Development Of Disease Research Articles

Vaginal microbiome differences between patients with adenomyosis with different menstrual cycles and healthy controls

BackgroundAdenomyosis is a commonly observed benign gynecological disease that affects the quality of life and social psychology of women of childbearing age. However, because of the unknown etiology and incidence of adenomyosis, its pathophysiological mechanism remains unclear; further, because no noninvasive, accurate, and individualized diagnostic methods are available, treatment and efficacy evaluations are limited. Notably, the interaction between the changes in the microecological environment of the female reproductive tract and human immunity, endocrine, and other links leads to the occurrence and development of diseases. In addition, the vaginal microbiome differs in different menstrual cycles; therefore, assessing the differences between the microbiomes of patients with adenomyosis and healthy individuals in different menstrual cycles will improve the understanding of the disease and provide references for the search for noninvasive diagnosis and individualized precision treatment of adenomyosis. This study aimed to explored the data of individuals in different menstrual cycles.ResultsDifferences in the vaginal microbiome between patients with adenomyosis and healthy individuals were observed. At phylum level, the relative abundance of Firmicutes in the adenomyosis group was higher than that in the control group, which contributed the most to the species difference between the two groups. At the genus level, Lactobacillus was the most dominant in both groups, Alpha-diversity analysis showed significant differences in the adenomyosis and control group during luteal phase (Shannon index, p = 0.0087; Simpson index, p = 0.0056). Beta-diversity index was significantly different between the two groups (p = 0.018). However, based on Weighted Unifrac analysis, significant differences were only observed throughout the luteal phase (p = 0.0146). Within the adenomyosis group, differences between women with different menstrual cycles were also observed. Finally, 50 possible biomarkers including were screened and predicted based on the random forest analyse.ConclusionsThe vaginal microbiome of patients with adenomyosis and healthy individuals differed during menstrual periods, especially during the luteal phase. These findings facilitate the search for specific biological markers within a limited range and provide a more accurate, objective, and individualized diagnostic and therapeutic evaluation method for patients with adenomyosis, compared to what is currently available.

Lifetime prevalence of psychotic-like experiences and associated factors in Chile.

Psychotic-like experiences (PLEs), which include hallucinations and delusional experiences, are usually present in healthy populations, and their persistence, quality, and severity are associated with the development of psychiatric diseases, including schizophrenia and other poor psychosocial outcomes. Urbanicity, depression, and other psychosocial stressors have been associated with PLEs. However, evidence of PLEs in Latin American (LATAM) countries is still scarce, and there are no studies about PLEs in Chile. The main aim of this study is to describe the prevalence of PLEs in a nationally representative sample according to othersocial determinants of health. The last results of the Chilean National Health Survey (ENS 2016-2017) were analyzed. PLEs were obtained from the Composite International Diagnostic Interview (CIDI) 3.0 and included in this survey. Other psychosocial variables (age, sex, educational level, financial stress, depressive symptoms, and urbanicity) were also included for further analysis. Exclusion criteria were (1) > = 65 and < 18years old, and (2) previous diagnosis or treatment for schizophrenia or bipolar disorder. Descriptive statistics were used to describe data, and Poisson regression models were performed to weight variables and find psychosocial correlations with PLEs. 2095 subjects were considered for this study (women 62.9% and mean age = 42.5, SD = 13.5). The lifetime prevalence of the PLEs (> = 1 PLE) in Chile was 12.9%. Visual hallucinations were the most common PLE (9.6%), and ideas of reference were the least common (0.4%). The Poisson regression model showed a higher prevalence of PLEs in the Gran Concepción conurbation (OR = 2.56) and Gran Valparaíso conurbation (OR = 1.69) compared with non-big cities. On the other hand, the 18-24year group had higher PLEs prevalence compared to other age groups. No correlations were found with educational status, financial stress, or depressive symptoms. A relatively high prevalence of PLEs was found in the Chilean general population, particularly in youth living in large urban areas (Gran Valparaíso and Gran Concepción), which is compatible with previous research. Considering that there were no correlations between low educational level and financial or depressive symptoms, it is necessary to have more studies that correlate other urban relevant variables, such as natural disasters, drug consumption, and domestic or neighborhood violence.

