Berberine ameliorates experimental varicocele-induced damages at testis and sperm levels; evidences for oxidative stress and inflammation.

The present study was performed to show the ameliorative effect of berberine (BBR), as an antioxidant and anti-inflammatory agent, against experimental varicocele (VCL)-induced molecular and histological damages. For this purpose, 50 mature Wistar rats were divided into control, control-sham, VCL-sole, 50 mg/kg and 100 mg/kg BBR-treated VCL-induced groups. The tissue levels of interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), nitric oxide (NO), total antioxidant capacity (TAC), malondialdehyde (MDA), superoxide dismutase (SOD) and gluthatione peroxidase (GSH-px) as well as the mRNA levels of testicular CuZn SOD, MnSOD, EC-SOD and GSH-px were evaluated. The serum concentration of testosterone and germ cells mRNA damage were analysed. Finally, the sperm viability, motility, DNA integrity and chromatin condensation were analysed. Observations revealed that, the BBR significantly downregulated VCL-increased IL-6, TNF-α and NO levels, upregulated the CuZn SOD, MnSOD, EC-SOD and GSH-px mRNA level, decreased testicular MDA content, enhanced serum testosterone level and ameliorated testicular TAC, SOD and GSH-px levels. The animals in BBR-treated groups exhibited diminished mRNA damage versus non-treated VCL-induced group. The BBR has significantly (p < 0.05) improved sperm parameters. In conclusion, the BBR by promoting testicular antioxidant potential and by downregulating inflammatory reactions fairly promotes spermatogenesis and upregulates the sperm quality.

The effect of vitamin E & vitamin B on sperm function in rat varicocele model.

We assessed the effect of vitamin E and vitamin B (Vit E & Vit B) and their combination on sperm functional parameters in the rat varicocele model. Male rats (n = 120) were divided into control (n = 30), sham (n = 30) and varicocele induction (n = 60) groups. After 2 months, 10 rats from each group were sacrificed to verify varicocele model. This part of results showed that sperm parameters, DNA damage, lipid peroxidation and residual histone were adversely effected in the varicocele group. From the 50 remaining rats in varicocele group, 10 rats received Vit B complex (6, 9.6, 30.4, 9.6 and 0.006 mg/kg for B6, B2, B9, B1 and B12 respectively), 10 rats received Vit E (40 mg/kg), 10 rats received Vit B & E, 10 rats only received water and 10 rats were only received sesame oil as a solvent for Vit E, for 2 months. From 40 remaining rats in control and sham groups, 20 rats only received water and other 20 rats only received sesame oil for 2 months. Then, all the aforementioned parameters were assessed. These results showed that Vit B antioxidant was more efficient in improvement of sperm parameters, chromatin integrity and lipid peroxidation in varicocelized rats compared with Vit E.

One-carbon cycle support rescues sperm damage in experimentally induced varicocoele in rats.

OBJECTIVES: To investigate whether micronutrients in support of the one-carbon cycle and glutathione synthesis are effective in improving sperm damage after surgical varicocoele induction in rats and whether any effect is achieved without a rebound reductive stress as seen with oral antioxidants. MATERIALS AND METHODS: Surgical varicocoele was induced in adult male Wistar rats and resulted in significant damage to the testis and sperm cells measured at 2 and 4 months after surgery. At 2 months after surgery, rats received a 2-month oral supplementation in support of the one-carbon cycle containing B vitamins (B2, B3, B6, folic acid and B12), N-acetyl-cysteine, zinc, small amounts of vitamin E, and a natural source of betalains and quercetine (Condensyl® ; Parthenogen SAGL, Lugano, Switzerland and Nurilia SARL, Lyon, France). RESULTS: One-carbon cycle supplementation, compared to untreated controls, significantly improved the morphometric characteristics of testis (P < 0.05), sperm concentration, motility and abnormal morphology (P < 0.001), sperm chromatin condensation (aniline blue staining, P < 0.05), sperm DNA damage (acridine orange staining, P < 0.05) and sperm lipid peroxidation (BODIPY C11, P < 0.001). The improvement in both nuclear condensation and DNA damage and the lack of excessive inhibition of lipid peroxidation confirmed that no reductive stress had occurred. CONCLUSIONS: Micronutrients in support of the one-carbon cycle are effective in the treatment of surgically induced varicocoele in rats, probably by activating natural antioxidant defences and epigenetics. These results support the idea that essential micronutrients including B vitamins may also have a positive influence in clinical varicocoele, which should be tested in prospective clinical trials.

Neuroprotective Effects of Oxytocin Hormone after an Experimental Stroke Model and the Possible Role of Calpain-1.

