Band 43, Heft 4

Objectives The aim of the study was to analyze the performance of the anti-mullerian hormone (AMH) level for the diagnosis of polycystic ovary syndrome in women with morbid obesity. Study design A single-centre cross-sectional study was conducted in 50 women of reproductive age with a body mass index (BMI) ≥ 40 kg/m 2 . Each patient underwent a clinical examination, biological and hormonal assays, and an ovarian ultrasound between the third and the fifth day of the menstrual cycle. Polycystic ovary syndrome was diagnosed according to the Rotterdam’s criteria. Results The mean age of participants was 34.2 ± 7.5 years. Polycystic ovary syndrome was diagnosed in 20 women (40%). Age and anthropometric parameters did not differ between women with and without polycystic ovary syndrome. The mean AMH level was significantly higher in women with polycystic ovary syndrome (3.4 ± 3.6 vs 1.3 ± 1.2 ng/ml, p=0.010). It was positively correlated with the Ferriman and Gallwey score (r=0.496, p=0.016), total testosterone level (r=0.524, p < 10 −3 ) and the LH/FSH ratio (r=0.290, p=0.046). In women aged between 35 and 45 years, the optimum cut-off level for the diagnosis of polycystic ovary syndrome was 0.81 ng/mL, providing a sensitivity and a specificity of 90 and 71%, respectively with an area under the ROC curve of 0.857. Conclusions AMH level was significantly higher in morbid obese women with polycystic ovary syndrome compared with those without polycystic ovary syndrome. Specific thresholds for this population must be assessed to improve the sensitivity and specificity of AMH for the diagnosis of polycystic ovary syndrome.

Objectives Hepatocellular carcinoma (HCC), the most common form of liver cancer, is a leading cause of tumor-associated mortality worldwide. Diagnosis based upon non-invasive criteria is currently challenged by the need for molecular information that requires tissue or liquid biopsies. The progression of HCC is often associated with chronic inflammation, expression levels of inflammatory mediators, chemokine, and cytokines. In this study, we try to evaluate the PI3K and pro-inflammatory cytokines, TGF-β, IL-1, and IL-6 expression level in patients with liver cancer. Materials and methods The kupffer cells were isolated from patient’s specimens. Real-time PCR was applied to evaluate the expression level of PI3K in cell lines or tumors. The concentrations of TGF-β, IL-1, and IL-6 were measured by the quantitative ELISA kit. Results PI3K mRNA expression in cancer cells was increased markedly vs. normal cells. The ELISA results demonstrated over expression of TGF-β, IL-1, and IL-6 in patients and positive correlation between tumor size and stage. Discussion This study suggests that targeting the expression level of PI3K and pro-inflammatory chemokine and cytokines, TGF-β, IL-1, and IL-6, may be a potential diagnostic strategy in HCC patients.

Objectives Alpha-1-antitrypsin (AAT) has different phenotypes. Evidence suggests that the abundance of each of these phenotypes may be associated with a disease. The purpose of this study was to evaluate the frequency of AAT phenotypes in patients with liver cirrhosis as well as in healthy individuals. Methods In this study, 42 patients with liver cirrhosis were selected. The results of the previous research done by the researcher on healthy individuals were used to construct the control group. After obtaining informed consent, 5 mL of fasting venous blood sample was taken, and phenotypes were analyzed by isoelectric focusing. Data were analyzed using Chi-square and Fisher’s exact tests at a significant level of 0.05. Results The results of this study indicated that all 42 healthy subjects had an MM allele (100%). However, among 42 patients, 35 (83.3%) had an MM allele, 5 (11.9%) had an MS allele, and 2 (4.8%) had MZ allele. The difference between the two groups was significant (p=0.02). There was no difference between men and women in the allele type (p=0.557). Conclusions This study revealed that MS and MZ alleles were observed only in patients with liver cirrhosis, and none of these alleles were found in healthy subjects. Therefore, MS and MZ alleles can be further investigated as risk factors for liver cirrhosis.

