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In the recent years, Real-time PCR technique introduced as a choice method for diagnosis of infectious diseases in many laboratories. During each cycle of the PCR reaction, this technique combines the polymerase chain reaction chemistry with the utilization of fluorescent reporter molecules for monitoring the production of amplification products. Therefore, the set of features including the high sensitivity and specificity, repeatable data and low contamination risk has made the Real-time PCR technology as an attractive alternative to conventional PCR. This technique is often used to quantify the level of gene expression. Since the whole Real-time PCR reaction is performed within a closed tube, the risk of contamination is reduced and eventually prevent falsepositive results. The aim of present study was to provide a general overview on different types of Real-time PCR methods, their benefits and applications.

Introduction: Glycoprotein B (gB) is the major antigen for induction of humoral responses against human cytomegalovirus (HCMV) making it an attractive candidate for immune prophylaxis. In the present study, the humoral immune response of BALB/c mice to a truncated HCMV gB protein fused with GFP was evaluated. Methods: The truncated gB coding sequence was synthesized and cloned in pEGFPN1 eukaryotic expression vector and expressed in HEK 293T cell line. After optimization, expression of the recombinant truncated HCMV gB was verified using HRP-conjugated polyclonal antibody specific for HCMV gB.The level of humoral immune responses was assessed in mice using DNA/DNA, peptide/peptide, and DNA/ peptide (prime-boost) immunization strategies. Results: Cloning of the truncated gB coding sequence in the pEGFPN1 was verified by restriction enzyme analysis and sequencing. After optimizing the transfection procedure the number of the GFP positive cells reached 32%. Western blot analysis confirmed the in vitro expression of the truncated HCMV gB protein with an apparent molecular weight of approximately 70 kDa. In vivo prime-boost immunization using HCMV gB DNA/peptide regimen showed significantly higher humoral immune responses compared to the control groups. Conclusion: This study demonstrated that the pEGFPN1 eukaryotic expression vector could be used to optimize and evaluate the expression of this truncated protein.The results also showed that the DNA/peptide vaccination could induce a significant antibody response in animal model.

Background:Rotaviruses cause diarrhea in infants and young children worldwide. Rotavirus outer capsid protein, VP7 is major neutralizing antigen that is important component of subunit vaccine to prevent rotavirus infection.Many efforts have been done to produce recombinant VP7 that maintain native characteristics.We used baculovirus expression system to produce rotavirus VP7 protein and to study its immunogenicity. Methods: Simian rotavirus SA11 full-length VP7 ORF was cloned into a cloning plasmid and then the cloned gene was inserted into the linear DNA of baculovirus Autographa californica Nuclear Polyhedrosis Virus (AcNPV) downstream of the polyhedrin promoter by in vitro recombination reactions. The expressed VP7 in the insect cells was recognized by rabbit hyperimmune serum raised against SA11 rotavirus by Immunofluorescence and western blotting assays. Rabbits were immunized subcutaneously by cell extracts expressing VP7 protein. Results: Reactivity with anti-rotavirus antibody suggested that expressed VP7 protein had native antigenic determinants.Injection of recombinant VP7 in rabbits elicited the production of serum antibodies,which were able to recognize VP7 protein from SA11 rotavirus by Western blotting test and neutralized SA11 rotavirus in cell culture.Conclusion: Recombinant outer capsid glycoprotein (VP7) of rotavirus expressed in insect cells induces neutralizing antibodies in rabbits and may be a candidate of rotavirus vaccine.

"nBackground: GB virus C (GBV-C) is a flavivirus that was characterized in 1995. The prevalence of GBV-C RNA in HIV-in­fected subjects has not been previously studied in Iran and was therefore determined."nMethods: We have investigated serum samples of 80 patients from Imam Khomeini Hospital, Tehran, Iran, whose HIV in­fection was confirmed in our laboratory by Western-blotting. We used nested-PCR to detect GBV-C/HGV RNA in their sera."nResults: GBV-C/HGV RNA was detected in 15 (18.8%) of 80 patients. There was no significant difference in GBV-C/HGV RNA preva­lence between males and females, in different age groups and HIV viral loads groups."nConclusion: The prevalence of GBV-C RNA was high in HIV-infected patients. There was no association between GBV-C RNA prevalence and specific gender, age, and HIV viral loads groups.

Background: Rotaviruses cause diarrhea in infants and young children worldwide. Rotavirus outer capsid protein, VP7 is major neutralizing antigen that is important component of subunit vaccine to prevent rotavirus infection. Many efforts have been done to produce recombinant VP7 that maintain native characteristics. We used baculovirus expression system to produce rotavirus VP7 protein and to study its immunogenicity. Methods: Simian rotavirus SA11 full-length VP7 ORF was cloned into a cloning plasmid and then the cloned gene was inserted into the linear DNA of baculovirus Autographa californica Nuclear Polyhedrosis Virus (AcNPV) downstream of the polyhedrin promoter by in vitro recombination reactions. The expressed VP7 in the insect cells was recognized by rabbit hyperimmune serum raised against SA11 rotavirus by Immunofluorescence and western blotting assays. Rabbits were immunized subcutaneously by cell extracts expressing VP7 protein. Results: Reactivity with anti-rotavirus antibody suggested that expressed VP7 protein had native antigenic determinants. Injection of recombinant VP7 in rabbits elicited the production of serum antibodies, which were able to recognize VP7 protein from SA11 rotavirus by Western blotting test and neutralized SA11 rotavirus in cell culture. Conclusion: Recombinant outer capsid glycoprotein (VP7) of rotavirus expressed in insect cells induces neutralizing antibodies in rabbits and may be a candidate of rotavirus vaccine.

Objectives: The present study aims to examine the hypothetical model of the relationship between food insecurity and Non-alcoholic fatty liver disease (NAFLD) in a sample of Iranian adults., Methods: In this cross-sectional study, 275 subjects (18-70 years old) who met the inclusion criteria were recruited. Fatty liver was diagnosed by abdominal ultrasonography, and eligible patients underwent liver fibro scan assessment to determine fibrosis and steatosis. Food insecurity was assessed using the validated six-item Short Questionnaire of Household Food Security Scale (SQHFSS). Data were analyzed using SPSS 24.0 and IBM SPSS Amos 24.0., Results: Among 275 subjects (44.37 ± 11.67 years old, 51.6% male) included in the analysis, 23.6% were food insecure. Food insecurity, general and abdominal obesity were associated with an increased risk of NAFLD, even after multiple adjustments (OR: 2.95, 95% CI: 1.02, 8.57; OR: 3.27, 95% CI: 1.50, 7.11; and OR: 3.81, 95% CI: 1.55, 9.32, respectively). According to the primary hypothesis, food insecurity and NAFLD were fitted into a model (χ 2 /df = 1.36, GFI = 0.982, AGFI = 0.952, CFI = 0.954, IFI = 0.959, SRMR = 0.040, RMSEA = 0.037); accordingly, food insecurity and obesity (general and abdominal) directly affected NAFLD (β = 0.12, P = 0.03; β = 0.13, P = 0.02; β = 0.31, P < 0.001, respectively)., Conclusion: Food insecurity was a predictor of, and directly associated with, NAFLD. Social determinants should be considered in the pathogenesis of NAFLD, although the possible underlying biological mechanisms in this association are yet to be determined., (© 2024. The Author(s).)

