Selenium mitigates methotrexate-induced testicular injury: Insights from male NMRI mice model.

BACKGROUND AND AIM: Chemotherapy, particularly with methotrexate (MTX), often elicits testicular toxicity, leading to impaired spermatogenesis and hormone imbalances. This study aimed to investigate the potential protective effects of selenium (Se) against MTX-induced testicular injury. MATERIALS AND METHODS: Male mice were divided into control, MTX, Se, and MTX + Se groups. Histopathological examination involved the preparation of testicular tissue sections using the Johnsen's tubular biopsy score (JTBS) for spermatogenesis evaluation. Biochemical tests included the assessment of testosterone, malondialdehyde (MDA), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels. Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to analyze the expression of caspase 3 (casp3), tumor protein 53 (p53), B-cell lymphoma 2 (Bcl2), and Bcl2-associated X protein (Bax) genes. Statistical analysis was performed using ANOVA and Tukey's tests (p < .05). RESULTS: Histopathological analysis revealed significant testicular damage in the MTX group, with decreased spermatogenesis and Leydig cell count, while Se administration mitigated these effects, preserving the structural integrity of the reproductive epithelium. Biochemical analysis demonstrated that MTX led to elevated malondialdehyde (MDA) levels and reduced testosterone, LH, and FSH levels, suggesting oxidative stress and Leydig cell dysfunction. Gene expression analysis indicated that MTX upregulated proapoptotic genes (casp3, p53, and bax) while downregulating the antiapoptotic Bcl2 gene. In contrast, Se treatment reversed these trends, highlighting its potential antiapoptotic properties. CONCLUSION: Our findings underscore the potential of Se as a therapeutic agent to mitigate the reproductive toxicity associated with MTX-induced testicular injury. Se exerts protective effects by regulating oxidative stress, preserving hormone balance, and modulating apoptotic pathways. These results suggest that Se supplementation could be a promising strategy to alleviate chemotherapy-induced testicular damage and preserve male fertility.

Physiological Evidence and Therapeutic Outcomes of Vitamin D on Cardiovascular Diseases.

Vitamin D hormone is an important regulator of various physiological functions, and its deficiency is characterized by an imbalance in parathyroid hormone and calcium homeostasis. The role of vitamin D in cardiovascular physiology is well demonstrated in animal and humanbased studies. In this context, hyperlipidemia, increased atherogenic plaques, cardiac inflammation, hypertension, myocarditis, myocardial infarction, and heart failure are some of the commonest known conditions connected with vitamin D deficiency. Supplementation of vitamin D is recommended to achieve normal serum vitamin D concentrations, nonetheless, in clinical trials often seen discrepancies concerning the supplementation effects and effectiveness. This review summarizes the data on the role of vitamin D in cardiovascular health along with some recent clinical findings regarding the effects of vitamin D supplementation.

Efficacy of oseltamivir in the treatment of patients infected with Covid-19.

Objective: The recent unprecedented pandemic caused by Sars-Cov-2 (the new coronavirus 2019), is threatening public health around the world. Although several studies have been performed, there is no identified treatment for Covid-19 patients. Here we assessed the efficacy of oseltamivir in combination therapy, by comparing two different therapeutic regimens in hospitalized patients, in improving outcomes and find better treatment for Covid-19 patients. Methods: This is a single-center retrospective cohort study of 285 confirmed Covid-19 in patients at (XXX). Depending on the date of admission, the patients were divided into two groups; group 1 (oseltamivir group) from February 20, 2020 to March 15, 2020 received Oseltamivir with routine regimen and group 2 (control group) from March 20, 2020 to April 20, 2020 received routine regimen alone that included Azithromycin 500 mg/day and Hydroxychloroquine 200 mg/12 h.Endpoints including duration of hospitalization, requirement to admission to intensive care unit (ICU) and mechanical ventilation, outcome and mortality rate. Results: A total of 285 patients were enrolled in the two months, 120 patients for group 1 and 165 for group 2. The median time from admission to discharge was significantly shorter in the oseltamivir group compared to the control group (4.9 vs 6.6 days, p < 0.001). Additionally, the mortality rate was found to be lower in the oseltamivir group than in the control group (1.7% vs 6,7%, p = 0.06) which was statistically significant by multivariate analysis (p = 0.03). The incidence of admission to the ICU (6.7% vs 11.5%, p = 0.1) and mechanical ventilation (2.5% vs 4.8%, p = 0.3) were also decreased in the oseltamivir group, but was not statistically significant. Conclusions: This study showed that administration of oseltamivir was associated with shorter length of hospital stay and earlier recovery and discharge of hospital, and a lower mortality rate.

