VDR gene polymorphisms are associated with the increased susceptibility to COVID-19 among iranian population: A case-control study.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the pathogenesis is unclear. Host genetic background is one of the main factors influencing the patients' susceptibility to several viral infectious diseases. This study aimed to investigate the association between host genetic polymorphisms of two genes, including vitamin D receptor (VDR) and vitamin D binding protein (DBP), and susceptibility to COVID-19 in a sample of the Iranian population. This case-control study enrolled 188 hospitalized COVID-19 patients as the case group and 218 suspected COVID-19 patients with mild signs as the control group. The VDR (rs7975232, rs731236 and rs2228570) and DBP (rs7041) gene single nucleotide polymorphisms (SNPs) were genotyped by Polymerase Chain Reaction Restriction - Fragment Length Polymorphism (PCR-RFLP) method. A significant association between rs2228570 SNP in the VDR gene and the susceptibility of COVID-19 was found between case and control groups. The CT genotype (Heterozygous) of rs2228570 C > T polymorphism showed significant association with a 3.088 fold increased odds of COVID-19 (p < .0001; adjusted OR: 3.088; 95% CI: 1.902-5.012). In addition, a significant association between CC genotype of rs2228570 CT polymorphism and increased odds of COVID-19 in male and female groups (p = .001; adjusted OR: 3.125; 95% CI: 1.630-5.991 and p = .002; adjusted OR: 3.071; 95% CI: 1.485-6.354 respectively) were determined. Our results revealed no significant differences in the frequency of genotype and allele of VDR (rs7975232 and rs731236) and DBP (rs7041) between SARS-CoV-2-infected patients and controls (p > .05). Our results showed that polymorphism of VDR (rs2228570) probably could influence individual susceptibility to COVID-19. The polymorphisms of VDR (rs7975232 and rs731236) and DBP (rs7041) were not associated with SARS-CoV-2 infection susceptibility.

Overview and Recent Advances of Regulatory T cell Therapy in Solid Organ Transplantation.

Solid organ transplant recipients are in high demand for developed immune-modulating agents to control allo-immune responses following transplantation. The immunosuppressive agents offer the recipients improved short-term graft survival; nonetheless, this benefit is tempered by unavoidable long-term adverse events of these medications. Active control of allo-response using therapeutic cell transfer has gained much attraction during the last few years. It is widely established that regulatory T cells (Tregs) control immune responsiveness to allo-antigens and contribute to the induction of tolerance. Here, it is aimed to review recent results regarding Tregs and chimeric antigen receptor (CAR) Tregs therapy in solid organ transplantation and discuss strategies to overcome technical challenges of developing successful Tregs/CAR Tregs therapy.

CAR T cells: Living HIV drugs.

Human immunodeficiency virus type 1 (HIV-1), the virus that causes AIDS (acquired immunodeficiency syndrome), is a major global public health issue. Although the advent of combined antiretroviral therapy (ART) has made significant progress in inhibiting HIV replication in patients, HIV-infected cells remain the principal cellular reservoir of HIV, this allows HIV to rebound immediately upon stopping ART, which is considered the major obstacle to curing HIV infection. Chimeric antigen receptor (CAR) cell therapy has provided new opportunities for HIV treatment. Engineering T cells or hematopoietic stem cells (HSCs) to generate CAR T cells is a rapidly growing approach to develop an efficient immune cell to fight HIV. Herein, we review preclinical and clinical data available for the development of CAR T cells. Further, the advantages and disadvantages of clinical application of anti-HIV CAR T cells will be discussed.

Relative Frequency of Blood-Borne Viruses in Hemodialysis-Dependent and Kidney Transplant Recipients in Iran.

