: SARS-CoV-2 infected patients usually present with severe viral pneumonia. Similar to SARS-CoV, the virus enters respiratory tract cells via the angiotensin-converting enzyme receptor 2. The structural proteins play an essential role in budding the virus particles released from different host cells. To date, an approved vaccine or treatment option of a preventive character to avoid severe courses of COVID-19 is still not available. CONCLUSIONS: In the present study, we provide a brief review of the general biological features of CoVs and explain the pathogenesis, clinical symptoms and diagnostic approaches regarding monitoring future infectivity and prevent emerging COVID-19 infections.