Search Results (7,050)

Chronic kidney disease (CKD) has now reached epidemic proportions in many parts of the world, primarily due to the high incidence of diabetes and hypertension. By 2040, CKD is predicted to be the fifth-leading cause of years of life lost. Developing strategies to prevent CKD and to reduce its progression to kidney failure is thus of great public health significance. Hypertension is known to be both a cause and a consequence of kidney damage and an eminently modifiable risk factor. An increased risk of hypertension, especially among women, has been linked to chronic exposure to the ubiquitous food contaminant cadmium (Cd). The mechanism is unclear but is likely to involve its action on the proximal tubular cells (PTCs) of the kidney, where Cd accumulates. Here, it leads to chronic tubular injury and a sustained drop in the estimated glomerular filtration rate (eGFR), a common sequela of ischemic acute tubular necrosis and acute and chronic tubulointerstitial inflammation, all of which hinder glomerular filtration. The present review discusses exposure levels of Cd that have been associated with an increased risk of hypertension, albuminuria, and eGFR ≤ 60 mL/min/1.73 m² (low eGFR) in environmentally exposed people. It highlights the potential role of 20-hydroxyeicosatetraenoic acid (20-HETE), the second messenger produced in the kidneys, as the contributing factor to gender-differentiated effects of Cd-induced hypertension. Use of GFR loss and albumin excretion in toxicological risk calculation, and derivation of Cd exposure limits, instead of β₂-microglobulin (β₂M) excretion at a rate of 300 µg/g creatinine, are recommended. Full article

Background: Type 2 diabetes (T2D) is a global health epidemic with rising prevalence within Asian populations, particularly amongst individuals with high visceral adiposity and ectopic organ fat, the so-called Thin-Outside, Fat-Inside phenotype. Metabolomic and microbiome shifts may herald T2D onset, presenting potential biomarkers and mechanistic insight into metabolic dysregulation. However, multi-omics datasets across ethnicities remain limited. Methods: We performed cross-sectional multi-omics analyses on 171 adults (99 Asian Chinese, 72 European Caucasian) from the New Zealand-based TOFI_Asia cohort at 4-years follow-up. Paired plasma and faecal samples were analysed using untargeted metabolomic profiling (polar/lipid fractions) and shotgun metagenomic sequencing, respectively. Sparse multi-block partial least squares regression and discriminant analysis (DIABLO) unveiled signatures associated with ethnicity, glycaemic status, and sex. Results: Ethnicity-based DIABLO modelling achieved a balanced error rate of 0.22, correctly classifying 76.54% of test samples. Polar metabolites had the highest discriminatory power (AUC = 0.96), with trigonelline enriched in European Caucasians and carnitine in Asian Chinese. Lipid profiles highlighted ethnicity-specific signatures: Asian Chinese showed enrichment of polyunsaturated triglycerides (TG.16:0_18:2_22:6, TG.18:1_18:2_22:6) and ether-linked phospholipids, while European Caucasians exhibited higher levels of saturated species (TG.16:0_16:0_14:1, TG.15:0_15:0_17:1). The bacteria Bifidobacterium pseudocatenulatum, Erysipelatoclostridium ramosum, and Enterocloster bolteae characterised Asian Chinese participants, while Oscillibacter sp. and Clostridium innocuum characterised European Caucasians. Cross-omic correlations highlighted negative correlations of Phocaeicola vulgatus with amino acids (r = −0.84 to −0.76), while E. ramosum and C. innocuum positively correlated with long-chain triglycerides (r = 0.55–0.62). Conclusions: Ethnicity drove robust multi-omic differentiation, revealing distinctive metabolic and microbial profiles potentially underlying the differential T2D risk between Asian Chinese and European Caucasians. Full article

