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Background: Global rise in cannabis abuse during reproductive years has placed a large number of men at risk for the adverse consequences of δ-9-tetrahydrocannabinol (THC), the primary active component of cannabis. It has been reported that THC affects male fertility and causes testicular cell dysfunction and apoptosis. This study aimed to investigate the possible protective role of zinc pretreatment against the toxic effects of THC in cultured mouse Sertoli cells and the underlying mechanism. Method: The Mus Musculus Sertoli cell line (TM4) was cultured, exposed to THC alone (470 µM, 24 h), co-administered with zinc (8 µM, 48 h), and investigated in three groups: control, THC, and THC + zinc. The MTT was performed to evaluate cell viability. TUNEL assay was also applied for the detection of cell apoptosis and a western blot was performed for measuring protein expression levels of Caspase3, Pro-caspase3, SOD, and PDGF-A. objective: Background: Global rise in marijuana abuse during reproductive years has placed a large number of men at risk for the adverse consequences of δ-9-tetrahydrocannabinol (THC), the primary active component of marijuana. It has been reported that THC affects male fertility and causes testicular cells dysfunction and apoptosis. Result: THC significantly decreased cell viability (p Conclusion: The present data suggest that THC induces Sertoli cell damage through a multitarget mechanism. Zinc was reported to protect against THC-induced Sertoli cell damage due to its anti-apoptotic and antioxidant activities, indicating its clinical importance against THC-induced testicular toxicity among addicted men. conclusion: The present data suggests that THC induces Sertoli cell damage through a multitarget mechanism. Zinc is able to protect against THC-induced Sertoli cell damages due to its anti-apoptotic and antioxidant activities and indicates the clinical importance of zinc against THC-induced testicular toxicity among addicted men.

Widespread and prolonged therapy with ganciclovir (GCV) may result in the emergence of GCV-resistant mutations in human cytomegalovirus (HCMV) genome. The aim of this study was to detect the UL97 mutations associated with GCV resistance in kidney transplant recipients.Forty-nine kidney recipients with positive HCMV DNAemia, who received GCV therapy were included in this study. A 707 bp fragment of UL97 gene spanning codons (436 to 655) was amplified by nested PCR and sequenced.Thirteen (26.5 %) out of 49 recipients contained mutations associated with amino acid changes. Two UL97 mutations related to GCV resistance were detected in 2 recipients (4 %), including alanine to valine (A594V) and proline to leucine (P521L). The D605E mutation was identified in 8 out of 49 (16.3 %) recipients. Silent mutations G598G, G503G, L553L, L634L, D456D and G579G were commonly observed.Our results indicate that mutations in the UL97 gene associated with GCV resistance may occur in 1 in 25 recipients treated with GCV. In addition, a higher mutation rate of D605E was detected in our recipients. This study provides the first evidence of the prevalence and pattern of GCV related mutations in Iranian Turkish recipients (Tab. 2, Fig. 1, Ref. 28).

The opioid system may exert positive direct and/or indirect effects on spermatogenesis at multiple levels including the levels of the central nervous system and at the testes/sperm levels. However, long term opioid use could be associated with several reproductive complications that place the users at risk of hypogonadism and even infertility. There is little available information regarding the contribution of opioids and their apoptotic effects on testis Sertoli cells. Here, the effects of DAMGO (mu opioid receptor’s agonist), DPDPE (delta opioid receptor’s agonist) and DYN 1-9 (kappa opioid receptor’s agonist) on Sertoli cell viability and apoptosis were investigated. METHODS: Cultured Sertoli cells were exposed to each agonist (0.1–100 μM, for 24 or 48 hours) and their apoptotic effects were investigated. RESULTS: Cell viability was decreased and apoptosis was increased in the cells exposed to DAMGO in a concentration- dependent manner, while in the cells exposed to DPDPE, no signifi cant changes were observed. In cells exposed to DYN 1-9, the viability did not signifi cantly change, however apoptosis increased signifi cantly, following the exposure to the high concentration of DYN 1-9. CONCLUSION: These data suggest that mu and Kappa, but not delta receptors mediated apoptosis in Sertoli cells may be involved, at least in part, in testicular homeostasis and/or reproductive dysfunction (Tab. 1, Fig. 3, Ref. 52). Text in PDF www.elis.sk