BACKGROUND: Different mechanisms will be activated during ischemic stroke. Calpain proteases play a pivotal role in neuronal death after ischemia damage through apoptosis. Anti-apoptotic activities of the oxytocin (OT) in different ischemic tissues were reported in previous studies. Recently, a limited number of studies have noted the protective effects of OT in the brain. In the present study, the neuroprotective potential of OT in an animal model of transient middle cerebral artery occlusion (tMCAO) and the possible role of calpain-1 in the penumbra region were assessed. METHODS: Adult male Wistar rats underwent 1 hour of tMCAO and were treated with nasal administration of OT. After 24 hours of reperfusion, infarct size was evaluated by triphenyltetrazolium chloride. Immunohistochemical staining and Western blotting were used to examine the expression of calpain-1. Nissl staining was performed for brain tissue morphology evaluation. RESULTS: OT reduced the infarct volume of the cerebral cortex and striatum compared with the ischemia control group significantly (P < .05). Calpain-1 overexpression, which was caused by ischemia, decreased after OT administration (P < .05). The number of pyknotic nuclei in neurons increased dramatically in the ischemic area and OT attenuated the apoptosis of neurons in the penumbra region (P < .01). CONCLUSION: We provided evidence for the neuroprotective role of OT after tMCAO through calpain-1 attenuation.

The Effect of Irisin on Proliferation, Apoptosis, and Expression of Metastasis Markers in Prostate Cancer Cell Lines.

INTRODUCTION: Irisin is a newly discovered myokine released from skeletal muscle during exercise. The matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that play a key role in the metastatic process via degrading extracellular matrix. The aim of this study was to investigate the effect of irisin on expression of metastatic markers MMP2 and MMP9 and induced apoptosis in human prostate cancer cells. METHODS: In this study, we examined the effect of different concentrations of irisin on induced apoptosis and cell viability of two cell lines, LNCaP and DU-145, by using flow cytometry and MTT assay, respectively. The expression of MMP2 and MMP9 genes was also analyzed by real-time PCR after irisin treatment. Data were analyzed using the comparative cycle threshold 2-∆∆Ct method. RESULTS: Cell viability was reduced in both LNCaP and DU-145 cell lines at different concentrations of irisin. However, this decreased cell viability was strongly significant (p < 0.05) only at 5 and 10 nM concentrations of irisin in the LNCaP cell line. Furthermore, irisin could induce apoptosis in both cell lines at a concentration of 10 nM compared to 5 nM. Real-time PCR results also demonstrated a decreased expression in MMP2 and MMP9 genes in a concentration-dependent manner in both cell lines. CONCLUSION: These results showed the anticancer effects of irisin on cell viability of both LNCaP and DU-145 cell lines and also on the expression of MMP2 and MMP9 genes occurred in a dose- and time-dependent manner.

The role of altered long noncoding RNAs in overall survival of ovarian cancer: A systematic review and meta-analysis.

In recent years, tremendous research efforts have been focused on investigating the effect of dysregulation of lncRNAs on cancer progression, most of which confirm a positive link. This inspired us to conduct the present meta-analysis to explore whether aberrant expression of multiple lncRNAs has a role in patients' outcome in ovarian cancer. This comprehensive meta-analysis pertains to the evaluation of association between dysregulated lncRNAs expression level with eventual outcome and clinicopathological characteristics of ovarian cancer patients. We systematically searched PubMed, Web of Science, and Scopus to find all eligible articles. Pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) for overall survival, disease-free survival and progression-free survival were measured with a fixed or random effects model. A total of 34 studies were included in the meta-analysis. Dysregulation of lncRNAs were contributed to shorter overall survival (34 studies, 1180 patients HR = 2.12, 95% CI: 1.73 ± 2.60, random-effects) in ovarian cancer. Furthermore, altered lncRNAs were also related to decreased progression-free survival (8 studies, 1180 patients HR: 1.88, 95% CI: (1.35-2.62) and disease-free survival (2 studies, 285 patients, HR: 6.07, 95% CI: 1.28-28.78) in this disease. Our analyses supported the robust prognostic significance of altered lncRNAs in ovarian cancer. However, more extended studies are encouraged to evaluate the clinical application potential of these lncRNAs in the prognosis evaluation of ovarian cancer.

The novel coronavirus Disease-2019 (COVID-19): Mechanism of action, detection and recent therapeutic strategies.