Pentraxin 3 as a marker of development and severity of stable coronary artery disease

Inflammation plays a crucial role in the development of atherosclerotic plaques. Pentraxin 3 (PTX3) is produced at the site of inflammation and has been identified as a specific marker of atherosclerosis, vascular inflammation, and progression of the coronary artery disease (CAD). The aim of the study was to establish if PTX3 has potential relations with classical markers of cardiovascular risk, and if PTX3 may act as an independent risk factor of CAD occurrence and advancement. The study included 98 patients with stable CAD confirmed in coronary angiography (CAD group) (median age 65 interquartile range [IQR] 61-72 years; 72% men). The control group consisted of 40 patients without CAD. The CAD group had significantly higher PTX3 concentration compared to the control group. There was a correlation with age, male gender, lipid profile and intima-media thickness. There was no correlation between PTX3 concentration and the number of coronary vessels with significant atherosclerotic lesions and the advancement of atherosclerotic lesions on the Gensini scoring scale. The cut-off point was determined for 0.89 ng/ml for the exclusion of angiographically significant atherosclerotic lesions. Patients with CAD have significantly higher concentration of PTX3. There was no correlation between PTX3 and the advancement of angiographically significant atherosclerotic lesions in coronary arteries. Low PTX3 concentration may serve as an indicator for the absence of atherosclerosis.

Systemic Management of Advanced Adrenocortical Carcinoma.

Adrenocortical cancer (ACC) is a rare and aggressive disease. Surgery has traditionally been the primary treatment for locally advanced disease with ongoing controversy around the optimal neoadjuvant and adjuvant treatment options. Unfortunately, local recurrence and the eventual development of metastatic disease is common and five-year survival rates are poor. While many trials have evaluated novel systemic agents to treat advanced adrenocortical cancer, only a few drugs have demonstrated any response at all. To date, only one drug, mitotane, is approved in the US for ACC and no regimen has clearly shown an increase in overall survival. In advanced metastatic or unresectable disease, data supports the first line regimen of EDP chemotherapy + mitotane as the primary treatment modality. In the second line, while data is limited, we would recommend consideration of immunotherapy using a PD(L)1 agent combined with a TKI/VEGF inhibitor or combination immunotherapy with PD1/CTLA-4 drugs. In all cases, we always prefer a clinical trial as available. This article reviews data from multiple studies evaluating novel systemic agents against ACC and discusses current systemic therapy combinations and ongoing clinical trials.

Unveiling the bidirectional role of MMP9: A key player in kidney injury

Matrix metalloproteinases (MMPs) are a group of zinc-dependent proteolytic metalloenzymes that are involved in numerous pathological conditions, including nephropathy. MMP9, a member of the MMPs family, is categorized as a constituent of the gelatinase B subgroup, and its involvement in extracellular matrix (ECM) remodeling and renal fibrosis highlights its importance in the development and progression of renal diseases. The exact role of MMP9 in the development of kidney diseases is still controversial. This study investigated the dual role of MMP9 in kidney injury, discussing its implications in the pathogenesis of kidney diseases and investigating the design and mechanism of MMP9 inhibitors based on previous studies. This study provides an effective basis for the development of novel and selective MMP9 inhibitors for treating renal diseases.

Mitigating Effects of Tanacetum balsamita L. on Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD).