Background: Emigration of health workers has emerged as a significant obstacle in Iran, compelling policymakers to implement a diverse range of interventions and reforms to enhance healthcare services. It is imperative to comprehend the efficacy of emigration control interventions. To explore the intricate dynamics of elite emigration, this study employs a system dynamics modeling approach. The objective is to scrutinize Iranian health workers' emigration, examine the relationships, and evaluate the impact of various factors involved., Objectives: The general purpose of this study is to analyze the policy interventions affecting the emigration of human resources in the field of health in Iran based on the system's dynamic approach., Method: The research consists of four phases including analyzing the emigration status of health workers in developing countries, studying health personnel emigration in Iran, developing a System Dynamics (SD) model, and determining evidence-based policy interventions to address health worker emigration. These phases involve realist review, document analysis, qualitative interviews, data integration, and policy scenario planning. The primary objective is to gain a profound understanding of the underlying causes, mechanisms, and consequences of migration, as well as assess the impact of policies, in order to prioritize effective interventions., Results: It seems that the SD model developed in this study can highlight the interconnectedness of various factors that influence health worker emigration, including demographic changes, economic conditions, and characteristics of healthcare systems., Conclusion: This study uses a systems dynamics approach to analyze health worker emigration from Iran, focusing on policies that promote retention and explore the implications of emigration on the healthcare system. By examining interrelationships and feedback loops within the healthcare system and socioeconomic factors, the study aims to identify effective policy interventions that can mitigate the negative effects of emigration.

Background: Iran is facing an epidemiological transition with the increasing burden of non-communicable diseases, such as obesity-related disorders and cardiovascular diseases (CVDs). We conducted a population-based prospective study to assess the prevalence and incidence rates of CVDs and obesity-related metabolic disorders and to evaluate the predictive ability of various CVD risk assessment tools in an Iranian population., Method: We enrolled 5,799 participants in Amol, a city in northern Iran, in 2009-2010 and carried out the first repeated measurement (RM) after seven years (2016-2017). For all participants, demographic, anthropometric, laboratory, hepatobiliary imaging, and electrocardiography data have been collected in the enrollment and the RM. After enrollment, all participants have been and will be followed up annually for 20 years, both actively and passively., Results: We adopted a multidisciplinary approach to overcome barriers to participation and achieved a 7-year follow-up success rate of 93.0% with an active follow-up of 5,394 participants aged 18-90 years. In the RM, about 64.0% of men and 81.2% of women were obese or overweight. In 2017, about 16.2% and 5.2% of men had moderate or severe non-alcoholic fatty liver disease, while women had a significantly higher prevalence of metabolic syndrome (35.9%), and type 2 diabetes mellitus (20.9%) than men. Of 160 deceased participants, 69 cases (43.1%) died due to CVDs over seven years., Conclusion: The most prevalent obesity-related chronic disease in the study was metabolic syndrome. Across the enrollment and RM phases, women exhibited a higher prevalence of obesity-related metabolic disorders. Focusing on obesity-related metabolic disorders in a population not represented previously and a multidisciplinary approach for enrolling and following up were the strengths of this study. The study outcomes offer an evidence base for future research and inform policies regarding non-communicable diseases in northern Iran., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Motamed, Zamani, Maadi, Ajdarkosh, Roozafzai, Keyvani, Poustchi, Shakeri, Ashrafi, Perumal, Rabiee, Moradi-Lakeh, Khoonsari, Kheyri, Sohrabi, Doustmohammadian, Amirkalali, Safarnezhad Tameshkel, Gholizadeh, Hosseini and Karbalaie Niya.)

Background: This study aimed to evaluate the non-inferiority of the FluGuard (a quadrivalent recombinant vaccine manufactured by Nivad Pharmed Salamat Company in Iran) by comparing its immunogenicity and safety with Vaxigrip Tetra (a quadrivalent inactivated vaccine manufactured by Sanofi Pasteur in France)., Materials and Methods: In this double-blind, randomized controlled trial, eligible volunteers aged 18-60 were randomized to receive either FluGuard or Vaxigrip Tetra vaccines. Immunogenicity was evaluated using the Hemagglutination Inhibition (HAI) assay and reported with the geometric mean titer (GMT), seroprotection, and seroconversion. In addition, vaccine safety was assessed by interviewing participants through phone calls., Results: Out of 110 randomized volunteers, 51 and 53 were entered into the final analysis in the Vaxigrip and FluGuard groups, respectively. Vaxigrip had a higher seroprotection rate for the H1N1 strain compared with FluGuard (98 % vs. 91 %). Besides, FluGuard had higher seroprotection rates for H3N2 (74 % vs. 69 %), B-Yamagata (87 % vs. 84 %), and B-Victoria (66 % vs. 41 %) strains compared with Vaxigrip. In all four strains, FluGuard was non-inferior to Vaxigrip with the upper bounds of the 95 % CI on the ratio of the GMTs < 1.5: H1N1 (1.25), H3N2 (0.94), B-Yamagata (0.62), and B-Victoria (0.59). Furthermore, FluGuard was non-inferior to Vaxigrip with the upper bounds of the 95 % CI on the difference between the seroconversion rates < 10 %: H1N1 (2 %), H3N2 (10 %), B-Yamagata (-10 %), and B-Victoria (-29 %). The prevalence of solicited adverse drug reactions did not differ between groups. Furthermore, participants did not experience serious adverse events., Conclusion: Our findings support the non-inferiority of the FluGuard vaccine to the Vaxigrip vaccine regarding immunogenicity and safety., Clinical Trial Registry: The study protocol was approved by the Iranian Registry of Clinical Trials (IRCT20210901052358N5)., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Davood Yadegarynia reports financial support was provided by Nivad Pharmed Salamt Pharmaceutical Company. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Cervical cancer is one of the most common malignancies in women, and its treatment has many side effects. Therefore, in this research, the effects of the LaSota strain of oncolytic Newcastle disease virus vaccine on cervical intraepithelial neoplasia (CIN) patients were investigated., Methods: 15 patients who met the inclusion criteria and diagnosed as CIN II and CIN III were included in the study. The vaccine was injected inside the cervix (neoplasia site) at increasing doses during 21 days, and they were evaluated for adverse events. NDV antibody titer was measured in 90 days and the levels of ki-67 and p16 proteins were studied by immunohistochemistry. Also, the levels of some important inflammatory cytokines in the serum of CIN patients were measured and finally the patients were evaluated according to the final outcomes and the reduction of tumor lesions., Results: Only in the first dose of vaccine some patients showed flu-like symptoms. The accumulation of NDV antibodies started on the 7th day of the study and increased until the 90th day. Administration of LaSota vaccine had no significant effect on the expressions of Ki-67 and p16 proteins. Nevertheless, a decrease in the serum levels of Il-1β was observed in patients after the administration of the vaccine, but the serum levels of both Il-2 and INF-γ upregulated significantly. Also, vaccine administration had no significant effect in reducing CIN grades and lesions., Conclusions: In general, we concluded that LaSota strain of NDV vaccine has no therapeutic effectiveness in CIN patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Cholesterol 25-hydroxylase ( CH25H ) and its product 25-hydroxycholesterol (25HC) showed antiviral effects against various viruses in vitro . CH25H expression is regulated in mice by pro-inflammatory cytokine interferons (IFNs) in mice but data on its possible correlation with IFNs in humans are still unclear. We examined gene expression of CH25H , IFN - α , and IFN - β and serum levels of 25HC in Iranian patients with mild and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Fifty intensive care unit (ICU) patients and outpatients with SARS-CoV-2 and 25 healthy controls were studied. Gene expression of CH25H and relevant inflammatory cytokines was quantified in peripheral blood mononuclear cells by real-time polymerase chain reaction. The expression of CH25H and serum levels of 25HC were significantly higher in ICU patients with SARS-CoV-2. Notably, IFN - α levels increased in healthy controls. However, compared to healthy controls, IFN - β was considerably higher in outpatients. Finally, statistical analysis shows that no correlation was found between CH25H and IFN - α expression; nevertheless, a lower correlation was found with IFN - β . The data revealed that CH25H and 25HC levels increase after SARS-CoV-2 infection. In other words, decreased levels of those factors in severe patients compared with mild patients may indicate the importance of their function in controlling the progression of the disease.