Diabetes mellitus, both type 1 (T1D) and type 2 (T2D), has become the epidemic of the century and a major public health concern given its rising prevalence and the increasing adoption of a sedentary lifestyle globally. This multifaceted disease is characterized by impaired pancreatic beta cell function and insulin resistance (IR) in peripheral organs, namely the liver, skeletal muscle, and adipose tissue. Additional insulin target tissues, including cardiomyocytes and neuronal cells, are also affected. The advent of stem cell research has opened new avenues for tackling this disease, particularly through the regeneration of insulin target cells and the establishment of disease models for further investigation. Human-induced pluripotent stem cells (iPSCs) have emerged as a valuable resource for generating specialized cell types, such as hepatocytes, myocytes, adipocytes, cardiomyocytes, and neuronal cells, with diverse applications ranging from drug screening to disease modeling and, importantly, treating IR in T2D. This review aims to elucidate the significant applications of iPSC-derived insulin target cells in studying the pathogenesis of insulin resistance and T2D. Furthermore, recent differentiation strategies, protocols, signaling pathways, growth factors, and advancements in this field of therapeutic research for each specific iPSC-derived cell type are discussed. Full article

Non-polio enteroviruses continue to cause numerous epidemics world-wide that range from mild to severe disease, including acute flaccid paralysis, meningitis, severe respiratory infections and encephalitis. Using publicly available data we present a comprehensive global and regional temporal distribution of non-polio enteroviruses, with a focus on highly prevalent genotypes. We found that regional distribution did vary compared to global prevalence where the top prevalent genotypes included CVA6 and EV-A71 in Asia, EV-D68 in North America and CVA13 in Africa, while E-30 was prevalent in Europe, South America and Oceania. In 2020, the COVID-19 pandemic did interrupt non-polio enterovirus detections globally, and cases rebounded in subsequent years, albeit at lower prevalence and with decreased genotype diversity. Environmental surveillance for non-polio enteroviruses does occur and has been used in some regions as an early-warning system; however, further development is needed to effectively supplement potential gaps in clinical surveillance data. Overall, monitoring for non-polio enteroviruses is critical to identify true incidence, improve understanding of genotype circulation, provide an early warning system for emerging/re-emerging genotypes and allow for better outbreak control. Full article

In this paper, we propose a diffusion-type predator–prey interaction model with harvest and disease in prey, and conduct stability analysis and pattern formation analysis on the model. For the temporal model, the asymptotic stability of each equilibrium is analyzed using the linear stability method, and the conditions for Hopf bifurcation to occur near the positive equilibrium are investigated. The simulation results indicate that an increase in infection force might disrupt the stability of the model, while an increase in harvesting intensity would make the model stable. For the spatiotemporal model, a priori estimate for the positive steady state is obtained for the non-existence of the non-constant positive solution using maximum principle and Harnack inequality. The Leray–Schauder degree theory is used to study the sufficient conditions for the existence of non-constant positive steady states of the model, and pattern formation are achieved through numerical simulations. This indicates that the movement of prey and predators plays an important role in pattern formation, and different diffusions of these species may play essentially different effects. Full article

Surveillance of swine influenza A virus (swIAV) traditionally focuses on respiratory matrices, yet emerging evidence suggests that fecal shedding and secondary environmental contamination may also contribute to viral dissemination. In this study, we collected and analyzed nasal, rectal, environmental, milk, and colostrum samples from naturally infected pigs in a commercial farm in Minas Gerais, Brazil. IAV RNA was detected in 25% of samples, including 42% from asymptomatic animals, with nasal swabs showing higher detection rates (30%) than rectal swabs (20%), though rectal Ct values were consistently higher, indicative of lower viral loads. We successfully isolated viable viruses from feces and effluent samples. Whole-genome sequencing revealed co-circulation of enzootic pH1N1 clade #2 (HA) and pN1 clade #4 (NA), alongside human-origin H3N2 sequences clustering within clade 3C.2a1b.2a.2a.1, and N2 segments related to pre-3C human lineages from 2001 to 2002. Phylogenetic and p-distance analyses support both recent reverse zoonosis and historical transmission events. Detection of complete HA/NA sequences from rectal swabs and treated effluent further emphasizes the surveillance value of non-respiratory matrices. The integration of respiratory and fecal/environmental sampling appears important to achieve more comprehensive IAV monitoring in swine herds and may have significant implications for One Health strategies in Brazil and beyond. Full article