Sindbis virus (SINV) and Chikungunya virus (CHIKV) are among the most widely spread mosquito-borne viruses worldwide. Due to the key role of mosquitoes in the transmission cycle of vector-borne diseases, models such as Maximum Entropy (MaxEnt) have been used in recent years to predict the environmental suitability and ecological niches of mosquito vectors. Infection of three mosquito species (Anopheles maculipennis s.l., Culex tritaeniorhynchus, and Culiseta longiareolata) with CHIKV has recently been reported in Iran. However, given the importance of vector-borne diseases in the country, there is a need for extensive studies on the infection of mosquitoes with CHIKV and SINV in different areas of the country. Accordingly, the current research was conducted to investigate the infection of mosquitoes with the two aforementioned viruses in the northwestern part of Iran and also to model the ecological niches of the vectors of these mosquito-borne viruses in the country. In the current study, 4639 mosquito specimens, consisting of 2515 adults and 2124 larvae, were collected from the wetlands of West Azerbaijan Province and identified. Ten species belonging to four genera were identified in this study. The specimens were allocated to 149 pools for the determination of infection with CHIKV and SINV. The amplification pattern of five pools comprising two mosquito species (Culex pipiens complex and Cx. Theileri) corresponded to the reference strain of SINV, and the isolates were sequenced to confirm the presence of SINV genome. No cases of CHIKV infection were found among the 149 examined mosquito pools. Data on the distribution of Cx. Pipiens complex and Cx. Theileri were mapped using ArcMap 10.5. Prediction maps of the presence probability for these species revealed that they are most likely to be found in and spread to the north, northwest, south, and southeastern areas of the country and in areas with abundant water resources. For the first time in Iran, our study investigated the presence probability of SINV vectors using ecological niche modeling. Ecological niche profiling showed that the most suitable habitats for Cx. pipiens are mainly concentrated in the north and northwestern parts of the country, whereas Cx. theileri is mostly located in the northwest and western regions. However, there were some other areas of low suitability for these two species in the country. Further studies in a broader geographical area with more species of mosquitos and the determination of infection with other mosquito-borne viruses can provide a clear understanding of the potential spread of mosquito-borne diseases in various regions of Iran.

Background: Esophageal cancer (EC) is a common cancer worldwide. Despite epidemiological studies, the etiology of EC is undetected. It was recommended that tobacco, alcohol, food carcinogens, and infectious agents may be involved in the pathogenesis of EC. Accumulating evidence suggests the role of human papillomavirus (HPV) on EC. Objectives: The aim of this study was to evaluate the prevalence and association of HPV with EC. Methods: In this case-control study, 86 samples of formalin-fixed and paraffin-embedded esophageal tissues were gathered from the pathology laboratory, Imam Khomeini Hospital, Urmia, West Azerbaijan, Iran. A total of 43 samples were esophageal cancers (cases) and 43 samples were esophageal non-cancerous tissues (controls). The tissues were sectioned and deparaffinized, and deoxyribonucleic acid was extracted. The polymerase chain reaction test was conducted to detect HPV, using general (GP5+/GP6+) and type-specific (E6/E7) primers. HPV types were confirmed by sequencing. The data were analyzed by the SPSS software. Results: Out of 86 samples, 23 (26.74%) were positive for HPV (15 cases, and 8 controls). By type-specific primers, high-risk HPVs were detected in the cases (3 HPV-16, 10 HPV-18, 1 HPV-31, and 1 HPV-33) and the controls (6 HPV-18, 1 HPV-31, and 1 HPV-33). No significant association was observed between HPV and EC (P = 0.078). Conclusions: Although no significant association was observed between HPV and EC, high-risk HPV genotypes were found in esophageal cancers more than non-cancerous esophageal tissues. To confirm this result, more studies should be carried out in other populations.

