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Crimean-Congo hemorrhagic fever virus raises the risk of neurodegenerative disease Additionally, it is important to take a look at the cellular and molecular mechanisms of viral infections that result in neurological diseases, regardless of whether the neurological disorders are brought on by the virus entering and multiplying in the brain or by neuroinflammation that affects brain function. Highlights Crimean-Congo hemorrhagic fever is a priority viral infection with pandemic potential and is regarded as an emerging infectious disease. [Extracted from the article]

Abstract Background: Newcastle disease virus (NDV) is one of the major pathogens in poultry and vaccination is intended to control the disease, as an effective solution, yet. Fusion protein (F) on surface of NDV, has a fundamental role in virus pathogenicity and can induce protective immunity, alone. With this background, here our aim was to construct a baculovirus derived recombinant bacmid shuttle vector (encoding F-protein) in order to express it in insect cell line. Materials and Methods: In this experimental study, at first complete F gene from avirulent strain La Sota of NDV was amplified by RT-PCR to produce F cDNA. The amplicon was cloned into T/A cloning vector and afterwards into pFastBac Dual donor plasmid. After the verification of cloning process by two methods, PCR and enzymatic digestion analysis, the accuracy of F gene sequence was confirmed by sequencing. Finally, F-containing recombinant bacmid was subsequently generated in DH10Bac cell and the construct production was confirmed by a special PCR panel, using F specific primers and M13 universal primers. Results: Analysis of confirmatory tests showed that the recombinant bacmid, expressing of F-protein gene in correct sequence and framework, has been constructed successfully. Conclusion: The product of this F-containing recombinant bacmid, in addition to its independent application in the induction of protective immunity, can be used with the other individual recombinant baculoviruses, expressing HN and NP genes to produce NDV-VLPs in insect cell line.

