Search Results (10,213)

Human sarcocystosis is a neglected zoonotic infection caused by protozoa of the genus Sarcocystis. Although sporadic cases and outbreaks have been reported worldwide, the global burden of human infections has not been comprehensively synthesized. This study aimed to estimate the pooled prevalence and global distribution of Sarcocystis infections in humans. A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines and registered with PROSPERO (CRD420251159944). PubMed, Scopus, Web of Science, Ovid, Nursing & Allied Health Premium, and Google Scholar were used for retrieving relevant studies. Observational studies published from 2000 onward reporting human Sarcocystis infections confirmed by microscopic and/or molecular methods were included. A random-effects model was used to estimate pooled prevalence. Heterogeneity was assessed using the I² statistic. Subgroup analyses and meta-regression were performed to explore sources of heterogeneity. Seventeen studies comprising 66,329 participants met the inclusion criteria. The pooled prevalence of human Sarcocystis infection was 0.85% (95% confidence interval [CI]: 0.33–2.19), with substantial heterogeneity (I² = 98.2%). Prevalence estimates showed marked variation across continents, countries, participant groups, diagnostic methods, Sarcocystis species, and clinical forms of sarcocystosis. Although human Sarcocystis infection appears relatively rare, its prevalence is geographically heterogeneous across studies published between 2000 and 2024. The robustness of the pooled prevalence estimate is limited by the small number of studies, uneven geographical coverage, and substantial heterogeneity. Differences in diagnostic approaches, study populations, infecting species, and disease phenotypes likely contributed to this variability. Enhanced surveillance and standardized application of sensitive molecular diagnostics are essential to better define the epidemiology, burden, and public health significance of human sarcocystosis. Full article

Background/Objectives: Traditional medicinal plants play a crucial role in infants’ healthcare in underdeveloped countries and communities where access to modern medicine is limited. In Limpopo, the Vhavenda tribe has a custom of feeding babies as young as a day old with tshiunza, a very light and warm, soft porridge prepared in medicinal plant extracts, believed to help treat various ailments and boost the immune and digestive systems. However, reports of negative side effects, including vomiting, haematuria, renal inflammation and hospitalisations, highlight safety concerns of these traditional practices. This study aimed to profile the chemical composition of soft porridge samples prepared in aqueous extracts of medicinal plants reported to be commonly used in infants’ food in the Venda region of Limpopo; Annona senegalensis (roots), Piliostigma thonningii (leaves), Carissa edulis (roots) and Bauhinia galpinii (leaves). Methods: Ultrahigh-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-qTOF-MS) was used for metabolic profiling, followed by putative compound identification using feature-based molecular networking and a compound fragmentation predictor tool, SIRIUS. To evaluate the toxicity of these plants, a cytotoxicity assay was conducted using plant extracts on African monkey kidney cells. Results: Different classes of polyphenols, including flavonoids (flavan-3-ols and flavonols) and hydroxycinnamoyl amides, were among the dominant compounds putatively identified in the methanolic extracts of soft porridge prepared from the four plant extracts. A. senegalensis aqueous extracts were inactive (IC₅₀ > 500 µg/mL, 55.57% viability at 500 µg/mL), while P. thonningii was non-cytotoxic (105–132% viability within the tested concentration range). Conclusions: Although no toxic compounds were identified and no cytotoxic potential was observed in the tested plant extracts, this does not translate to the safe use of medicinal plants in infants’ food. Therefore, future studies should conduct pharmacological and toxicological evaluations to better understand the potential risks of these plant extracts to infant health. Full article

