Band 44, Heft 2

Objectives The increasing prevalence of coronary artery disease [CAD] poses worrying statistics. Atherosclerosis of coronary vessels is the main culprit for the spectrum of CAD especially acute coronary syndrome. Atherosclerosis is regarded as a consequence of inflammatory changes in the coronaries. Our study aimed to assess the role of risk factors and inflammatory markers with acute ST-elevation myocardial infarction [STEMI]. Methods 100 patients with ST-elevation Myocardial infarction [STEMI] and 100 age and sex matched controls were included in the study. A history of risk factors like smoking, hypertension, diabetes and hypertension was noted. A venous blood sample was obtained for analysis of inflammatory markers. The data thus obtained was statistically analyzed. Results The cases had a significant number of risk factors such as smoking, hypertension, and diabetes mellitus, previous history of CAD, increased body mass index [BMI], and raised high sensitive C-reactive protein [hs-CRP]. Patients with anterior myocardial infarction were older and had hypertension and diabetes mellitus. Patients with inferior myocardial infarction had high BMI, raised erythrocyte sedimentation rate [ESR] and alcoholism. Smokers, patients with diabetes mellitus, high total cholesterol, Low-density lipoprotein [LDL] cholesterol, and hs-CRP were more prone to complications. Conclusions Patients with a greater number of risk factors and raised inflammatory markers were at high risk of STEMI and its complications. An approach to control the modifiable risk factors like obesity and lifestyle changes can reduce the disease burden.

Objectives Investigation the association of pro-inflammatory markers interleukin (IL)-1β and IL- 10 expression, serum levels of C-reactive protein (CRP), cyclooxygenase-2 (COX2), High-density lipoprotein (HDL), Apolipoprotein A1 (ApoA1), and ATP Binding Cassette Subfamily A Member 1 (ABCA1) inflammatory proteins with atherosclerosis index (homocysteine) in normal-weight and obese male subjects. Methods 59 males including 30 obese (Body mass index (BMI) of ≥30 kg/m 2 ) and 29 normal-weight (BMI of 18.5–24.9 kg/m 2 ) were joined to this study. Plasma levels of IL-1β and IL-10 (pg/mL), CRP (pg/mL), COX-2 (ng/mL), APOA1 (mg/dL), ABCA1 (ng/mL), HDL, Cholesterol, and Triglyceride (TG) (mg/dL), and homocysteine (µmol/L) was measured. Association of these biomarkers with homocysteine was determined. Results Obese subjects had higher serum levels of IL10, IL1β, CRP, COX-2, TG, and cholesterol concentrations (all p<0.05 except IL-10 and cholesterol) and low levels of HDL, APOA1, and ABCA1 (non-significant differences) in comparison to normal-weight group. Homocysteine levels were high in obese men with no significant differences between the two groups. In obese subjects, homocysteine had a significant inverse correlation with APOA1, ABCA1, and HDL, and a strong and moderate positive correlation was found with CRP and TG levels, respectively. Conclusions High level of homocysteine and its correlation with inflammation proteins and markers in obese subjects appear to be contributed with atherosclerosis development.

Objectives Meteorin-like peptide (Metrnl), the newly discovered adipokines involves in glucose and lipid metabolism and energy homeostasis. The aim of the present study was to explore the potential predictors of Metrnl by emphasizing the Irisin, glycemic indices, and lipid profile biomarkers in type 2 diabetic patients. Methods This cross-sectional study was carried out on 32 obese types 2 diabetic patients, 31 healthy obese, and 30 healthy normal weight people between August 2020 and March 2021. Serum Metrnl and Irisin, fasting blood glucose (FBS), fasting insulin (FI), fasting insulin (FI), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), HbA 1c and eAG levels were measured in a standard manner. To assay insulin resistance and insulin sensitivity, the homeostatic model assessment insulin resistance (HOMA‐IR) and quantitative check index (QUICKI) model were used. Quantile regression analysis with the backward elimination method was used to explore predictors. The significant level was defined as p<0.05. Results Between variables entered into the model, only the group item showed to be the main predictor of Metrnl in type 2 diabetic patients. Besides, the serum level of Irisin was lower in diabetic patients, and a significant difference was detected between obese diabetic patients and the normal weight group (p=0.024). Conclusions Given the multi-causality of diabetes and also the possible therapeutic role of Metrnl in the management of type 2 diabetic patients’ abnormalities, designing future studies are needed to discover other predictors of Metrnl and the related mechanisms of Metrnl in the management of diabetes.