Introduction: Klebsiella pneumoniae is an opportunistic pathogen accounting for 5-7% of hospital acquired infections. The emergence of carbapenem-resistant Klebsiella pneumoniae has been increasing rapidly over recent years causing many therapeutic problems worldwide. This study aimed to research the antimicrobial resistance profile, detect β-lactamase genes among clinical isolates of K. pneumoniae, and determine their clonal relatedness. Methodology: All Klebsiella pneumoniae isolates were obtained from teaching hospitals in Urmia, Iran. Antimicrobial susceptibility testing was done by the disk diffusion method. Furthermore, minimum inhibitory concentrations of imipenem were determined by applying Etest strips. Screening of β-lactamase-producing isolates was performed by the combined disk method and modified Hodge test. The detection of β-lactamase genes was conducted by polymerase chain reaction (PCR), and isolates’ clonal relatedness was evaluated by random amplified polymorphic DNA (RAPD)-PCR. Results: Overall, 45 out of 182 (24.7%) K. pneumoniae isolates were non-susceptible to imipenem. The combined disk method and modified Hodge test revealed that 93.3% and 71.1% of the imipenem non-susceptible isolates were β-lactamase producers, respectively. The presence of blaVIM, blaNDM, blaKPC, and blaIMP genes was confirmed in 48.9%, 15.6%, 11.1%, and 6.7% of the β-lactamase-producing isolates, respectively. RAPD-PCR revealed that 73% of these isolates were classified into six different clusters. Conclusions: A relatively high prevalence of β-lactamase genes was seen among multidrug-resistant isolates of K. pneumoniae. Most patients infected with β-lactamase-producing isolates had a history of long-term hospitalization and nosocomial infections. The predominance of β-lactamase genes in intensive care unit and internal units alarm clinicians to the growth of hospitalization and mortality rates.

Cytomegalovirus (CMV) is one of the most important infections in renal transplant recipients. Kidney transplant is the last hope for the patients with end stage renal diseases. Cytomegalovirus infection can threaten patients and graft survival after transplantation. Four hundred and thirty-four renal transplant recipients contributed to this study. PCR and RFLP analyses were performed in order to determine CMV viremia and its genotypes. CMV viremia was detected in 68 (15.9%) recipients. The mean post-transplantation time in our recipients was 50 months, ranging from 1 to 354 months. Viremia was detected in 31.2%, 30.7%, 17.5%, 10.2%, and 6.4% of the recipients in 0-3, 4-6, 7-12, 13-24, and more than 24 months post-transplantation, respectively. The distribution of gB1, gB2, gB3, and gB4 genotypes was detected as 26.5%, 20.5%, 17.6%, and 5.9%, respectively. Mixed genotype infection was observed in 29.4% of the recipients. Incidence of viremia was higher in the first 6 months after the transplantation compared with the later stages. Moreover, CMV gB1 and mixed genotype infection were more common in our recipients. J. Med. Virol. 88:1622-1627, 2016. © 2016 Wiley Periodicals, Inc.