The appearance of several coronavirus pandemics/epidemics during the last two decades (SARS-CoV-1 in 2002, MERS-CoV in 2012, and SARS-CoV-2 in 2019) indicates that humanity will face increasing challenges from coronaviruses in the future. The emergence of new strains with similar transmission characteristics as SARS-CoV-2 and mortality rates similar to SARS-CoV-1 (∼10% mortality) or MERS-CoV (∼35% mortality) in the future is a terrifying possibility. Therefore, getting enough preparations to face such risks is an inevitable necessity. The present study aims to review the drug achievements and challenges in the fight against SARS-CoV-2 with a combined perspective derived from pharmacology, pharmacotherapy, and medicinal chemistry insights. Appreciating all the efforts made during the past few years, there is strong evidence that the desired results have not yet been achieved and research in this area should still be pursued seriously. By expressing some pessimistic possibilities and concluding that the drug discovery and pharmacotherapy of COVID-19 have not been successful so far, this short essay tries to draw the attention of responsible authorities to be more prepared against future coronavirus epidemics/pandemics., Competing Interests: The authors declare no competing financial interest., (© 2023 American Chemical Society.)

Background: The Coronavirus disease 2019 (COVID-19) pandemic influences all around the world. The SARS-CoV-2 ORF8 accessory gene represents multiple functions in virus-host interaction. The current study aimed to compare the ORF8 substitutions and epitope features of these substitutions in the various SARS-CoV-2 outbreaks including delta, alpha, and wild type variants in Iran from 2020 to 2022. In addition, we evaluate B cell, HLA I and II epitopes, by in-silico approach to ORF8 binding site prediction., Methods: The samples were collected from patients diagnosed with SARS-CoV-2 infection via a real-time PCR assay. Then, a conventional PCR was carried out for ORF8 mutations analysis and further Sanger sequencing. Possible important alterations in epitope features of the ORF8 were evaluated by epitope mapping. B cell, HLA class I and II epitopes, evaluated by online databases ABCpred, NetMHCpan-4.1, and NetMHCIIpan-3.2, respectively., Results: The current study results could not represent novel variations in seven full-length ORF8 sequences or major ORF8 deletions in 80 evaluated samples. In addition, we could not find any ORF8 A382 during each outbreak of variants. Epitope mapping represents differences between the Alpha and other variants, especially in B cell potential epitopes and HLA I., Conclusion: The immunoinformatic evaluation of ORF8 suggested epitopes represent major differences for the Alpha variant in comparison with other variants. In addition, having mild pathogenesis of the Omicron variant does not seem to be associated with ORF8 alteration by phylogenetic evaluation. Future in-vitro studies for a clear conclusion about the epitope features of ORF8 are required., Competing Interests: No conflict of interests., (© 2023 Kamuzu University of Health Sciences.)

Autophagy is one of the important mechanisms in cell maintenance, which is considered associated with different pathological conditions such as viral infections. In this current study, the expression level and polymorphisms in some of the most important genes in the autophagy flux in COVID-19 patients were evaluated. This cross-sectional study was conducted among 50 confirmed COVID-19 patients and 20 healthy controls. The COVID-19 patients were divided into a severe group and a mild group according to their clinical features. The expression levels of ATG5, ATG16L1, LC3, and BECN1 were evaluated by the 2 -∆∆CT method and beta-actin as the internal control. The polymorphisms of the ATG5 (rs506027, rs510432) and ATG16L1 (rs2241880 or T300A) were evaluated by the Sanger sequencing following the conventional PCR. The mean age of the included patients was 58.3 ± 17.9 and 22 (44%) were female. The expression levels of the LC3 were downregulated, while BECN1 and ATG16L1 genes represent an upregulation in COVID-19 patients. The polymorphism analysis revealed the ATG16L1 rs2241880 and AGT5 rs506027 polymorphism frequencies are statistically significantly different between COVID-19 and Healthy controls. The autophagy alteration represents an association with COVID-19 pathogenesis and severity. The current study is consistent with the alteration of autophagy elements in COVID-19 patients by mRNA expression-level evaluation. Furthermore, ATG16L1 rs2241880 and AGT5 rs506027 polymorphisms seem to be important in COVID-19 and are highly suggested for further investigations., (© 2022 Scandinavian Societies for Pathology, Medical Microbiology and Immunology.)