Objectives During normal menstrual cycles, serum levels of progesterone vary widely between cycles of same woman and between women. This study investigated the profiles of pregnanediol during the luteal phase. Methods Data stemmed from a previous multicenter prospective observational study and concerned 107 women (who contributed 326 menstrual cycles). The study analyzed changes in observed cervical mucus discharge, various hormones in first morning urine, and serum progesterone. Transvaginal ultrasonography and cervical mucus helped identifying the day of ovulation. Changes in pregnanediol glucuronide levels during the luteal phase were examined and classified according to the length of that phase, a location parameter, and a scale parameter. Associations between nine pregnanediol glucuronide profiles and other hormone profiles were examined. Results Low periovulatory pregnanediol glucuronide levels and low periovulatory luteinizing hormone levels were associated with delayed increases in pregnanediol glucuronide after ovulation. That ‘delayed increase profile’ was more frequently associated with cycles with prolonged high LH levels than in cycles with rapid pregnanediol glucuronide increases. A ‘plateau-like profile’ during the luteal phase was associated with longer cycles, cycles with higher estrone-3-glucuronide and pregnanediol glucuronide during the preovulatory phase, and cycles with higher periovulatory pregnanediol glucuronide levels. Conclusions Distinct profiles of urinary progesterone levels are displayed during the luteal phase. These profiles relate to early hormone changes during the menstrual cycle. In everyday clinical practice, these findings provide further evidence for recommending progesterone test seven days after the mucus peak day. The search for other correlations and associations is underway.

Objectives Epigenetic alterations like methylation of tumor suppressor genes or oncogenes, in respiratory epithelium have been associated with lung cancer. Hypermethylation of genes promoter is an epigenetic event, and is responsible to tumor suppressor genes inactivation as well as oncogenes activation. This study aimed to assess the role of methylation status in promoter of RASSF1 and ATIC genes their potential implication in the pathogenesis of lung tumor in Iranian patients. Methods In this study, we collected 100 tissue samples (50 lung cancer tissues and 50 adjacent non-cancerous lung tissues) from Iranian lung cancer patients. The genomic DNA was extracted, and methylation status of both RASSF1 and  ATIC genes was investigated by methylation-sensitive high-resolution melting (MS-HRM) assay technique and Real-Time PCR. Cancer Genome Atlas (TCGA) dataset was also analyzed for further validation of the gene’s methylation. Results Methylation of RASSF1 gene promoter was significantly higher in lung tumor tissues. However, promoter methylation levels of ATIC gene was significantly lower in lung tumor tissues. These results were additionally confirmed by TCGA analysis. Promoter methylation of both RASSF1 and ATIC genes was significantly associated with lymph node metastasis, and clinical stage of lung cancer. The receiver operating characteristic (ROC) curve analysis indicated a high accuracy of promoter methylation in these genes as a diagnostic biomarker for lung cancer. Conclusions Methylation levels of both RASSF1 and ATIC genes promoters were associated with lung cancer pathogenesis in Iranian population, and may be a suitable biomarker for diagnosis and prognosis of lung cancer in early stage of tumorigenesis.