The West Nile virus (WNV) transmission cycle includes a wide range of migratory wetland birds as reservoirs, mosquitoes as biological vectors, and equines and humans as dead-end hosts. Despite the presence of potential vector species, there is no information about the existence of WNV in mosquito vectors in Iran. The Iranian West Azerbaijan Province is located in the northwestern part of Iran and has borders with Turkey, Iraq, Armenia, and the Republic of Azerbaijan. The current study was conducted to identify the wetland mosquitoes of the West Azerbaijan Province and their infection with WNV. In this study, 2143 specimens were collected, comprising 1541 adults and 602 larvae. Six species belonging to four genera were collected and identified: Anopheles maculipennis sensu lato (s.l.), Culex (Cx.) hortensis, Cx. pipiens s.l., Cx. theileri, Culiseta longiareolata, and Aedes (Ae.) (Ochlerotatus) caspius. In total, 45 pools of mosquitoes were examined. Two of the adult pools collected from the same location showed the presence of WNV in Ae. (Och.) caspius, from Sangar, Makoo County, as confirmed by PCR and sequencing. Due to the discovery of WNV in the mosquito population of the region, and the presence of wetlands and significant populations of migratory birds, the health sector should carefully monitor the factors involved in the cycle of this disease.

Ethanol enhances apoptosis in testicular germ cells. Zinc reduces ethanol-induced apoptosis of somatic cells through inhibition of caspase-mediated pathways. Little is known about the effects of ethanol on Sertoli cells and the effects of Zinc on ethanol-induced testicular injury. The hypothesis tested was that ethanol enhances apoptosis of Sertoli cells through up-regulation of caspase-3 and Zinc inhibits ethanol-induced effects. Cultured Sertoli cells (TM4) were exposed to ethanol (160mM), Zinc (8μM) and Zinc prior to ethanol for duration of 24 or 48h and their effects on TM4 cell viability was then investigated by MTT assay. Caspase-3 mRNA expression was also investigated using real-time RT-PCR. Cell viability decreased and caspase-3 mRNA expresstion increased in cells exposed to ethanol, while exposure to Zinc showed opposite effects. Pretreatment with Zinc recovered ethanol-induced anti-proliferative effects and over-expression of caspase-3. Zinc reduced ethanol-induced Sertoli cell toxicity and apoptosis via caspase-3 mediated pathways.

BK polyomavirus (BKV) as a member of polyomavirus family is prevalent in the human population. BKV persists in renal tissue after asymptomatic infection in childhood. The reactivation of BKV in renal transplant recipients sometimes can lead to BKV associated nephropathy. BKV isolates are classified into four serologically distinct subtypes. Present study was carried out to investigate the distribution pattern of BKV subtypes in Iranian Turkish renal transplant recipients.Urine samples from 12 kidney transplant recipients infected with BKV were analyzed by RFLP-PCR technique for classification of subtypes.Our analysis showed that all samples were infected with BKV type I. BK virus types II, III, and IV were not detected in our patients.Based on the results of the present study, BKV subtype I was the most frequently detected subtype in renal transplant recipients. To our knowledge, the present study provides the first data regarding distribution of BKV subtypes in Iranian renal transplant recipients.

Viral infections are a real threat in kidney transplant recipients because of their immunocompromised condition. This study aimed to evaluate herpes simplex virus-2 (HSV-2) seropositivity among kidney transplant recipients.Serum samples of 91 kidney transplant recipients from Urmia, Iran, were examined serologically for antibodies against HSV-2 using an enzyme-linked immunosorbent assay.The mean time from transplantation at HSV-2 testing was 5.04 +/- 4.45 years. The anti-HSV-2 immunoglobulin G antibody was positive in 5.4% of the kidney transplant recipients. Seropositive patients did not present any clinical manifestations of genital herpes infection. There was no association between HSV-2 seropositivity and age, gender, history of hemodialysis and transplantation, blood transfusion, or immunosuppressive regimen.Seroprevalence of HSV-2 is not high among our kidney transplant recipients. However, it remains a source of concern, considering the compromised immune system in this specific population.