Background: Respiratory syncytial virus (RSV) is an important cause of children's pulmonary infections. However, there are fewer studies on RSV infections in adults. The purpose of this study was to describe the clinical manifestations, para-clinical characteristics, and outcome of RSV infection among adult patients who were referred to the Imam Khomeini Hospital Complex during the winter and spring of 2022-2023., Methods: From December 21, 2022, to May 20, 2023, we conducted a cross-sectional study on hospitalized adults having positive RT-PCR results for RSV. We further assessed the clinical and para-clinical characteristics and outcomes of the RSV groups., Results: We screened 1375 adults with suspected acute respiratory infections (ARIs) and confirmed RSV infections in 59 of them (4.3%). Of these, 23 patients were excluded from further analysis due to outpatient management, leaving 36 hospitalized patients with confirmed RSV infection (61.01%). The mean age of the hospitalized patients was 53.28 ± 20.37 years (range: 15-83), with a slightly higher proportion of females (52.80%) compared to males (47.20%). Dyspnea, productive cough, and fever were the most common symptoms, with a mean symptom duration of 10.50 days. Ischemic heart disease, hypertension, and liver failure were common underlying conditions. Notably, biochemical and inflammatory markers such as CRP, ESR, and LDH were significantly elevated beyond the normal range. Finally, five patients (13.9%) who received intensive care treatments died., Conclusions: Although the rate of RSV infection was not high among Iranian adults, a greater proportion of patients required hospitalization (61%). There was a significant link between liver failure, an elevated INR, more than 30% bilateral pulmonary involvement, abdominal pain, longer ICU stays, and immunodeficiency cases with increased mortality from RSV infection. We suggest that RSV infection may act as a secondary factor in decompensating pre-existing liver failure, which was present in certain patients with underlying conditions, potentially leading to life-threatening consequences., Competing Interests: Declarations. Ethical approval: The Imam Khomeini Hospital Complex (IKHC) and Tehran University of Medical Sciences (TUMS) Ethics Committee, Tehran, Iran (No. IR.TUMS.IKHC.REC.1402.277) approved the study’s conduct in accordance with the Declaration of Helsinki and International Standard Guidelines. Proper written informed consent was obtained from all the participants and the parents or legal guardians of any participant under the age of 16. This study was approved by the ethics committee of Tehran University of Medical Sciences, Tehran, Iran (No: IR.TUMS.IKHC.REC.1402.277). Consent for publication: Not applicable (N/A). Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: The prevalence of dengue fever (DF), a mosquito-borne viral disease, is rising worldwide. Its severe manifestations like thrombocytopenia and plasma leakage are associated with increased mortality. Ultrasound-detected gallbladder wall thickening (GBWT) has been suggested as a potential indicator of the severity of the disease., Aims: This systematic review and meta-analysis evaluated the predictive value of GBWT in identifying patients at risk for severe dengue., Methods: Following the PRISMA 2020 guidelines, we conducted a systematic search of Web of Science, PubMed, Embase, and Scopus. Among the inclusion criteria were original studies that assessed GBWT across various dengue severity categories. Then, we performed a meta-analysis using a random effects model and subgroup analyses based on severity criteria to determine the relationship between GBWT and severe dengue., Results: For the meta-analysis, 19 studies qualified for the inclusion criteria. There was a significant association between GBWT and severe dengue, according to the odds ratio (OR) of 2.35 (95% CI 1.88-2.82, p < 0.001). The subgroup analysis revealed consistent results for thrombocytopenia (OR: 2.65) and plasma leakage (OR: 2.26), among other severity criteria., Conclusions: A reliable ultrasound indicator, GBWT can help identify patients at risk for severe dengue early on, improving clinical decision-making and patient outcomes. However, the possibility of differential diagnosis requires cautious interpretation., Competing Interests: Declarations. Ethics approval and consent to participate: This study is a systematic review and meta-analysis, and therefore, no ethics approval or consent to participate was required. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Given the surge in mpox outbreaks in 2022 and the advancements in domestic and international vaccine research, the effectiveness of smallpox vaccines in providing cross-protection against mpox remains crucial. Having learned from the COVID-19 pandemic, it is significant to continue evaluating existing vaccines to ensure their safety and efficacy. Developing new vaccines for widespread use against mpox and its emerging strains also serves as a preventive strategy in the ongoing battle against this dynamic infection. Here's an opportunity to control human-to-human transmission, give short deadlines, and avoid vaccine disparity. Public health systems must take decisive action to prevent the global spread of mpox, particularly among vulnerable groups. This action should include strengthening global surveillance, improving vaccine access, and ensuring equitable distribution, particularly in resource-poor settings, to prevent future outbreaks. This review aims to assess recent advancements and barriers in mpox vaccine development, emphasizing cross-protection and equitable vaccine distribution in resource-poor settings., (© The Author(s), 2025.)

Antimicrobial resistance (AMR) is one of the global health challenges of the 21st century that is faced with the twin threats of global climate change and greater longevity, which pose a synergistic risk to the management of AMR. Antimicrobial agents are in high demand due to the challenges faced by increasing life expectancy and the dynamic changes in disease ecology prompted by climate change. In light of global aging and climate change, the complexity and importance of addressing antibiotic resistance are further highlighted by this interplay of issues., (© 2024. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

Background: Psychological discomfort and sleep problems are considered separate disorders. Due to the high prevalence of both disorders among people living with HIV (PLWH), this study was designed to evaluate how those challenges are present among PLWH., Method: A cross-sectional study was conducted using data from a national survey of 1185 confirmed PLWH from 15 provinces in Iran from April to August 2019. Psychological discomfort and sleep quality were assessed using standardized versions of related Persian questionnaires. Logistic regression was used to assess the association between psychological discomfort and sleep quality in PLWH., Results: The overall prevalence of poor sleep quality, depression, anxiety, and stress was 47.71%, 50.95%, 44.26%, and 41.77%, respectively. The results of multivariate-adjusted logistic regression showed that each psychological discomfort covariate increased the odds of poor sleep quality. Depression by adjusting for anxiety and stress, anxiety by adjusting for depression and stress, and stress by adjusting for depression and anxiety all increased the odds of poor sleep quality., Conclusion: A high prevalence of psychological discomfort was observed in PLWH. Depression, anxiety, and stress were strongly associated with sleep quality. PLWH needed more attention and social support in order to reduce sleep and psychological issues., (© 2023. The Author(s).)