Recent outbreaks of highly pathogenic human RNA viruses from probable zoonotic origin have highlighted the relevance of epidemic preparedness as a society. However, research in vaccinology and virology, as well as epidemiologic surveillance, is often constrained by the biological risk that live virus experimentation entails. These also involve expensive costs, time-consuming procedures, and advanced personnel expertise, hampering market access for many drugs. Most of these drawbacks can be circumvented with the use of pseudotyped viruses, which are surrogate, non-pathogenic recombinant viral particles bearing the surface envelope protein of a virus of interest. Pseudotyped viruses significantly expand the research potential in virology, enabling the study of non-culturable or highly infectious pathogens in a safer environment. Most are derived from lentiviral vectors, which confer a series of advantages due to their superior efficiency. During the past decade, many studies employing pseudotyped viruses have evaluated the efficacy of vaccines or monoclonal antibodies for relevant pathogens such as HIV-1, Ebolavirus, Influenza virus, or SARS-CoV-2. In this review, we aim to provide an overview of the applications of pseudotyped viruses when evaluating the neutralization capacity of exposed individuals, or candidate vaccines and antivirals in both preclinical models and clinical trials, to further help develop effective countermeasures against emerging neutralization-escape phenotypes. Full article

Background/Objectives: Moschus (musk) has long been used in traditional Tibetan medicine to prevent and treat epidemic febrile illnesses. However, its antiviral mechanisms remain poorly understood. Given the urgent need for effective treatments against viral respiratory tract infections (VRTIs), this study aimed to systematically investigate the molecular targets and pharmacological pathways through which Moschus may exert therapeutic effects. Methods: Based on the identification of bioactive compounds with favorable pharmacokinetics, we applied integrated network pharmacology and multi-omics analyses to systematically identify key therapeutic targets involved in VRTIs. Gene Set Enrichment Analysis (GSEA) and immune infiltration further revealed strong associations with multiple immune cell subsets, reflecting their pivotal roles in immunomodulatory mechanisms during viral infections. Molecular docking confirmed the strong binding affinities between Moschus compounds and these key targets. Results: Notably, testosterone exhibited the strongest and most consistent binding across key targets, suggesting its potential as a pivotal bioactive compound. Importantly, the antiviral effects of Moschus may be mediated in part by the downregulation of the key genes MCL1, MAPK3, and CDK2, which are involved in the regulation of viral replication, apoptosis, and host immune responses. Conclusions: This study provides a comprehensive mechanistic framework supporting the multi-target antiviral potential of Moschus, offering a scientific basis for its further development as a therapeutic agent against VRTIs. Full article

Culicoides (Diptera, Ceratopogonidae) are small biting midges and are known as vectors for many arboviruses, including bluetongue virus (BTV) and epizootic hemorrhagic disease virus (EHDV). Tengchong County of Yunnan Province, China, which borders Myanmar, has many private farms with goats, sheep, and cattle. To estimate the risk of Culicoides-borne viral diseases such as bluetongue (BT) and epizootic hemorrhagic disease (EHD) in this area, an investigation of the diversity and abundance of Culicoides in Tengchong between May 2024 and April 2025 was performed. As a result, 70 collections totaling approximately 93,000 Culicoides were carried out at five farms (cattle + Asian buffaloes, goats, and sheep, respectively). Nineteen species were identified, and eight potential cryptic species were found. A total of 13 cox1 sequences and 4 28S sequences for 13 specimens were generated. The most dominant species were Obsoletus (44.1%), C. homotomus (23.3%), and C. arakawae (12.9%) at the bovine farm; C. tainanus (68.0%), C. orientalis (12.6%), and C. newsteadi (Asia) (6.3%) at the goat farm; and C. tainanus (73.6%), C. fenggangensis (7.3%), and C. sp. nr palpifer (6.3%) at the sheep farm. In this investigation, C. tainanus, Obsoletus, and C. orientalis were the most dominant potential BTV vectors, and the period between July and October may be the main period for epidemics of Culicoides-borne viruses in Tengchong. Full article