Objectives Endometriosis is a gynecological disease associated with an imbalance between oxidative species production and anti-oxidative defenses. In women, endometriosis has been reported to associate with increased incidence of cardiovascular events. As such, this study aimed to analyze the oxidation-responsive AMPK/SIRT1/PGC-1α/SIRT3 pathway in the heart of a mouse model of endometriosis. The effect of metformin, an insulin-sensitizing and anti-oxidative drug with already shown positive results in endometriotic tissue was studied. Methods Thirty-six female B6CBA/F1 mice were divided into 4 groups (Control-C, Surgery-induced Endometriosis and Metformin-EM (50 mg/kg/day orally administrated for 3 months), Endometriosis-E and Metformin-M). Immunofluorescent labelling of SIRT1 and SIRT3 was performed in the heart tissue. Assessment of expression of AMPKα, SIRT1, PGC-1α, SIRT3, SOD2, and GPx1 was performed by Western Blotting. The quantification of microRNA(miR)-34a, miR-195, miR-217, miR-155 and miR-421, involved in the regulation of expression of SIRT1 and SIRT3, was performed by Real-Time PCR. Results Data showed an increase in phospho-AMPKα and in GPx1 expression in the EM group when compared to the C group, but not in the total AMPK, SIRT1, PGC-1α, SIRT3 and SOD2, suggesting a GPx1 expression increase independently of the AMPK/SIRT1/PGC-1α/SIRT3 pathway. MicroRNAs, excepting miR-217, showed a consistent trend of increase in the M group. Conclusions Our study showed that endometriosis does not significantly affect the expression of the components of the AMPK/SIRT1/PGC-1α/SIRT3 pathway in the heart. However, it indicates that an oxidative condition underlying endometriosis is required for metformin to evidence an increment in the expression of the anti-oxidative enzyme GPx1.

Objectives In this study, it was aimed to evaluate the hypoxia-inducible factor-1α (HIF-1α) and ischemia-modified albumin (IMA) levels of patients diagnosed with COVID-19 in the intensive care unit (ICU) and healthy controls. To our knowledge, this is the first study investigate HIF-1α and IMA levels in COVID-19 patients in ICUs and comparing them with a healthy control group. For this reason, our study is original and will contribute to the literature. Methods A total of 70 intensive care patients diagnosed with COVID-19, and 72 healthy controls were included in the study. Results When we compared the patient and healthy control group; there were no statistically significant differences between the groups in terms of age and gender (p>0.05). No exitus was observed in the patient group. We found weak correlation between HIF-1α and IMA (r: 0.320). However, there were statistically significant differences in HIF-1α and IMA levels in the patient group. The receiver operating characteristic (ROC) curve demonstrated an area under curve (AUC) value of 0.651 for HIF-1α and 0.937 for IMA. Conclusions The HIF-1α and IMA levels were significantly higher among COVID-19 patients in ICU compared with healthy controls. HIF-1α and IMA levels can be used as reliable markers for the prognosis of COVID-19.

Objectives The present case-control study investigates whether TP53 Arg72Pro variant (rs1042522) serves as a risk factor for recurrent pregnancy loss (RPL) in Greek women. Methods The study group consisted of 100 patients with at least two miscarriages of unexplained etiology, before the 24th week of gestation. The control group included 106 women with no pregnancy loss history. DNA was extracted and genotyped using specific primers for PCR amplification of the Arg72 and Pro72 alleles. Sanger sequencing was used for the discrimination between heterozygotes and homozygotes for Arg72Pro variant. Results This is the first study demonstrating the statistically significant higher frequency of TP53 Arg72Pro variant in Greek RPL women compared to controls (38% vs. 6.6%; OR=8.6682, 95% CI: 3.6446–20.6160; p<0.0001). GC genotype (Arg/Pro) and CC genotype (Pro/Pro) were statistically more common in RPL patients than in controls (16% vs. 1.9%; p=0.0027, and 22 vs. 4.7%; p=0.0008, respectively). C allele frequency was statistically significant higher in RPL group than in controls (30.0 vs. 5.7%; p<0.0001). According to the inheritance mode analysis, the model that best fit the data was the dominant model (OR=8.67, 95% CI=3.64–20.62; p<0.0001). Conclusions The is the first study disclosing strong evidence that TP53 rs1042522 is significantly associated with a higher risk for recurrent pregnancy loss in Greek women following a dominant model, thus, serving as a genetic marker for identifying women at increased risk of recurrent miscarriages.

