The Effect of Eurycoma Longifolia Jack on Spermatogenesis in Estrogen-Treated Rats

INTRODUCTION: There is little data concerning the ability of Eurycoma longifolia Jack (EL) to reverse the inhibitory effects of estrogen on testosterone production and spermatogenesis. The aim of the present study was to determine the effect of EL on testicular histology and sperm count in estrogen-treated male rats. METHODS: Adult male Sprague-Dawley rats weighing 200-250 g were divided into four groups of six rats each. Group A (control) was given solvent in the same manner as the treated groups were given EL. Group B was treated with EL (8 mg/kg body weight) orally. Group C was treated with estradiol (E2) (intramuscular dose of 500 &#956;g/kg body weight), and group D received a combined treatment of oral EL and intramuscular E2. After fourteen consecutive days of treatment, rats from all groups were sacrificed and subjected to spermatogenic and epididymal sperm cell counts. RESULTS: The spermatogenic cell count in the E2-treated group was significantly decreased as compared to the control (p < 0.05) and EL+E2-treated groups (p < 0.05). A similar finding was found for the epididymal sperm count; the E2-treated group had a significant decrease in the count compared to the control (p < 0.05) and EL+E2-treated groups (p < 0.05). Rats that were treated with EL alone exhibited significantly higher sperm counts and sperm motility when compared to the control group (p < 0.05). CONCLUSIONS: EL extract acts as a potential agent for reversing the effects of estrogen by increasing spermatogenesis and sperm counts in rats after fourteen consecutive days of treatment

Chronic consumption of fructose dysregulates genes related to glucose and lipid metabolism in prostate tissue

Fructose is commonly used as a taste enhancer in many processed foods. Excessive fructose consumption is highly associated with obesity and development of cancer particularly prostate cancer. This study aimed to investigate the biochemical and molecular changes in the prostate tissue of rats treated with 20% fructose for six months. A total of 18 rats weighted 200-250 g were divided into two groups, where each group consisted of 9 rats. Control group is given normal diet, while the treated group was given normal diet and 20% fructose in drinking water. After six months of treatment, both groups were sacrificed for further analysis. Body weight, blood pressure and glucose were measured. Lipid profiles were determined using quantitative colorimetric assay. Transcripts level of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), leptin (LEP), angiopoietin 1 (ANGPT1), microRNA (miR)-34a, miR-10b and miR-192 were determined using quantitative PCR, while the protein levels of 11β-HSD1 and leptin were determined using ELISA. The results showed that 20% fructose diet significantly increased blood glucose level as compared to the control (p<0.05). The transcript levels of LEP and miR-192 were significantly lower in the fructose-treated group as compared to the control (p<0.05). There was a significant linear relationship between prostate LEP and serum LDL/VLDL level as well as between the level of prostate LEP and serum total cholesterol level (p<0.05). Thus, our results showed that chronic consumption of fructose could down-regulate LEP and miR-192 expression in prostate tissue, and promote higher accumulation of fat in the tissue. Additionally, downregulation of miR-192 has been reported to be associated with the pathogenesis of prostate cancer. Thus, it can be concluded that long-term fructose diet leads to higher blood glucose level and down-regulation of LEP and miR-192 expression in prostate tissue

Hyperandrogenism and Its Possible Effects on Endometrial Receptivity: A Review

Endometrial receptivity is a state of the endometrium defined by its readiness for embryo implantation. When the receptivity of the endometrium is impaired due to hyperandrogenism or androgen excess, this condition can lead to pregnancy loss or infertility. Hyperandrogenism encompasses a wide range of clinical manifestations, including polycystic ovary syndrome (PCOS), idiopathic hirsutism, hirsutism and hyperandrogaenemia, non-classical congenital adrenal hyperplasia, hyperandrogenism, insulin resistance, acanthosis nigricans (HAIR-AN), ovarian or adrenal androgensecreting neoplasms, Cushing’s syndrome, and hyperprolactinaemia. Recurrent miscarriages have been shown to be closely related to elevated testosterone levels, which alter the endometrial milieu so that it is less favourable for embryo implantation. There are mechanisms for endometrial receptivity that are affected by excess androgen. The HOXA gene, aVβ3 integrin, CDK signalling pathway, MECA-79, and MAGEA-11 were the genes and proteins affect endometrial receptivity in the presence of a hyperandrogenic state. In this review, we would like to explore the other manifestations of androgen excess focusing on causes other than PCOS and learn possible mechanisms of endometrial receptivity behind androgen excess leading to pregnancy loss or infertilit