The metabolic syndrome and its associated co-morbidities have been recognized as predisposing risk factors for the development of metabolic-associated fatty liver disease (MAFLD). The present study reports on the beneficial effect of the Tanacetum balsamita methanol-aqueous extract (ETB) at 150 and 300 mg/kg bw on biochemical parameters related to oxidative stress, metabolic syndrome, and liver function in rat animal models with induced MAFLD. ETB was found to be non-toxic with LD50 > 3000 mg/kg and did not affect cell viability of hepatic HEP-G2 cells in a concentration up to 800 μg/mL. The pathology was established by a high-calorie diet and streptozotocin. Acarbose and atorvastatin were used as positive controls. At the higher dose, ETB reduced significantly (p < 0.05) the blood glucose levels by about 20%, decreased lipase activity by 52%, total cholesterol and triglycerides by 50% and 57%, respectively, and restored the amylase activity and leukocytes compared to the MAFLD group. ETB ameliorated oxidative stress biomarkers reduced glutathione and malondialdehyde in a dose-dependent manner. At 300 mg/kg, the beneficial effect of the extract on antioxidant enzymes was evidenced by the elevated catalase, glutathione peroxidase, and superoxide dismutase activity by 70%, 29%, and 44%, accordingly, compared to the MAFLD rats. ETB prevents the histopathological changes related to MAFLD. ETB, rich in 3,5-dicafeoylquinic, chlorogenic, and rosmarinic acids together with the isorhamnetin- and luteolin-glucoside provides a prominent amelioration of MAFLD.

Space-Like Irradiation Exacerbated Cognitive Deficits and Amyloid Pathology in CRND8 Mouse Model of Alzheimer's Disease.

Space radiation was linked to neurological damage and behavioral deficits which raised concerns of increased degenerative risk on the brain and development of Alzheimer's disease following space travel. In this study, we investigated the effects of irradiation by 56Fe and 28Si in CRND8 mice, an Alzheimer's disease mouse model. Six-month-old CRND8 mice were exposed to whole body irradiation by 56Fe and 28Si at 0.5 Gy and 2 Gy doses. Behavior tests were administered 1-month to 3-months post-irradiation. Amyloid deposition and other pathological changes were analyzed 3-months and/or 6-months post-irradiatio. The Novel Object Recognition test showed some decline in 8-month-old mice compared to non-irradiated CRND8 mice. Male mice also showed a loss of freezing behavior in the fear conditioning contextual test following irradiation. Golgi staining revealed a loss of spines in hippocampal neurons after irradiation. Total amyloid immunohistochemistry showed a robust increase in 3-months post-irradiation 56Fe groups which became normalized to non-irradiated group by 6-months post-irradiation. However, 2 Gy 28Si caused a trend towards increased plaque load at 3-months post-irradiation which became significant at 6-months post irradiation only in male CRND8 mice. While 0.5 Gy Fe did not induce obvious changes in the total number of iba-1 positive microglia, more hippocampal microglia were found to express PCNA after 0.5 Gy Fe treatment, suggesting potential involvement of microglial dysfunction. Overall, our study provides new evidence of gender-specific and ion-dependent effects of space radiation on cognition and amyloid pathology in AD models.

TM6SF2 E167K variant decreases PNPLA3-mediated PUFA transfer to promote hepatic steatosis and injury in MASLD.

Transmembrane 6 superfamily member 2 (TM6SF2) E167K variant is closely associated with the occurrence and development of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the role and mechanism of TM6SF2 E167K variant during MASLD progression are not yet fully understood. The Tm6sf2167K knock-in (KI) mice were subjected to high-fat diet (HFD). Hepatic lipid levels of Tm6sf2167K KI mice were detected by lipidomics analysis. Thin-layer chromatography (TLC) was used to measure the newly synthesized triglyceride (TG) and phosphatidylcholine (PC). The TM6SF2 E167K variant significantly aggravated hepatic steatosis and injury of HFD-induced mice. Decreased polyunsaturated PC level and increased polyunsaturated TG level were found in liver tissue of HFD-induced Tm6sf2167K KI mice. Mechanistic studies demonstrated that the TM6SF2 E167K variant increased the interaction between TM6SF2 and PNPLA3, and impaired PNPLA3-mediated transfer of polyunsaturated fatty acids (PUFAs) from TG to PC. The TM6SF2 E167K variant increased the level of fatty acid-induced malondialdehyde and reactive oxygen species, and decreased fatty acid-downregulated cell-membrane fluidity. Additionally, the TM6SF2 E167K variant decreased the level of hepatic PC containing C18:3, and dietary supplementation of PC containing C18:3 significantly attenuated the TM6SF2 E167K-induced hepatic steatosis and injury in HFD-fed mice. The TM6SF2 E167K variant could promote its interaction with PNPLA3 and inhibit PNPLA3-mediated transfer of PUFAs from TG to PC, resulting in the hepatic steatosis and injury during MASLD progression. PC containing C18:3 could act as a potential therapeutic supplement for MASLD patients carrying the TM6SF2 E167K variant.