Objectives Type 2 diabetes (T2D) is a major risk factor for cardiovascular disorders (CVD), characterized by pathological diastolic as well as systolic dysfunction, ventricular dilation, and cardiomyocyte hypertrophy. CVD is the main cause of death in postmenopausal women. Estradiol (E2) has protective effects on cardiovascular function. The biological effects of E2 are mainly mediated by classical estrogen receptors (ERs). The present study aimed to investigate the cardioprotective effects of classical ERs in ovariectomized (OVX) diabetic female rats. Methods T2D was induced in female rats by high-fat diet feeding along with a low dose of streptozotocin. Then diabetic animals were divided into eight groups: Sham-control, OVX, OVX + Vehicle (Veh), OVX + E2, OVX + E2 + MPP (ERα antagonist), OVX + E2 + PHTPP (ERβ antagonist), OVX + E2 + Veh, OVX + E2 + MPP + PHTPP. Animals received E2, MPP, and PHTPP every four days for 28 days. At the end blood was collected, serum separated, and used for biochemical parameters. Heart tissue was used for cardiac angiotensin II and cytokines measurement. Results E2 treatment improved the metabolic disorders caused by T2D, and its receptor antagonists intensified the effects of T2D on the metabolic status. Also, E2 therapy decreased cardiac inflammatory cytokines, and MPP and PHTPP increased cardiac inflammation by increasing TNF-α and IL-6 and decreasing IL-10. Conclusions Classical ERs have protective effects on diabetic hearts by improving the metabolic status and inflammatory balance.

Objectives This study aimed to evaluate the level of adrenocorticotropic hormone (ACTH) and adrenal insufficiency in patients with mucocutaneous pemphigus lesions who use oral corticosteroids. Methods This descriptive-analytical study was performed on 54 patients (48.44 ± 12.74 years) with mucocutaneous pemphigus in 2019. Those patients taken corticosteroids in different doses and way. At first, collected patients information including age, sex, type of pemphigus, duration of use, patient dosage, duration of corticosteroid administration, and method of administration were collected daily. Adrenal gland function was measured by evaluating ACTH levels. Data were analyzed by using Pearson correlation coefficient and t-test. Results Our study showed that 37 cases (68.5%) had normal ACTH average hormone level (7.3–63.3 mL/pg), 11 cases (20.4%) were lower levels (<7.2 mL/pg), and 6 cases (11.1%) were higher levels (63.3 > mL/pg). Wo observed no significant relationship between ACTH and duration of corticosteroids usage (p=0.207). Conclusions Taking a maintenance dose of between 12.5 and 25 mg daily does not usually lead to adrenal insufficiency. The present study showed that the lower the daily dose of corticosteroids, the lower the likelihood of adrenal insufficiency.