Chronic hemodialysis: Evaluation of dialysis adequacy and mortality.

Objective: Dialysis efficacy is one of the important issues in patients undergoing hemodialysis. This study aimed to determine the adequacy of dialysis with mortality and hospital admissions in patients undergoing hemodialysis. Methods: This retrospective cohort study was conducted on patients who underwent dialysis. Dialysis adequacy was measured based on the Kt/V criterion. Age, sex, disease etiology, duration of dialysis, and access dialysis were evaluated. Results: 128 patients with a mean age of 61.48 ± 13.36 years were included in the study. 8 patients had a history of kidney transplantation. The mean dialysis time in the patients was 4.30 ± 3.39 years. The mean Kt/V in the patients was 1.40 ± 1.8 years. Of the 128 patients, 53 were hospitalized for cardiac or renal reasons. The number of fatalities was 9 cases out of 128. The cause of death in all the cases was heart problems. There was a statistically significant correlation between the adequacy of dialysis in terms of Kt/V and mortality, but it was not associated with hospitalization. Conclusion: Inadequate dialysis in terms of Kt/V is likely to increase the rate of mortality among dialysis patients.

Use of alginate hydrogel to improve long-term 3D culture of spermatogonial stem cells: stemness gene expression and structural features.

The quality and quantity of a spermatogonial stem-cell (SSC) culture can be measured in less time using a 3D culture in a scaffold. The present study investigated stemness gene expression and the morphological and structural characterization of SSCs encapsulated in alginate. SSCs were harvested from BALB/c neonatal mice testes through two-step mechanical and enzymatic digestion. The spermatogonial populations were separated using magnetic-activated cell sorting (MACS) using an anti-Thy1 antibody and c-Kit. The SSCs then were encapsulated in alginate hydrogel. After 2 months of SSC culturing, the alginate microbeads were extracted and stained to evaluate their histological properties. Real-time polymerase chain reaction (PCR) was performed to determine the stemness gene expression. Scanning electron microscopy (SEM) was performed to evaluate the SSC morphology, density and scaffold structure. The results showed that encapsulated SSCs had decreased expression of Oct4, Sox2 and Nanos2 genes, but the expression of Nanog, Bcl6b and Plzf genes was not significantly altered. Histological examination showed that SSCs with pale nuclei and numerous nucleolus formed colonies. SEM evaluation revealed that the alginate scaffold structure preserved the SSC morphology and density for more than 60 days. Cultivation of SSCs on alginate hydrogel can affect Oct4, Sox2 and Nanos2 expression.

Treatment With 25-Hydroxyvitamin D3 (Calcifediol) Is Associated With a Reduction in the Blood Neutrophil-to-Lymphocyte Ratio Marker of Disease Severity in Hospitalized Patients With COVID-19: A Pilot Multicenter, Randomized, Placebo-Controlled, Double-Blinded Clinical Trial.

OBJECTIVE: The goal of this randomized, double-blinded, placebo-controlled clinical trial was to investigate the therapeutic efficacy of oral 25-hydroxyvitamin D3 (25(OH)D3) in improving vitamin D status in vitamin D-deficient/vitamin D-insufficient patients infected with the SARS-CoV-2 (COVID-19) virus. METHODS: This is a multicenter, randomized, double-blinded, placebo-controlled clinical trial. Participants were recruited from 3 hospitals that are affiliated to [Institution Blinded for Review] and [Institution Blinded for Review]. RESULTS: A total 106 hospitalized patients who had a circulating 25(OH)D3 concentration of <30 ng/mL were enrolled in this study. Within 30 and 60 days, 76.4% (26 of 34) and 100% (24 of 24) of the patients who received 25(OH)D3 had a sufficient circulating 25(OH)D3 concentration, whereas ≤12.5% of the patients in the placebo group had a sufficient circulating 25(OH)D3 concentration during the 2-month follow-up. We observed an overall lower trend for hospitalization, intensive care unit duration, need for ventilator assistance, and mortality in the 25(OH)D3 group compared with that in the placebo group, but differences were not statistically significant. Treatment with oral 25(OH)D3 was associated with a significant increase in the lymphocyte percentage and decrease in the neutrophil-to-lymphocyte ratio in the patients. The lower neutrophil-to-lymphocyte ratio was significantly associated with reduced intensive care unit admission days and mortality. CONCLUSION: Our analysis indicated that oral 25(OH)D3 was able to correct vitamin D deficiency/insufficiency in patients with COVID-19 that resulted in improved immune function by increasing blood lymphocyte percentage. Randomized controlled trials with a larger sample size and higher dose of 25(OH)D3 may be needed to confirm the potential effect of 25(OH)D3 on reducing clinical outcomes in patients with COVID-19.

