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OBJECTIVE: Elevated asymmetric dimethylarginine (ADMA) levels, an endogenous inhibitor of nitric oxide synthase, are an important cardiovascular risk factor. In patients with diabetes, increased ADMA levels have been reported, which may be associated with endothelial dysfunction. In this study, effect of nebivolol on serum ADMA levels in hypertensive patients with type 2 diabetes have been compared with metoprolol, an another beta-blocker. METHODS: A total of 54 patients (27 female, 27 male; mean age: 53.0+/-8.7 years) with type 2 diabetes and hypertension were included in this randomized, open-label, prospective study. Patients were randomized to receive either nebivolol 5 mg/day (n=28) or metoprolol 100 mg/day (n=26) for 12 weeks. When the patients could not reach target blood pressure levels at the end of week 4, indapamide (2.5 mg/day) was added. Enzyme Linked Immunosorbent Assay was used for serum ADMA measurements. RESULTS: Similar reductions in blood pressure values were observed in both groups (p>0.05). In nebivolol group, there were no significant changes in serum ADMA levels compared to baseline (0.6+/-0.2 micromol/l vs 0.6+/-0.1 micromol/l, p>0.05), whereas in metoprolol group a 35.6% increase in serum ADMA levels was observed (0.6+/-0.1 micromol/l vs 0.7+/-0.2 micromol/l, p<0.01). CONCLUSION: We observed a significant increase in ADMA levels, a marker of endothelial dysfunction, during metoprolol treatment, whereas nebivolol had neutral effects on ADMA levels in patients with type 2 diabetes mellitus and hypertension. [ABSTRACT FROM AUTHOR]

Objective: This randomized clinical trial study aims to investigate the effects of antioxidant food supplementation on the total antioxidant capacity of seminal plasma, sperm DNA fragmentation, sperm chromatin quality, and semen parameters., Methods: In this study, a total of 48 subfertile men with moderate physical activity were included. Group 1 was recommended to use the antioxidant supplements, while antioxidant food supplements were not given to Group 2. Total antioxidant capacity, sperm DNA fragmentation, sperm chromatin structure, hormone levels, physical activities, and semen parameters were evaluated before and after treatment. Total antioxidant capacity, sperm DNA fragmentation, and sperm chromatin structure were assessed using ELISA, transferase dUTP nick end labeling, and aniline blue staining, respectively., Results: Sperm DNA fragmentation (p=0.003) and histone/protamine ratio (p<0.001) were significantly decreased in the patients receiving antioxidant treatment. There was no statistical difference in the total antioxidant capacity values of the post-treatment groups., Conclusion: Antioxidant therapy seems to improve sperm DNA fragmentation and histone/protamine ratios in subfertile patients., Clinical Trial Registration Number: NCT06042738.

This study explores the association of vitamin D-binding protein (VDBP) gene polymorphisms, vitamin D levels, and the severity of COVID-19, including the need for intensive care unit (ICU) hospitalization. We analyzed a cohort of 56 consecutive age- and gender-matched adult COVID-19-positive patients and categorized them into three groups: outpatients with mild illness, inpatients with moderate disease, and ICU patients. We measured levels of free, total, and bioavailable 25-hydroxyvitamin D [25(OH)D], VDBP, and albumin. VDBP polymorphisms rs5488 and rs7041 were identified using real-time PCR. A significant proportion of ICU patients were vitamin D-deficient (56.25%) compared to outpatients (10%) and inpatients (5%) ( p = 0.0003). ICU patients also had notably lower levels of VDBP (median: 222 mg/L) and total 25(OH)D (median: 18.8 ng/mL). Most patients carried heterozygous rs7041 (60.7%) and wild-type rs4588 (58.9%) genotypes. The distribution of rs7041 SNP varied significantly among groups ( p = 0.0301), while rs4588 SNP distribution did not ( p = 0.424). Heterozygous rs4588 patients had significantly lower VDBP levels ( p = 0.029) and reduced bioavailable 25(OH)D compared to those with wild-type rs4588 ( p = 0.020). Our findings indicate that VDBP gene polymorphisms, particularly rs7041 and rs4588, are associated with vitamin D status and the severity of COVID-19. The lower VDBP levels and bioavailable vitamin D in ICU patients suggest that these genetic variants may influence disease severity and hospitalization needs. These results highlight the potential role of VDBP polymorphisms in COVID-19 severity, suggesting that genetic screening could be valuable in assessing the risk of severe outcomes and guiding personalized treatment strategies.