Objectives The present study aims to investigate the effects of resistance training on sex hormones and sperm parameters in male rats under X-ray. Methods In this experimental study, 24 Sprague Dawley rats (200–250 g) were randomly assigned into four groups: healthy control, irradiated control, healthy training and irradiated training. Irradiation was induced at a dose of 4 Gy on the whole body. The resistance training protocol was performed for 10 weeks. Finally, blood serum was used to assess FSH, LH and testosterone and sperm quality. Data were analyzed using ANOVA and Tukey’s post hoc test. Results The results showed that radiation significantly reduced serum levels of LH (p=0.42), FSH (p=0.001) and testosterone (p=0.28) between radiation control and healthy control groups. Also, no significant difference was observed between serum levels of LH (p=0.135) and testosterone (p=0.419) in radiation resistance training and the healthy control groups. In addition, significant differences were observed between radiation resistance training and radiation control groups in sperm parameters such as sperm count (p=0.02) and progressively motile sperm (p=0.031). Conclusions It seems that short-term resistance training can improve sperm parameters, including sperm count and sperm motility through increasing serum levels testosterone and LH in male rat under X-ray.

Background Vaspin is an adipocytokine with insulin-sensitizing and anti-inflammatory traits. Objectives The purpose of this study was to evaluate the effect of high-intensity interval training (HIIT) on serum, visceral and subcutaneous adipose tissue vaspin levels in rats exposed to a diet high in fat and sugar (HFS). Materials and methods Thirty-two male Wistar rats were randomly divided into HFS and standard diet (SD) groups. After 12 weeks, each group was divided into sedentary and HIIT groups. HIIT program was performed 3 times/week for 8 weeks. Retroperitoneal adipose tissue, inguinal adipose tissue and serum were collected to analyze vaspin levels. Also, serum glucose and insulin levels, insulin resistance index (HOMA-IR) and retroperitoneal and inguinal fat weights were measured. Results HFS significantly increased weight gain, weight of inguinal (p=0.001) and retroperitoneal fat depots (p<0.001), serum glucose levels (p<0.001) and HOMA-IR (p<0.001). The HIIT was able to decline weight gain and fat mass (p<0.05) but did not affect inguinal and retroperitoneal fat depots’ vaspin levels. Eight weeks’ HIIT significantly increased serum vaspin (p=0.002) and decreased insulin (p=0.001) levels only in rats fed with SD. Conclusions Although the HIIT program can cause significantly reducing effects on weight gain and fat depots’ weights, it does not effect on circulating and fat depots’ vaspin levels in rats fed an HFS.

Objectives The aim of this study was to investigate the effects of curcumin on the viability, migration, and apoptosis of A549 lung cancer cells. Furthermore, RECK / MMPs axis as a probable regulator of cancer cell migration was assessed. Methods In this study, effect of curcumin on viability changes, cell migration, and percentage of apoptosis of A549 non-small cell lung carcinoma was examined. The methylation status of RECK gene was investigated using MS-HRM technique. Moreover, expression changes of genes involved in apoptosis and migration (including CASP3 , CASP8 , CASP9 , BAX , BCL2 , MMP9 , MMP2 , and RECK ) were investigated by quantitative Real-Time PCR. Results The results of MTT assay showed that the cytotoxic effect of curcumin was in a dose dependent manner. Flow cytometry results demonstrated a significant increase in the percentage of apoptotic cells in curcumin treated group. In addition, curcumin inhibited migration rate in lung cancer cells. qRT-PCR revealed that expression of the candidate genes was in line with suppressed growth and migration. This could be due to, decreased methylation of the RECK gene promoter after curcumin treatment. Conclusions Curcumin inhibited lung cancer cells through various molecular pathways. RECK / MMPs axis as a regulator of cancer cell migration was modulated after curcumin treatment and invasion of lung cancer cells was decreased.