Acute lung injury (ALI) seriously impairs health and well-being. Although Scutellaria baicalensis Georgi (SBG) extract has been shown to alleviate ALI, the effects of SBG acidic polysaccharides on ALI have not been revealed. In this study, a homogeneous acidic polysaccharide (SBGP1) was purified and characterized, and its impact on ALI was evaluated. Our findings illustrated that the average molecular weight of SBGP1 was 40764.6 Da, and it was mainly composed of GalA (53.14%), Ara (26.99%), Gal (7.75%), Glc (5.95%), and Rha (6.17%). The main chain of SBGP1 consisted of →4)-α-GalpA-6-OMe-(1→ and →4)-α-GalpA-(1→. Furthermore, SBGP1 exhibited a significant alleviating effect on ALI, as evidenced by decreased levels of TNF-α, IL-1β, IL-6, GSSG, and MDA, and increased levels of IL-4, IL-10, GSH, and SOD. Mechanistically, SBGP1’s role in alleviating ALI may be associated with the activation of the Rap1 signaling pathway. SBGP1 improved intestinal homeostasis, manifested as increased abundance of beneficial bacteria (Lactobacillus and norank_f_Muribaculaceae) and decreased abundance of harmful bacteria (Adlercreutzia, Ligilactobacillus, Massiliomicrobiota, and Mucispirillum). Interestingly, SBGP1-derived Lactobacillus johnsonii and propionic acid evidently improved the inflammatory response and oxidative stress in ALI mice. Overall, this study provides novel insights into SBGP1 as a potential therapeutic option for ALI. Full article

Adult hematopoietic stem cells (HSCs) and bone marrow (BM) mesenchymal stem/stromal cells (MSCs) are essential for lifelong hematopoiesis, skeletal homeostasis, immune competence, and tissue regeneration. The use of electronic cigarettes (E-cigs) among women of reproductive age continues to rise, raising concerns about potential adverse developmental effects; however, the long-term consequences of maternal E-cig vaping on offspring BM stem cell function and hematopoietic homeostasis remain incompletely understood. Here, using a rat model of maternal E-cig exposure (containing nicotine) during gestation, combined with longitudinal in vivo analyses and complementary ex vivo studies of human cells, we show that prenatal E-cig exposure is associated with persistent alterations in offspring BM stem cell function and lineage commitment. Gestational E-cig exposure was associated with expansion of the CD11b/c⁺ myeloid-enriched compartment, increased CD90⁺ stromal cells, and impaired osteogenic differentiation in rat offspring. Complementary experiments using primary human cells showed that nicotine exposure was associated with reduced T-cell proliferation and impaired cytotoxic activity in a proof-of-principle co-culture assay. Mechanistically, transcriptomic profiling followed by Gene Ontology and pathway enrichment analyses identified alterations in molecular programs associated with KLF4–Notch1 signaling, mitochondrial biogenesis, inflammation, and stem cell regulation in the BM of E-cig-exposed rat offspring. Changes in CCL11, FTO, and RUNX2 were additionally associated with an inflammatory and aging-related molecular phenotype that persisted from early life into adulthood, although these findings do not establish a causal CCL11–FTO–RUNX2 signaling axis or direct cellular senescence. Collectively, our study provides a phenotypic and mechanistic framework for understanding how maternal E-cig exposure may influence long-term offspring hematopoietic, skeletal, and immune health while highlighting the need for further studies to establish causal molecular mechanisms and determine their relevance to maternal E-cig use in humans. Full article

Despite significant therapeutic advances, T2DM remains a global public health challenge that leads to multiple complications, including cardiovascular, renal, hepatic, and neurodegenerative disorders. Mitochondrial dysfunction and impaired mitophagy remain fundamental, yet incompletely understood, mechanisms driving pancreatic β-cell failure, chronic inflammation, insulin resistance and diabetic complications. Emerging evidence indicates that noncoding RNAs (including microRNAs, long noncoding RNAs, and circular RNAs) are critical regulators of mitophagy and mitochondrial quality control mechanisms across metabolically active tissues. This review comprehensively examines the interplay between mitochondrial dysfunction, mitophagy impairment, and T2DM pathophysiology. It provides an overview of recent mechanistic insights into mitophagy–noncoding RNA interactions in T2DM, emphasizing tissue-specific effects, and highlights the translational potential of mitophagy-associated proteins and regulatory ncRNAs as diagnostic biomarkers and therapeutic targets. By bridging fundamental molecular biology with translational and clinical perspectives, further it provides a comprehensive framework to guide future research, accelerate biomarker discovery, and support the development of personalized interventions aimed at reducing the growing worldwide burden of T2DM and its complications. Full article