Safety and effectiveness of high-dose vitamin C in patients with COVID-19: a randomized open-label clinical trial.

BACKGROUND: Vitamin C is an essential water-soluble nutrient that functions as a key antioxidant and has been proven to be effective for boosting immunity. In this study, we aimed to assess the efficacy of adding high-dose intravenous vitamin C (HDIVC) to the regimens for patients with severe COVID-19 disease. METHODS: An open-label, randomized, and controlled trial was conducted on patients with severe COVID-19 infection. The case and control treatment groups each consisted of 30 patients. The control group received lopinavir/ritonavir and hydroxychloroquine and the case group received HDIVC (6 g daily) added to the same regimen. RESULTS: There were no statistically significant differences between two groups with respect to age and gender, laboratory results, and underlying diseases. The mean body temperature was significantly lower in the case group on the 3rd day of hospitalization (p = 0.001). Peripheral capillary oxygen saturations (SpO2) measured at the 3rd day of hospitalization was also higher in the case group receiving HDIVC (p = 0.014). The median length of hospitalization in the case group was significantly longer than the control group (8.5 days vs. 6.5 days) (p = 0.028). There was no significant difference in SpO2 levels at discharge time, the length of intensive care unit (ICU) stay, and mortality between the two groups. CONCLUSIONS: We did not find significantly better outcomes in the group who were treated with HDIVC in addition to the main treatment regimen at discharge. Trial registration irct.ir (IRCT20200411047025N1), April 14, 2020.

The effect of vitamin D supplementation on the progression of benign prostatic hyperplasia: A randomized controlled trial.

BACKGROUND AND AIMS: Inflammation and proliferation are the cause of benign prostatic hyperplasia (BPH) and are the key components of its mechanism of action. In this study we sought to determine the role of 25-hydroxyvitamin D in BPH, because of its anti-inflammatory activities, and its effect on prostate volume and BPH symptoms. METHODS: This randomized clinical trial (RCT) was conducted on 108 participants >50 years of age who had either asymptomatic or mild BPH symptoms according to the International Prostate Symptom Score (IPSS) questionnaire. Patients were randomly divided into two groups, intervention and control. The intervention group received 50 000 units of vitamin D3 and the control group received a placebo every two weeks for six months. Prostate ultrasound, routine clinical examinations, toucher rectal (TR), and laboratory tests were performed for all patients. After six months, the patients underwent another ultrasound evaluation, measurement of prostate-specific antigen (PSA) levels and completed the IPSS. Results of the evaluations before and after the intervention were compared between the groups using the chi-square, t-test, and logistic regression analysis. Repeated measure analysis was used to evaluate the effect of vitamin D intervention on the changes in the IPSS score. RESULTS: The mean age of the participants was 56 ± 9 years. In the control group, the mean prostate volume was higher compared to the intervention group (p < 0.001). The control group had a higher mean PSA level than the intervention group (p < 0.001). Although the IPSS score decreased over time in both groups, analysis of variance showed that the amount of change or decrease in IPSS score in the intervention group was significantly more than the control group (p < 0.001). CONCLUSIONS: The results of our study support the effect of vitamin D in reducing prostate volume and PSA levels, and in improving BPH symptoms. Further studies are needed to confirm these findings to verify the use of vitamin D as a treatment for BPH.

Safety and effectiveness of azithromycin in patients with COVID-19: An open-label randomised trial.