The present study evaluates the non-communicable disease (NCD) patterns and related risk factors among people living with HIV (PLWH) in Iran. This national cross-sectional survey study was conducted on 1173 confirmed PLWHs with a mean age of 35.35 (56.82 Over 50 years old, 33.90 Under 50 years old) admitted from 15 different provinces in the country. Logistic regression was used to analyze the association of factors with having at least one NCD comorbidity. From 1173 PLWH, 225(19.18%) participants experienced at least one NCD (15.20% and 38.69% among under- and over-50-year-old patients, respectively). The prevalence of heart disease, hypertension, diabetes, and sleep apnea among all patients was 1.59%, 2.05%, 1.55%, and 10.26%, respectively. The similar prevalence for each NCD among those over 50 years was 10.11%, 15.71%, 9.01%, 25.44%, and 1.01%, 1.12%, 1.04%, and 9.23% among those under 50 years, respectively. The odds of being at risk of at least one NCD stood higher in patients over 50 years (ORadj = 2.93, 95% CI 1.96-4.37), married (ORadj = 2.48, 95% CI 1.41-4.35), divorced or widowed (ORadj = 2.78, 95% CI 1.48-5.20), and obese (ORadj = 3.82, 95% CI 2.46-5.91). According to our findings regarding the prevalence of NCDs among patients under 50 years of age, we recommend that policymakers give greater consideration to this group in the screening and care programs for NCDs since adults and the elderly are both vulnerable to the risk factors for developing NCDs., (© 2023. Springer Nature Limited.)

Macrophages are essential mediators of innate immunity. Non-self-cells resist phagocytosis through the expression of the checkpoint molecule CD47. CD47, as the integrin-associated protein, is overexpressed on tumor and SARS-CoV-2-infected cells as a potential surface biomarker for immune surveillance evasion. CD47-signal-regulating protein alpha (SIRPα) interaction is a promising innate immunotarget. Previous findings based on monoclonal antibodies (mAbs) or fusion proteins that block CD47 or SIRPα have been developed in cancer research. While CD47 efficacy in infectious diseases, especially severe COVID-19 studies, is lacking, focus on macrophage-mediated immunotherapy that increases "eat me" signals in combination therapy with mAbs is optimistic. This integrin-related protein can be as a potential target to therapy for COVID-19. Here, we concentrate on the role of the CD47 signaling pathway as a novel therapeutic strategy for COVID-19-associated cancer treatment., Competing Interests: 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., (© 2023 The Author(s).)

Competing Interests: 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.

Over time, the antigenic evolution of emerging variants of SARS-CoV-2 has demanded the development of potential protective vaccines. Administration of additional doses of current vaccines based on the WT spike protein may boost immunity, but their effectiveness has dwindled for patients with more recent variants. Here, we studied the neutralization activity of post-WT strain-based vaccination and a structural simulation in-silico based on the interactions of the RBD-hACE2 as the key to initiating infection among the VOCs of SARS-CoV-2. Our data display shows that WT sera showed a markedly greater reduction in Delta and Omicron , suggesting that the Wuhan-based vaccines may be more susceptible to breakthrough and new VOCs. According to the MD simulation, mutations of Omicron result in a significant change in the variant charge distribution throughout the binding interface that consequently alters the critical interface electrostatic potential in comparison to other variants. This observation provides new insights into immunization policy and next-generation vaccine development., Competing Interests: The authors declare no competing interests., (© 2023 Published by Elsevier Ltd.)

The mpox (disease caused by the monkeypox virus) epidemic in 2022 provides a good opportunity to study the immune response to mpox. Vaccinia virus-infected monocytes could be recognized by monkeypox virus-specific CD4+ and CD8+ T cells, which produce inflammatory cytokines including IFNγ and TNFα. However, these cells are mostly unable to react to monkeypox virus-infected cells. The monkeypox virus also has no effect on the expression of MHC classes. Cells infected with monkeypox virus can prevent T cells from being activated via their T cell receptors. Insensitivity is an MHC-independent strategy for controlling antiviral T cells activation and inflammatory cytokines production. It is likely a critical aspect of virus spread in the infected host. The ability of monkeypox virus to spread efficiently as cell-associated viremia may be explained by the evasion strategies employed by the virus to subvert immunological surveillance by virus-specific T cells., 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 © 2023 Zandi, Shafaati and Hosseini.)