Background: HPV-31, -33, and -58, along with HPV-45 and -52, account for almost 11% of HPV-associated cancers. Our previous studies showed that after HPV-16 and -51, HPV-58 was common and HPV-31 was as frequent as HPV-18 among Iranian women with normal cytology. Hence, in this study, we aimed to investigate the intra-type variations in L1 genes of HPV-58, -31, and -33 to find the predominant lineages circulating in women with normal cytology., Methods: Complete coding sequencing of the L1 gene was amplified and nucleotide and amino acid sequences were compared to those of the references. The selective pressure on L1 protein and whether the variations of the L1 genes embed in L1 loops, or N-glycosylated sites were also investigated., Results: B1, A, and A1 (sub)lineages were common in the HPV-58, -33, and -31 samples, respectively. Ninety nucleotide mutations were observed. Twenty nine nucleotide changes corresponded to nonsynonymous substitutions in which seventeen mutations were located in L1 loops. Only one codon position in HPV-58 sequences was found as the positive selection. No difference was observed in N-glycosylation sites between reference and understudied amino acid sequences., Conclusion: In the current study, we reported, for the first time, the (sub) lineages, amino acid, and genetic diversity in the L1 gene of circulating HPV-58, -33, and -31, in women with normal cytology, in Iran. Such studies can not only have epidemiological values, but also aid to set vaccination programs., (© 2023. The Author(s).)

Background: Considering the role of calcium in the replication and morphogenesis of rotaviruses, it is hypothesized that decreased cytosolic calcium levels by using calcium channel blockers can subsequently interfere with rotavirus replication., Objective: The present study investigated the effects of two calcium ion channel blockers, amlodipine and diltiazem, against human rotavirus infection., Methods: Cytotoxic effects of the drugs on MA-104 cells were evaluated using the neutral red assay. The effects of amlodipine and diltiazem at non-toxic concentrations on human rotavirus were examined using cytopathic effect inhibition, TCID 50 , and real-time PCR assays., Results: The highest inhibitory effect was obtained at concentrations of 0.5 μg/ml of amlodipine and 3 μg/ml of diltiazem, leading to 4.6 and 5.5 logarithmic reductions in infectious rotavirus titer and four- and a five-fold increase in the C t values compared to the virus control, respectively ( p -value < 0.001). Conversely, infectious rotavirus titers were significantly elevated compared to the virus control at concentrations above 0.9 μg/ml of amlodipine and above 25 μg/ml of diltiazem., Conclusion: Our study suggests that in addition to cardiovascular diseases, calcium channel blockers at their optimal doses may also be used to treat gastroenteritis caused by rotavirus infection., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Obesity is considered a multisystem disease associated with higher mortality and morbidity in adults. This study explored the effects of two Moderate-Intensity Continuous Training (MICT) and High-Intensity Interval Training (HIIT) on body composition, maximal oxygen uptake (VO2max), and the gene expression of angiotensin-converting enzyme 2 (ACE2), fibronectin type III domain-containing protein 5 (FNDC5), and NLR family pyrin domain containing 3 (NLRP3) in adults with obesity. Methods: In a randomized controlled trial, 36 obese, inactive subjects (age: 45.16 ± 3.13 yrs.; mean, BW: 112.38 ± 20.1 kg, Height: 1.67 ± 0.07, and BMI: 39.66 ± 6.07 kg/m2) were randomly assigned to one of three groups: HIIT: (n = 12), MICT (n = 12), and control (n = 12). Both exercise groups received 40 min of training per session (three times/week) for eight weeks. Body composition, body fat percentage (BFP), VO2max, and the gene expression of ACE2, and NLRP3, were taken pre- and post-intervention using the qRT-PCR technique. The data were analyzed using SPSS software via parametric (ANOVA and ANCOVA) and non-parametric tests (Mann Whitney U and Kruskal-Wallis). Results: Our results showed that HIIT and MICT protocols could be effective in normalizing body composition measurements and VO2max, but HIIT could reduce body fat percentage (BFP) in obese subjects. Moreover, HIIT and MICT could significantly reduce the gene expression of NLRP3 ( p < 0.0001) and ACE2 ( p < 0.0001), while increasing the gene expression of FNDC5 ( p < 0.0001). There were negative correlations between the gene expression of FNDC5 and NLRP3, as well as ACE2. Furthermore, increased FNDC5 was negatively correlated with BFP (r = 0.392, p < 0.001). Conclusion: Overall, our results indicated that HIIT and MICT protocols had the greatest impact on the gene expression of NLRP3, ACE2, and FNDC5., (© 2022 Iran University of Medical Sciences.)

Purpose: The current study aimed to determine blaKPC, blaGES, blaVIM, blaNDM, blaOXA-23, and blaOXA-48 genes in clinical strains of Klebsiella pneumoniae isolated in Tehran, Iran to assess genetic diversity using MLVA as a typing method., Methods: A total of 181 K. pneumoniae isolates were obtained from various clinical samples. CLSI 2018 (clinical and laboratory standards institute) guidelines were used to determine antibiotic susceptibility and the Modified Hodge Test (MHT). To detect blaKPC, blaGES, blaVIM, blaNDM, blaOXA-23, and blaOXA-48, the polymerase chain reaction (PCR) method was used. The MLVA method was used to type K. pneumoniae isolates by using PCR for 8 Variable Number Tandem Repeats (VNTRs)., Results: Imipenem was the most effective antibiotic against K. pneumoniae, with 36.5% susceptibility. 100 (55.24%) of the isolates tested positive for KPC, and 30 (30%) tested positive for six genes. Thirty MLVA genotypes were distinguished, and an examination of diversity indexes (DIs) for eight loci revealed that seven different alleles were the most polymorphic, with the highest DI of 0.780., Conclusions: The present study showed that MLVA could be helpful for typing clinical strains of K. pneumoniae. Our K. pneumoniae isolates are thought to be derived from a small number of clones that have undergone minor genetic changes over time. The results also showed that this method had great potential to differentiate those strains with high phenotypic similarity. The current study has revealed some intriguing facts about K. pneumoniae genetic relatedness in Tehran, Iran., Competing Interests: Declaration of competing interest There are no conflicts to interest., (Copyright © 2022 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

The last generation of Coronavirus named COVID-19 is responsible for the recent worldwide outbreak. Concerning the widespread and quick predominance, there is a critical requirement for designing appropriate vaccines to surmount this grave problem. Correspondingly, in this revision, COVID-19 vaccines (which are being developed until March 29th, 2021) are classified into specific and non-specific categories. Specific vaccines comprise genetic-based vaccines ( mRNA , DNA ), vector-based, protein/recombinant protein vaccines, inactivated viruses, live-attenuated vaccines, and novel strategies including microneedle arrays ( MNAs ), and nanoparticles vaccines. Moreover, specific vaccines such as BCG , MRR , and a few other vaccines are considered Non-specific. What is more, according to the significance of Bioinformatic sciences in the cutting-edge vaccine design and rapid outbreak of COVID-19, herein, Bioinformatic principles including reverse vaccinology, epitopes prediction/selection and, their further applications in the design of vaccines are discussed. Last but not least, safety, challenges, advantages, and future prospects of COVID-19 vaccines are highlighted., Competing Interests: Conflict of Interests: There is no conflict of interests in this paper., (Copyright © 2022, Author(s).)