BACKGROUND: Hemodialysis (HD) patients and kidney transplant (KT) recipients are exposed to be infected by blood-borne viruses (BBVs). Current study was conducted to evaluate the prevalence of BBVs in HD and KT patients in the whole Iranian population. METHODS: From Jan 2016 to Dec 2017, 174 hemodialysis and 139 kidney transplant recipients enrolled in this survey. After blood sampling, serum samples were detected for HBV, HCV, HCMV, HIV and HTLV antibodies. Seropositive samples confirmed by Polymerase chain reaction (PCR) method. RESULTS: Overall, 6 (3.44%) and 3 (2.15%) of hemodialysis-dependent and transplantation patients had evidence of HCV infection, whereas no patients were HIV and HBV positive, two cases (1.14%) of hemodialysis and one case (0.71%) of transplantation patients demonstrated the HTLV-1 infection. 52 (37.4%) of patients received graft were positive for HCMV antibody. In addition, our study showed a co-infection of HCMV with HCV (3 patients, 2.15%) in transplantation patients. CONCLUSION: Prevalence of BBVs infection was lower in comparison to the previous studies. The current strict infection control practices in Iran appear to be effective in limiting dialysis and related infections after transplantation. Because BBVs infections constantly occur especially in dialysis and after transplantation units, our data will be useful to build a new strategic plan for the elimination of BBVs infection in kidney therapycenters.

Induction of protective immune response to intranasal administration of influenza virus-like particles in a mouse model.

Human influenza A viruses (IAVs) cause global pandemics and epidemics, which remains a nonignorable serious concern for public health worldwide. To combat the surge of viral outbreaks, new treatments are urgently needed. Here, we design a new vaccine based on virus-like particles (VLPs) and show how intranasal administration of this vaccine triggers protective immunity, which can be exploited for the development of new therapies. H1N1 VLPs were produced in baculovirus vectors and were injected into BALB/c mice by the intramuscular (IM) or intranasal (IN) route. We found that there were significantly higher inflammatory cell and lymphocyte concentrations in bronchoalveolar lavage samples and the lungs of IN immunized mice; however, the IM group had little signs of inflammatory responses. On the basis of our results, immunization with H1N1 influenza VLP elicited a strong T cell immunity in BALB/c mice. Despite T cell immunity amplification after both IN and IM vaccination methods in mice, IN-induced T cell responses were significantly more intense than IM-induced responses, and this was likely related to an increased number of both CD11bhigh and CD103+ dendritic cells in mice lungs after IN administration of VLP. Furthermore, evaluation of interleukin-4 and interferon gamma cytokines along with several chemokine receptors showed that VLP vaccination via IN and IM routes leads to a greater CD4+ Th1 and Th2 response, respectively. Our findings indicated that VLPs represent a potential strategy for the development of an effective influenza vaccine; however, employing relevant routes for vaccination can be another important part of the universal influenza vaccine puzzle.

A Significant Breakthrough in the Incidence of Childhood Cancers and Evaluation of its Risk Factors in Southern Iran.

BACKGROUND AND OBJECTIVE: This study investigates epidemiologic and practical information about the incidence and risk factors of childhood cancer in a population of Southern Iranian children. MATERIALS AND METHODS: A total number of 300 cancer patients along with 600 age- and gender-matched healthy control were interviewed by a trained physician regarding their demographic characteristics, and major family-associated risk factors, childhood malignancies. RESULTS: The average annual percentage change for cancers in the studied population is calculated as 45%. Our study indicated that possible risk factors which could contribute to the development of childhood cancer are maternal oral contraceptive pill use during pregnancy, exposure to radiation during pregnancy, parental smoking, residence near high voltage electricity lines, exposure to pesticides and fertilizers, patient allergy, contact with domestic animals and father's educational degree. Furthermore, new ecological risk factors such as air pollution due to nonstandard petroleum or toxic inhalant particles, nonhealthy food consumption, and satellite jamming are other predisposing factors. CONCLUSION: Our study reported a higher average annual percentage change of childhood cancers in our area, compared to the existing literature. In conclusion, detection and prevention of the consistent and possible new environmental risk factors such as nonstandard petroleum or satellite jamming from all around the country should be taking into consideration.

HBsAg mutations related to occult hepatitis B virus infection in HIV-positive patients result in a reduced secretion and conformational changes of HBsAg.