While many adjuvants have been discovered and used in research, only a few adjuvants have been permitted for use with human vaccination. We have previously shown that the administration of naloxone (NLX), a general opioid antagonist, during infection with a non-virulent strain of herpes simplex virus type 1 (HSV-1) could enhance protection against HSV-1 challenge. Here, the adjuvant activity of NLX has been evaluated using a DNA vaccine for HSV-1 as a model. BALB/c mice were divided into four groups; for experimental groups, mice received the glycoprotein D1 (gD1) DNA vaccine alone or in combination with the adjuvant NLX. A positive control group received the KOS strain of HSV-1, and a negative control group received PBS. All mice were immunized three times on days 0, 21 and 42. Three weeks after the last immunization, immune responses against HSV-1 were assessed. Our results indicate that the administration of NLX as an adjuvant increased the ability of the gD1 DNA vaccine to enhance cytolytic T lymphocyte activity, lymphocyte proliferation, delayed-type hypersensitivity and shifting the immune response toward a T helper (Th)1 pattern and improved protective immunity against HSV-1. NLX also increased the IgG2a/IgG1 ratio, though it did not affect the production of HSV-1 antiserum. In conclusion, administration of NLX as an adjuvant in combination with the gD1 DNA vaccine can enhance cell-mediated immunity and shift the immune responses to Th1.

Differences between the translation efficiencies mediated by the 5'-untranslated regions (5'-UTR) of genotypes (gt) 1 and 3 of hepatitis C virus (HCV) have been reported but it is unknown if such differences are biologically significant. The 5'-UTR was sequenced from paired serum and liver samples from 26 patients with chronic HCV hepatitis (11 gt 1a, 15 gt 3a). To determine whether there is a consistent difference between gts 1a and 3a translation efficiency, 5'-UTR (nt 1-356) and 5'-UTR plus core (nt 1-914) sequences were cloned into bicistronic, luciferase-encoding constructs and relative translation efficiencies (RTE) measured in Huh7 cells and BHK cells. The relationships between viral load, liver biopsy Ishak scores, degree of steatosis and translational activity of the patient-derived nucleotide sequence were examined. There were no differences in 5'-UTR sequence between serum and corresponding liver samples. The mean RTE of 5'-UTR sequences from gt 3a isolates was not significantly different from gt 1a whether or not the core encoding sequence was included, although inclusion of core led to a reduction in RTE by 93-97% for both genotypes. No correlation was found between RTE and serum HCV RNA levels, liver steatosis, inflammation, or fibrosis. However, a significant correlation was found between the presence of steatosis and infection with HCV gt 3a. It is concluded that there was no difference in translation efficiencies of 5'-UTRs from patients infected with gts 1a and 3a, and translation activity measured in vitro does not correlate with viral load or severity of liver disease.

The effects of combined radiotherapy (RT) and chemotherapy in the severity of cytogenetic alterations expressed as micronucleus (MN) in peripheral blood lymphocytes of patients treated for esophageal cancer was evaluated. To do this, blood was obtained from 23 and 15 esophageal cancer patients scheduled for chemo-radiotherapy and RT alone, respectively, before, during, and after treatment. Blood samples were cultured in RPMI-1640 complete medium containing 1% phytohemagglutinin and incubated in a CO2 incubator. Cytochalasin-B was added to the cultures at a final concentration of 5 μg/ml. Finally, harvesting, slide making, and analysis were performed according to standard procedures. Results indicate that there was no significant difference between the frequencies of MN in lymphocytes of individuals before being treated with RT alone or chemo-radiotherapy. In the middle of treatment, (after 12 fractions of RT) the frequency of MN increased significantly compared with their concurrent pre-treatment samples in both groups (four-fold). However, the frequency of MN observed for RT patients was not significantly different with those received chemo- and radiotherapy. At the end of treatment, (after 24 fractions of radiotherapy) an increase in the MN frequency was observed for chemo-radiation group significantly higher than RT group (P=0.022). Mild increase in MN frequency in lymphocytes of patients receiving chemoradiation only after the completion of treatment course might be indicative of resistance induced by chemotherapeutics to the clastogenic effects of radiation. Therefore, using these agents repeatedly for cancer treatment in combination with radiation might not cause severe adverse biological effects in normal tissues.