UKB.COVID19: an R package for UK Biobank COVID-19 data processing and analysis

COVID-19 caused by SARS-CoV-2 has resulted in a global pandemic with a rapidly developing global health and economic crisis. Variations in the disease have been observed and have been associated with the genomic sequence of either the human host or the pathogen. Worldwide scientists scrambled initially to recruit patient cohorts to try and identify risk factors. A resource that presented itself early on was the UK Biobank (UKBB), which is investigating the respective contributions of genetic predisposition and environmental exposure to the development of disease. To enable COVID-19 studies, UKBB is now receiving COVID-19 test data for their participants every two weeks. In addition, UKBB is delivering more frequent updates of death and hospital inpatient data (including critical care admissions) on the UKBB Data Portal. This frequently changing dataset requires a tool that can rapidly process and analyse up-to-date data. We developed an R package specifically for the UKBB COVID-19 data, which summarises COVID-19 test results, performs association tests between COVID-19 susceptibility/severity and potential risk factors such as age, sex, blood type, comorbidities and generates input files for genome-wide association studies (GWAS). By applying the R package to data released in April 2021, we found that age, body mass index, socioeconomic status and smoking are positively associated with COVID-19 susceptibility, severity, and mortality. Males are at a higher risk of COVID-19 infection than females. People staying in aged care homes have a higher chance of being exposed to SARS-CoV-2. By performing GWAS, we replicated the 3p21.31 genetic finding for COVID-19 susceptibility and severity. The ability to iteratively perform such analyses is highly relevant since the UKBB data is updated frequently. As a caveat, users must arrange their own access to the UKBB data to use the R package.

Association between serum hormone levels in early pregnancy and risk of hypertensive diseases of pregnancy in women undergoing assisted reproduction.

We examined the association between progesterone (P4), estradiol (E2), and human chorionic gonadotropin (hCG) levels in early pregnancy and the development of hypertensive diseases of pregnancy among women undergoing assisted reproduction. Retrospective study including patients who underwent frozen embryo transfer (FET), ovarian stimulation (OS), or unassisted conception (UC) and had a live singleton birth. The primary outcome was the development of hypertensive diseases of pregnancy (gestational hypertension, preeclampsia, HELLP, or eclampsia). Secondary outcomes were the development of fetal intrauterine growth restriction (IUGR), gestational diabetes mellitus, birth weight, and pre-term birth. Hormone levels and the development of the outcomes were correlated. A total of 681 patients were included; 189 had FET, 193 had OS, and 299 had UC. Patients undergoing FET or OS were not more likely to develop hypertensive diseases of pregnancy compared with UC patients. While median levels of E2 and P4 were significantly different between P-FET and NC-FET patients (E2: 252 vs 317pg/mL, P4: 64 vs 29ng/mL, respectively; both p < 0.01), rates of hypertensive diseases of pregnancy did not significantly differ between those two groups. In the multivariate analyses, P4, E2, and hCG were not associated with the development of hypertensive diseases of pregnancy, but progesterone levels were significantly higher among those with IUGR. This remained consistent when the analysis was limited to FET patients. P4, E2, and hCG levels did not correlate with the development of hypertensive diseases of pregnancy but elevated progesterone levels did correlate with the development of IUGR.

MiRNA-Mediated Mechanisms in the Generation of Effective and Safe Oncolytic Viruses.

MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression by inhibiting the translation of target transcripts. The expression profiles of miRNAs vary in different tissues and change with the development of diseases, including cancer. This feature has begun to be used for the modification of oncolytic viruses (OVs) in order to increase their selectivity and efficacy. OVs represent a relatively new class of anticancer drugs; they are designed to replicate in cancer tumors and destroy them. These can be natural viruses that can replicate within cancer tumor cells, or recombinant viruses created in laboratories. There are some concerns regarding OVs' toxicity, due to their ability to partially replicate in healthy tissues. In addition, lytic and immunological responses upon OV therapy are not always sufficient, so various OV editing methods are used. This review discusses the latest results of preclinical and clinical studies of OVs, modifications of which are associated with the miRNA-mediated mechanism of gene silencing.

A reaction–diffusion model of major emerging infectious diseases in a spatially heterogeneous environment and case study

During the outbreak of major emerging infectious diseases, virus droplets can survive in the environment as aerosols for hours to days, and their impact on human infectious diseases is often overlooked. In addition, the speed of transmission of infectious diseases is often closely related to transportation. Therefore, studying the impact of environmental viruses and transportation on disease development is significant for effective infectious disease prevention and control. We proposed a degenerate reaction–diffusion infectious disease model ([Formula: see text]) considering environmental virus interference and established a well-posedness and threshold system for this model. We have obtained the system solution approaches the disease-free equilibrium ([Formula: see text]) when the basic reproduction number [Formula: see text]. The system has at least one positive steady state solution (PSS) when [Formula: see text]. This paper used a non-standard finite difference method discretization model while data fitting and parameter estimation were performed based on data provided by the Health Commission. Further sensitivity analysis was conducted on [Formula: see text]. At the same time, we also discussed the impact of various parameters in the early stages of the outbreak of major emerging infectious diseases on the development of the disease. Research found that even if the contact rate between people is controlled at a shallow level, the disease may persist. In the early stages of major emerging outbreak of infectious diseases, immediately reducing the use of transportation can effectively reduce the speed of disease spread.

Recent Progress in CO Detection Probes Based on Different Fluorophores

AbstractCarbon monoxide (CO), a simple and well‐known toxic gas, is a naturally occurring gaseous transmitter that plays a crucial role in the regulation of physiological and pathological processes in living organisms. Usually, the development of various diseases can lead to the dysregulation of CO levels. Interestingly, CO has been shown to exert therapeutic effects in inflammation‐related disease models. Fluorescent probes for CO detection have become a vital research field in the past decades owing to their advantages of excellent selectivity, exceptional sensitivity, and real‐time in situ detection, which have been employed for the precise detection of CO in cells, tissues, and even living organisms. This paper reviews research advancements in CO fluorescent probes over the last decade, outlines the design concepts and detection mechanisms of relevant fluorescent probes, and provides design guidelines and future development prospects.

Impact of prenatal and postnatal maternal IBD status on offspring’s risk of IBD: a population-based cohort study

ObjectiveIn utero exposure to maternal inflammation may impact immune system development and subsequent risk of disease. We investigated whether a maternal diagnosis of IBD before childbirth is linked to a...

Contribution of T cell subsets to different food allergic diseases.

Food allergies occur due to a lack of tolerance to the proteins found in foods. While IgE- and non-IgE-mediated food allergies have different clinical manifestations, epidemiology, pathophysiology, and management, they share dysregulated T cell responses. Recent studies have shed light on the contributions of different T cell subsets to the development and persistence of different food allergic diseases. This review discusses the role of T cells in both IgE- and non-IgE-mediated food allergies and considers the potential future investigations in this context.

GGPPS Negatively Regulates the Formation of Neutrophil Extracellular Traps in Lipopolysaccharide-Induced Acute Lung Injury.

Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are life-threatening diseases. Neutrophil extracellular traps (NETs) play a key role in lung damage. Geranylgeranyl diphosphate synthase (GGPPS) is associated with the development of inflammatory diseases. We aimed to explore the role of GGPPS in NETs formation in ARDS/ALI. First, lung pathological changes in lipopolysaccharide (LPS)-induced ALI mice after myeloid-specific GGPPS deletion were evaluated. The level of NETs formation was analyzed by immunofluorescence, PicoGreen assay and Western blotting. Next, we determined the role of GGPPS in NETs formation and underlying mechanisms using immunofluorescence, flow cytometry, DCFH-DA, and SYTOX GREEN staining in vitro. Finally, the correlation between GGPPS expression incirculating neutrophils and dsDNA levels in plasma was evaluated. Myeloid-specific GGPPS deletion mice showed increased NETs deposition in lung tissue and aggravated histopathological damage of lung tissue. In vitro, GGPPS deficiency in neutrophils resulted in increased NETs formation by Phorbol-12-myristate-13-acetate (PMA), which was reversed by Geranylgeranyl diphosphate (GGPP). In addition, inhibitors blocking protein kinase C (PKC) and NADPH-oxidase (NOX) decreased NETs formation induced by GGPPS deletion. Importantly, GGPPS expression in circulating neutrophils was decreased in ARDS patients compared with the healthy control, and the level of dsDNA in plasma of ARDS patients was negatively correlated with the GGPPS expression. Taken together, GGPPS deficiency in neutrophils aggravates LPS-induced lung injury by promoting NETs formation via PKC/NOX signaling. Thus, neutrophil GGPPS could be a key therapeutic target for ARDS.

Role of hypoxia-inducible-factor-1α (HIF-1α) in ferroptosis of adipose tissue during ketosis

Postpartum cows experience lipolysis in adipose tissue due to negative energy balance (NEB), and accumulation of free fatty acids (FFA) leads to metabolic stress in adipose tissue. Ferroptosis is a type of cell death triggered by excessive buildup of iron-dependent lipid peroxides, which is involved in the occurrence and development of various metabolic diseases in nonruminants. However, it is still unclear whether ferroptosis occurs in the adipose tissue of ketotic cows and the regulatory mechanisms behind ferroptosis. Despite multiple studies demonstrating the significant involvement of hypoxia-inducible-factor-1α (HIF-1α) in regulating cellular dysfunction, its specific function in adipose tissue of ketotic dairy cows remains uncertain, particularly its regulation of oxidative stress and ferroptosis. The study aimed to explore the impact of HIF-1α on oxidative stress and ferroptosis in bovine subcutaneous adipose tissue and isolated adipocytes. The adipose tissue of clinical ketosis cows (n = 15) with a serum BHB concentration of 3.13 mM (interquartile range = 0.14) and healthy cows (n = 15) with a serum BHB concentration of and 0.58 mM (interquartile range = 0.13) was collected. The results showed that the concentrations of lipid peroxidation malondialdehyde (MDA), reactive oxygen species (ROS), Fe2+ and total iron were increased in adipose tissue of cows with ketosis, while the contents of glutathione (GSH) were reduced. Furthermore, the protein levels of HIF-1α, heme oxygenase 1 (HMOX1), catalase (CAT), superoxide dismutase 1 (SOD1), acyl-CoA synthetase 4 (ACSL4), and nuclear factor erythroid-derived 2-like 2 (NFE2L2) exhibited higher abundance in adipose tissue obtained from cows with ketosis, whereas the protein abundance of solute carrier family 7 member 11 (SLC7A11), glutamate cysteine ligase catalytic subunit (GCLC), kelch-like ECH-associated protein 1 (KEAP1), glutamate cysteine ligase regulatory subunit (GCLM) and glutathione peroxidase 4 (GPX4) were lower. To simulate the ferroptosis state of adipose tissue in ketotic cows, primary bovine adipocytes were isolated from the adipose tissue of healthy cows and cultured with erastin to construct ferroptosis model. Adipocytes were cultured with either an adenovirus overexpressing HIF-1α or small interfering RNA targeting HIF-for 48 h, followed by exposure to erastin (1 μM) for 24 h. Treatment with erastin led to higher protein abundance of CAT, SOD1, NFE2L2 and HMOX1, while it inhibited the protein expression levels of GCLC, SLC7A11, GCLM, GPX4 and KEAP1. Furthermore, erastin treatment elevated the levels of ROS, MDA, Fe2+, total iron and reduced the content of GSH. The overexpression of HIF-1α reversed the erastin-induced decreases in the protein abundance of GPX4 and SLC7A11, as well as the levels of MDA, ROS, Fe2+ and total iron, while significantly increasing protein abundance and content of CAT, SOD1, NFE2L2, HMOX1, GCLC, GCLM, GPX4, SLC7A11 and GSH. Conversely, the silencing of HIF-1α further exacerbated the erastin-induced levels of MDA, ROS, Fe2+ and total iron, while inhibiting the upregulation of SOD1, CAT, NFE2L2 and HMOX1. Collectively, these findings suggest that activation of HIF-1α may function as an adaptive mechanism to mitigate ferroptosis and alleviate oxidative stress in adipose tissue.