Anti-angiogenic effect of polygonum species: a comprehensive review of literature

Angiogenesis is a physiological, tightly regulated process which is characterized by the development of new blood vessels. Compounds with the potential to control angiogenesis would be highly valuable as therapeutics, as an imbalance in angiogenesis may lead to several pathological disorders, including cancer, retinopathy, and arthritis. In this study, the anti-angiogenic effect of Polygonum sp. has been comprehensively reviewed and this plant also has been known to possess other medicinal benefits such as antioxidative, anti-inflammatory, anti-proliferative, and anti-tumor agents. Hence, this study systematically identified the evidence reporting the anti-angiogenic effects of Polygonum sp. Four electronic databases, namely PubMed, Ovid MEDLINE, Scopus and Web of Science were searched for relevant articles. Based on the pre-set eligibility criteria, 50 relevant articles were identified, and ten qualified articles were selected and reviewed. It was demonstrated that four namely P. cuspidatum, P. barbatum, P. hydropiper, and P. perfoliatum showed anti-angiogenic activities mainly through inhibition of the vascular endothelial growth factor-signaling pathways. Therefore, these species Polygonum have the potential to be developed as natural anti-angiogenic agents for prevention and treatment of various diseases related to pathological angiogenesis

A randomized, double-blinded, placebo-controlled clinical trial on Lactobacillus-containing cultured milk drink as adjuvant therapy for depression in irritable bowel syndrome

Abstract Irritable bowel syndrome (IBS) is frequently linked with coexisting mental illnesses. Our previous study discovered that 32.1% of IBS patients had subthreshold depression (SD), placing them at higher risk of developing major depression. Gut microbiota modulation through psychobiotics was found to influence depression via the gut-brain axis. However, the efficacy of lessening depression among IBS patients remains ambiguous. The study’s aim was to investigate the roles of cultured milk drinks containing 109 cfu Lactobacillus acidophilus LA-5 and Lactobacillus paracasei L. CASEI-01 on depression and related variables among IBS participants with SD. A total of 110 IBS participants with normal mood (NM) and SD, were randomly assigned to one of four intervention groups: IBS-NM with placebo, IBS-NM with probiotic, IBS-SD with placebo, and IBS-SD with probiotic. Each participant was required to consume two bottles of cultured milk every day for a duration of 12 weeks. The following outcomes were assessed: depression risk, quality of life, the severity of IBS, and hormonal changes. The depression scores were significantly reduced in IBS-SD with probiotic and placebo from baseline (p < 0.001). Only IBS-SD with probiotic showed a significant rise in serotonin serum levels (p < 0.05). A significantly higher life quality measures were seen in IBS-SD with probiotic, IBS-SD with placebo, and IBS-NM with placebo (p < 0.05). All groups, both placebo and probiotic, reported significant improvement in IBS severity post-intervention with a higher prevalence of remission and mild IBS (p < 0.05). Dual strains lactobacillus-containing cultured milk drink via its regulation of relevant biomarkers, is a potential anti-depressive prophylactic agent for IBS patients at risk

Post-transcriptional regulation of microRNAs in cancer: from prediction to validation

MicroRNA (miRNA) is a small non-coding RNA with an established function to regulate genes at the post-transcriptional level leading to suppression or degradation of its messenger RNA expression (mRNA). Its dysregulation plays a vital role in a variety of biological and pathological processes including cancer. A lot of algorithms have been established to predict the target sites of miRNA, but experimentally identifying and validating its target region is still lacking. Guidance in experimental procedures is really needed to find genuine miRNA targets. Therefore, in this review, we provide an outline on the workflow in predicting and validating the targeted sites of miRNA using several methods as a guideline for the scientists. The final outcome of this type of experiment is essential to explore the major impact of miRNA-mRNA interaction involved in the biological processes and to assist miRNA-based drug development in the future

