Molecular characterization of human astrovirus infection in children under 5 years of age with acute gastroenteritis in Tehran, Iran, 2021-2022: co-infection with rotavirus.

Human astroviruses (HAstVs) are considered important causative pathogens of acute gastroenteritis (AGE) in children under 5 years of age worldwide, along with group A rotavirus (RVA), norovirus (NoV), and enteric adenovirus (EAdV). The present study was aimed to both detect HAstV and its co-infections and investigate genetic analysis of circulating HAstV and co-infected virus in hospitalized children under 5 years of age with AGE in Iran. Accordingly, a sum of 200 stool specimens were screened by PCR for HAstV during 2021-2022. The HAstV was found in 0.5% of 200 specimens (n = 1) while was co-infected with RVA. The genetic and phylogenetic analysis indicated HAstV1 genotype, which clustered with viruses from lineage 1b, which has not been previously reported in Iran. The detected RVA strain belonged to G1 lineage II/P[8]-lineage III, which has been reported previously in Iran as the most common strain. The further genetic analysis of RVA VP6 and NSP4 demonstrated an atypical genotype pattern G1P[8]-I1-E2, as a mono-reassortant of a Wa-like genogroup, which appeared to be reassorted with the NSP4 gene of E2 genotype of the G2P[4] DS-1 genogroup. Although the clinical outcomes of the AGE-causing viruses co-infection is not yet entirely clear, it seems that future studies will be helpful to merge clinical and epidemiological data of co-infecting viruses for a more accurate medical and clinical relevance in symptomatic children.

Medical, pharmaceutical, and nutritional applications of 3D-printing technology in diabetes.

AIMS: Despite numerous studies covering the various features of three-dimensional printing (3D printing) technology, and its applications in food science and disease treatment, no study has yet been conducted to investigate applying 3D printing in diabetes. Therefore, the present study centers on the utilization and impact of 3D printing technology in relation to the nutritional, pharmaceutical, and medicinal facets of diabetes management. It highlights the latest advancements, and challenges in this field. METHODS: In this review, the articles focusing on the application and effect of 3D printing technology on medical, pharmaceutical, and nutritional aspects of diabetes management were collected from different databases. RESULT: High precision of 3D printing in the placement of cells led to accurate anatomic control, and the possibility of bio-printing pancreas and ß-cells. Transdermal drug delivery via 3D-printed microneedle (MN) patches was beneficial for the management of diabetes disease. 3D printing supported personalized medicine for Diabetes Mellitus (DM). For instance, it made it possible for pharmaceutical companies to manufacture unique doses of medications for every diabetic patient. Moreover, 3D printing allowed the food industry to produce high-fiber and sugar-free products for the individuals with DM. CONCLUSIONS: In summary, applying 3D printing technology for diabetes management is in its early stages, and needs to be matured and developed to be safely used for humans. However, its rapid progress in recent years showed a bright future for the treatment of diabetes.

Application of Nanotechnology to Develop Carrageenan-based Films and Coatings as Carriers for Essential Oils.

This review highlights the effect of combining bioactive agents, especially nanoparticles, in carrageenan coating to increase the quality and stability of foods. This study is designed based on a review of previous studies. Biopolymer coatings and films are suitable for food and non-food packaging due to their degradability, renewable and edible nature. Edible coatings and films are based on polysaccharides, proteins, and lipids. They confer some beneficial effects on foods, such as improvement of appearance and texture, reducing the amount of moisture loss and oxidation, prevention of the release of gases and control of microbial growth, delaying ripening and adverse changes in color and taste, improvement of nutritional value, and increasing the shelf life of the product. These improvements lead to the prevention of food spoilage and increase the shelf life of various foods. In addition, nanomaterials and food additives such as antimicrobial and antioxidant agents, flavorings, and colors can be incorporated into food coatings and films to expand their applications. Nanotechnology can be applied in coatings and food films using nanoparticles. However, more research is still needed to gather information about coating formulations, especially when new materials are incorporated into them.

Carnitine in Alleviation of Complications Caused by Acute Valproic Acid Toxicity; an Exprimental Study on Mice.

