Assessment of Antidermatophytic Activities of Urtica dioica L against Microsporum canis in a Guinea Pig Model

Purpose: To investigate the antidermatophytic effects of Urtica dioica L. against Microsporum canis in vitro and in a guinea pig model.Methods: The in vitro antifungal activity of the extracts was measured by disc diffusion method and assessment of minimum inhibitory concentration (MIC). The dorsum of the guinea pigs was infected with M. canis and topically treated as follows: negative control (NC) received no treatment; positive control (PC) received terbinafine 1 %; DMSO group (negative control) received 10 % DMSO (vehicle); while three other groups, viz, SN10%, SN20% and SN30% received 10, 20 and 30 % hydroalcohol extract dissolved in 10 % DMSO, respectively.Results: Both extracts did not show considerable antifungal activity against M. canis compared with terbinafine. The MICs of aqueous and hydroalcoholic extracts were 30 and 20 mg.ml-1, respectively. PC and SN30% groups showed normal hair growth on day 15 while their skin looked healthy on day 30 post-inoculation. Lesion severity and clinical scores declined in SN30% and PC groups in comparison to NC group, on day 30 post-inoculation. Also, on day 30 post-inoculation, the clinical efficacy of the test formulations increased to 11.76, 23.52, 76.47, 5.88, and 94.11 % for SN10%, SN20%, SN30%, DMSO10%, and PC groups, respectively.Conclusions: The hydroalcoholic extract of this plant could be further developed, with a view to its possibe use as an adjunct remedy for topical treatment of tinea corporis.Keywords: Urtica dioica L., Microsporum canis, Kurdish Ethnomedicine, Antifungal, Hair growth, Lesion, Dermatophytosis, Tinea corpori

The Trend of Hydatidosis in Kermanshah Province, Western Iran (1986–2008)

Background: Hydatidosis is the larval stage of the Echinococcus granulosus. This disease is en­demic in Iran. There are many studies about hydatidosis in different regions of the country, but there is not any information about the disease in Kermanshah Province. This article will review all available data about hydatidosis in this province.Methods: Using web based search engines and a survey on medical student's theses, all the informa­tion about hydatid cysts in the province from 1986 -2008 was collected.Results: During these twenty years, at least 482 proven cases of hydatid cyst have been identified in the province. Accordingly, the trend of hydatid cyst operation in the province has been grow­ing and the average annual number of cases has reached 1.41/100,000. Frequency of disease in urban areas was slightly higher than rural areas and the rate of infection in housewives was more than others.Conclusion: Because of the growing trend of hydatid cyst operation in Kermanshah Province, which may be due to many different reasons, this province should be considered as one of the impor­tant endemic regions of hydatidosis in Iran

CRISPR interference at the FAAH-OUT genomic region reduces FAAH expression

FAAH-OUT encodes a putative long non-coding RNA which is located next to the FAAH gene on human chromosome 1. Recently an ~8 kb microdeletion, that removes upstream regulatory elements and the first 2 exons of FAAH-OUT, was reported in a pain insensitive patient (PFS) with additional clinical symptoms including a happy, non-anxious disposition, fast wound healing, fear and memory deficits, and significant post-operative nausea and vomiting induced by morphine. PFS also carries a hypomorphic SNP in FAAH that significantly reduces the activity of the encoded fatty-acid amide hydrolase enzyme. The FAAH and FAAH-OUT mutations identified in PFS result in elevated levels of anandamide (AEA), palmitoylethanolamide (PEA) and oleoylethanolamine (OEA) measured in peripheral blood. These bioactive lipids, which are normally degraded by FAAH, have diverse biological functions including known roles in pain pathways. Here we report the first mechanistic insights into how the FAAH-OUT microdeletion affects FAAH function. Gene editing in a human cell line to mimic the FAAH-OUT microdeletion observed in PFS results in reduced expression of FAAH. Furthermore, CRISPRi experiments targeting the promoter region of FAAH-OUT or a short highly evolutionarily conserved element in the first intron of FAAH-OUT also result in reduced expression of FAAH. These experiments confirm the importance of FAAH-OUT and specific genomic elements within the ~8 kb microdeleted sequence to normal FAAH expression. Our results also highlight the potential of CRISPRi and gene editing strategies that target the FAAH-OUT region for the development of novel FAAH-based analgesic and anxiolytic therapies