A growing body of documents shows microbiota produce metabolites such as short-chain fatty acids (SCFAs) as crucial executors of diet-based microbial influence the host and bacterial pathogens. The production of SCFAs depends on the metabolic activity of intestinal microflora and is also affected by dietary changes. SCFAs play important roles in maintaining colonic health as an energy source, as a regulator of gene expression and cell differentiation, and as an anti-inflammatory agent. Additionally, the regulated expression of virulence genes is critical for successful infection by an intestinal pathogen. Bacteria rely on sensing environmental signals to find preferable niches and reach the infectious state. This review will present data supporting the diverse functional roles of microbiota-derived butyrate, propionate, and acetate on host cellular activities such as immune modulation, energy metabolism, nervous system, inflammation, cellular differentiation, and anti-tumor effects, among others. On the other hand, we will discuss and summarize data about the role of these SCFAs on the virulence factor of bacterial pathogens. In this regard, receptors and signaling routes for SCFAs metabolites in host and pathogens will be introduced., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

BACKGROUND : Hepatitis C virus (HCV) genotype distribution is different in various regions. A variety of strategies could be used to detect HCV genotypes and subtypes. The aim of the present study was to introduce a genotyping method by an in-house protocol that could be used to determine HCV drug-resistant variants and phylogeny studies. METHODS : Samples from 91 patients with thalassemia were used for HCV genotyping by Cobas 4800 platform, and 50 cases of 1a, 1b, and 3a genotypes underwent amplification and sequencing of NS5A and NS5B by using consensus primers via conventional reverse transcription-polymerase chain reaction (RT-PCR) method. An ABI 3730xl system used for direct sequencing. Raw sequences were analyzed by popular bioinformatics software MEGA6 and CLC workbench 5. Phylogenetic construction was drawn using 1000 replicates bootstrap by the neighbor-joining method. Multiple sequence alignment (MSA) was performed for mutation detection. RESULTS : Sequencing results of 50 HCV isolates subtypes 1a (31/45), 3a (15/22) and 1b (4/8) NS5A and NS5B genes showed there were 72 NS5A and 105 NS5B mutations. Moreover, 8 resistant associated substitutions (RASs) were identified in nine thalassemia cases by multiple sequence alignment (MSA) protein analysis. The phylogenetic tree construct drew confirmed by the Cobas HCV genotyping results. CONCLUSION : The phylogenetic analysis could be a useful tool for HCV genotyping in case of determining the drug-resistant substitutions; however, it is time-consuming and needs expert analysis and interpretation. This preliminary study in Iranian patients with thalassemia introduces specific conventional RT-PCR to find RASs to direct acting antivirals (DAAs) and subtype determination at the same time., Competing Interests: CONFLICT OF INTEREST All authors declare that they have no financial interests related to the material in the manuscript., (© 2022 Middle East Journal of Digestive Diseases.)

BACKGROUND : Interaction between immune modulators and inflammatory factors is considered as one of the main underlying pathologies of non-alcoholic fatty liver disease (NAFLD). Hence we aimed to assess the association between these cytokines and melatonin. METHODS : We enrolled adult patients diagnosed with fatty liver by ultrasonography in a crosssectional study. All of them underwent Fibroscan evaluation. The subjects who met the inclusion and exclusion criteria for NAFLD were involved. A normal group who did not have NAFLD, viral or non-viral hepatitis, and without a history of pancreatobiliary surgery, bariatric surgery, and intake of any medication that influence the liver was also selected. The participants were categorized into the three following groups: 1) fibrosis>9.1 kPa and steatosis>290 dbm, 2) fibrosis: 6-9.0 kPa and steatosis 240-290 dbm, and 3) normal group with fibrosis<6.0 kPa and steatosis<240 dbm. Laboratory assessment and a questionnaire including demographic, anthropometric, laboratories, and clinical data were completed for each of them. RESULTS : Totally 97 subjects were enrolled in the present study. The mean age of the subjects was 42.2±11.3 years. 60% of them (59 patients) were female. Serum levels of melatonin, interleukin (IL)-1B, IL-18, and IL-33 increased according to the advancing of NAFLD state. Based on multiple linear regression model, melatonin was significantly associated with IL-1B (β=2.8, P <0.001,95% CI=1.41-4.19), IL-18 (β=0.018, P =0.0005, 95% CI=0.006-0.03), and IL-33 (β=0.31, P =0.045, 95% CI=0.008-0.62) after adjustment for other variables. CONCLUSION : Melatonin level has a strong association with these cytokines. This linkage probably influences on the development and progression of NAFLD. Therefore it can be hypothesized that the therapeutic approach that affects this process may have a significant impact., Competing Interests: CONFLICT OF INTEREST The authors declare no conflict of interest related to this work., (© 2022 Middle East Journal of Digestive Diseases.)