Introduction: Hyperammonemia and hepatotoxicity are well-known complications of valproic acid (VPA) poisoning. The objective of this study is to evaluate the potential role of carnitine in mitigating the adverse effects of acute VPA toxicity in mice. Methods: 54 male mice (25-30 g) were randomly assigned to one of three categories, including acute, sub-acute, and chronic poisoning. Each category contained 3 groups, each consisting of 6 mice (Group 1: control, Group 2: VPA treated, and Group 3: VPA + carnitine treated). The animals were sacrificed 24 hours after the initial injection, and their blood, liver, and brain samples were compared between groups of each category regarding liver function biomarkers, oxidative stress markers, ammonia level, and liver histopathologic changes using one-way ANOVA followed by Tukey's multiple comparison test. Results: The administration of VPA increased the serum level of aspartate aminotransferase (AST) (p=0.003) and alanine aminotransferase (ALT) (p=0.001), as well as serum, and brain level of ammonia (p=0.0001 for both) in the intervention group. Elevated levels of lipid peroxidation and oxidative stress (p=0.0001 for both) in the liver tissue, decreased liver glutathione (p=0.0001) and ferric ion-reducing antioxidant power (FRAP) (p=0.0001), and histopathologic changes in the form of moderate to severe inflammation were observed. Administration of VPA + carnitine reduced AST (p=0.05) and ALT (p=0.01), increased the FRAP, reduced free oxygen radicals and liver lipid peroxidation (p=0.0001 for all), and decreased tissue damage in the form of moderate inflammation. The administration of carnitine was ineffective in reducing brain or plasma ammonia levels in acute VPA-treated animals (p = 0.0115). Conclusions: Although the administration of carnitine has been suggested as a protective remedy in cases of VPA toxicity, according to the present study, it did not have an antidotal effect and did not prevent encephalopathy or liver injury in acute VPA toxicity.

The predominance of recombinant Norovirus GII.4Sydney[P16] strains in children less than 5 years of age with acute gastroenteritis in Tehran, Iran, 2021-2022.

The present study was aimed to both detect emerging noroviruses and investigate RdRp and VP1-based dual typing of circulating noroviruses in hospitalized children less than 5 years of age with acute gastroenteritis (AGE) in Iran. For this purpose, a total of 200 stool specimens were screened during 2021-2022 by real-time RT-PCR for genogroup I and II (GI and GII) and dual-typed by sequence analysis of PCR products, using a web-based norovirus Typing Tool and phylogenetic analysis. The GI and GII noroviruses were detected in 20% of 200 specimens. The GII.4 norovirus was found to be the most common VP1 genotype (53%) followed by GII.8 (32%), GII.7 (6%), GII.17 (6%), and GII.3 (3%). The GII.P16 norovirus was also found as the predominant RdRp type (53%) followed by GII.P8 (32%), GII.P7 (6%), GII.P17 (6%), and GII.P31 (3%). To our knowledge, this is the first report that highlights the dominancy of recombinant norovirus GII.4Sydney[P16] and newly emerging of norovirus GII.8 [P8], GII.17 [P17] and GII.3 [P16] in Iran. These findings further indicate inter-genotype recombinant strains of noroviruses.

Potential role of EBV and Toll-like receptor 9 ligand in patients with systemic lupus erythematosus.

SLE is a multisystem autoimmune disease characterized by multiple immunological abnormalities including production of autoantibodies. While the etiology of SLE is largely unknown, it is generally accepted that both genetic and environmental factors contribute to disease risk and immune dysregulation. Production of IFN-α is important for protecting the host against infections; however, over stimulation of innate immune pathways can induce autoimmune disease. Environmental factors, particularly Epstein-Barr virus (EBV), have been proposed to play an important role in SLE disease. Improper engagement of Toll-like receptor (TLR) pathways by endogenous or exogenous ligands may lead to the initiation of autoimmune responses and tissue injury. EBV is shown to be a potent stimulant of IFN-α by TLR signaling cascades. Given the highlighted role of IFN-α in SLE pathogenesis and potential role of EBV infection in this disease, the present study is aimed at exploring the in vitro effects of EBV infection and CPG (either alone or in combination) on IFN-α. We also examined the expression level of CD20 and BDCA-4 and CD123 in PBMCs in 32 SLE patients and 32 healthy controls. Our results showed PBMCs treated with CPG-induced higher levels of IFN-α and TLR-9 gene expression fold change compared to cells treated with either EBV or EBV-CPG. Moreover, PBMCs treated with CPG produced significantly higher IFN-α concentration in supernatant compared to cells treated with EBV but not EBV-CPG. Our results further highlight the potential role of EBV infection and TLRs in SLE patients although more studies are warranted to ascertain the global imprint that EBV infection can have on immune signature in patients with SLE.

Electrospinning of Nanofibers Incorporated with Essential Oils: Applications in Food.

