An Integrated Bioinformatics Approach to Identify Network Derived Hub Genes in Starving Zebrafish

The present study was aimed at identifying causative hub genes within modules formed by co-expression and protein–protein interaction (PPI) networks, followed by Bayesian network (BN) construction in the liver transcriptome of starved zebrafish. To this end, the GSE11107 and GSE112272 datasets from the GEO databases were downloaded and meta-analyzed using the MetaDE package, an add-on R package. Differentially expressed genes (DEGs) were identified based upon expression intensity N(µ = 0.2, σ2 = 0.4). Reconstruction of BNs was performed by the bnlearn R package on genes within modules using STRINGdb and CEMiTool. ndufs5 (shared among PPI, BN and COEX), rps26, rpl10, sdhc (shared between PPI and BN), ndufa6, ndufa10, ndufb8 (shared between PPI and COEX), skp1, atp5h, ndufb10, rpl5b, zgc:193613, zgc:123327, zgc:123178, wu:fc58f10, zgc:111986, wu:fc37b12, taldo1, wu:fb62f08, zgc:64133 and acp5a (shared between COEX and BN) were identified as causative hub genes affecting gene expression in the liver of starving zebrafish. Future work will shed light on using integrative analyses of miRNA and DNA microarrays simultaneously, and performing in silico and experimental validation of these hub-causative (CST) genes affecting starvation in zebrafish

Insulin Can Improve the Normal Function of the Brain by Preventing the Loss of the Neurons

Background: Insulin promotes the expression of genes related to brain function, thus preventing the neurodegeneration process. The present study was designed to find the neuroprotective effect of insulin by reducing neuron loss in the brain. Materials and Methods: In this study, 20 adult male NMRI mice were divided into two groups: control and insulin. The control group was intact, and the insulin group received 100 µL of insulin at a 72-hour interval by intraperitoneal (I.P.) injection for 30 days. At the end of the study, the brain was removed. The volume of the brain and the total number of neurons and glia were estimated by stereological techniques, and also the gene expression of NSR, PI3K, AKT, IGF-1, and FOXO-1 was measured using real-time PCR. Results: The results showed that the total number of neurons decreased in the control group compared to the experimental group. Furthermore, the expression of NSR, PI3K, AKT, IGF-1, and FOXO-1 genes was lower in the control group than in the insulin group. Conclusion: The results showed that treating mice with insulin prevented reducing the number of neurons and gene expression related to normal brain function. So, insulin could have neuroprotective effects against neuron loss. Insulin may be beneficial as a new approach to avoiding neuron loss in regenerative medicine

