Evaluation of autophagy induction on HEV 239 vaccine immune response in a mouse model.

Hepatitis E virus (HEV) infection remains a serious threat to life and productivity in developing world. Vaccine seems to be an effective, safe, and affordable approach to address HEV disease burden. The HEV genome consists of three open reading frames (ORFs). Of these, ORF2 encodes a single structural protein (pORF2) for the HEV capsid which has been studied extensively as vaccine candidates. Recently, it has been recognized that autophagy plays an important role in innate and adaptive immunity defense against intracellular pathogens. This mechanism could therefore promote a protective immune response by inducing CD4+ and CD8+ T cells. In this study, HEV 239 and Beclin1 proteins were expressed in prokaryotic host cell [Escherichia coli (BL21)]. HEV 239 protein with different formulations (+Alum, +Beclin1, and +Alum-Beclin1) were used as candidate vaccines and administrated subcutaneously in BALB/c mice on 0, 14, and 28 days. Finally, elicited cellular and humoral immunity were evaluated. Taken together, although our results indicated that mice immunized with HEV 239 protein formulated with Alum, Beclin1, and Alum + Beclin1 displayed humoral and cellular response that was not significant in comparison with each other (P > 0.05); whereas they were significant while compared with control groups (P < 0.05). A comprehensive understanding of the intricate interplay between autophagy and immune response remains to be unraveled. Further study will clear the detailed impact of autophagy manipulation to enhance vaccine efficacy and boost the immune responses against the disease. © 2018 IUBMB Life, 70(3):207-214, 2018.

Antiretroviral drug resistance mutations in naïve and experienced patients in Shiraz, Iran, 2014.

Resistance to antiretroviral agents is a significant concern in the clinical management of HIV-infected individuals, particularly in areas of the world where treatment options are limited. In this study, we aimed to identify HIV drug-resistance-associated mutations in 40 drug-naïve patients and 62 patients under antiretroviral therapy (ART) referred to the Shiraz HIV/AIDS Research Center - the first such data available for the south of Iran. HIV reverse transcriptase and protease genes were amplified and sequenced to determine subtypes and antiretroviral- resistance-associated mutations (RAMs). Subtype CRF35-AD recombinant was the most prevalent in all patients (98 of 102, 96 %), followed by subtype A1, and subtype B (one each, 2 %). Among the 40 ART-naïve patients, two mutations associated with nucleoside reverse transcriptase inhibitor (NRTI) resistance (two with Y115F and T215I) and three associated with non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance (two with G190S and Y181C, four with V179T) were found. Among ART-experienced patients, four mutations associated with resistance to NRTI, four with NNRTI, and five with protease inhibitors (PI) were found. Twenty patients with high levels of resistance were already on second-line therapy. We document for the first time in this region of Iran high levels of ART resistance to multiple drugs. Our findings call for more vigilant systematic ART resistance surveillance, increased resistance testing, careful management of patients with existing regimens, and strong advocacy for expansion of available drugs in Iran.

Targeting CD47 as a therapeutic strategy: A common bridge in the therapy of COVID-19-related cancers.

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.

Alzheimer's disease and microorganisms: the non-coding RNAs crosstalk.