Objectives This study aims to investigate the population status of selenium in Colombia and other associated factors. Methods Cross-sectional study, in population of urban or rural origin (n=412). Main outcome measures were: median serum selenium, thyrotropin, the prevalence of and positivity of anti-thyroid peroxidase, anti-thyroglobulin, and anti-TSH receptor. Results This study found that 96.6% of the subjects had normal selenium levels, and no significant associations were found between the population median of selenium and overweight/obesity, sociodemographic variables, age, goiter, and thyroid antibody positivity. Conclusions In Colombia, the population status of selenium is normal, and the geological characteristics may contribute to the state of selenium in this population. However, additional studies are required to evaluate the content of selenium in plants and other foods.

Objectives There is evidence that mitochondrial dysfunction mediated by hyperglycemia increases the incidence of diabetes and age-related insulin resistance. Thus, maintaining mitochondrial integrity may provide alternative therapeutic approach in diabetes treatment. This study aimed to evaluate the effect of Bambusa vulgaris leaf extract on mitochondrial biogenesis in the pancreas of diabetic rats. Methods 11 weeks old male rats (n=30) were purchased, and sorted into the following groups: control, diabetic control, diabetes + metformin (100 mg/kg), diabetes + Aq. B. vulgaris (100 mg/kg), diabetes + Aq. B. vulgaris (200 mg/kg), and diabetes + Aq. B. vulgaris (300 mg/kg). Diabetes was induced in the rats by a single dose of 65 mg/kg streptozotocin (STZ). The mRNA expression of genes related to mitochondria biogenesis (pgc-1α, Nrf2, GSK3β, AMPK and SIRT2) and genes of Nrf2-Keap1-ARE signaling pathway were determined by reverse transcriptase polymerase chain reaction. Molecular docking studies including lock and key docking and prime MM-GBSA were incorporated to identify the lead chemical compounds in Bambusa vulgari. Results The results showed that B. vulgaris leaf extract promotes mitochondrial biogenesis via altering the mRNA expression of mitochondrial master regulator pgc-1α, other upstream genes, and the Nrf2-Keap1-ARE antioxidant pathway. Through molecular docking results, cryptochlorogenic acid, hesperidin, orientin, vitexin, scopolin, and neochlorogenic were found as the crucial chemicals in B. vulgaris with the most modulating effect on PGC-1α, AMPK, and GSK3. Conclusions This study thus suggests that B. vulgaris leaf extract restores the integrity of mitochondria in diabetic rats.

Objectives Androgen receptor (AR) play a key role in the onset and progression of prostate cancer. Epigallocatechin-3-gallate (EGCG) is a polyphenolic compound and the active ingredient in green tea, which is involved in modulating gene expression through epigenetic alterations. Previous studies have shown that EGCG at low concentrations reduces the expression of AR and prostate-specific antigen (PSA) in the LNCaP cell line of prostate cancer. In this study, the effect of higher EGCG concentrations on AR and PSA expression in LNCaP prostate cancer cell line was investigated. Methods In this study, LNCaP prostate cancer cell line was used and after MTT test, concentrations of 40, 60 and 80 μg/mL EGCG were used for treatment. Then, the expression of AR and PSA genes was evaluated by RT-PCR. AR protein expression was also assessed by Western blotting. Results The present study showed that treatment of LNCaPs cells by EGCG reduces cell proliferation. The IC50 value was 42.7 μg/mL under experimental conditions. It was also observed that EGCG at concentrations of 40 and 80 μg/mL increased the expression of AR and PSA (p<0.05). Conclusions The present study showed that the effect of EGCG on AR expression was different at different concentrations, so that unlike previous studies, higher concentrations of EGCG (80 and 40 μg/mL) increased AR and PSA expression. It seems that due to the toxic effects of EGCG in high concentrations on cancer cells and the possibility of its effect on normal cells, more caution should be exercised in its use.