Novel coronavirus SARS-CoV-2, designated as COVID-19 by the World Health Organization (WHO) on the February 11, 2020, is one of the highly pathogenic ß-coronaviruses which infects human. Early diagnosis of COVID-19 is the most critical step to treat infection. The diagnostic tools are generally molecular methods, serology and viral culture. Recently CRISPR-based method has been investigated to diagnose and treat coronavirus infection. The emergence of 2019-nCoV during the influenza season, has led to the extensive use of antibiotics and neuraminidase enzyme inhibitors, taken orally and intravenously. Currently, antiviral inhibitors of SARS and MERS spike proteins, neuraminidase inhibitors, anti-inflammatory drugs and EK1 peptide are the available therapeutic options for SARS-CoV-2 infected individuals. In addition, Chloroquine, which was previously used for malarial and autoimmune disease, has shown efficacy in the 2019-nCoV infection treatment. In severe hypoxaemia, a combination of antibiotics, α-interferon, lopinavir and mechanical ventilation can effectively mitigate the symptoms. Comprehensive knowledge on the innate and adaptive immune responses, will make it possible to propose potent antiviral drugs with their effective therapeutic measures for the prevention of viral infection. This therapeutic strategy will help patients worldwide to protect themselves against severe and fatal viral infections, that potentially can evolve and develop drug resistance, and to reduce mortality rates.

Berberine reinforces Sertoli cells niche and accelerates spermatogonial stem cells renewal in experimentally-induced varicocele condition in rats.

BACKGROUND: Varicocele is present in 10-20% of the male infertile population. PURPOSE: Present study was done to demonstrate the reinforcing effect of berberine (BBR), as an antioxidant and anti-inflammatory agent, on Sertoli cells-related niche and spermatogonial stem cells (SSCs) self-renewal in experimentally-induced VCL condition. STUDY DESIGN: 50 mature male Wistar rats were divided into control, control-sham, non-treated VCL-induced, 50 mg kg-1 and 100 mg kg-1 BBR-treated VCL-induced groups. METHODS: The Leydig and Sertoli cells distribution and Leydig cells steroidogenic activity, expression of glial cell line-derived neurotrophic factor (GDNF), proto-oncogene Rearranged during Transfection (c-RET) receptor, Ets variant gene 5 (Etv5) and B-cell chronic lymphocytic leukemia (CLL)/lymphoma 6, member B (Bcl-6b) at mRNA and protein levels were analyzed. The mRNA integrity and DNA fragmentation were assessed. Finally, the serum levels of testosterone, inhibin B and testicular total antioxidant capacity, total thiol molecules, catalase, and malondialdehyde were evaluated. RESULTS: Observations revealed that, the BBR significantly enhanced VCL-reduced Leydig and Sertoli cells population, maintained Leydig-Sertoli cells network, enhanced GDNF, c-RET Etv5 and Bcl6b expression, up-regulated testicular antioxidant and endocrine status. CONCLUSION: The BBR by boosting Leydig-Sertoli cells network up-regulates the GDNF, Etv5 and Bcl-6b expression/synthesis in SSCs, which in turn improves SSCs self-renewal activities. Thus, the BBR could be considered as an appropriate agent for antioxidant therapy of VCLs. However, more studies with bigger sample number and focus on BBR-induced effects on other genes involving in the self-renewal process are needed to have more deterministic results.

Evaluation of ebselen supplementation on cryopreservation medium in human semen.

BACKGROUND: An effect of cryopreservation on human sperm is sublethal cryodamage, in which cell viability post-thaw is lost more rapidly at later times than in fresh cells. OBJECTIVE: This study examined whether the addition of an antioxidant to cryopreservation medium could improve the post-thaw parameters and evaluation of sperm chromatin quality of cryopreserved human spermatozoa from men with normal semen parameters. MATERIALS AND METHODS: Semen samples (n=35) were collected by masturbation and assessed following WHO standards. Individual samples were classified as two portions. One portion (n=10) was for elucidate the concentration of ebselen.Then the samples(n=25) were divided in to 5groups.The first aliquot remained fresh.The second aliquots was mixed with cryopreservation medium.The third aliquots were mixed with cryopreservation medium containing solvent of ebselen.The forth and fifth aliquots were mixed with cryopreservation medium containing 1.25 and 2.5 µm of ebselen.Samples were frozen and thawed samples were assessed for sperm parameters.Three-way ANOVA Multivariate measures were used to assess. According to this assesment the differences are observed in existent groups in post-thaw count, motility index, vitality staining, and morphology and DNA fragmentation. RESULTS: After freezing the media containing of ebselen, DNA fragmentation is significantly different in comparison with control group. ebselen with 1.25 µm dose was significantly associated with post-thaw DNA fragmentation (p=0.047). Similarly ebselen with 2.5 µm dose was significantly associated with post-thaw DNA fragmentation (p=0.038). But other parameters were not altered. CONCLUSION: These results suggest that the addition of ebselen to cryopreservation medium doesnot improve post-thaw parameters and DNA fragmentation of sperm.