The effects of letrozole-induced maternal hyperandrogenism on sexual behaviors, testicular histology, and serum biochemical traits in male offspring rats: An experimental study

Background: Intrauterine endocrine abnormalities have profound effects on the development of physiological disorders. Objective: This study aimed to assess the effects of in utero exposure to letrozole (an aromatase inhibitor) and its late consequences on the reproductive and metabolic performance of an adult male offspring. Materials and Methods: 15 pregnant Sprague-Dawley rats (8 wk, 155 gr) were randomly assigned into 5 experimental groups (n = 3/each) and orally received either letrozole at doses of 0.25, 0.75, 1.00, and 1.25 mg/kg body weight (BW) or vehicle (control) on the gestation days of 16, 17, and 18. Pregnancy outcome, sexual behaviors on postnatal day 60, serum biochemical features, and the histopathology of testes were assessed in male offspring. Results: Compared to control group, delayed labor (21.83 vs. 24.25, p < 0.0001) and reduced litter size (n = 12.25 vs. n = 2, p < 0.0001) were recorded in 1.25 mg/kg BW group. A reduction in high-density lipoprotein level and the elevation of testes weight, BW gain, anogenital distance, as well as the serum concentrations of testosterone, triglycerides, cholesterol, and glucose were observed in 1.25 mg/kg BW (p < 0.0001) and 1.00 mg/kg BW (p < 0.0001) groups in comparison to control. A larger number of anogenital female sniffing, pursuit, and mounting behaviors were also observed in 1.25 mg/kg BW group in comparison to control (p < 0.0001). Severe testicular defects including necrosis and disruption of the epithelium of seminiferous tubules, sloughing of epithelial cells, and spermatogenesis arrest were observed in letrozole-treated groups, in a dose-dependent manner. Conclusion: Maternal exposure to letrozole can adversely affect the reproductive and metabolic performance of male offspring rats, suggesting an incomplete sex differentiation. Key words: Androgens, Aromatase inhibitors, Rat, Sexual activities, Testes histopathology

The role of Iranian medicinal plants in experimental surgical skin wound healing: An integrative review

Objective(s): Wounds are physical injuries that cause a disturbance in the normal skin anatomy and function. Also, it has a severe impact on the cost of health care. Wound healing in human and mammalian species is similar and contains a complex and dynamic process consisting of four phases for restoring skin cellular structures and tissue layers. Today, therapeutic approaches using herbal medicine have been considered. Although the benefits of herbal medicine are vast, some medicinal plants have been shown to have wound healing effects in different experimental studies. Therefore, the current review highlights information about the potency of herbal medicine in the experimental surgical skin wound healing.Materials and Methods: Electronic database such as PubMed, Google Scholar, Scopus, and Medscape were searched for Iranian medicinal plants with healing activity in experimental surgical skin wounds. In this area, some of the most important papers were included.Results: There are numerous Iranian medicinal plants with skin wound healing activity, but clinical application and manufacturing are very low in comparison to the research volume.Conclusion: In normal instances, the human/animal body usually can repair tissue damage precisely and completely; therefore, the utilization of herbs is limited to special conditions or in order to accelerate the healing process

Comparison of IL-28B favorable genotype frequency between healthy and patients infected with HCV

Introduction: Combination of interferon-alpha (IFN-α) and Ribavirin (RBV) drugs is used for treatment of hepatitis C virus (HCV) chronic infection. Various factors play role in the response rate of HCV infected patients to treatment. HCV genotype along with viral load, age, race, obesity, insulin resistance, fibrosis and interleukin 28B gene (IL-28B) polymorphisms are considered the most important ones. In recent years, it has been claimed that some polymorphisms close to IL-28B gene play a significant role in response to combined therapy among which IL-28B polymorphisms have a more important role in sustained virological response (SVR). In this study, frequency of genotypes of rs8099917 polymorphism of interleukin 28B gene in 2 groups of Iranian healthy individuals and HCV infected patients living in Tehran was compared.   Materials & Methods: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to compare the frequency of genotypes of rs8099917 polymorphism between 105 healthy individuals and 105 chronic HCV infected patients. The results were analyzed with SPSS version 15 using χ2 test.   Findings: The genotype frequency of this polymorphism in the healthy individuals was demonstrated as GG: 1%, GT: 25.7% and TT: 73.3%, while in HCV infected patients, it was shown as GT: 58.1% and TT: 41.9%.. No GG genotype was detected in the patients infected with HCV.   Discussion & Conclusion: Our investigation came to the conclusion that  a significant difference existed between the 2 groups of Iranian healthy and HCV infected individuals regarding the frequency of rs8099917 genotypes and frequency of favorable TT genotype, because it was higher among the healthy individuals than that of the patients infected with HC