The mounting evidence regarding the pathogenesis of COVID-19 indicated that the cytokine storm has an axial role in the severity of this disease, which may lead to thrombotic complications, acute respiratory distress syndrome (ARDS), and myocardial damage, among other consequences. It has recently been demonstrated that statins are known to have anti-viral, anti-inflammatory, anti-thrombotic, and immunomodulatory features; however, their advantage has not been evaluated in COVID-19. This study aimed to investigate the protective effects of lovastatin in intensive care unit (ICU) patients with COVID-19. The case-control study consists of 284 ICU patients, which classified into three groups as follows: 1) the patients who no received lovastatin as a control (92 patients), 2) patients received 20 mg per day lovastatin (99 patients), and 3) patients received 40 mg per day lovastatin (93 patients). Each group's demographic and clinical parameters, along with CRP, interleukin (IL)-6, IL-8 levels, and mortality rate, were studied in three-time points. The results showed that there was no statistically significant difference between our study groups in terms of age and sex. (P > 0.05). Besides, in patients, receiving lovastatin the CRP, IL-6, IL-8 levels were significantly decreased from T1 to T3 than to the control group. Our results also showed that the use of lovastatin in COVID-19 patients significantly reduced the length of hospitalization in the ICU compared with the control group. In addition, our results showed that the mortality rate in patients receiving lovastatin was lower when compared to the control group; however, this difference was not statistically significant. Since the cytokine storm is a significant factor in the pathology of SARS-CoV-2, our findings highlighted the potential use of lovastatin to mitigate the inflammatory response induced by SARS-CoV-2 infection., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A growing body of evidence indicates that neutrophil elastase (NE) is involved in the pathogenesis of respiratory infectious diseases, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study aimed to analyze the dynamic changes in serum levels of NE associated with inflammation, disease activity, and mortality rate in patients with COVID-19. We measured the serum concentrations of NE, C-Reactive protein (CRP), interleukin (IL)- 4, IL-6, IL-8, IL-10, and vitamin D levels in 83 ICU and 69 non-ICU patients compared with 82 healthy subjects (HS) in three-time points (T1-T3). Serum levels of NE, IL-6, IL-8, and CRP in ICU and non-ICU patients were significantly higher than HS (P < 0.001) in three-time points. Also, serum levels of NE, IL-6, IL-8, and CRP in ICU patients were significantly higher than in non-ICU patients (P < 0.05). On the day of admission (T1), the levels of NE, CRP, IL-6, IL-8 were gradually decreased from T1 to T3. At the same time, IL-4 and IL-10 were gradually increased from T1 to T2 and then reduced to T3. Further analyses demonstrated that the levels of NE, IL-6, and IL-8 in deceased patients were significantly higher than in recovered patients (P < 0.05). The ROC curve analysis demonstrated that markers, including NE, IL-6, and IL-8, were valuable indicators in evaluating the activity of COVID-19. Overall, our results signify the critical role of NE in the pathogenesis of COVID-19, and also, further support that NE has a potential therapeutic target for the attenuation of COVID-19 severity., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The present investigation was performed to determine the stability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) under several industrial processing situations in dairies, including pasteurization, freezing, and storage in acidic conditions. Ten treatments were selected, including high-temperature short-time (HTST)-pasteurized low-fat milk, low-temperature long-time-pasteurized low-fat milk, extended shelf life (ESL)-pasteurized low-fat milk, HTST-pasteurized full-fat milk, LTLT-pasteurized full-fat milk, ESL-pasteurized full-fat milk, pasteurized cream, ice cream frozen and stored at -20 or -80°C, and Doogh (as a fermented milk drink with initial pH < 3.5) refrigerated for 28 days. The viral particles were quantified by RT-PCR methodology. Besides, the virus infectivity was assessed through fifty-percent tissue culture infective dose (TCID 50 ) assay. These products were seeded with a viral load of 5.65 log TCID 50 /mL as a simulated cross-contamination condition. Pasteurization techniques were sufficient for complete inactivation of the SARS-CoV-2 in the most dairy products, and 1.85 log TCID 50 /mL virus reduction in full-fat milk (fat content = 3.22%). Freezing (either -20°C or -80°C) did not result in a virally safe product within 60 days of storage. Storage at high acidic conditions (initial pH < 3.5) completely hampered the viral load at the end of 28 days of refrigerated storage. This research represents an important practical achievement that the routine HTST pasteurization in dairies was inadequate to completely inactivate the viral load in full-fat milk, probably due to the protective effect of fat content. Furthermore, freezing retain the virus infectivity in food products, and therefore, relevant contaminated foods may act as carriers for SARS-CoV-2., Competing Interests: The authors declare no potential conflict of interest., (© 2021 Wiley Periodicals LLC.)

BACKGROUND Inflammation has a significant impact on the development and progression of fatty liver diseases.In this study, we aimed to investigate the relation between serum levels of nuclear factor kappa B (NFkB) and Forkhead box protein P3 (FOXP3)with fibrosis severity among patients with non-alcoholic fatty liver disease(NAFLD). METHODS In a prospective study, the patients suspicios of havingfatty liver were enrolled. The exclusion criteria lack of viral hepatitis, autoimmune hepatitis, Wilson's or other known liver diseases,history of liver or biliary surgery,bariatric surgery, and medications that influence liver metabolism. The participantsunderwent liver fibroscan. According to liver fibrosis, the patients weredivided into two groups; 1)fibrosis less than 7.2 KP,2)advanced NAFLD, fibrosis ≥7.3 KP. A10 cc fasting blood sample was taken from each patient for laboratory assessments.The variables between the two groups were compared using Chi-square or Fisher's exact test.The independence of cytokines was assessed by a logistic regression test. RESULTS Totally 90 patients were enrolled.The mean age was 42.21 ± 11 years. Of them, 50 and 47 participants were allocated to groups 1 and 2, respectively. In the univariate analysis, we revealed asignificant difference between age, body mass index (BMI), fasting blood glucose, liver enzymes, total cholesterol, andtriglyceride levels. Also, there was a significant difference betweenthe levels of NFKB and FOXP3 in group one compared with group two of the participants,as FOXP3(9.17 ± 10.0 vs. 18.63 ± 12.9; p < 0.001) and NFKB (1.70 ± 1.70; p < 0.01). After excluding the confounding factors, we observed a significant association between fibrosis level and cytokine levels in logistic regression. CONCLUSION Serum levels of NFKB and FOXP3 increased by advancing liver fibrosis in patients with NAFLD.This is an independent association. The identification of intermediary regulatory factors would be necessary., Competing Interests: CONFLICT OF INTEREST The authors declare no conflict of interest related to this work., (© 2021 The Author(s).)

Exosomes are a nano-vesicle surrounded by a bilipid layer that can release from almost all cells and could be detected in tissues and biological liquids. These vesicles contain lipids, proteins, and nucleic acids (including DNA, mRNA, and miRNA) inside and on the exosomes' surface constitute their content. Exosomes can transfer their cargo into the recipient cell, which can modify recipient cells' biological activities. Recently it has been deciphering that the miRNA pattern of exosomes reveals the cellular pathophysiological situation and modifies various biological processes. Increasing data regarding exosomes highlights that the exosomes and their cargo, especially miRNAs, are implicated in the pathophysiology of various disorders, such as autoimmune disease. The current evidence on the deciphering of mechanisms in which exosomal miRNAs contributed to autoimmunity was indicated that exosomal miRNA might hold information that can reprogram the function of many of the immune cells involved in autoimmune diseases' pathogenesis. In the present study, we summarized the pathogenic role of exosomal miRNAs in several autoimmune diseases, including myasthenia gravis (MG), psoriasis, inflammatory bowel disease (IBD), type 1 diabetes (T1D), multiple sclerosis (MS), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjogren's Syndrome (SS), systemic sclerosis (SSc), vitiligo, and autoimmune thyroid diseases (AITD). Moreover, in this work, we present evidence of the potential role of exosomal miRNAs as therapeutic and diagnostic agents in autoimmune diseases., (Copyright © 2021. Published by Elsevier B.V.)