The mammalian brain has an endogenous central circadian clock that regulates central and peripheral cellular activities. At the molecular level, this day-night cycle induces the expression of upstream and downstream transcription factors that influence the immune system and the severity of viral infections over time. In addition, there are also circadian effects on host tolerance pathways. This stimulates adaptation to normal changes in environmental conditions and requirements (including light and food). These rhythms influence the pharmacokinetics and efficacy of therapeutic drugs and vaccines. The importance of circadian systems in regulating viral infections and the host response to viruses is currently of great importance for clinical management. With the knowledge gained from the COVID-19 pandemic, it is important to address any outbreak of viral infection that could become endemic and to quickly focus research on any knowledge gaps. For example, responses to booster vaccination COVID-19 may have different time-dependent patterns during circadian cycles. There may be a link between reactivation of latently infected viruses and regulation of circadian rhythms. In addition, mammals may show different seasonal antiviral responses in winter and summer. This article discusses the importance of the host circadian clock during monkeypox infection and immune system interactions., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Monkeypox virus is a member of the Orthopoxvirus genus and the Poxviridae family. Orthopoxviruses are among the most intricate animal viruses. The pathogenicity of human monkeypox infection has been emphasized in response to its recent emergence in non-endemic countries and the threat of bioterrorism. It is always necessary to take appropriate precautions in exposure to emerging or re-emerging infections. Here, we focus on the current state of the human monkeypox infection outbreak, research & development of immune responses, and clinical interventions to prevent and treat the human monkeypox virus and other human poxviruses., (© 2022 Wiley Periodicals LLC.)

The non-endemic monkeypox outbreak in 2022 is the largest outside of Africa in recorded history. The assumption is that monkeypox, an emerging zoonotic disease, has a high potential for epidemic spread with increased human outbreaks in recent years. The vaccinia-based smallpox vaccination has been discontinued globally for more than 40 years. Additionally, there are now more vulnerable populations. Populations who have not received the vaccine are more susceptible to monkeypox viral infection, while smallpox cannot spontaneously recur. As a member of the orthopoxvirus family and because of its potential for rapid adaptation in humans, the monkeypox virus (MPXV) has emerged as a pathogen that needs further study. Many non-endemic countries with no prior history of travel to an endemic region had increased global health concerns after the finding of MPXV cases in May 2022. Here, we summarize the clinical significance of MPXV and its unique infection characteristics. Finally, this review sheds light on worries regarding its resurgence in global health., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Many questions on the SARS-CoV-2 pathogenesis remain to answer. The SARS-CoV-2 genome encodes some accessory proteins that are essential for infection. Notably, accessory proteins of SARS-CoV-2 play significant roles in affecting immune escape and viral pathogenesis. Therefore SARS-CoV-2 accessory proteins could be considered putative drug targets. IFN-I and IFN-III responses are the primary mechanisms of innate antiviral immunity in infection clearance. Previous research has shown that SARS-CoV-2 suppresses IFN-β by infecting host cells via ORF3a, ORF3b, ORF6, ORF7a, ORF7b, ORF8, and ORF9b. Furthermore, ORF3a, ORF7a, and ORF7b have a role in blocking IFNα signaling, and ORF8 represses IFNβ signaling. The ORF3a, ORF7a, and ORF7b disrupt the STAT1/2 phosphorylation. ORF3a, ORF6, ORF7a, and ORF7b could prevent the ISRE promoter activity. The main SARS-CoV-2 accessory proteins involved in immune evasion are discussed here for comprehensive learning on viral entry, replication, and transmission in vaccines and antiviral development., Competing Interests: Conflict of interest statement The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Competing Interests: All authors report no conflicts of interest relevant to this article.