Nonobstructive azoospermia (NOA) is a severe and heterogeneous form of male factor infertility caused by dysfunction of spermatogenesis. Although various factors are well defined in the disruption of spermatogenesis, not all aspects due to the heterogeneity of the disorder have been determined yet. In this review, we focus on the recent findings and summarize the current data on epigenetic mechanisms such as DNA methylation and different metabolites produced during methylation and demethylation and various types of small noncoding RNAs involved in the pathogenesis of different groups of NOA., (Copyright © 2024 Copyright: ©The Author(s)(2024).)

Apoptosis, or programmed cell death, maintains tissue homeostasis by eliminating damaged or unnecessary cells. However, cells can evade this process, contributing to conditions such as cancer. Escape mechanisms include anoikis, mitochondrial DNA depletion, cellular FLICE inhibitory protein (c-FLIP), endosomal sorting complexes required for transport (ESCRT), mitotic slippage, anastasis, and blebbishield formation. Anoikis, triggered by cell detachment from the extracellular matrix, is pivotal in cancer research due to its role in cellular survival and metastasis. Mitochondrial DNA depletion, associated with cellular dysfunction and diseases such as breast and prostate cancer, links to apoptosis resistance. The c-FLIP protein family, notably CFLAR, regulates cell death processes as a truncated caspase-8 form. The ESCRT complex aids apoptosis evasion by repairing intracellular damage through increased Ca2+ levels. Antimitotic agents induce mitotic arrest in cancer treatment but can lead to mitotic slippage and tetraploid cell formation. Anastasis allows cells to resist apoptosis induced by various triggers. Blebbishield formation suppresses apoptosis indirectly in cancer stem cells by transforming apoptotic cells into blebbishields. In conclusion, the future of apoptosis research offers exciting possibilities for innovative therapeutic approaches, enhanced diagnostic tools, and a deeper understanding of the complex biological processes that govern cell fate. Collaborative efforts across disciplines, including molecular biology, genetics, immunology, and bioinformatics, will be essential to realize these prospects and improve patient outcomes in diverse disease contexts., (© 2024. The Author(s).)