Znečištění životního prostředí a endokrinně podmíněná neplodnost samců ryb

There are a large number of natural and synthetic environmental contaminants (ECs) known or suspected to mimic or interfere with male reproductive endocrine functions. Our current knowledge is largely addressed to ECs that induce oestrogen-induced feminization. However, there are several ECs that cause alternations in androgen production similar to oestrogenic ECs, but they do not induce vitellogenin-induced feminization. The mechanisms of action of these chemicals are still unclear due to the fact that androgen receptor (AR) functions in androgen-mediated male reproductive physiology are largely unknown. In the present study, we examined the effects of vinclozolin (VZ) (100, 400 and 800 ?g/L) and di-(2-ethylhexyl)-phthalate (DEHP) (1, 10 and 100 ?g/L) on male reproductive performance in goldfish following 30 days of exposure. Since both VZ and DEHP act as agonists and/or antagonists of hormonal receptors, estrogen receptor subtypes (er) and androgen receptor (ar) mRNA levels were studied. For studying their oestrogenic activity, one group of goldfish were exposed to 17?-estradiol (E2). In DEHP treated goldfish, sperm production, motility and velocity were decreased at 1, 100 and 10 ?g/L, respectively. Our previous study has shown that sperm production, motility and velocity were decreased in goldfish exposed to 800 ?g/L VZ. These suggest that DEHP and VZ are capable of interfering with spermatogenesis and sperm maturation. In E2 treated goldfish, none of the males produced sperm, indicating E2-suppressed spermatogenesis. Similar to E2 treated goldfish, 11-KT levels were decreased in goldfish exposed to ?10 and ?1 ?g/L DEHP at day 15 and 30, respectively. In VZ treated goldfish, 11-KT levels were decreased in goldfish exposed to 800 ?g/L VZ following 7 d, but increased in goldfish exposed to 100 ?g/L VZ following 30 d of exposure. E2 levels remained unchanged and increased in DEHP and E2 treated goldfish, respectively. In VZ treated goldfish, LH levels were increased at 100 ?g/L. In contrast, LH levels were decreased in DEHP and E2 treated goldfish following 15 d of exposure. There were also positive relationships between LH and 11-KT levels suggesting that inhibition or stimulation of androgen production were mediated by DEHP- or VZ-induced alternations in pituitary function. In VZ treated goldfish, gnrh3 mRNA levels were decreased following 7 d of exposure and increased at low dose following 30 d of exposure. kiss1 or kiss2 mRNA levels were also increased in VZ treated goldfish, while gpr54 mRNA remained unchanged. In DEHP treated goldfish, gnrh3, kiss1 and its receptor (gpr54) mRNA levels did not change during the period of exposure. In E2 treated goldfish, gnrh3 mRNA levels were decreased at day 7, but kiss1 and gpr54 mRNA levels were increased at day 30 of exposure. These results suggest that, in contrast to DEHP, VZ effects on pituitary and testicular functions are mediated by disruption of hypothalamus function and upstream neuroendocrine regulators. The brain ar and testicular lhr mRNA levels were changed in VZ and E2 treated goldfish depending on dose and period of treatment, however they remained unchanged in DEHP treated goldfish. These differences suggest that DEHP may act through an independent hormonal receptor pathway, while VZ acts through a receptor pathway. vtg, er and cyp19a1b remained unchanged in DEHP and VZ treated goldfish but increased in E2 treated goldfish. These indicate that neither VZ nor DEHP acts as oestrogenic compound to impair male fertility. In conclusion, DEHP and VZ reduced sperm quality in goldfish due to stimulation and inhibition of 11-KT production which were mediated by alternations in pituitary function to produce LH or by disruption of the transfer of Cholesterol to steroidogenesis. Upstream neuroendocrine regulators (gnrh3 and kiss-1/gpr54) were disrupted in VZ treated goldfish. Taken together, VZ and DEHP differentially act on brain and testis to impair fertility endpoints

Renal vein thrombosis due to metastatic germ cell tumor, report of a case with a very rare clinical scenario

Abstract Background Renal metastasis is a rare manifestation of germ cell tumors. Extension of malignant lesions into the renal vein can complicate the scenario. Case This report presents a 35‐year‐old man with primary stage IS NSGCT. Fourteen months after radical orchiectomy he presented with metastasis in the lung, kidney, and para‐aortic lymph nodes. He received multiple lines of salvage treatments including chemotherapy and surgery. Intraoperative exploration during radical nephrectomy and retroperitoneal lymphadenectomy revealed intra‐renal vein involvement with a prominent teratomatous component. Conclusion Defining the exact extent of malignant lesions, especially endovascular lesions, is very important to clarify how advanced the malignant lesions are. The surgeons must be aware of the risk factors that predict vascular involvement, and therefore, providing intraoperative access to vascular surgery procedures when needed

Quantitation of bacteria in gastric biopsy specimen from patients with gastrointestinal disorders: relationship between counts and clinical features

Background: H. pylori is the only bacteria that infect humans gastric for which endoscopy examination is routinely recommended. The risk of development of gastrointestinal disorders (GIDs) in the presence of H. pylori infection depends on a variety of factors including bacterial, host, and environmental ones that mostly relate to the pattern of bacterial load. The aim of this study is to evaluate the relationship between H. pylori disease associated clinical features and bacterial count. Methods: A prospective study of the concentrations of bacteria in the gastric and their relationship to clinical features was conducted with 200 H. pylori suspected patients with GIDs. Initially, clinical status was evaluated and recorded by questionnaire. Then, RUT and 16SrRNA PCR were performed for identification of H. pylori. Finally, gastric biopsy specimens were analyzed for bacterial count by using specific primers and probe for 23SrRNA and using Taq-Man real-time PCR technology. Statistical analyses were performed using the c2 test. Pvalues less than 0.05 were taken to indicate statistical significance. Results: Of whom 200 samples, 164 (82%) had confirmed H. pylori positive. For 164 patients with GIDs, the count of H. pylori in gastric biopsies were a value of 104 to 1012 CFU/ml. The results revealed that more relationships between acid reflux and 104 CFU/ml (p = 0.006) and vomiting and 104 CFU/ml (p = 0.046). Conclusion: This study has demonstrated a relationship between bacterial load and clinical features in patients with GIDs. In conclusion, GIDs are similar to many other bacterial infections in that bacterial burden in the host is related to clinical features. Further studies are required to determine whether this is a function of the host, the infecting strain, or a combination of the two

