Impact of Hydroxychloroquine on Fructose-induced Metabolic Syndrome in Rats: Promising Protective Effect

BACKGROUND: Hydroxychloroquine (HCQ) is used in the treatment of malaria and rheumatoid arthritis for a long time. Its effects on inflammation and immune modulation were noted. AIM: This study aims to investigate the effects of HCQ in fructose-induced metabolic syndrome and to explore its possible mechanisms. METHODS AND MATERIALS: Sixty male Sprague-Dawley rats were divided into Group I (negative control), Group II fed on high-fructose diet, and Group III fed on high fructose and subdivided into Group III-a (HCQ 50 mg/kg), Group III-b (HCQ 100 mg/kg), Group III-c (HCQ 200 mg/kg), and Group III-d (metformin 100 mg/kg). Body weight, blood glucose, liver enzymes, and lipid profile were measured. Insulin level, homeostatic model assessment (HOMA), soluble-intercellular adhesion molecule, and vascular cell adhesion molecule were assayed. Tumor necrosis factor (TNF)-α, adipokines (leptin, resistin, and adiponectin), and histological examination of pancreas were assessed. RESULTS: HCQ induces good effects on lipid profile and improves significantly HOMA, endothelial stress markers, and adiponectin, and reduces leptin and TNF-α levels. In addition, significant improvement in structural changes was noted in pancreas with different doses of HCQ. CONCLUSION: Favorable effects of HCQ in fructose-induced metabolic syndrome are promising and can be used early in those at risk of diabetes

The Impact of Age, Gender, Temporality, and Geographical Region on the Prevalence of Obesity and Overweight in Saudi Arabia: Scope of Evidence

OBJECTIVES: The objectives of this scoping review are to estimate the prevalence of obesity and overweight in the Saudi community and in different age groups, genders, and geographical location, in addition to the change in prevalence over time. METHODS: This scoping review of evidence was conducted in accordance with the Joanna Briggs Institute methodology for scoping reviews and was reported following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. The population of this review was categorized into four age groups: young adults (18-25 years), adults (26-45), (mid-life adults) (46-60) and old people (60+). Each group was then categorized by gender into males and females. We included studies of adults aged 18 years and above. The pooled prevalence of obesity and overweight of the population, based on BMI, was estimated after stratification based on the age, gender, and geographical area. In addition, the change in the prevalence of obesity/overweight over time from 2011 to 2021 was investigated from the pooled data. The Metaprop program in Stata was used for statistical analysis. RESULTS: A total of 39 studies with 640,952 participants were included in this review. The pooled prevalence of obesity and overweight in the age group of ≤25 years old, including both genders, was 30%. However, it was higher in young males (40%) compared to young females (25%). The prevalence of obesity and overweight among young adults has dropped by over 40% between 2012 and 2021. The overall pooled prevalence rate of obesity and overweight in the age groups >25 years old (adults, mid-life, and old people), including both genders, was 66%, with similar prevalence among males (68%) and females (71%). In addition, a similar prevalence was observed among both adult and old people (62% and 65%, respectively), but was higher in the mid-life group (76%). Furthermore, mid-life women had the highest prevalence among all groups (87%), compared to 77% among males in the same age group. The same difference in prevalence between the gender persisted in older females compared to older males (79% vs. 65%, respectively). There is a noticeable drop in the pooled prevalence of overweight and obesity among adults > 25 years old of over 28% between 2011 and 2021. There was no difference in the prevalence of obesity/overweight by geographical region. CONCLUSIONS: Despite the noticeable drop in the prevalence of obesity in the Saudi community, the prevalence of high BMI is high in Saudi Arabia irrespective of age, gender, or geographical location. Mid-life women have the highest prevalence of high BMI, which makes them the focus of a tailored strategy for intervention. Further research is needed to investigate which are the most effective interventions to address obesity in the country

HBV and HIV/HBV Infected Patients Have Distinct Immune Exhaustion and Apoptotic Serum Biomarker Profiles