Background: Mechanisms by which varicocele causes infertility are not clear and few studies have reported that some miRNAs show expression alterations in men with varicocele. Recently, sperm promoter methylation of MLH1 has been shown to be higher in men diagnosed with varicocele. This study aimed to assess the potential effects of miR-145, which was determined to target MLH1 mRNA in silico on sperm quality and function in varicocele., Methods: Sperm miR-145 and MLH1 expressions of six infertile men with varicocele (Group 1), nine idiopathic infertile men (Group 2), and nine fertile men (control group) were analyzed by quantitative PCR. Sperm DNA fragmentation was evaluated by TUNEL and the levels of seminal oxidative damage and total antioxidant capacity were analyzed by ELISA., Results: Our results have shown that sperm expression of miR-145 was decreased in Group 1 compared to Group 2 (P = 0.029). MLH1 expression was significantly higher in Group 2 than the controls (P = 0.048). Total antioxidant level and sperm DNA fragmentations of Group 1 and Group 2 were decreased (P = 0.001 and P = 0.011, respectively). Total antioxidant capacity was positively correlated with sperm concentration (ρ = 0.475, P = 0.019), total sperm count (ρ = 0.427, P = 0.037), motility (ρ = 0.716, P < 0.0001) and normal morphological forms (ρ = 0.613, P = 0.001) and negatively correlated with the seminal oxidative damage (ρ=-0.829, P = 0.042) in varicocele patients., Conclusion: This is the first study investigating the expressions of sperm miR-145 and MLH1 in varicocele patients. Further studies are needed to clarify the potential effect of miR-145 on male fertility., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Male infertility is a multifactorial heterogeneous reproductive disorder in which genetic, epigenetic, and environmental factors play a role in the development of disease. Recent studies have shown that retrotransposon expression alterations may be related to impairment of spermatogenesis. Therefore, in this pilot study, we aimed to investigate whether HERV-K6 and HERV-K11 insertional variations have a role in idiopathic infertility among normozoospermic men. Genomic DNA isolated from the blood samples of 41 infertile normozoospermic and 45 fertile normozoospermic men were analyzed by inter-retrotransposon polymorphism polymerase chain reaction. HERV-K6 variation rates in the infertile and the fertile group were 0-58.3% and 0-53.4%, respectively. The variation rates of HERV-K11 were 0-75.0% in infertile and 0-77.8% in fertile men. The HERV-K6 and HERV-K11 insertion rates of the fertile group were higher than the infertile group (P < 0.0001 and P = 0.007, respectively). The findings of the study suggest that HERV-K6 and HERV-K11 retrotransposon insertion show variation among individuals, and their insertions might be associated with male infertility., (© 2023. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Background: Due to the growing evidence of the importance of iron status in immune responses, the biomarkers of iron metabolism are of interest in novel Coronavirus Disease 2019 (COVID-19). The present prospective study was carried out to compare iron status indicated by levels of ferritin with the levels of two novel biomarkers related to iron homeostasis, hephaestin and hypoxia-inducible factors-1 (HIF-1α) in the serum of patients with COVID-19 in comparison with a control group., Methods and Results: Blood samples from 34 COVID-19 patients and from 43 healthy volunteers were collected and the levels of HEPH and HIF-1α were measured by ELISA and compared with levels of serum ferritin. COVID-19 patients had higher serum levels of ferritin than those levels in control group (P < 0.0001). Conversely levels of HIF-1α and HEPH in the COVID-19 group were significantly lower than those of control group (P < 0.0001 for both). An inverse correlation between hephaestin and ferritin as well as between HIF-1α and ferritin was found among all subjects (P < 0.0001), and among COVID-19 patients, but not to statistical significance., Conclusion: Levels of hephaestin and HIF-1α were found to be inversely related levels of ferritin across all participants in the study, and to our knowledge this is the first report of hephaestin and HIF-1α as potential markers of iron status. Further studies are needed to corroborate the findings, utilizing a broader range of markers to monitor inflammatory as well as iron status., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: COVID-19 is known to be transmitted by direct contact, droplets or feces/orally. There are many factors which determines the clinical progression of the disease. Aminoacid disturbance in viral disease is shown in many studies. İn this study we aimed to evaluate the change of aminoacid metabolism especially the aspartate, glutamine and glycine levels which have been associated with an immune defence effect in viral disease., Methods: Blood samples from 35 volunteer patients with COVID-19, concretized diagnosis was made by oropharyngeal from nazofaringeal swab specimens and reverse transcriptase-polymerase chain reaction, and 35 control group were analyzed. The amino acid levels were measured with liquid chromatography-mass spectrometry technology. Two groups were compared by Kolmogorov-Smirnov analysis, Kruskal-Wallis and the Mann-Whitney U . The square test was used to evaluate the tests obtained by counting, and the error level was taken as 0.05., Results: The average age of the patient and control group were 48.5 ± 14.9 and 48.8 ± 14.6 years respectively. The decrease in aspartate (p = 5.5 × 10 -9 ) and glutamine levels (p = 9.0 × 10 -17 ) were significiantly in COVID group, whereas Glycine (p = 0.243) increase was not significiant., Conclusions: Metabolic pathways, are affected in rapidly dividing cells in viral diseases which are important for immun defence. We determined that aspartate, glutamine and glycine levels in Covid 19 patients were affected by the warburg effect, malate aspartate shuttle, glutaminolysis and pentose phosphate pathway. Enteral or parenteral administration of these plasma amino acid levels will correct the duration and pathophysiology of the patients' stay in hospital and intensive care., Competing Interests: Conflict of interestThe authors declare that there are no potential conflicts of interest regarding the research, authorship and publication of this article., (© The Author(s), under exclusive licence to Association of Clinical Biochemists of India 2022.)