Immune responses and severe dengue: what have we learned?

With the marked rise in dengue globally, developing well tolerated and effective vaccines and therapeutics is becoming more important. Here we discuss the recent developments in the understanding of immune mechanisms that lead to severe dengue and the learnings from the past, that can help us to find therapeutic targets, prognostic markers, and vaccines to prevent development of severe disease. The extent and duration of viraemia often appears to be associated with clinical disease severity but with some variability. However, there also appear to be significant differences in the kinetics of viraemia and nonstructural protein 1 (NS1) antigenemia and pathogenicity between different serotypes and genotypes of the DENV. These differences may have significant implications for development of treatments and in inducing robust immunity through dengue vaccines. Although generally higher levels of neutralizing antibodies are thought to protect against infection and severe disease, there have been exceptions and the specificity, breadth and functionality of the antibody responses are likely to be important. Although there have been many advances in our understanding of dengue pathogenesis, viral and host factors associated with occurrence of severe dengue, vascular leak and the immune correlates of protection remain poorly understood.

Suppression of the host antiviral response by non-infectious varicella zoster virus extracellular vesicles.

Varicella zoster virus (VZV) is a ubiquitous human virus that predominantly spreads by direct cell-cell contact and requires efficient and immediate host immune evasion strategies to spread. The mechanisms of immune evasion prior to virion entry have not been fully elucidated and represent a critical gap in our complete understanding of VZV pathogenesis. This study describes a previously unreported antiviral evasion strategy employed by VZV through the exploitation of the infected host cell's small extracellular vesicle (sEV) machinery. These findings suggest that non-infectious VZV sEVs could travel throughout the body, affecting cells remote from the site of infection and challenging the current understanding of VZV clinical disease, which has focused on local effects and direct infection. The significance of these sEVs in early VZV pathogenesis highlights the importance of further investigating their role in viral spread and secondary disease development to reduce systemic complications following VZV infections.

Sex Differences in Cardiovascular Diseases: Exploring the Role of Microbiota and Immunity.

Cardiovascular diseases (CVDs) are the most common cause of mortality and morbidity in Western countries, thus representing a global health concern. CVDs show different patterns in terms of the prevalence and presentation in men and women. The role of sex hormones has been extensively implicated in these sex-specific differences, due to the presence of the menstrual cycle and menopause in women. Moreover, the gut microbiota (GM) has been implicated in cardiovascular health, considering the growing evidence that it is involved in determining the development of specific diseases. In particular, gut-derived metabolites have been linked to CVDs and kidney disorders, which can in turn promote the progression of CVDs. Considering the differences in the composition of GM between men and women, it is possible that gut microbiota act as a mediator in regard to the sex disparities in CVDs. This narrative review aims to comprehensively review the interplay between sex, GM, and CVDs, discussing potential mechanisms and therapeutic options.