Investigation of Drug-resistance substitutions in HIV-1 RT Protein in Iranian HIV Infected Patients

Abstract: Background:Currently, more than 37 million people are living with human immunodeficiency virus type 1. Reverse transcription (RT) is a main part in the life cycle of retroviruses which is   responsible for synthesis of DNA complementary to an RNA or DNA template.  Recently several inhibitors have been introduced to target RT protein; however, drug resistance is one of the greatest challenges in the improvement of effective treatment for human immunodeficiency virus (HIV) infection. Here, we determined the resistance mutations in the RT gene in treatment failure patients and searched for the dominant subtype among them.  Methods:HIV viral load and a reverse transcriptase nested polymerase chain (RT-nested PCR) reactions were performed in 15 patients with treatment failure to amplify the RT gene. Drug resistance mutations, as well as the viral subtypes, were analyzed using by using several bioinformatics software and online tools. Results: The frequency of RT related drug-resistance mutations in patients was 33.3%, among which the major mutation consisted of 20% of all those occurring in codon 184. Moreover, the results showed 6.6% and 26.6% of patients were resistant to Non-Nucleoside RT Inhibitor (NNRTIs) and Nucleoside RT Inhibitors (NRTIs), respectively. In addition, the vast majority of samples (12 patients of 15) belonged to subtype CRF35-AD.Conclusions:The present study reports updates on the mutations related to RT resistance in Iranian HIV patients receiving treatment, show that 20% of the samples had a high-level of resistance to Lamivudine, and Emtricitabine which should be confirmed for further antiretroviral (AVR) regimens for HIV infected patients. Also, two new mutations related to resistance to Nevirapine, Doravirine, Zidovudine, and Stavudine were introduced in this investigation.The present results could be used as predictive information on the response to anti-RT, and also highlight the importance of considering the periodic monitoring of HIV resistance test in HIV infected patients

Studying the Frequency of Favorable Allele of rs12979860 Polymorphism of IL-28B in Healthy and HCV Infected Iranian Individuals

Background & Objective: Hepatitis C Virus (HCV) is one of the important risk factors for liver cirrhosis and hepatocellular carcinoma. Some of the host genetic factors such as interleukin 28B (IL-28B) may influence the response to the antiviral therapy. IL28B is a member of the interferon (IFN) family which causes an antiviral response. Previous studies indicated that rs12979860 polymorphisms of the IL-28B gene can influence persistent antiviral response. Therefore, in this study, the frequency of genotypes of rs12979860 polymorphisms in two groups of healthy and HCV infected Iranian individuals were evaluated. Materials & Methods: In this cross sectional study, PCR-RFLP method was used to evaluate the frequency of genotypes of rs12979860 polymorphisms in 105 healthy individuals and 105 chronic HCV infected patients. Results: The frequency of rs12979860 genotypes in healthy individuals was CC: 50.5%, CT: 45.7%, and TT: 3.8%. In HCV infected patients it was CC: 22.9%, CT: 63.8%, and TT: 13.3%. The frequency of rs12979860 genotypes had significant difference between two groups; however it is not associated with sex. Conclusion: A significant difference was observed between healthy individuals and HCV infected patients in the frequency of rs12979860 genotypes. The favorable CC genotypes and unfavorable TT genotypes was more detected in healthy individuals and HCV infected patients, respectively

Tissue presentation of human pegivirus infection in liver transplanted recipients

Human pegivirus-1 (HPgV-1) is known for its protective role in HIV co-infected individuals. This immunomodulatory effect raised questions concerning the possible role of HPgV-1 infection and the risk of rejection in liver transplanted patients. We aimed to evaluate the possible protective effect of HPgV-1 on graft outcome of liver transplanted patients. A total of 283 patients were recruited. Formalin-fixed paraffin-embedded tissue samples were collected from the explanted liver. HBV-DNA, HCV-RNA, and HPgV-1-RNA were determined using PCR and multiplex RT-PCR assays. The clinical course of patients including the occurrence of acute cellular rejection was compared between HPgV-1-infected vs. uninfected patients. HBV-DNA, HCV-RNA and HPgV-1-RNA were detected in 42.6%, 4.9%, and 7.8% of samples, respectively. None of the HPgV-1-infected patients experienced graft rejection. Group LASSO logistic regression revealed that HPgV-1 infection was the only factor which significantly reduced the odds of graft rejection (OR = 0.5, 95% CI = 0.29–0.89). No significant association was found between the presence of HPgV-1 with HBV and HCV infections. The lack of graft rejection in HPgV-1-infected liver transplanted patients might indicate a possible role of this virus for graft surveillance. Since these are still preliminary findings, prospective studies should further elucidate the role of HPgV-1 in liver transplantation outcomes