With the COVID-19 pandemic globally, the ongoing threat of new challenges of mucosal infections was once again reminded human beings. Hence, access to the next-generation vaccine to elicit mucosal immunity is required to reduce virus shedding. SARS-CoV-2 retains a unique polybasic cleavage motif in its spike protein, recognized by the host furin protease. The proteolytic furin cleavage site at the junction of S1/S2 glycoprotein plays a key role in the pathogenesis of SARS-CoV-2. Here, we examined the protective immunity of a double-deleted PRRA/GTNGTKR motifs cold-adapted live-attenuated candidate vaccines as a called "KaraVac." using a hamster animal model of infected attenuated SARS-CoV-2. The KaraVac vaccinated hamsters were challenged against the wild-type (WT) SARS-CoV-2. No apparent bodyweight loss and histopathological lesions were observed in the hamsters. The establishment of sterilizing immunity was induced via stimulating a robust neutralizing antibody (NAb) response in a hamster model. Consequently, deletions in the spike sequence and inoculation into hamsters provide resistance to the subsequent challenge with WT SARS-CoV-2. We have suggested that deletion of the furin cleavage site and GTNGTKR motifs in the spike sequence attenuates the virus from the parental strain and can be used as a potent immunogen., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Viral infectious diseases have various neurological manifestations, whether they are epidemic or pandemic in nature. Nonspecific encephalopathy is the most common central nervous system (CNS) manifestation. The spectrum of nervous evidence varies for viral pathogens. Some infectious viruses, such as the Ebola virus, exhibit direct neurotropism. Others, such as the Rift Valley fever virus, have the potential for neurotropism. Direct neurotropism is unknown in monkeypox virus, SARS-CoV-2, MERS-CoV, and even smallpox. As seen in the COVID-19, there may be evidence of para-infectious neurological syndrome. There have only been a few reports of neurological diseases caused by monkeypox infection. Future efforts to prevent the spread of infectious disease surges can reduce mortality complications, the therapeutic burden on the health-care system, and prevent further spread. This study describes the clinical and neurological complications of monkeypox infection, particularly encephalitis, as well as the laboratory diagnosis of these cases., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Newcastle disease virus (NDV) belongs to the genus Avaluvirus and Paramyxoviridae family, and it can cause acute, highly contagious Newcastle disease in poultry. The two proteins, haemagglutinin neuraminidase (HN) and Fusion (F), are the main virulence factor of the virus and play an essential role in immunogenicity against the virus. In most paramyxoviruses, the F protein requires HN protein to fuse the membrane, and HN proteins substantially enhance the viruses' fusion activity., Results: The present study describes the successful cloning and expression of HN protein from NDV in Bacillus subtilis WB800 using the modified shuttle vector pHT43. HN coding sequence was cloned into the pGet II vector. It was then subcloned into the PHT43 shuttle vector and transferred to Escherichia coli for replication. The recombinant plasmid was extracted from E. coli and used to transform B. subtilis by electroporation. After induction of recombinant B. subtilis by IPTG, total cell protein and the protein secreted into the media were analysed through a time course using SDS-PAGE. The expressed HN protein was purified using cation exchange chromatography followed by metal affinity chromatography, using the 6× His epitope introduced at the carboxyl terminus of the recombinant protein. The accuracy of the PHT43-HN construct was confirmed by sequencing and enzymatic digestion. SDS-PAGE results showed that the recombinant HN protein was successfully expressed and secreted into the medium. Moreover, the purified HN protein showed neuraminidase activity with characteristics similar to the indigenous HN NDV protein. B. subtilis is a free endotoxin host that could be a favourite prokaryotic platform for producing the recombinant HN protein., Conclusion: The establishment of this expression and purification system has allowed us to explore further the biochemical characteristics of HN protein and obtain material that could be suitable for a new production of NDV candidate vaccine with high immunogenicity., (© 2022. The Author(s).)

Background: Small non-coding RNAs have emerged as essential modulators of viral infections such as hepatitis C virus (HCV). Cellular miRNAs directly regulate the viral infectivity and indirectly by targeting virus-host factors. The current study investigates the inhibitory effect of let-7b miRNA on HCV replication in the Hepatocarcinoma cell line (Huh7.5)., Methods and Results: The algorithm-based search revealed that let-7b, a high score microRNA, has target sequences on the HCV genome. The Huh7.5 cells were stably transduced with let-7b lentiviral vectors (Huh7.5/let-7b) and mock (Huh7.5/scrambled). The expression of the let-7b level was assessed by real-time PCR assay and Red fluorescence microscope. A dual-luciferase assay was conducted to evaluate the liver-specific let-7b and HCV genome interaction. In the next step, for establishing HCVcc, Full-length HCV-RNA was transduced to naïve Huh7.5, Huh7.5/scrambled, and Huh7.5/let-7b cells. The results of in silico analysis and dual-luciferase reporter assay exhibited a specific interaction of HCV-NS5B and let-7b. Real-time PCR analysis revealed that in contrast to infected naïve Huh7.5 cells and Huh7.5/scrambled, a significant decrease in HCV-RNA load was seen in Huh7.5/let-7b cells. On the other hand, the Flow Cytometry test showed that let-7b could significantly induce the apoptosis pathway in Huh7.5/let-7b., Conclusions: The results also suggest that let-7b, as a target of the HCV genome, potentially reduces HCV replication and raises cell apoptosis rate. We suggest that let-7b directly downregulates HCV replication and may serve as a unique antiviral therapy., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