This study aimed to estimate the end-of-season influenza vaccine effectiveness (VE) for the 2024/25 season in Beijing, China. Methods: We used a test-negative design (TND) to assess influenza VE among outpatients with influenza-like illness (ILI) enrolled through the influenza virological surveillance in sentinel hospitals in Beijing from week 44, 2024 to week 14, 2025. Cases were ILI patients who tested positive for influenza; controls were those who tested negative. Results: Among 18,405 ILI patients tested, 3690 (20.0%) were positive for influenza, with A(H1N1)pdm09 as the predominant strain (98.9%). The overall influenza vaccination coverage was 12.4%. Adjusted VE was 48.3% (95%CI: 40.4%–55.3%) against any influenza and 48.2% (95%CI: 40.3%–55.1%) against A(H1N1)pdm09, with the highest VE observed in adults aged 18–59 years (79.0%). The adjusted VE was similar for those vaccinated in 2023/24 only (53.1%) or both 2023/24 and 2024/25 seasons (50.8%), but lower for those vaccinated only in the 2024/25 season (48.5%). The adjusted VE was higher during the epidemic period (52.5%) than in the pre-epidemic (48.1%) and post-epidemic (35.3%) periods. Conclusions: Our findings indicate moderate VE against laboratory-confirmed influenza, especially A(H1N1)pdm09, during the end of the 2024/25 season in Beijing, China. Influenza vaccination provided protective effects across different epidemic periods. These timely estimates support ongoing public health communication and immunization strategies. Full article

In late 2019, a new virus, SARS-CoV-2, emerged in Wuhan, China, causing COVID-19 and the subsequent global pandemic. As of 30 April 2023, more than 774 million cases of COVID-19 had been reported worldwide, including over 7.5 million in Mexico. Despite advances in vaccination, epidemic surges of COVID-19 continued to occur globally, highlighting the importance of sharing and disseminating the experiences gained during these first years to better understand the virus’s evolution and respond accordingly. For this reason, the National Council for Science and Technology (CONACYT) organized the meeting “Challenges and Opportunities for Genomic Surveillance of SARS-CoV-2 in Mexico” from 15 to 17 August 2022, to present the efforts and results accumulated over more than two years of the pandemic. In this meeting report, we summarize the key findings of each participant and provide their contact information. Full article

Purpose: The adenoid microbiota plays a key role in adenoid hypertrophy (AH). This study explored the molecular epidemiology and antimicrobial resistance of Haemophilus. Influenzae (H. influenzae) strains in pediatric AH patients. Methods: Retrospective analysis of pediatric AH patients undergoing endoscopic adenoidectomy. Adenoid tissue samples were cultured to screen for pathogens. H. influenzae strains were identified by 16S rRNA sequencing and serotyped via q-PCR. Multilocus sequence typing (MLST) and ftsI gene analysis were conducted using PubMLST. β-lactamase genes (bla_TEM-1, bla_ROB-1) were detected by PCR, and antibiotic susceptibility testing (AST) was performed using the Etest method. For imipenem-resistant strains, the acrRAB efflux pump gene cluster and ompP2 porin gene were sequenced and compared with those of the wild-type strain Rd KW20. Results: Over 8 months, 56 non-duplicate H. influenzae strains were isolated from 386 patients. The detection rate was highest in children under 5 years (30.5%) compared to those aged 5–10 years (13.4%) and 10–15 years (8.7%). Of 49 sub-cultured strains, all were non-typeable H. influenzae (NTHi). MLST identified 22 sequence types (STs) and 13 clonal complexes (CCs), with CC11 (26.5%), CC3 (14.3%), and CC107 (14.3%) being predominant. Common STs included ST103 (22.4%), ST57 (10.2%), and ST107 (10.2%). Most strains belonged to the ftsI group III-like+ (57.1%). β-lactamase positivity was 98.0% (48/49), with bla_TEM-1 (95.9%) and bla_ROB-1 (18.4%) detected. AST showed low susceptibility to ampicillin (10.2%), amoxicillin–clavulanate (34.7%), azithromycin (12.2%), and trimethoprim–sulfamethoxazole (14.3%). Among the β-lactamase-positive strains, 44/48 were β-lactamase-positive ampicillin-resistant (BLPAR); none were β-lactamase-negative ampicillin-resistant (BLNAR). Imipenem susceptibility was 91.8% (45/49). No carbapenemases were found in the imipenem-resistant strains, but mutations in acrRAB (88.12–94.94% identity) and ompP2 (77.10–82.94% identity) were observed. Conclusions: BLPAR NTHi strains of CC11 are major epidemic strains in pediatric AH. Imipenem resistance in H. influenzae likely results from porin mutations rather than carbapenemase activity. Enhanced surveillance of H. influenzae’s role in AH and its resistance patterns is warranted. Full article