As no specific pharmacological treatment has been validated for use in coronavirus disease 2019 (COVID-19), we aimed to assess the effectiveness of azithromycin (AZM) in these patients at a referral centre in Iran. An open-label, randomised controlled trial was conducted on patients with laboratory-confirmed COVID-19. A total of 55 patients in the control group receiving hydroxychloroquine (HCQ) and lopinavir/ritonavir (LPV/r) were compared with 56 patients in the case group who in addition to the same regimen also received AZM. Patients with prior cardiac disease were excluded from the study. Furthermore, patients from the case group were assessed for cardiac arrythmia risk based on the American College of Cardiology (ACC) risk assessment for use of AZM and HCQ. The main outcome measures were vital signs, SpO2 levels, duration of hospitalisation, need for and length of intensive care unit admission, mortality rate and results of 30-day follow-up after discharge. Initially, there was no significant difference between the general conditions and vital signs of the two groups. The SpO2 levels at discharge were significantly higher, the respiratory rate was lower and the duration of admission was shorter in the case group. There was no significant difference in the mortality rate between the two groups. Patients who received AZM in addition to HCQ and LPV/r had a better general condition. HCQ+AZM combination may be beneficial for individuals who are known to have a very low underlying risk for cardiac arrhythmia based on the ACC criteria.

Role of Helicobacter pylori infection in the manifestation of old age-related diseases.

Helicobacter pylori is one of the most prevalent infection worldwide. It affects individuals of different age groups. Elderly people tend to resist eradication treatment and worsening of infection can lead to several gastric and non-gastric pathologies. Aging-associated cellular and molecular alteration can increase the risk of other pathologies such as osteoporosis, Alzheimer's disease, Parkinson's disease, respiratory and renal dysfunction, and cancer in geriatric patients, more than other age groups. This review article highlights some of the most common old age diseases and the role of H. pylori infection as a risk factor to worsen the conditions, presented by the molecular evidences of these associations. These studies can help clinicians to understand the underlying pathogenesis of the disease and identify high-risk patients, aiding clearer diagnosis and treatment.

Biological evidence of the relationship between Helicobacter pylori and associated extragastric diseases.

BACKGROUND: Gram-negative bacterium, Helicobacter pylori is notorious for various pathologies like peptic ulcers, gastritis, functional dyspepsia, and various cancers. METHODS: Systemic effects of its toxins have led scientists' attention toward the extragastric pathologies associated with it. To date, it has been shown to have an effect on almost all the systems in the human body. RESULTS: Various studies have been conducted to obtain the relation between H. pylori infection, and other diseases. CONCLUSION: In this review, we aim to discuss the extragastric diseases associated with H. pylori and the biological factors that relate them to it.

Molecular evidence of role of vitamin D deficiency in various extraskeletal diseases.

BACKGROUND: Role of vitamin D is not only limited to skeletal system but various other systems of the body, such as immune system, endocrine system, and cardiopulmonary system. MATERIALS AND METHODS: It is supported by the confirmations of systems-wide expression of vitamin D receptor (VDR), endocrinal effect of calcitriol, and its role in immune responses. RESULTS: Expression of VDR in various systems, immunoregulatory and hormonal response of vitamin D and deficiency of vitamin D may establish various pathologies in the body. CONCLUSION: This review provides molecular evidence of relation of vitamin D with extra skeletal.

Seroprevalence of Human Fasciolosis in Pirabad, Lorestan Province, Western Iran.

BACKGROUND: The purpose of this study was to perform seroepidemiological investigation for determining the status of human fasciolosis in Pirabad Village, Lorestan Province, western Iran. METHODS: Blood samples were taken from residents of the village including 801 individuals. Sera were separated and stored at -20°C until used. The samples were analyzed using ELISA. RESULTS: Anti-Fasciola antibodies were detected in 6 (0.7%) individuals. Difference between age, sex and drinking or swimming in the surface water with seropositivity to fasciolosis was not significant. Out of 7 shepherds, 1 (14.3%) was seropositive. Due to the small number of shepherds, comprehensive statistical inference in this regard cannot be done. Significant difference was detected between seropositivity to fasciolosis and consuming local freshwater vegetables during the last 6 months (P=0.001). CONCLUSION: Metacercariae carrying local freshwater plants might be the main source of contamination because consumption of these kinds of vegetables was confirmed by all participants. Awareness of local communities regarding the danger of freshwater plant consumption, through health education programs, will decrease the risk of infection.