Nowadays, modern food preservation techniques have emerged in the last decade. Recently, a combination of nanotechnology and active packaging has allowed the incorporation of bioactive compounds, such as essential oils, into nanoscale electrospun fibers. This phenomenon provides a new horizon in food safety and preservation. The incorporation of essential oils into electrospun nanofibers can extend the duration of antimicrobial and antioxidant activity of essential oils, which subsequently leads to longer shelf life, better preservation, and superior quality of food. In the current paper, the essential oils incorporated into nanofibers have been reviewed. The fabrication of nanofibers is usually carried out using different substances by applying various manufacturing methods, including needleless and needle-based electrospinning techniques. In this study, an emphasis on the antioxidant and antibacterial effects of electrospun nanofibers loaded with essential oils and their application in food models has been laid. Nevertheless, other challenges associated with using nanofibers incorporated with essential oils, such as their impact on organoleptic properties, cytotoxicity, and durability, have been discussed to achieve a holistic view of applying the electrospinning techniques in the food industry.

Piperonylbutoxide as a Dubious Cause of Cardiac Manifestations in Pyrethroid Insecticide Poisoning; a Letter to Editor.

There is little evidence regarding pyrethroid poisoning manifesting with cardiac problems in the literature. Many authors, however, adopted that pyrethroids have a direct effect on heart tissue and can cause cardiotoxicity. Interestingly, no experimental studies have yet determined its mechanism of toxicity on cardiac muscle cells. This letter aims to describe the probable cause of clinical manifestations attributed to piperonylbutoxide, an ignored ingredient in pesticide poisoning, which is added to many pesticide products to increase their insecticidal potency. We think that cardiac manifestations in some cases of pyrethroid poisoning are due to the concomitant piperonylbutoxide toxicity and its possible effect on norepinephrine release from adrenal gland, which might explain changes in cardiac findings. Thus, it is necessary for all clinical toxicologists to determine suspicious ingredients when they are facing a doubtful manifestation.

In vitro Effect of EBV Infection on HERV-K18 env Expression in the Presence and Absence of Vitamin D in Multiple Sclerosis Patients.

Background: HERV-K env is associated with several neurological disorders, including MS. Clinical studies have demonstrated a plausible interaction between HERV-K env and other MS risk factors. The present study aimed to investigate the possible association between HERV-K18 env and TGF-ß. We further assessed the in vitro effect of EBV infection on HERV-K18 env expression in the presence and absence of vitamin D in MS patients. Methods: PBMCs from 20 MS patients and 20 healthy controls were infected with the B95.8 EBV, seeded into 24-well plates and incubated in the presence or absence of 100 nM of 1,25(OH)D3. The expression levels of HERV-K18 env and TGF-ß were measured using real-time PCR. Results: While the expression level of HERV-K18 env was significantly higher in MS patients than the healthy controls, this trend for TGF-ß was significantly reverse. Interestingly, an inverse correlation was found between HERV-K18 env and TGF-ß expression in MS patients, although the in vitro stimulation of PBMCs with EBV and vitamin D showed no significant differences in terms of HERV-K18 expression. Conclusion: Our findings highlight the potential role of HERV-K18 env in MS patients.

WITHDRAWN: Electrospinning of Nanofibers Incorporated with Essential Oils: Applications in Food

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The role of human endogenous retroviruses (HERVs) in Multiple Sclerosis and the plausible interplay between HERVs, Epstein-Barr virus infection, and vitamin D.

Multiple Sclerosis (MS) is one of the chronic inflammatory diseases with neurological disability in the central nervous system (CNS). Although the exact cause of MS is still largely unknown, both genetic and environmental factors are thought to play a role in disease risk. Human Endogenous Retroviruses (HERVs) are endogenous viral elements of the human genome whose expression is associated with MS. HERVs are normally silenced or expressed at low levels, although their expression is higher in MS than in the healthy population. Several studies highlighted the plausible interaction between HERVs and other MS risk factors, including viral infection like Epstein-Barr viruses and vitamin D deficiency which may lead to high expression of HERVs in these patients. Understanding how HERVs act in this scenario can improve our understanding towards MS etiology and may lead to the development of antiretroviral therapies in these patients. Here in this review, we try to examine the different HERVs expression implicated in MS and their association with EBV infection and vitamin D status.

Co-administration of rotavirus nanospheres VP6 and NSP4 proteins enhanced the anti-NSP4 humoral responses in immunized mice.