A Review on Environmental Contaminants-Related Fertility Threat in Male Fishes: Effects and Possible Mechanisms of Action Learned from Wildlife and Laboratory Studies

Increasing global rates of diminished fertility in males has been suggested to be associated with exposure to environmental contaminants (ECs). The aquatic environments are the final repository of ECs. As the reproductive system is conserved in vertebrates, studies on the effects of ECs on fertility endpoints in fishes provide us with valuable information to establish biomarkers in risk assessment of ECs, and to understand the ECs-related fertility threat. The aim of the present review was to evaluate associations between ECs and fertility determinants to better understand ECs-related male fertility threat in male fishes. Wildlife studies show that the reproductive system has been affected in fishes sampled from the polluted aquatic environment. The laboratory studies show the potency of ECs including natural and synthetic hormones, alkylphenols, bisphenols, plasticizers, pesticides, pharmaceutical, alkylating, and organotin agents to affect fertility determinants, resulting in diminished fertility at environmentally relevant concentrations. Both wildlife and laboratory studies reveal that ECs adverse effects on male fertility are associated with a decrease in sperm production, damage to sperm morphology, alternations in sperm genome, and decrease in sperm motility kinetics. The efficiency of ECs to affect sperm quality and male fertility highly depends on the concentration of the contaminants and the duration of exposure. Our review highlights that the number of contaminants examined over fertility tests are much lower than the number of contaminants detected in our environment. The ECs effects on fertility are largely unknown when fishes are exposed to the contaminants at early developmental stages. The review suggests the urgent need to examine ECs effects on male fertility when a fish is exposed at different developmental stages in a single or combination protocol. The ECs effects on the sperm genome are largely unknown to understand ECs-related inheritance of reproductive disorders transmitted to the progeny. To elucidate modes of action of ECs on sperm motility, it is needed to study functional morphology of the motility apparatus and to investigate ECs-disrupted motility signaling

Optimizing Material Removal Rate (MRR) in WEDMing Titanium Alloy (Ti6Al4V) Using the Taguchi Method

Abstract: Selection of optimal cutting parameters has always been a critical issue to achieve high-quality in the machining process. In this study Design of Experiment (DOE) method for selection of optimal cutting parameters during WEDM of titanium alloy (Ti6Al4V) is experimentally studied. Moreover, the behaviour of three control parameters such as Pulse ON Time (A), Pulse OFF Time (B) and Peak Current (C) on machining performance, including Material Removal Rate (MRR) and Surface Roughness (SR) is studied using Analysis of Variance (ANOVA). This study has been establishedasa second-order mathematical model based on the Response Surface Methodology (RSM). The experimental plan was based on the face cantered, Central Composite Design (CCD). The residual analysis and confirmation runs indicate that the proposed models could adequately describe the performance of the factors that are being investigated. The results are particularly useful for scientists and engineers to determine which subset of the process variable has the greatest influence on the process performance

Adverse reactions of anti-tuberculosis drugs in hospitalized patients: incidence, severity and risk factors

Tuberculosis (TB) has been a common chronic infectious disease in human communities. Besides disease-related complications, there could be serious adverse reactions due to anti-tuberculosis (anti-TB) drug therapy. To assess the incidence and severity of adverse drug reactions (ADRs) induced by anti-TB drugs. To determine possible covariates associated with detected ADRs. All patients with respiratory TB admitted to a teaching hospital who received anti-TB drugs during the research period entered the study and were monitored for ADRs. Socio-demographic and medical history of patients were used as independent covariates. The relationship between independent covariates with frequency and severity of ADRs was analysed using multivariate logistic regression. Preliminary analyses of the Mann-Whitney, Chi-square, Kruskal-Wallis and the Fisher's exact tests were applied to determine factors unlikely associated with the independent variables. Among 204 patients admitted, there were 92 patients (45.1%) with ADRs induced by anti-TB drugs. Patients with a previous history of anti-TB drugs usage (OR = 5.81, 95% confidence interval [95%CI]: 1.31-25.2), patients with a history of drug allergy (OR = 6.68, CI: 1.28-36.2), those from Afghani ethnic (OR = 4.91, 95%CI: 1.28-18.30) as well as smoker patients with concurrent diseases (OR = 19.67, CI: 1.24-341.51) had a higher rate of ADR incidence. Being female (OR = 1.63, 95%CI: 1.96-36.40) and having previous history of ADR (OR = 17.46, 95%CI: 1.96-20.42) were identified as risk factors. Anti-TB drugs could cause severe and frequent adverse effects. Females, those with a previous history of ADRs to anti-TB drugs and Afghani patients, should be considered as high-risk groups