BACKGROUND: Occult hepatitis B infection (OBI) is a frequent finding in human immunodeficiency virus (HIV)-infected patients. While several related mutations in the hepatitis B virus (HBV) genome have been reported, their distinct impact on HBsAg synthesis is largely obscure. METHODS: Thirty-one (18%) out of 172 HIV-infected patients, who were selected from HBsAg-negative patients, were positive for HBV-DNA assigned as being OBI-positive. We generated a series of expression constructs of variant HBsAg with "a" determinant amino acid substitutions including P127L, P127T, S136Y, and P127T + S136Y using site-directed mutagenesis. The expression of variant HBsAg was examined by transient transfection in hepatoma cells, followed by HBsAg immunoassay and immunofluorescence stained with specific anti-HBs antibodies. The potential impact of amino acid substitutions at different positions for conformational changes in the HBsAg was investigated using bioinformatics. RESULTS: All variants comprising either single or combined mutations resulted in significantly reduced HBsAg detection in supernatants and in cell lysates of hepatoma cells transfected with the constructs. Moreover, intracellular immunofluorescence staining of cytoblocks showed perinuclear and cytoplasmic fluorescence of HBsAg constructs with significantly diminished fluorescent intensity in comparison to the wild type. Altered protein conformations by predictive models, indicating an impaired detection by the host's immune response as well as by commercial antibody-based test assays. CONCLUSION: Mutations in the "a" determinant region of HBV as often found in OBI remarkably impair the detection of HBsAg from serum and infected cells, emphasizing the relevance of alternative methods such as HBV-DNA quantification for high-risk groups like HIV-infected individuals. J. Med. Virol. 89:246-256, 2017. © 2016 Wiley Periodicals, Inc.

Evolution of hepatitis B virus surface gene and protein among Iranian chronic carriers from different provinces.

BACKGROUND AND OBJECTIVES: Iranian chronic HBV carrier's population has shown a unique pattern of genotype D distribution all around the country. The aim of this study was to explore more details of evolutionary history of carriers based on structural surface proteins from different provinces. MATERIALS AND METHODS: Sera obtained from 360 isolates from 12 Different regions of country were used for amplification and sequencing of surface proteins. A detailed mutational analysis was undertaken. RESULTS: The total ratio for Missense/Silent nucleotide substitutions was 0.96. Sistan and Kermanshah showed the lowest rate of evolution between provinces (P = 0.055). On the other hand, Khorasan Razavi and Khoozestan contained the highest ratio (P = 0.055). The rest of regions were laid between these two extremes. Azarbayjan and Guilan showed the highest proportion of immune epitope distribution (91.3% and 96%, respectively). Conversely, Sistan and Tehran harbored the least percentage (66.6% and 68.8%, respectively). Kermanshah province contained only 5.2%, whereas Isfahan had 54.5% of B cell epitope distribution. In terms of T helper epitopes, all provinces showed a somehow homogeneity: 22.58% (Fars) to 46.6% (Khuzestan). On the other hand, distribution of substitutions within the CTL epitopes showed a wide range of variation between 6.6% (Khuzestan) and 63% (Kermanshah). CONCLUSION: Further to low selection pressure found in Iranian population, the variations between different regions designate random genetic drift within the surface proteins. These finding would have some applications in terms of specific antiviral regimen, design of more efficient vaccine and public health issues.

Use of stimulant substances among university students in tehran: a qualitative study.

OBJECTIVE: There is evidence to show an increase in use of stimulant substances among university students. This study is a qualitative assessment of the existing situation and the underlying reasons for stimulant use among the students of Tehran University of Medical Sciences in 2006. METHODS: Three qualitative methods have been used: focus group discussions with 7 groups (60 individuals) consisting of male and female students in the dormitories and in the university environment, in-depth interview with 20 drug user students, and interview with 20 key informants including counselors, managers and guards of dormitories, staff of the office for Culture and Welfare Affairs of students and members of students' organizations. Purposeful or opportunistic method was used for sampling. RESULTS: Ecstasy and methylphenidate (Ritalin) were mentioned as the stimulants used by the students. The main declared reasons for ecstasy use were desire to have fun and excitement, desire to modernity, participation in parties, curiosity and living without family. The high expense of ecstasy pills and the training provided by media were mentioned as the main protective factors. Most respondents believed that use of methylphenidate was more prevalent than ecstasy use. In contrary to the drugs used for fun and enjoyment, methylphenidate is used for increasing learning abilities and academic achievement. Other pointed- out factors were ease of use and being stigma-free. Conclusion Increasing risk perception via training, social alternatives to risky activities and parental training for continuing care and advice in the college period are recommended.