Background: The aim of this study was to evaluate the risk factors for hospitalizations of cases with positive and negative COVID-19 tests., Methods: In this case-control study, the case and control groups consisted of 292 COVID-19 patients and 296 non-COVID-19 patients. Patients who referred to a reference laboratory in Tehran (Iran) in March 2020 were selected and interviewed. The patients were contacted by telephone and data were recorded through a questionnaire., Results: The sample of this study consisted of 588 patients (349 [59%] females, 239 [41%] males) with a mean age of 42 ± 15. The results of this study showed that comorbidities like diabetes (OR = 7.42), hypertension (OR = 4.85), asthma and respiratory diseases (OR = 5.64) in addition to symptoms including fever (OR = 6.67), chills (OR = 11.2), anorexia (OR = 11.3), dyspnea (OR = 4.8), weakness and lethargy (OR = 5.7) were the most predictive variables for hospitalization of non-COVID-19 cases. Furthermore, demographical variables like male gender (OR = 3.71), high age (>50; OR = 3.12), BMI (>25; OR = 2.37), travel (OR = 2.79), comorbidities including diabetes (OR = 5.26), hypertension (OR = 3.7) and underlying immunosuppressant patients receiving corticosteroid therapy (OR = 3.62) in addition to symptoms like anorexia [OR = 2.55] and dyspnea (OR = 6.99) tend to increase the risk of hospital admission in COVID-19 patients, suggesting their predictive values for hospitalization of COVID-19 patients., Conclusion: Our results indicated that different factors tend to increase the odds of hospital admission in patients with positive and negative COVID-19 tests, suggesting their predictive values for hospitalization., (Copyright © 2021. Published by Elsevier B.V.)

A cell-surface heparan proteoglycan called Syndecan-1 (SDC-1) has multiple roles in healthy and pathogenic conditions, including respiratory viral infection. In this study, we explore the dynamic alternation in the levels of SDC-1 in cases with COVID-19. A total of 120 cases definitely diagnosed with COVID-19 were admitted to the Firoozgar Hospital, Tehran, Iran, from December 1, 2020, to January 29, 2021, and included in our study. Also, 58 healthy subjects (HS) were chosen as the control group. Patients were classified into two groups: 1) ICU patients and (63 cases) 2) non-ICU patients (57 cases). The dynamic changes of serum SCD-1, CRP, IL-6, IL-10, IL-18, and Vit D levels a well as the disease activity were investigated in three-time points (T1-T3). Our results indicated that the COVID-19 patients had significantly increased SCD-1, CRP, IL-6, IL-10, and IL-18 levels than in HS, while the Vit D levels in COVID-19 patients were significantly lower than HS. Further analysis demonstrated that the SCD-1, CRP, IL-6, IL-10, and IL-18 levels in ICU patients were significantly higher than in non-ICU patients. Tracking dynamic changes in the above markers indicated that on the day of admission, the SCD-1, CRP, IL-6, IL-10, and IL-18 levels were gradually increased on day 5 (T2) and then gradually decreased on day 10 (T3). ROC curve analysis suggests that markers mentioned above, SDC-1, IL-6, and IL-18 are valuable indicators in evaluating the activity of COVID-19. All in all, it seems that the serum SDC-1 levels alone or combined with other markers might be a good candidate for disease activity monitoring., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that was first found in 2019 in Wuhan, China, caused coronavirus disease 2019 (COVID-19). It then spread worldwide rapidly, causing the 2019-2020 coronavirus pandemic. To date, it has been indicated that various transmission ways might be participated in outbreaks of COVID-19. Among these, food products, whether raw or processed, might be carriers for SARS-CoV-2. Therefore, this study was aimed to evaluate the effect of cooking and microwave process of meat products and bread on the stability of SARS-CoV-2. In this regard, sausages and hamburger as meat products and toast bread were inoculated with a viral load of 5.70 log fifty percent tissue culture infective dose (TCID 50 )/mL in order to create a simulated cross-contamination condition. The results showed that frying of hamburger at 225ºC for about either 6 or 10 min resulted in complete inactivation of SARS-CoV-2. Furthermore, a 5-log decrease in SARS-CoV-2 load was observed in sausages as a consequence of cooking process at 78ºC for either 20 or 30 min. Additionally, the effect of microwave oven at power of 630 watt on stability of SARS-CoV-2 showed that exposing toast bread for either 30 s or 1 min in this power led to a 5-log decrease in SARS-CoV-2 load in the toast bread., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

During the past decade, accumulating evidence from the research highlights the suggested effects of bacterial communities of the human gut microbiota and their metabolites on health and disease. In this regard, microbiota-derived metabolites and their receptors, beyond the immune system, maintain metabolism homeostasis, which is essential to maintain the host's health by balancing the utilization and intake of nutrients. It has been shown that gut bacterial dysbiosis can cause pathology and altered bacterial metabolites' formation, resulting in dysregulation of the immune system and metabolism. The short-chain fatty acids (SCFAs), such as butyrate, acetate, and succinate, are produced due to the fermentation process of bacteria in the gut. It has been noted remodeling in the gut microbiota metabolites associated with the pathophysiology of several neurological disorders, such as Alzheimer's disease, multiple sclerosis, Parkinson's disease, amyotrophic lateral sclerosis, stress, anxiety, depression, autism, vascular dementia, schizophrenia, stroke, and neuromyelitis optica spectrum disorders, among others. This review will discuss the current evidence from the most significant studies dealing with some SCFAs from gut microbial metabolism with selected neurological disorders., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

COVID-19 is an acute respiratory infection accompanied by pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has affected millions of people globally. To date, there are no highly efficient therapies for this infection. Probiotic bacteria can interact with the gut microbiome to strengthen the immune system, enhance immune responses, and induce appropriate immune signaling pathways. Several probiotics have been confirmed to reduce the duration of bacterial or viral infections. Immune fitness may be one of the approaches by which protection against viral infections can be reinforced. In general, prevention is more efficient than therapy in fighting viral infections. Thus, probiotics have emerged as suitable candidates for controlling these infections. During the COVID-19 pandemic, any approach with the capacity to induce mucosal and systemic reactions could potentially be useful. Here, we summarize findings regarding the effectiveness of various probiotics for preventing virus-induced respiratory infectious diseases, especially those that could be employed for COVID-19 patients. However, the benefits of probiotics are strain-specific, and it is necessary to identify the bacterial strains that are scientifically established to be beneficial.