Objectives Diabetes has a negative effect on learning and memory performance, and it is a risk factor for Alzheimer’s disease and dementia development. The present study aims to investigate the effects of two kinds of endurance exercise including high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) as well as metformin on impaired memory and learning related to streptozotocin (STZ) induced diabetes in rats. Methods Forty adult male rats (250 ± 20 g weight) were divided into five groups (n=8), including control, diabetic, as well as diabetic rats treated with metformin (300 mg/kg), and HIIT (20 m/min), and MICT (15 m/min) exercises. Diabetes was induced by STZ (60 mg/kg, i.p.). Serum glucose concentration and oxidative stress markers (SOD, CAT, thiol, and MDA) in the cortex and hippocampus were determined by colorimetric assay. Behavioral tests were performed with a passive avoidance test. Results The diabetic groups treated with metformin and both HIIT, and MICT exercises improved the latency and the staying time in the darkroom and lightroom. The entrance frequency into the darkroom also was restored (p<0.01–p<0.001). In both HIIT and MICT exercises as well as metformin groups the oxidative stress induced by diabetes has been reversed and attenuation of the serum glucose level has been observed compared to non-treated diabetic ones (p<0.05–p<0.001). Conclusions The results of the present study revealed both HIIT and MICT exercises had protective effects against oxidative stress and behavioral impairments induced by diabetes and these effects were comparable to the effects of metformin.

Objectives Sedentary life style separated during COVID-19 pandemic. Patients with cardiovascular diseases (CVD) are vulnerable with sedentary life style. Therefore, the aim of this study was to investigate the effect of 8 weeks of combined and high intensity interval training (HIIT) on C Reactive protein, galectin-3, leptin, fibrinogen and insulin resistance index in coronary heart disease after COVID-19. Methods Thirty-six cardiovascular patients (55.14 ± 1.4 years, 78.6 ± 5.1 kg) were divided into three groups of combined exercise (n=13), HIIT (n=12) and control group (n=11). Combined exercise consisted of aerobic (4 weeks) and aerobic + HIIT exercise (4 weeks), three sessions per weeks. The protocol of the HIIT group included performing high intensity interval training, three sessions per weeks for 8 weeks. Blood samples were taken 24 h before the first training session and 48 h after the last training. C Reactive protein (CRP), galectin-3, leptin, fibrinogen measured with ELISA kit. Results CRP, galectin-3 and fibrinogen decreased significantly after 8 weeks of combined training and HIIT (compare to pre-test). Also, insulin resistance index after 8 weeks of combined exercise showed a significant decrease compare to pre-test (p<0.05). After 8 weeks, CRP, galectin-3 and insulin resistance significantly decreased compare to control group (p<0.05). Conclusions In the patient with CVD, combined exercise training may be more effective than HIIT in reducing metabolic and heart risk factors after an epidemic such as COVID-19. However, change of leptin need to more studies.

Objectives This in vivo study aimed to evaluate the effect of various concentrations of artemisinin (Art) alone or together with N-acetyl cysteine (NAC) on spermatological indices, antioxidant status, and histopathological parameters of testicular tissue in adult male mice. Methods Six groups of five healthy male mice (25–30 g) were randomly assigned to different experimental groups. These groups received DMSO and corn oil (0.1%) as an Art solvent (Control), 50 mg kg −1 Art (Art-50), 250 mg kg −1 Art (Art-250), 50 mg kg −1 Art + 150 mg kg −1 NAC (Art-50+NAC-150), 250 mg kg −1 Art + 150 mg kg −1 NAC (Art-250+NAC-150) and 150 mg kg −1 NAC (NAC-150) for a period of 7 days. Testes and epididymis were prepared to evaluate the malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), peroxidase (POX), spermatological indices, and histological parameters. Results We showed that the high dose of Art (Art-250) significantly reduced the sperm count, motility, viability, and the activity of CAT and increased the levels of MDA compared to the control group. Also, the overdose of Art caused adverse changes in testicular tissue. Co-administration of NAC with Art (Art-250+NAC-150) corrected the adverse effects of Art. Conclusions The current study reports that a high dose of Art affects, spermatological parameters, antioxidant/stress oxidative status of the male reproductive system, and NAC is capable neutralize all adverse effects caused by Art.