Purpose: Sex chromosome abnormalities are associated with male infertility. The aim of this study was to characterize the clinical, cytogenetic, and molecular findings of 12 infertile men with isodicentric Y-chromosome [idic(Y)] abnormalities diagnosed over a period of 13 years., Materials and Methods: Chromosomal analyses of peripheral blood samples were done using standard procedures. Fluorescence in situ hybridization (FISH) analysis was performed on metaphase spreads of the patients. Multiplex polymerase chain reaction (PCR) using several sequence-tagged site (STS) primer sets within the long arm of Y-chromosome was used to detect AZF deletions.The breakpoints and copy number variations (CNV) were identified by array comparative genomic hybridization analysis (aCGH) analysis.The short-stature homeobox (SHOX) gene deletions were verified using multiplex ligation-dependent probe amplification (MLPA) analysis., Results: Twelve infertile men were diagnosed cytogenetically with idic(Y). The karyotypes of two of the patients were non-mosaic, and the remaining karyotypes showed various degrees of mosaicism. SHOX gene deletion was found in two of the four patients with short stature, and the remaining two patients had shown a 45,X dominant cell line (33.3%). The most common breakpoints for idic(Yq) and idic(Yp) were found to be in Yq11.222 and Yp11.32, respectively. Semen analysis of ten patients (83.3%) demonstrated azoospermia, and the remaining two patients (16.7%) showed severe oligoasthenoteratozoospermia (OAT). In total, 33% (4/12) of idic(Y) patients with or without microsurgical testicular sperm extraction (microTESE) had sperm retrieval., Conclusions: Twelve patients with idic(Y) and different breakpoints of Y-chromosome were characterized using multiple detection strategies. Sperm retrieval outcomes of patients either with idic(Yp) or idic(Yq) showed the possibility to find sperm by microTESE., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Genetic variants affecting the interaction of FSH-FSHR may negatively affect the male reproductive potential. The aim of this case-control study was to evaluate FSHB c.-211G>T and FSHR c.2039A>G variants in a cohort of infertile men from Central Black Sea Region in Turkey. One hundred and nine infertile men and 50 proven fertile controls were enrolled in the study. Genotyping was assessed by RFLP. The genotype frequencies of FSHB -211G>T and FSHR 2039A>G showed significant variation between infertile and fertile groups (χ 2 , p = 0.046, GG vs. GT+TT, and p = 0.008, AA vs. AG+GG). FSHB -211GG was found to be higher in patients with OAT compared to fertile controls (82.3% vs. 64.0%, χ 2 , p = 0.028). The distribution of FSHR 2039A>G alleles was different between infertile and fertile men (χ 2 , p = 0.005, total infertile vs. fertile groups, p = 0.019, OAT vs. NOA vs. fertile groups). Further analysis showed that the frequencies of FSHR 2039AA wild-type genotype were higher in the oligoasthenoteratozoospermic and non-obstructive azoospermic groups compared with the controls (χ 2 , 39.3% vs. 17.0%, p = 0.012, and 37.5% vs. 17.0%, p = 0.025 respectively). Our results showed wild-types of FSHB -211G>T and FSHR 2039A>G variants may cause susceptibility to male infertility in the Central Black Sea Region of Turkey., (© 2022 Wiley-VCH GmbH.)

The main aim of this study was to investigate the relationship of the carriership of rs2228145 allelic variations of IL-6R with two other allelic variations in IL-6 gene at rs1800795 and rs1800796 loci and with the laboratory data of a healthy cohort of the Turkish population. The data of 121 healthy Turkish subjects (aged 12-84 years) including the past diseases, comorbidities were collected. The laboratory parameters were compared by the frequency of alleles of rs2228145 (C>A). The possible association of polymorphism at rs2228145 locus with the age, gender, and body mass index (BMI) and the frequencies of alleles of rs1800795 and rs1800796 polymorphisms were evaluated. The majority of the subjects had allele A at rs2228145 locus and allele G at rs1800796 locus. The number of white blood cells, platelets, neutrophils and monocytes were significantly higher in the subjects with allele C than those with allele A at rs2228145 locus (P < 0.05). The concentrations of total and direct bilirubin, iron, Sex Hormone Binding Globulin (SHBG) and folic acid of the subjects with allele C were significantly lower than those with allele A (P < 0.05). The uric acid and fasting insulin levels were higher in the subjects with allele C compared with those allele A (P = 0.04). The diversities of the hematological parameters, laboratory findings of liver function tests and renal panel and hormone levels may be explained by the variants of rs2228145 locus at IL-6R gene among healthy Turkish individuals., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: Microdeletion on Y-chromosome is a well-known genetic cause of infertility in azoospermic and oligozoospermic men. RNA transcripts possess microRNA (miRNA) response elements (MRE) that may interact with competing endogenous RNAs (ceRNA), thus repressing their activity. MiRNAs originally targeting transcripts of genes deleted in the Y-chromosome azoospermia factor (AZF) region are expected to be oriented to binding sites of new targets. We investigated miRNAs targeting genes of each AZF locus (AZFa, AZFb, AZFb-c, and AZFc) to determine their corresponding ceRNA using in silico analysis., Methods: The miRNAs targeting most of the genes deleted in each AZF locus were identified using the miRWalk database. Twelve miRNAs exhibiting potential ceRNA activity were identified and analyzed using the ComiR database. Detected ceRNAs for each AZF locus were processed in the GeneMANIA database for interaction prediction, and the most probably interacted genes were identified., Results: RPPA2, TMED3, STX7 and ATRX, GOGLB1, KMT2C genes were found potential ceRNAs for the AZFa and AZFb regions, respectively. Furthermore, CNB5, KCNC4, NDUFS1 and TROBP, HEMK1, and ORAI2 genes were the potential ceRNAs for the partially AZFb-c-overlapped region and AZFc regions, respectively., Conclusion: Our findings suggest that AZF loci deletion may change post-transcriptional regulation of gene expression through miRNA competition., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)