A 34-year-old female clinical virology assistant was punctured with a contaminated lancet used for sampling from a suspected Hand, Foot, and Mouth disease (HFMD) patient. Five days after a puncture, the disease symptoms manifested, including high fever, ague, and stiff neck. Skin rashes suddenly appeared after day 6. Stiff neck and fever were relieved two days after the rash appeared, and rashes disappeared gradually by the next five days. Samples for molecular detection and virus cultivation were taken from the patient. Real-time PCR found the enteroviral RNA in the throat swab and skin rashes. The specific CPE of Enteroviruses appeared on the Vero cell line after three days of incubation. In this case transmission occurs through needle injury and results in the systemic disease, so unusual and unexpected viral transmission should be considered when dealing with samples., (© 2022 The Authors.)

Background: Newcastle disease (ND) virus (NDV) is one of the major pathogens in poultry farms that causes severe economic damages to the poultry industry, especially broiler chicken and turkey farms. Despite the endemicity of ND and its many epidemics in the country, the nature of the Iranian strain of the Newcastle virus is still largely unknown. This study aimed to characterise and evaluate NDV isolates obtained from commercial poultry farms in Iran in 2019 through haemagglutinin-neuraminidase (HN) gene sequencing., Method: HN gene of each NDV isolate was amplified and sequenced using specific primers followed by phylogenetic analysis of full length of HN gene open reading frame and amino acid (aa) sequence of HN., Results: Phylogenetic analysis of the HN gene showed that the virus is very closely related to genotypes VII and III. Analysis of HN gene nucleotide sequences showed that all isolates encode proteins with a length of 571 aa., Conclusion: Results of the present study are useful for a better understanding of molecular epidemiology of indigenous NDV strains and determining important molecular differences between fields and commonly used vaccine strains related to main immunogenic proteins., (© 2021 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

More than a year after the SARS-CoV-2 pandemic, the Coronavirus disease 19 (COVID-19) is still a major global challenge for scientists to understand the different dimensions of infection and find ways to prevent, treat, and develop a vaccine. On January 30, 2020, the world health organization (WHO) officially announced this new virus as an international health emergency. While many biological and mechanisms of pathogenicity of this virus are still unclear, it seems that cytokine storm resulting from an immune response against the virus is considered the main culprit of the severity of the disease. Despite many global efforts to control the SARS-CoV-2, several problems and challenges have been posed in controlling the COVID-19 infection. These problems include the various mutations, the emergence of variants with high transmissibility, the short period of immunity against the virus, the possibility of reinfection in people improved, lack of specific drugs, and problems in the development of highly sensitive and specific vaccines. In this review, we summarized the results of the current trend and the latest research studies on the characteristics of the structure and genome of the SARS-CoV- 2, new mutations and variants of SARS-CoV-2, pathogenicity, immune response, virus diagnostic tests, potential treatment, and vaccine candidate., (Copyright © 2021 Elsevier B.V. All rights reserved.)

This article provides a brief overview of DNA vaccines. First, the basic DNA vaccine design strategies are described, then specific issues related to the industrial production of DNA vaccines are discussed, including the production and purification of DNA products such as plasmid DNA, minicircle DNA, minimalistic, immunologically defined gene expression (MIDGE) and Doggybone™. The use of adjuvants to enhance the immunogenicity of DNA vaccines is then discussed. In addition, different delivery routes and several physical and chemical methods to increase the efficacy of DNA delivery into cells are explained. Recent preclinical and clinical trials of DNA vaccines for COVID-19 are then summarized. Lastly, the advantages and obstacles of DNA vaccines are discussed., (© 2021 Future Medicine Ltd.)