Alzheimer's disease (AD) is a complex, multifactorial disorder, influenced by a multitude of variables ranging from genetic factors, age, and head injuries to vascular diseases, infections, and various other environmental and demographic determinants. Among the environmental factors, the role of the microbiome in the genesis of neurodegenerative disorders (NDs) is gaining increased recognition. This paradigm shift is substantiated by an extensive body of scientific literature, which underscores the significant contributions of microorganisms, encompassing viruses and gut-derived bacteria, to the pathogenesis of AD. The mechanism by which microbial infection exerts its influence on AD hinges primarily on inflammation. Neuroinflammation, activated in response to microbial infections, acts as a defense mechanism for the brain but can inadvertently lead to unexpected neuropathological perturbations, ultimately contributing to NDs. Given the ongoing uncertainty surrounding the genetic factors underpinning ND, comprehensive investigations into environmental factors, particularly the microbiome and viral agents, are imperative. Recent advances in neuroscientific research have unveiled the pivotal role of non-coding RNAs (ncRNAs) in orchestrating various pathways integral to neurodegenerative pathologies. While the upstream regulators governing the pathological manifestations of microorganisms remain elusive, an in-depth exploration of the nuanced role of ncRNAs holds promise for the development of prospective therapeutic interventions. This review aims to elucidate the pivotal role of ncRNAs as master modulators in the realm of neurodegenerative conditions, with a specific focus on Alzheimer's disease.

A case series of pediatric COVID-19 with complicated symptoms in Iran.

People in different age groups are susceptible to SARS-CoV-2 infection as a newly emerging virus. However, the clinical course, symptoms and disease outcome vary from case to case. Although COVID-19 is usually milder in children than adults, some studies reported nonspecific symptoms. Here, we report eight pediatric cases of COVID-19 admitted in the Taleghani Children Hospital in Gorgan city, north of Iran, with complicated symptoms. The current case series poses several challenges to the pediatricians regarding the pediatric cases of COVID-19. As most literature relating to adults are not always transferable to children, clinicians should be warned about such presentations among children with COVID-19.

COVID-19 in Pediatrics: Demographic, Clinical, Laboratory, and Radiological Characteristics of Infected Patients With SARS-CoV-2.

The COVID-19 disease usually leads to mild infectious disease in children, but some develop serious complications. Here, we describe the characteristics of children with COVID-19 in northern Iran, the Golestan province. Ninety-one confirmed cases were enrolled in the study, aged 0-18 years. Demographic, clinical, comorbidity, laboratory, and radiological data were compared based on the disease severity (admitted to intensive care unit (ICU) or not) and disease outcome (recovered or deceased). Sixteen (17.5%) cases were hospitalized in ICU, and 8/91 (8.8%) deceased. Fever and cough were the most common clinical symptoms. Among all symptoms notified there were no significant differences between severe and milder cases, or between those who deceased and recovered. Failure to thrive (FTT), malignant disease and neurological disease were significantly more prevalent in severe cases as was frequently reported comorbidities. Laterality, ground-glass opacity, and lung consolidation were the most common findings in chest computed tomography. The data confirms that the COVID-19 disease has various presentations in children, and clinical, laboratory, and radiological findings may help predict the development of severe forms of COVID-19 among children.

Antitumor Effects of HPV DNA Vaccine Adjuvanted with Beclin-1 as an Autophagy Inducer in a Mice Model

Background: There is a growing interest in development of an effective adjuvant system for improving DNA vaccines. Recent findings have confirmed an important role for autophagy in both innate and adaptive immunity. The current study was undertaken to determine the efficacy of autophagy induction with Beclin-1, as a novel adjuvant system, in mice immunized with human papilloma virus (HPV) DNA vaccine. Methods: To determine whether autophagy induction with Beclin-1 enhances the efficacy of HPV DNA vaccine, female C57BL/6 mice were challenged with TC-1 tumor cells and were immunized three times at one-week intervals. Two weeks after the final immunization, the mice were sacrificed, and the antitumor effects were assessed by measurement of lymphocyte proliferation, cytotoxicity, cytokine production, and tumor regression. Results: Beclin-1 in combination with HPV-16 DNA vaccine encoding the E7 antigen induced a higher level of lymphocyte proliferation and cytotoxicity than the DNA vaccine alone. The novel combination increased the production of IFN-γ and highly inhibited tumor progression in comparison with DNA vaccine alone. Conclusion: Administration of Beclin-1, as an autophagy inducer, with HPV DNA vaccine produces antitumor effects, providing an effective adjuvant for the induction of a strong antitumor immune response.