Background: Hepatitis B virus (HBV) infection is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma worldwide. Due to their shared routes of transmission, approximately 10% of HIV-infected patients worldwide are chronically coinfected with HBV. Additionally, liver disease has become a major cause of morbidity and mortality in HBV/HIV coinfected patients due to prolonged survival with the success of antiretroviral therapy. The relationship between immune exhaustion markers (PD-1/PD-L1) and apoptotic markers such as Fas/FasL, TGFβ1, TNF-α, and Th1/Th2 cytokines are not clearly delineated in HBV/HIV coinfection. Methods: Levels of soluble Fas/FasL, TGFβ1, TNF-α, and sPD-1/sPD-L1 as well as Th1 and Th2 cytokines were evaluated in the sera of HBV-monoinfected (n=30) and HBV/HIV-coinfected (n=15) patients and compared to levels in healthy controls (n=20). Results: HBV-monoinfected patients had significantly lower levels of the anti-inflammatory cytokine IL-4 (P < 0.05) and higher levels of apoptotic markers sFas, sFasL, and TGFβ-1 (P < 0.001) compared to healthy controls. Coinfection with HIV was associated with higher levels of sFas, TNF-α, and sPD-L1 (P < 0.005), and higher levels of the pro-inflammatory cytokines IL-6, IL-8, and IL-12p70 (P < 0.05) compared to healthy controls. Patients with HBV infection had a unique biomarker clustering profile comprised of IFN-γ, IL12p70, IL-10, IL-6, and TNF-α that was distinct from the profile of the healthy controls, and the unique HIV/HBV profile comprised GM-CSF, IL-4, IL-2, IFN-γ, IL12p70, IL-7, IL-10, and IL-1β. In HBV monoinfection a significant correlation between sFasL and PD1(r = 0.46, P= < 0.05) and between sFas and PDL1 (r = 0.48, P= < 0.01) was observed. Conclusion: HBV-infected and HBV/HIV-coinfected patients have unique apoptosis and inflammatory biomarker profiles that distinguish them from each other and healthy controls. The utilization of those unique biomarker profiles for monitoring disease progression or identifying individuals who may benefit from novel immunotherapies such as anti-PD-L1 or anti-PD-1 checkpoint inhibitors appears promising and warrants further investigation

Use of a recombinant Salmonella enterica serovar Typhimurium strain expressing C-Raf for protection against C-Raf induced lung adenoma in mice

BACKGROUND: Serine-threonine kinases of the Raf family (A-Raf, B-Raf, C-Raf) are central players in cellular signal transduction, and thus often causally involved in the development of cancer when mutated or over-expressed. Therefore these proteins are potential targets for immunotherapy and a possible basis for vaccine development against tumors. In this study we analyzed the functionality of a new live C-Raf vaccine based on an attenuated Salmonella enterica serovar Typhimurium aroA strain in two Raf dependent lung tumor mouse models. METHODS: The antigen C-Raf has been fused to the C-terminal secretion signal of Escherichia coli α-hemolysin and expressed in secreted form by an attenuated aroA Salmonella enterica serovar Typhimurium strain via the α-hemolysin secretion pathway. The effect of the immunization with this recombinant C-Raf strain on wild-type C57BL/6 or lung tumor bearing transgenic BxB mice was analyzed using western blot and FACS analysis as well as specific tumor growth assays. RESULTS: C-Raf antigen was successfully expressed in secreted form by an attenuated Salmonella enterica serovar Typhimurium aroA strain using the E. coli hemolysin secretion system. Immunization of wild-type C57BL/6 or tumor bearing mice provoked specific C-Raf antibody and T-cell responses. Most importantly, the vaccine strain significantly reduced tumor growth in two transgenic mouse models of Raf oncogene-induced lung adenomas. CONCLUSIONS: The combination of the C-Raf antigen, hemolysin secretion system and Salmonella enterica serovar Typhimurium could form the basis for a new generation of live bacterial vaccines for the treatment of Raf dependent human malignancies

Protective Immunity to Listeria Monocytogenes Infection Mediated by Recombinant Listeria innocua Harboring the VGC Locus

In this study we propose a novel bacterial vaccine strategy where non-pathogenic bacteria are complemented with traits desirable for the induction of protective immunity. To illustrate the proof of principle of this novel vaccination strategy, we use the model organism of intracellular immunity Listeria. We introduced a, low copy number BAC-plasmid harbouring the virulence gene cluster (vgc) of L. monocytogenes (Lm) into the non-pathogenic L. innocua (L.inn) strain and examined for its ability to induce protective cellular immunity. The resulting strain (L.inn::vgc) was attenuated for virulence in vivo and showed a strongly reduced host detrimental inflammatory response compared to Lm. Like Lm, L.inn::vgc induced the production of Type I Interferon's and protection was mediated by Listeria-specific CD8+ T cells. Rational vaccine design whereby avirulent strains are equipped with the capabilities to induce protection but lack detrimental inflammatory effects offer great promise towards future studies using non-pathogenic bacteria as vectors for vaccination