The global obesity epidemic and associated metabolic disorders present urgent public health challenges. This study employed a multi-omics approach (lipidomics, metabolomics, and gut microbiome analysis) to investigate how Bletilla striata polysaccharides (BSPs) and composite polysaccharides modulate liver lipid metabolism and gut microbiota in high-fat diet (HFD)-induced obese mice. HFD elevated hepatic phosphatidylcholines, cholesteryl esters (CEs), and acylcarnitines (CARs), alongside increased cecal choline and trimethylamine. BSP interventions reduced hepatic CEs, free fatty acids (FAs), CARs, and cecal sarcosine while restoring gut microbial diversity. Notably, BSP enriched beneficial genera, including Jeotgalicoccus and Atopostipes, and the network analysis revealed negative correlations between these genera and hepatic triglycerides (TGs), implicating the gut–liver axis in lipid metabolism regulation. These findings elucidate the anti-obesity mechanisms of polysaccharides through gut microbiota remodeling and cross-tissue metabolic interactions, providing a foundation for leveraging plant polysaccharides in developing safer, effective obesity therapies. Full article

Obesity is a growing global health concern with widespread impacts on physical, psychological, and social well-being. Clinically, it is a major driver of type 2 diabetes (T2D), cardiovascular disease (CVD), non-alcoholic fatty liver disease (NAFLD), and cancer, reducing life expectancy by 5–20 years and imposing a staggering economic burden of USD 2 trillion annually (2.8% of global GDP). Despite its significant health and socioeconomic impact, earlier obesity medications, such as fenfluramine, sibutramine, and orlistat, fell short of expectations due to limited effectiveness, serious side effects including valvular heart disease and gastrointestinal issues, and high rates of treatment discontinuation. The advent of glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., semaglutide, tirzepatide) has revolutionized obesity management. These agents demonstrate unprecedented efficacy, achieving 15–25% mean weight loss in clinical trials, alongside reducing major adverse cardiovascular events by 20% and T2D incidence by 72%. Emerging therapies, including oral GLP-1 agonists and triple-receptor agonists (e.g., retatrutide), promise enhanced tolerability and muscle preservation, potentially bridging the efficacy gap with bariatric surgery. However, challenges persist. High costs, supply shortages, and unequal access pose significant barriers to the widespread implementation of obesity treatment, particularly in low-resource settings. Gastrointestinal side effects and long-term safety concerns require close monitoring, while weight regain after medication discontinuation emphasizes the need for ongoing adherence and lifestyle support. This review highlights the transformative potential of incretin-based therapies while advocating for policy reforms to address cost barriers, equitable access, and preventive strategies. Future research must prioritize long-term cardiovascular outcome trials and mitigate emerging risks, such as sarcopenia and joint degeneration. A multidisciplinary approach combining pharmacotherapy, behavioral interventions, and systemic policy changes is critical to curbing the obesity epidemic and its downstream consequences. Full article

Background/Objectives: Syphilis, a re-emerging global public health issue, has shown increasing incidence over the past decade, particularly among key populations such as men who have sex with men (MSM), people living with HIV, and pregnant women. This narrative review aimed to synthesize global epidemiological trends of syphilis from 2015 to 2025, with a focus on surveillance gaps, regional disparities, and structural determinants. Methods: A broad narrative approach was used to collect and analyze epidemiological data from 2015 to 2025. The literature was retrieved from databases (PubMed, Scopus) and official reports from the WHO, CDC, and ECDC. Included materials span observational studies, surveillance reports, and modeling data relevant to global trends and public health responses. Results: Globally, syphilis incidence has increased, with notable surges in North America, Europe, and Asia. MSM remain disproportionately affected, while congenital syphilis is resurging even in high-income countries. Low- and middle-income countries report persistent burdens, especially among women of reproductive age, often exacerbated by limited screening and surveillance infrastructure. The COVID-19 pandemic disrupted syphilis-related services and further exacerbated underreporting, hindering timely detection and response efforts. Surveillance systems vary widely in their completeness and quality, which significantly hinders global data comparability and coordinated public health responses. Conclusions: Despite its curability, syphilis continues to spread due to fragmented prevention strategies, inequities in access to care, and insufficient surveillance. Strengthening diagnostic access, integrating prevention efforts into broader health systems, and addressing social determinants are essential. Improved surveillance, equitable access, and innovation—including diagnostics and potential vaccine research—are critical to controlling the global syphilis epidemic. Full article