Objectives This study was conducted to evaluate the efficacy of rectal progesterone suppositories on pregnancy outcomes of pregnant women diagnosed with PPROM at the gestational age of 26–34 weeks, as well as on maternal and neonatal outcomes. Methods This is a double-blind, randomized clinical trial in pregnant women with PROM with gestational age of 26–24 weeks, conducted between February 2020 and December 2020 in Sayyad Shirazi Hospital, Gorgan, Iran. Results According to the results of the present study; Rectal progesterone suppository in pregnant women with PPROM is associated with improved delivery outcomes such as neonatal APGAR score, increased latent delivery stage without complications or severe and dangerous complications, without increased risk of mortality and NICU hospitalization in infants, so prescribing suppository rectal progesterone in pregnant women with PPROM with a gestational age of 26 to 34 weeks is associated with positive outcomes and is recommended based on the findings and opinions of the researchers. Conclusions According to the results of the present study; Rectal progesterone suppository in pregnant women with PPROM is associated with improved delivery outcomes such as neonatal APGAR score, increased latent delivery stage without complications or severe and dangerous complications, without increased risk of mortality and NICU hospitalization in infants, so prescribing suppository rectal progesterone in pregnant women with PPROM with a gestational age of 26 to 34 weeks is associated with positive outcomes and is recommended based on the findings and opinions of the researchers.

Objectives We aim to discuss the hematological cancer cases that opted for ovarian tissue cryopreservation (OTC) as fertility preservation before the gonadotoxic chemotherapy agent. Case presentation The ovarian tissue cryopreservation (OTC) was started in August 2020 in our center. Up to now, there were four cases have been performed and included in this report. The ovarian tissue cortex was cryopreserved with cryoprotectant using Kitazato™ (Tokyo, Japan) media and fit in the closed system devices. A total of four post-OTC patients were included. The mean age was 24 years old, whereas the mean serum AMH level was 30.43 pmol/L. Most of them were diagnosed with lymphoma, except one was leukemia. All of them received additional GnRH analog following OTC as a chemoprotective agent before cancer treatment. Currently, they are recovering well and on regular follow-up with the hematological department. Conclusions Although The OTC is an ultimate option for prepubertal girls, it can be proposed as a good strategy for adult cancer women who could not delay cancer therapy.

Many studies conducted after the pandemic period revealed that, while COVID-19 primarily injured the lungs, it also affects other organs in the form of cardiovascular complications, metabolic derangements, renal damage, and so on. Although we know that inflammatory cascades, complement activation, and pro-inflammatory cytokines are all involved in vasculitic processes that cause organ damage, we do not know the exact mechanism of complications such as acute respiratory distress syndrome (ARDS), cardiovascular ischemia, deep vein thrombosis, pulmonary thromboembolism, and brain injuries (embolism) that are frequently observed in COVID 19. The currently available biomarkers do not predict the severity of the aforementioned complications. As a result, more specific biomarkers such as serum calcium binding protein (S100B), glial fibrillary acid protein (GFAP), myelin basic protein (MBP), neuron-specific enolase (NSE), hs-TNI, (highly sensitive cardiac troponin) – HBDH, (Hydroxybutyrate Dehydrogenase), CK-MB (creatine kinase myocardial band), ST2 (suppression of tumorigenicity 2) are in need for early detection & improved clinical outcome.

Lung cancer is the second most common cancer and the most lethal cancer worldwide. Melatonin, an indoleamine produced in the pineal gland, shows anticancer effects on a variety of cancers, especially lung cancer. Herein, we clarify the pathophysiology of lung cancer, the association of circadian rhythm with lung, and the relationship between shift work and the incidence of lung cancer. Special focus is placed on the role of melatonin receptors in lung cancer, the relationship between inflammation and lung cancer, control of cell proliferation, apoptosis, autophagy, and immunomodulation in lung cancer by melatonin. A review of the drug synergy of melatonin with other anticancer drugs suggests its usefulness in combination therapy. In summary, the information compiled may serve as a comprehensive reference for the various mechanisms of action of melatonin against lung cancer, as a guide for the design of future experimental research and for advancing melatonin as a therapeutic agent for lung cancer.

Esketamine, which is an S-enantiomer of ketamine, is better than conventional antidepressants and even better than R-ketamine. This article discusses the mechanism of action of Esketamine, how different it is from other antidepressants, its side effect profile, indications for use, various routes of administration and the review of existing literature on Esketamine.