COVIDiSTRESS Global Survey dataset on psychological and behavioural consequences of the COVID-19 outbreak

This N = 173,426 social science dataset was collected through the collaborative COVIDiSTRESS Global Survey – an open science effort to improve understanding of the human experiences of the 2020 COVID-19 pandemic between 30th March and 30th May, 2020. The dataset allows a cross-cultural study of psychological and behavioural responses to the Coronavirus pandemic and associated government measures like cancellation of public functions and stay at home orders implemented in many countries. The dataset contains demographic background variables as well as measures of Asian Disease Problem, perceived stress (PSS-10), availability of social provisions (SPS-10), trust in various authorities, trust in governmental measures to contain the virus (OECD trust), personality traits (BFF-15), information behaviours, agreement with the level of government intervention, and compliance with preventive measures, along with a rich pool of exploratory variables and written experiences. A global consortium from 39 countries and regions worked together to build and translate a survey with variables of shared interests, and recruited participants in 47 languages and dialects. Raw plus cleaned data and dynamic visualizations are available

Immune Response to Lactobacillus plantarum Expressing Borrelia burgdorferi OspA Is Modulated by the Lipid Modification of the Antigen

Over the past decade there has been increasing interest in the use of lactic acid bacteria as mucosal delivery vehicles for vaccine antigens, microbicides and therapeutics. We investigated the mechanism by which a mucosal vaccine based in recombinant lactic acid bacteria breaks the immunological tolerance of the gut in order to elicit a protective immune response.We analyzed how the lipid modification of OspA affects the localization of the antigen in our delivery vehicle using a number of biochemistry techniques. Furthermore, we examined how OspA-expressing L. plantarum breaks the oral tolerance of the gut by stimulating human intestinal epithelial cells, peripheral blood mononuclear cells and monocyte derived dendritic cells and measuring cytokine production. We show that the leader peptide of OspA targets the protein to the cell envelope of L. plantarum, and it is responsible for protein export across the membrane. Mutation of the lipidation site in OspA redirects protein localization within the cell envelope. Further, we show that lipidated-OspA-expressing L. plantarum does not induce secretion of the pro-inflammatory cytokine IL-8 by intestinal epithelial cells. In addition, it breaks oral tolerance of the gut via Th1/Th2 cell mediated immunity, as shown by the production of pro- and anti-inflammatory cytokines by human dendritic cells, and by the production of IgG2a and IgG1 antibodies, respectively.Lipid modification of OspA expressed in L. plantarum modulates the immune response to this antigen through a Th1/Th2 immune response

COVIDiSTRESS Global Survey dataset on psychological and behavioural consequences of the COVID-19 outbreak

This N = 173,426 social science dataset was collected through the collaborative COVIDiSTRESS Global Survey - an open science effort to improve understanding of the human experiences of the 2020 COVID-19 pandemic between 30th March and 30th May, 2020. The dataset allows a cross-cultural study of psychological and behavioural responses to the Coronavirus pandemic and associated government measures like cancellation of public functions and stay at home orders implemented in many countries. The dataset contains demographic background variables as well as measures of Asian Disease Problem, perceived stress (PSS-10), availability of social provisions (SPS-10), trust in various authorities, trust in governmental measures to contain the virus (OECD trust), personality traits (BFF-15), information behaviours, agreement with the level of government intervention, and compliance with preventive measures, along with a rich pool of exploratory variables and written experiences. A global consortium from 39 countries and regions worked together to build and translate a survey with variables of shared interests, and recruited participants in 47 languages and dialects. Raw plus cleaned data and dynamic visualizations are available.Measurement(s) psychological measurement center dot anxiety-related behavior trait center dot Stress center dot response to center dot Isolation center dot loneliness measurement center dot Emotional Distress Technology Type(s) Survey Factor Type(s) geographic location center dot language center dot age of participant center dot responses to the Coronavirus pandemic Sample Characteristic - Organism Homo sapiens Sample Characteristic - Location global Machine-accessible metadata file describing the reported data:Peer reviewe