Inconveniences associated with the efficacy and safety of the World Health Organization (WHO) approved/prequalified live attenuated rotavirus (RV) vaccines, sounded for finding alternative non-replicating modals and proper RV antigens (Ags). Herein, we report the development of a RV candidate vaccine based on the combination of RV VP6 nanospheres (S) and NSP4112-175 proteins (VP6S + NSP4). Self-assembled VP6S protein was produced in insect cells. Analyses by western blotting and transmission electron microscopy (TEM) indicated expression of VP6 trimer structures with sizes of ≥140 kDa and presence of VP6S. Four group of mice were immunized (2-dose formulation) intra-peritoneally (IP) by either¨VP6S + NSP4¨ or each protein alone (VP6S or NSP4112-175) emulsified in aluminium hydroxide or control. Results indicated that VP6S + NSP4 formulation induced significant anti-VP6 IgG (P < 0.001) and IgA (P < 0.05) as well as anti-NSP4 IgG (P < 0.001) and enhancement of protective immunity. Analyses of anti-VP6S and anti-NSP4 IgG subclass (IgG1 and IgG2a) showed IgG1/IgG2a ≥6 and IgG1/IgG2a ≥3 ratios, respectively indicating Th2 polarization of immune responses. The combination of VP6S + NSP4 proteins emulsified in aluminum hydroxide adjuvant might present a dual universal, efficient and cost-effective candidate vaccine against RV infection.

Overall Status of Epstein-Barr virus Infection, IFN-a, and TLR-7/9 in Patients with Systemic Lupus Erythematous.

BACKGROUND: Systemic lupus erythematous (SLE) is a multisystem autoimmune disorder. While studying the pathogenesis of SLE is prevalent, both infectious and non-infectious elements are regarded to exert an important impact on the disease's development. OBJECTIVE: To explore the overall status of EBV, TLR7, TLR9, and IFN-α gene expression in 32 patients suffering from SLE and 32 healthy controls. METHODS: Plasma and PBMCs were separated from fresh whole blood. To measure EBV DNA load and mRNA levels of IFN-a, TLR-7 and9 in PBMCs, molecular techniques were employed. The production of IFN-α, ds-DNA IgG antibody, and EBNA-1 IgG levels were also measured in plasma by ELISA. RESULTS: SLE patients showed significantly higher EBV load (p=0.001) and transcriptional levels of TLR7 (p=0.0001), IFN-α (p=0.0001), and TLR9 (p=0.0001) than controls. Moreover, the plasma levels of IFN-α (p=0.0002) and EBNA-1specific IgG antibodies (p=0.01) were significantly higher in SLE patients. CONCLUSION: The results stressed on the potential role of EBV infection and TLRs in SLE patients although more research is needed to determine the global impact that EBV infection can have on immune signature in patients with SLE.

Potential role of viral infection and B cells as a linker between innate and adaptive immune response in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease that involves several organ systems. Although B cells play a key role in SLE pathogenesis, the mechanisms behind B cell dysregulation in SLE development remained controversial. Finding the modules containing highly co-expressed genes in B cells could explain biological pathways involved in the pathogenesis of SLE, which may further support the reasons for the altered function of B cells in SLE disease. A total of three microarray gene expression datasets were downloaded from Gene Expression Omnibus. SLE samples were prepared from the purified B lymphocyte cells of the patients who have not received immunosuppressive drugs as well as high dose immunocytotoxic therapies or steroids. A weighted gene co-expression network was then constructed to find the relevant modules implicated in the SLE progression. Among 17 identified modules, 3 modules were selected through mapping to STRING and finding the ones that had highly connection at the protein level. These modules clearly indicate the involvement of several pathways in the pathogenesis of SLE including viral infection, adaptive immune response, and innate immune response in B lymphocytes. The WGCN analysis further revealed the co-expressed genes involved in both innate and adaptive immune systems. Mix infections and primary immunodeficiency might also dysregulate B lymphocytes, which may facilitate SLE development. As such, identifying novel biomarkers and pathways in lupus would be of importance.

Illuminating the in vitro effects of Epstein-Barr virus and vitamin D on immune response in multiple sclerosis patients.

Given the complexity of immune complex diseases including multiple sclerosis (MS) and the plausible interactions between different risk factors, delineating the interplay between them would be imperative. The current study aimed to evaluate the in vitro effects of Epstein-Barr virus (EBV) and vitamin D on immune response in MS patients and healthy controls. The status of vitamin D and EBV load was evaluated using multiple techniques. In vitro EBV-infected peripheral blood mononuclear cells (PBMCs), in the presence or absence of vitamin D, were checked for IL-10, IFN-γ, and vitamin D receptor. MS patients showed significantly higher plasma levels of 1,25-(OH)2D but not 25-OHD, increased EBV load, and lower levels of vitamin D receptor (VDR) expression compared with healthy controls. Interestingly, an inverse correlation was observed between VDR expression and EBV load in PBMCs. Indeed, the levels of IFN-γ and IL-10 production were significantly higher in supernatant collected from in vitro EBV-infected PBMCs in MS patients compared with controls. While all vitamin D-treated PBMCs showed reduced levels of IFN-γ production, in vitro treatment of vitamin D showed no influence in IL-10 production. EBV and vitamin D were found to exert opposite in vitro effects on immune dysregulation in these patients. Our results highlight the complex interactions of different risk factors with immune system.