Hepatitis C virus (HCV) is a positive-sense, single-stranded RNA virus that causes chronic hepatitis and hepatocellular carcinoma. Cellular microRNAs (miRNAs) directly modulate the viral infectivity and indirectly through targeting virus-related host factors. They play an essential role in the progression of different stages of HCV infection. The roles of miR-196 family in HCV infection and hepatocellular carcinoma progression remain poorly understood. Using ViTa databases, miR-196a as a high-score miRNA targeting the NS 5 A region of HCV genome was selected. Using dual luciferase assay and an established cell-cultured HCV (HCVcc) system, the effect of miR-196a on HCV genome was assessed. In silico analysis demonstrated the significant role of miR-196a in the downregulation of HCV replication. Using dual luciferase assay, the liver-specific miR-196a and NS 5 A gene binding was confirmed. To assess the experimental role of miR-196a, an HCVcc system was established in the Huh 7.5 cell lines. The HCV-RNA 1b derived from an infected patient was transfected into Huh 7.5 cells containing miR-196a lentiviral vectors (Huh 7.5/miR-196a), mocks (Huh 7.5/mock vector), and naïve Huh 7.5 cells. The rate of reduction of the HCV genome replication was assessed using relative real-time PCR assay. These results represent miR-196a overexpression and its roles in regulating HCV genome replication. However, miR-196a may inhibit HCV replication and accelerate the early stages of apoptosis. Overexpression of miR-196a in Huh 7.5 replicon cell is a potential new strategy to prevent hepatitis C infection. The results of this study suggest that miR-196a directly downregulates HCV replication and may serve as a new antiviral therapy., (© 2021 The Societies and John Wiley & Sons Australia, Ltd.)

Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) strains are a major cause of hospital-acquired infections and are considered a serious public health concern. MRSA isolates have abundant virulence factors that are the basis for their pathogenicity. The accessory gene regulator (agr) locus co-ordinates the expression of these genes. The aim of this study was to determine the presence and frequency of various virulence genes encoding enterotoxins and adhesins as well as to identify agr specificity groups in MRSA isolates., Methods: This descriptive study included a total of 296 MRSA strains isolated from clinical samples collected in Tehran Heart Center (Tehran, Iran) between October 2004 and March 2013. Following DNA extraction, PCR-based assays were used to evaluate the presence of various virulence genes. IBM SPSS Statistics for Windows v.21.0 was used for statistical analysis., Results: The results indicated that the most frequent toxin genes were see (120/296; 40.5%), followed by sea (79/296; 26.7%); the other genes were encoded less frequently. The presence of seb and seh was not found in any of the isolates. Furthermore, the most frequent adhesin genes were clfA, spa, cna, map/eap and bbp, found in 281 (94.9%), 275 (92.9%), 267 (90.2%), 265 (89.5%) and 264 (89.2%) isolates, respectively. The majority of isolates belonged to agr group I (53.0%), followed by agr group III (1.4%). None of the isolates belonged to agr group II., Conclusions: The relatively high frequency of various virulence genes suggests the emergence and pathogenic potential of MRSA isolates containing these genes in the study area., (Copyright © 2017 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.)

Introduction: Antiseptics and disinfectants have been used widely in hospitals and other health care settings to control the growth of microorganisms. However, some disinfectant resistant strains were reported. The objectives of our study were to evaluate correlation between the efflux pump genes, drugs and disinfectant resistant among clinical isolates of E.coli., Methods: A total of 102 of E. coli strains were isolated from urine sample of hospitalized patients. The antibiotic susceptibility was carried out by disc diffusion method. Didecyl di-methyl ammonium chloride (DDDMAC) was used as Quaternary ammonium compound (QAC) disinfectant which was used in Heart Center Hospital. PCR reaction was carried out for detection of qacE and qac∆E efflux pump genes., Result: Almost all the strains had higher resistance to ampicillin, ciproflaxacin, cotrimaxazole and cephalothin. Totally 49% (n: 50) of strains were produced ESBL. Almost all the strains have MIC value between 0.00195 to 0.0078 mg/l for DDDMAC. Correlation between presence of qacE and qac∆E genes and antibiotic resistance was perceived. Presence of qacE and qac∆E genes among strains that have high disinfectant MIC value were 96.9% and 93.7% respectively. In addition, 98% of ESBL producing strains harbored qacE gene and 94% of ESBL producing strains harbored qac∆E gene., Conclusion: Our study indicated that there was a strong correlation between presence of qacE and qac∆E genes with resistance to some antibiotics and growth in media which contain high concentration of disinfectant. In conclusion, other mechanisms also play important role in resistant to antimicrobial agents but the role of efflux pumps in resistant to antimicrobial agents should not be neglected., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