Oncogenic Role of miR-200c-3p in High-Grade Serous Ovarian Cancer Progression via Targeting the 3′-Untranslated Region of DLC1

High-grade serous ovarian cancer (HGSC) is the most common ovarian cancer with highly metastatic properties. A small non-coding RNA, microRNA (miRNA) was discovered to be a major regulator in many types of cancers through binding at the 3′-untranslated region (3′UTR), leading to degradation of the mRNA. In this study, we sought to investigate the underlying mechanisms involved in the dysregulation of miR-200c-3p in HGSC progression and metastasis. We identified the upregulation of miR-200c-3p expression in different stages of HGSC clinical samples and the downregulation of the tumor suppressor gene, Deleted in Liver Cancer 1 (DLC1), expression. Over expression of miR-200c-3p in HGSC cell lines downregulated DLC1 but upregulated the epithelial marker, E-cadherin (CDH1). Based on in silico analysis, two putative binding sites were found within the 3′UTR of DLC1, and we confirmed the direct binding of miR-200c-3p to the target binding motif at position 1488–1495 bp of 3′UTR of DLC1 by luciferase reporter assay in a SKOV3 cell line co-transfected with vectors and miR-200c-3p mimic. These data showed that miR-200c-3p regulated the progression of HGSC by regulating DLC1 expression post-transcription and can be considered as a promising target for therapeutic purposes

Roles of microRNAs in Regulating Apoptosis in the Pathogenesis of Endometriosis

Endometriosis is a gynecologic disorder characterized by the presence of endometrial tissues outside the uterine cavity affecting reproductive-aged women. Previous studies have shown that microRNAs and their target mRNAs are expressed differently in endometriosis, suggesting that this molecule may play a role in the development and persistence of endometriotic lesions. microRNA (miRNA), a small non-coding RNA fragment, regulates cellular functions such as cell proliferation, differentiation, and apoptosis by the post-transcriptional modulation of gene expression. In this review, we focused on the dysregulated miRNAs in women with endometriosis and their roles in the regulation of apoptosis. The dysregulated miRNAs and their target genes in this pathophysiology were highlighted. Circulating miRNAs as potential biomarkers for the diagnosis of endometriosis have also been identified. As shown by various studies, miRNAs were reported to be a potent regulator of gene expression in endometriosis; thus, identifying the dysregulated miRNAs and their target genes could help discover new therapeutic targets for treating this disease. The goal of this review is to draw attention to the functions that miRNAs play in the pathophysiology of endometriosis, particularly those that govern cell death

Ethanol-Induced Changes in PKCε: From Cell to Behavior

The long-term binge intake of ethanol causes neuroadaptive changes that lead to drinkers requiring higher amounts of ethanol to experience its effects. This neuroadaptation can be partly attributed to the modulation of numerous neurotransmitter receptors by the various protein kinases C (PKCs). PKCs are enzymes that control cellular activities by regulating other proteins via phosphorylation. Among the various isoforms of PKC, PKCε is the most implicated in ethanol-induced biochemical and behavioral changes. Ethanol exposure causes changes to PKCε expression and localization in various brain regions that mediate addiction-favoring plasticity. Ethanol works in conjunction with numerous upstream kinases and second messenger activators to affect cellular PKCε expression. Chauffeur proteins, such as receptors for activated C kinase (RACKs), cause the translocation of PKCε to aberrant sites and mediate ethanol-induced changes. In this article, we aim to review the following: the general structure and function of PKCε, ethanol-induced changes in PKCε expression, the regulation of ethanol-induced PKCε activities in DAG-dependent and DAG-independent environments, the mechanisms underlying PKCε-RACKε translocation in the presence of ethanol, and the existing literature on the role of PKCε in ethanol-induced neurobehavioral changes, with the goal of creating a working model upon which further research can build