Objectives Isolated ovarian agenesis in the absence of Mullerian duct anomalies are rare events which are usually discovered after menarche and incidentally in the context of an intervention for other indications, such as laparoscopy or assisted reproduction techniques. Case presentation We hereby present a case of unilateral ovarian agenesis in the presence of the ipsilateral fallopian tube. Conclusions Older studies had reported an incidence of true congenital unilateral ovarian agenesis to be 1 in 11,241 females Sivanesaratnam V. Unexplained unilateral absence of ovary and fallopian tube. Eur J Obstet Gynecol Reprod Biol 1986;22:103–5, but this is likely an understatement given the increase of relevant literature in recent years and the frequency of laparoscopy nowadays.

Brown adipose tissue (BAT) remains active in adults, oxidizing fatty acids or glucose and releasing energy in the form of heat. Brown adipocytes and enhanced thermogenesis are targets for treating obesity and its comorbidities. BAT shows high synthesis activity and secretes several signaling molecules. The brown adipokines, or batokines, take action in an autocrine, paracrine, and endocrine manner. Batokines have a role in the homeostasis of the cardiovascular system, central nervous system, white adipose tissue, liver, and skeletal muscle and exert beneficial effects on BAT. The systemic function of batokines gives BAT an endocrine organ profile. Besides, the batokines Fibroblast Growth Factor-21, Vascular Endothelial Growth Factor A, Bone Morphogenetic Protein 8, Neuregulin 4, Myostatin, and Interleukin-6 emerge as targets to treat obesity and its comorbidities, deserving attention. This review outlines the role of six emerging batokines on BAT and their cross-talk with other organs, focusing on their physiological significance and diet-induced changes. Highlights – Brown adipose tissue is a therapeutic target to combat obesity and its comorbidities by modulating the batokines profile and activating thermogenic activity. – FGF21 is released by BAT during thermogenesis and exerts beneficial effects on the cardiovascular system. – VEGF-A is the batokine that regulates BAT by autocrine mechanisms and promotes the maintenance of angiogenesis and thermogenesis. – BMP8 is expressed during thermogenesis and promotes the regulation of energy metabolism between the hypothalamus and the BAT. – NRG-4 is a batokine that belongs to the epidermal growth factor family members and exerts beneficial effects on the liver and insulin resistance. – Myostatin is a batokine harmful to skeletal muscle, and BAT activation is a significant target to avoid myostatin’s deleterious effects on muscle bioenergetics. – IL-6 improves glucose metabolism in adipocytes and the liver and acts in the maintenance of thermogenesis. – Batokines represent promising therapeutic targets for treating obesity and its comorbidities.

Major Depressive Disorder (MDD) is a mood disorder classified as a persistent depressive mood and loss of interest lasting for more than two weeks and accompanied by a list of symptoms outlined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) diagnostic criteria. MDD affects approximately 264 million people worldwide and is the most prevailing form of neuropsychiatric disorder. Owing to the probable hypothesized pathophysiology of MDD being an outcome of abnormalities in the amino acid neurotransmitter system, including glutamate (the primary excitatory neurotransmitter) and γ -aminobutyric acid (GABA), SAGE-217 (Zuranolone) is being evaluated as a possible therapeutic treatment for MDD. Zuranolone is a synthetic, neuroactive steroid (NAS) and positive allosteric modulator (PMA) of GABAA receptors, regulating both synaptic and extra-synaptic release of GABA. It is administered as a once-daily oral dose for 2 weeks due to its low-moderate clearance. A change in total HAM-D score from baseline was the primary end-point of all the trials. A phase II trial conducted to evaluate the efficacy and safety of Zuranolone (30 mg, once-daily dose), described a significant reduction in total HAM-D score at day 14 and reported the drug to be well tolerated with headache, dizziness, nausea, and somnolence as the most common adverse events (AE). Additional phase III trials were also conducted to evaluate similar outcomes, the interim topline results of which have been released. Consequently, this article attempts to briefly analyze the pharmacology of Zuranolone, review the available clinical data and outcomes regarding its use, and evaluate its place as a prospective novel therapy in the effective management of MDD.