Combined use of lactic-acid-producing bacteria as probiotics and rotavirus vaccine candidates expressing virus-specific proteins.

Due to the lower efficacy of currently approved live attenuated rotavirus (RV) vaccines in developing countries, a new approach to the development of safe mucosally administered live bacterial vectors is being considered, using probiotic bacteria as an efficient delivery platform for heterologous RV antigens. Lactic acid bacteria (LAB), which are considered food-grade bacteria and normal microbiota, have been utilized throughout history as probiotics and developed since the 1990s as a delivery system for recombinant heterologous proteins. Over the last decade, LAB have frequently been used as a platform for the delivery of various RV antigens to the mucosa. Given the appropriate safety profile for neonates and providing the benefits of probiotics, recombinant LAB-based vaccines could potentially address the need for a subunit RV vaccine. The present review focuses mainly on different recombinant LAB vaccine constructs for RV and their potential as an alternative recombinant vaccine against RV disease.

Investigation of an outbreak caused by an unknown infectious pathogen in rural Zola.

This case study was written as part of a fellowship in biosafety and biosecurity organised by the German Biosecurity Programme, namely the Global Partnership Initiated Biosecurity Academia for Controlling Health Threats (GIBACHT). Among other objectives, the fellowship focuses on equipping participants with the skills of developing their own country-specific case studies with focus on biosafety- and biosecurity-related scenarios. Upon completion of the underlying case study, participants should be able to identify some existing gaps with regards to early detection and investigation of outbreaks, describe the key steps in outbreak investigation, explain the role of communication and coordination among the various stakeholders in outbreak investigations and analyse epidemiological data obtained during outbreak investigations. They should also be able to suggest appropriate control and prevention measures for specific disease outbreaks with focus on foodborne outbreaks and to distinguish between biosafety and biosecurity concepts.

Vitamin D and Covid-19: From potential therapeutic effects to unanswered questions.

Evidence suggests that vitamin D supplementation could potentially be effective either in treatment or prevention of coronavirus disease 2019 (Covid-19). Indeed, several studies and trials have begun to investigate the impact of vitamin D supplementation on patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this review, we focus on the potential mechanisms of vitamin D in the pathogenesis of Covid-19. We consider whether deficiency of vitamin D may be one of the underlying biological factors that could explain the excess mortality seen among non-Caucasians. We also raise several important questions which need to be addressed to provide a clear picture of the extent to which vitamin D supplementation may benefit patients with Covid-19, particularly those with underlying risk factors.

Effect of Cytomegalovirus Recombinant Phosphoprotein 150 (pp150) on Maturation and Function of Murine Dendritic Cells: an In-Vitro Study.

BACKGROUND: Tegument protein pp150 of cytomegaloviruses (CMVs) plays a vital role in all stages of viral life cycle, representing the most important tegument protein candidate for HCMV treatment. However, the exact role of pp150 in immune regulation is yet to be elucidated. OBJECTIVE: To examine the effects of pp150 on the maturity and function of murine dendritic cells (DCs). METHODS: Maturity status (CD40, CD86, and MHC-II expression) and phagocytic capacity of DCs (dextran uptake assay) were characterized. Gene expression profiles of ROR-γ, GATA-3, T-bet, and FOXP-3 as well as the protein expression of INF-γ (Th1), IL-4 (Th2), IL-35 (Treg), IL-17A (Th17), IL-22, TNF-α, IL-6, and IL-2 were evaluated in T cells co-cultured with DCs. RESULTS: A significant increase in CD40, CD86, and CCR7 expression and a reduction in the phagocytosis rate were observed in pp150-stimulated DCs compared with unstimulated DCs. T cells co-cultured with stimulated DCs showed higher expressions of ROR-γ, IL-6, IL-2, IL-17A, IL-22, and TNF-α. CONCLUSION: Despite improvements in maturity status, pp150-stimulated DCs did not seem to be able to induce Th1 or Th2 immunity. In fact, Th17 and its mediators, IL-17A and IL-22, might be the main inflammatory factors involved in pp150-stimulated DC's mechanism of action. However, it is necessary to conduct further investigations to corroborate these observations.