Anti-androgen vinclozolin impairs sperm quality and steroidogenesis in goldfish.

International audienceIn mammals, vinclozolin (VZ) is known as anti-androgen, which causes male infertility via androgen receptor (AR) antagonism. In aquatic animals, the VZ effects on reproductive functions are largely unknown and results are somewhat contradictory. To understand VZ adverse effects on male reproduction, mature goldfish (Carassius auratus) were exposed to three nominal VZ concentrations (100, 400, and 800 μg/L) and alternations in gonadosomatic (GSI) and hepatosomatic indices (HSI), 17β-estradiol (E(2)), 11-ketotestosterone (11-KT) and sperm quality were investigated compared to the solvent control. One group was exposed to E(2) (nominal concentration of 5 μg/L), an estrogenic compound, as a negative control. Following one month exposure, GSI and HSI were unchanged in all VZ treated groups compared to solvent control. Sperm volume, motility and velocity were reduced in fish exposed to 800 μg/L VZ. This was associated with the decrease in 11-KT level, suggesting direct VZ effects on testicular androgenesis and sperm functions. In goldfish exposed to 100 μg/L VZ, 11-KT was increased but E(2) remained unchanged. This is, probably, the main reason for unchanged sperm quality at 100 μg/L VZ. In goldfish exposed to E(2), GSI and 11-KT were decreased, E(2) was increased and no sperm was produced. The present study shows different dose-dependent VZ effects, which lead to impairment in sperm quality via disruption in steroidogenesis. In addition to VZ effects through competitive binding to AR, our data suggests potential effects of VZ by direct inhibition of 11-KT biosynthesis in fish as well as abnormalities in sperm morphology

Alternations in neuroendocrine and endocrine regulation of reproduction in male goldfish (Carassius auratus) following an acute and chronic exposure to vinclozolin, in vivo

International audienceThe fungicide vinclozolin (VZ) is in use globally and known to disrupt reproductive function in male. The present study tested the hypothesis that VZ disrupts testicular function in goldfish (Carassius auratus) by affecting brain-pituitary-testis axis. Goldfish were exposed to 100,400 and 800 mu g/L VZ and 5 mu g/L 17 beta-estradiol (E-2) for comparison. In VZ treated goldfish, 11-ketotesteosterone (11-KT) secretion was changed depending on dose and duration period of treatment. Following 7 days of exposure, 11-KT was decreased in goldfish exposed to 800 mu g/LVZ, while it was increased in goldfish exposed to 100 mu g/L VZ after 30 days of exposure. Circulating E-2 level was unchanged in VZ treated goldfish, however the E-2/11-KT ratio was increased in a concentration-related manner. In E-2 treated goldfish, circulatory 11-KT and E-2 levels were decreased and increased, respectively, which resulted in an increase in the E-2/11-KT ratio. Exposure to VZ at 100 E(2)g/L caused a significant increase in the circulatory luteinizing hormone (LH) after 30 days. In E-2 treated fish circulatory LH was decreased, significantly. Transcripts of genes encoding gonadotropin-releasing hormone and androgen receptor in the brain, and those of genes encoding LH and follicle-stimulating hormone receptors, StAR, CYP17, and 3 beta-HSD in the testis changed in VZ-treated goldfish depending on concentration and period of treatment. mRNA of genes encoding vitellogenin and estrogen receptor in the liver and cytochrome P450 aromatase in the brain were increased in E-2-treated goldfish. The results suggest that VZ-induced changes in 11-KT were due to disruption in brain-pituitary-testis axis and provide integrated characterization of VZ-related reproductive disorders in male fish