We previously described a heterozygous mouse model overexpressing human HA-tagged 24S-hydroxylase (CYP46A1) utilizing a ubiquitous expression vector. In this study, we generated homozygotes of these mice with circulating levels of 24OH 30-60% higher than the heterozygotes. Female homozygous CYP46A1 transgenic mice, aged 15 months, showed an improvement in spatial memory in the Morris water maze test as compared to the wild type mice. The levels of N-Methyl-D-Aspartate receptor 1, phosphorylated-N-Methyl-D-Aspartate receptor 2A, postsynaptic density 95, synapsin-1 and synapthophysin were significantly increased in the hippocampus of the CYP46A1 transgenic mice as compared to the controls. The levels of lanosterol in the brain of the CYP46A1 transgenic mice were significantly increased, consistent with a higher synthesis of cholesterol. Our results are discussed in relation to the hypothesis that the flux in the mevalonate pathway in the brain is of importance in cognitive functions.

The two oxysterols, 27-hydroxycholesterol (27OH) and 24S-hydroxycholesterol (24OH), are both inhibitors of cholesterol synthesis and activators of the liver X receptor (LXR) in vitro. Their role as physiological regulators under in vivo conditions is controversial, however. In the present work, we utilized a previously described mouse model with overexpressed human sterol 27-hydroxylase (CYP27A1). The levels of 27OH were increased about 12-fold in the brain. The brain levels of HMG-CoA reductase mRNA and HMG-CoA synthase mRNA levels were increased. In accordance with increased cholesterol synthesis, most of the cholesterol precursors were also increased. The level of 24OH, the dominating oxysterol in the brain, was decreased by about 25%, most probably due to increased metabolism by CYP27A1. The LXR target genes were unaffected or slightly changed in a direction opposite to that expected for LXR activation. In the brain of Cyp27(-/-) mice, cholesterol synthesis was slightly increased, with increased levels of cholesterol precursors but normal mRNA levels of HMG-CoA reductase and HMG-CoA synthase. The mRNA levels corresponding to LXR target genes were not affected. The results are consistent with the possibility that both 24OH and 27OH are physiological suppressors of cholesterol synthesis in the brain. The results do not support the contention that 27OH is a general activator of LXR target genes in this organ.

There is a significant flux of the neurotoxic oxysterol 27-hydroxycholesterol (27OHC) from the circulation across the blood-brain barrier. Because there is a correlation between 27OHC and cholesterol in the circulation and lipoprotein-bound cholesterol does not pass the blood-brain barrier, we have suggested that 27OHC may mediate the effects of hypercholesterolemia on the brain. We previously demonstrated a modest accumulation of 27OHC in brains of patients with sporadic Alzheimer's disease (AD), consistent with a role of 27OHC as a primary pathogenetic factor. We show here that there is a 4-fold accumulation of 27OHC in different regions of the cortexes of patients carrying the Swedish amyloid precursor protein (APPswe) 670/671 mutation. The brain levels of sitosterol and campesterol were not significantly different in the AD patients compared with the controls, suggesting that the blood-brain barrier was intact in the AD patients. We conclude that accumulation of 27OHC is likely to be secondary to neurodegeneration, possibly a result of reduced activity of CYP7B1, the neuronal enzyme responsible for metabolism of 27OHC. We discuss the possibility of a vicious circle in the brains of the patients with familial AD whereby neurodegenerative changes cause an accumulation of 27OHC that further accelerates neurodegeneration.