Introduction: Diabetic nephropathy (DN) is a major complication of diabetes Mellitus. Early detection and intervention of DN can slow its progression and improve patients' outcomes. Neutrophil gelatinase-associated lipocalin (NGAL) as a marker of tubular damage might become a useful biomarker for the evaluation of renal involvement in diabetic patients. We aimed to evaluate the serum and urine NGAL(s-NGAL and u-NGAL) in type 2 diabetic patients and its correlation with different stages of diabetic nephropathy., Methods: This cross-sectional study was designed on 198 subjects consisted of 50 controls and 148 type 2 diabetes patients (50 normoalbuminuric, 58 microalbuminuric, and 40 macroalbuminuric). The study was conducted with measuring s-NGAL and u-NGAL, albumin and spot urine creatinine were also measured., Results: A highly increased level of s-NGAL was detected in macroalbuminuric group compared with controls, normoalbuminurics and microalbuminurics (P < .01). Highly raised u-NGAL levels were observed in macroalbuminurics in comparison with controls (P < .01). ROC curve demonstrated the best sensitivity and specificity of s-NGAL/u-NGAL for the macroalbuminuric state (sensitivity, 26% and 60%; specificity, 98% and 72%; respectively), in which the best cut-off points for the detection of macroalbuminuric state for s-NGAL/u-NGAL were 300 ng/mL and 71.4 ng/mL, respectively., Conclusion: Serum and urine-NGAL are elevated in type 2 diabetic patients, with or without albuminuria, s-NGAL level clearly correlates with severity of renal damage caused by DN and u-NGAL increases in macroalbuminuric state. S-NGAL could be a useful, noninvasive, available and practical test for evaluation of diabetic renal involvement. We could suggest u-NGAL as a probable predictor of macroalbuminuria.

Aim: The associations between serum levels of melatonin and concentrations of tumor necrosis factor (TNF)-a and interleukin (IL)-6 were assessed among patients with different degrees of non-alcoholic fatty liver disease., Background: Non-alcoholic fatty liver disease (NAFLD) has become a very common worldwide disease., Methods: In this cross-sectional study, adult patients diagnosed with fatty liver disease by Fibroscan evaluation were included if they met the inclusion/exclusion criteria for NAFLD. The participants were categorized into the three following groups: 1) fibrosis> 9.1KP and steatosis >290 dbm; 2) fibrosis: 6-9.0 KP and steatosis 240-285; and 3) fibrosis < 5.8 KP and steatosis<240 dbm. Post-fasting, 5 ml of venous blood was collected for laboratory assessment, and a questionnaire including demographic, anthropometric, laboratories and clinical data was completed., Results: A total of 97 participants were included. The mean age was 42.21±11 years, and 59 patients (60.0%) were female. Melatonin levels as well as pro-inflammatory cytokines levels were correlated with advancing fibrosis and steatosis in univariate analysis. A significant association was observed between these cytokines and advancing fibrosis, severe steatosis levels, and melatonin concentrations. Furthermore, in the multiple linear regression model, melatonin levels showed a significant association with these cytokines., Conclusion: Melatonin may have protective effects on tissue injury during advancing liver fibrosis via cytokines modulation. Therefore, it can be considered as a potential therapeutic management strategy for NAFLD., Competing Interests: The authors declare that they have no conflict of interest., (©2021 RIGLD, Research Institute for Gastroenterology and Liver Diseases.)

After the announcement of a new coronavirus in China in December 2019, which was then called SARS-CoV-2, this virus changed to a global concern and it was then declared as a pandemic by WHO. Human leukocyte antigen (HLA) alleles, which are one of the most polymorphic genes, play a pivotal role in both resistance and vulnerability of the body against viruses and other infections as well as chronic diseases. The association between HLA alleles and preexisting medical conditions such as cardiovascular diseases and diabetes mellitus is reported in various studies. In this review, we focused on the bioinformatic HLA studies to summarize the HLA alleles which responded to SARS-CoV-2 peptides and have been used to design vaccines. We also reviewed HLA alleles that are associated with comorbidities and might be related to the high mortality rate among COVID-19 patients. Since both genes and patients' medical conditions play a key role in both severity of the disease and the mortality rate in COVID-19 patients, a better understanding of the connection between HLA alleles and SARS-CoV-2 can provide a wider perspective on the behavior of the virus. Such understanding can help scientists, especially in terms of protecting healthcare workers and designing effective vaccines., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Mina Mobini Kesheh et al.)

Background: Human papillomavirus (HPV) infection is considered as the most common viral sexually transmitted infection worldwide. This poses an increasingly interdisciplinary medical challenge. Since there is vast scattered information in databases about HPV and the correlated diseases, we decided to collect useful data so that the experts can get a more comprehensive view of HPV. Methods: In this article, HPV-associated diseases, prevalence, prevention, and new treatments are discussed. The retrieved articles reporting the latest data about the required information for our review were selected through searching in Web of Science, Scopus, Medline (PubMed), EMBASE, Cochrane Library, Ovid, and CINHAL with language limitations of English and German. Results: There are 2 groups of HPVs: (1) low-risk HPV types that can lead to genital warts, and (2) high-risk HPV types that are involved in HPV-associated oncogenesis. About 70% of all sexually active women are infected and most of these infections heal within many weeks or months. In the case of HPV-persistence, a risk of preneoplasia or carcinoma exists. These types of viruses are responsible for the existence of genitoanal, gastrointestinal, urinary tract, and head and neck tumors. There is still no definite successful treatment. The detection of HPV-related condylomata occurs macroscopically in women and men, and the diagnosis of the precursors of cervical carcinoma in women is possible by Pap smear. Conclusion: For extragenital manifestations, there is no structured early detection program. Meanwhile, studies on HPV vaccines confirm that they should be used for the primary prevention of HPV-dependent diseases. However, we need more research to find out the real advantages and disadvantages of vaccines., Competing Interests: Conflicts of Interest: None declared, (© 2021 Iran University of Medical Sciences.)

Severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2) infection, the causative agent of COVID-19, now represents the sixth Public Health Emergency of International Concern (PHEIC)-as declared by the World Health Organization (WHO) since 2009. Considering that SARS-CoV-2 is mainly transmitted via the mucosal route, a therapy administered by this same route may represent a desirable approach to fight SARS-CoV-2 infection. It is now widely accepted that genetically modified microorganisms, including probiotics, represent attractive vehicles for oral or nasal mucosal delivery of therapeutic molecules. Previous studies have shown that the mucosal administration of therapeutic molecules is able to induce an immune response mediated by specific serum IgG and mucosal IgA antibodies along with mucosal cell-mediated immune responses, which effectively concur to neutralize and eradicate infections. Therefore, advances in the modulation of mucosal immune responses, and in particular the use of probiotics as live delivery vectors, may encourage prospective studies to assess the effectiveness of genetically modified probiotics for SARS-CoV-2 infection. Emerging trends in the ever-progressing field of vaccine development re-emphasize the contribution of adjuvants, along with optimization of codon usage (when designing a synthetic gene), expression level, and inoculation dose to elicit specific and potent protective immune responses. In this review, we will highlight the existing pre-clinical and clinical information on the use of genetically modified microorganisms in control strategies against respiratory and non-respiratory viruses. In addition, we will discuss some controversial aspects of the use of genetically modified probiotics in modulating the cross-talk between mucosal delivery of therapeutics and immune system modulation.