FAST-1 antisense RNA epigenetically alters FXN expression

Copyright © The Author(s) 2018. Friedreich ataxia (FRDA) is a multisystem genetic disorder caused by GAA repeat expansion mutations within the FXN gene, resulting in heterochromatin formation and deficiency of frataxin protein. Elevated levels of the FXN antisense transcript (FAST-1) have previously been detected in FRDA. To investigate the effects of FAST-1 on the FXN gene expression, we first stably overexpressed FAST-1 in non-FRDA cell lines and then we knocked down FAST-1 in FRDA fibroblast cells. We observed decreased FXN expression in 3 each FAST-1 overexpressing cell type compared to control cells. We also found that FAST-1 overexpression is associated with both CCCTC-Binding Factor (CTCF) depletion and heterochromatin formation at the 5′UTR of the FXN gene. We further showed that knocking down FAST-1 in FRDA fibroblast cells significantly increased FXN expression. Our results indicate that FAST-1 can act in Trans in a similar manner to the cis-acting FAST-1 overexpression that has previously been identified in FRDA fibroblasts. The effects of stably transfected FAST-1 expression on CTCF occupancy and heterochromatin formation at the FXN locus suggest a direct role for FAST- 1 in the FRDA molecular disease mechanism. Our findings also support the hypothesis that inhibition of FAST-1 may be a potential approach 40 for FRDA therapy.1 in the FRDA molecular disease mechanism. Our findings also support the hypothesis that inhibition of FAST-1 may be a potential approach for FRDA therapy.European Union Seventh Framework Programm

Supplementation of freezing and thawing media with brain-derived neurotrophic factor protects human sperm from freeze-thaw-induced damage

Objective To investigate the effects of brain-derived neurotrophic factor (BDNF) supplementation to freezing and thawing media on frozen-thawed human sperm parameters. Design Laboratory study. Setting University hospital. Patient(s) Semen samples from 21 healthy fertile men. Intervention(s) We measured reactive oxygen species (ROS) by flow cytometry using the probes dichlorofluorescin diacetate for intracellular hydrogen peroxide (H2O2) and dihydroethidium for intracellular superoxide anion (O2��), sperm plasma membrane integrity by flow cytometry, caspase-3 activity using ELISA, and AKT phosphorylation status using Western blot in sperm that was cryopreserved and thawed in media either supplemented with BDNF or without BDNF supplementation (control). Main Outcome Measure(s) Sperm motility, viability, ROS levels, caspase-3 activity and AKT phosphorylation. Result(s) The percentage of motile and viable sperm cells was significantly higher in BDNF-supplemented groups as compared with the nonsupplemented (control) group. There was a significant difference in AKT phosphorylation status between BDNF-supplemented groups and the control group. Moreover, the levels of intracellular H2O2 and caspase-3 activity were significantly lower in the sperm cells that were frozen and thawed in media supplemented with BDNF compared with in the control group. Conclusion(s) BDNF supplementation to sperm freezing or thawing media has protective effects against oxidative stress and apoptosis in frozen-thawed human spermatozoa and could improve sperm function, probably through the activation of AKT. © 2016 American Society for Reproductive Medicin

Interleukin 4 gene polymorphism (−589C/T) and the risk of asthma: a meta-analysis and met-regression based on 55 studies

Background: Numerous investigations have previously evaluated the association of interleukin (IL) 4 gene polymorphisms and the risk of asthma, conferring inconsistent results. To resolve the incongruent outcomes yielded from different single studies, we conducted the most up-to-date meta-analysis of IL4 gene −589C/T (rs2243250) polymorphism and susceptibility to asthma. Methods: A systematic literature search was performed in ISI web of science, Scopus, Medline/PubMed databases prior to September 2020, and the pooled odds ratio (OR) and their corresponding 95% CI were calculated to determine the association strength. Results: Literature search led to retrieving of 49 publications (55 case-control studies) containing 9572 cases and 9881 controls. It was revealed that IL4 gene −589C/T polymorphism increased the risk of asthma across all genetic models, including dominant model (OR = 1.22), recessive model (OR = 1.17), allelic model (OR = 1.21), and TT vs. CC model (OR = 1.34), but not the CT vs. TT model. The subgroup analysis by age indicated that IL4 gene -589C/T polymorphism was significantly associated with asthma risk in both pediatrics and adults. Additionally, the subgroup analysis by ethnicity revealed significant association in Asian, American, and Europeans. Finally, subgroup analysis by East Asian and non-East Asian populations indicated significant associations. Conclusions: The current meta-analysis revealed that IL4 gene -589C/T polymorphism was a susceptibility risk in both pediatrics and adults in the whole and different ethnic groups

P-52: Brain-Derived Neurotrophic Factor Promotes The Development of Human Ovarian Early Follicles during Growth In Vitro

Background Cryopreservation of ovarian cortex is increasingly used to preserve fertility before cancer therapy. Recently, studies show that Brain-derived neurotrophic factor (BDNF) may be involved in oocyte maturation. Brain-derived neurotrophic factor (BDNF) is member of neurotrophin family that has anti-apoptotic effects on nervous system. Recent researches show that it also plays key role in female reproductive system such as nuclear and cytoplasmic maturation and embryo development. Therefore, the present study was ..