Cadmium (Cd), a highly toxic and mobile heavy metal, has emerged as a severe environmental concern in global agroecosystems, posing a substantial threat to human health. Although prior studies have established that ZAT6 and ZAT10 positively regulate Arabidopsis tolerance to Cd toxicity, the underlying molecular mechanisms remain largely elusive. The present study provides evidence that a class I TCP transcription factor, TCP9, significantly enhances Arabidopsis tolerance to Cd toxicity through the direct activation of ZAT6 and ZAT10 expression. The real-time quantitative PCR (RT-qPCR) analysis indicates that the expression of TCP9 was induced under Cd toxicity. Meanwhile, the tcp9 mutant exhibited heightened sensitivity to Cd toxicity, accompanied by elevated Cd accumulation in both shoots and roots. Notably, the complemented lines exhibited phenotypic characteristics analogous to those observed in the wild-type (WT) plants. Further physiological and biochemical analyses revealed that, in comparison to WT, the tcp9 mutant displayed elevated hydrogen peroxide (H₂O₂) accumulation and reduced contents of catalase (CAT), ascorbate peroxidase (APX), and peroxidase (POD) under Cd toxicity. Furthermore, TCP9 directly interacted with the promoters of ZAT6 and ZAT10 in vitro, facilitating their transcription and consequently enhancing plant tolerance to Cd toxicity. Overall, our findings showed that TCP9 enhances Cd tolerance via modulating ZAT6 and ZAT10, thereby identifying TCP9 as a potential key target for improving plant tolerance to Cd toxicity. Full article

Healthcare-associated infections (HAIs) caused by multidrug-resistant Klebsiella spp. represent a critical and escalating global public health threat. Carbapenem-resistant Klebsiella pneumoniae (CRKP) has been designated a critical-priority pathogen by the World Health Organization, and in the 2024 WHO Bacterial Priority Pathogens List, it was the top-ranked pathogen overall. The convergence of carbapenem resistance with hypervirulence in emerging strains has further complicated therapeutic decision-making. This review provides a narrative synthesis of the evidence published between 2020 and 2025 on the prevalence, resistance mechanisms, molecular epidemiology, clinical outcomes, and therapeutic strategies for Klebsiella pneumoniae infections acquired in healthcare settings, with particular attention to the Eastern European and Romanian context. PubMed/MEDLINE, Embase, Web of Science, and the Cochrane Library were searched for relevant publications from January 2020 to June 2025, supplemented by WHO and ECDC surveillance reports. Studies were selected narratively for their relevance to the themes addressed. No new quantitative pooling was undertaken; all summary estimates reported below are cited from the published meta-analyses and surveillance reports that generated them. In the most recent global meta-analysis of hospital-acquired CRKP infection, which pooled 61 studies and 513,307 patients from 14 countries, the global prevalence of CRKP among nosocomial K. pneumoniae infections was 28.69% (95% CI: 26.53–30.86%), with pronounced regional variation from 14.29% in high-income North America to 66.04% in South Asia, and 42.05% in Western Europe. Pooled mortality among patients infected with CRKP has been estimated in a separate meta-analysis at 42.14%, compared with 21.16% among patients infected with carbapenem-susceptible strains, rising to 54.30% in bloodstream infections. Surveillance data place Romania third in Europe for carbapenem resistance among invasive K. pneumoniae isolates, at 50.30%, with a distinctive predominance of NDM plus OXA-48-like co-producers. Ceftazidime-avibactam is recommended for KPC- and OXA-48-producing strains, whereas metallo-beta-lactamase producers require aztreonam-containing combinations. CRKP in HAIs constitutes a global epidemiological emergency characterised by marked regional heterogeneity in carbapenemase distribution, high attributable mortality and rapidly evolving molecular profiles. Locally adapted surveillance, rapid molecular diagnostics, and stewardship programmes are required since empirical therapy cannot be standardised across regions. Full article

Polygonatum cyrtonema Hua polysaccharides (PCPs) are bioactive components with antioxidant and immunomodulatory properties. However, whether the polysaccharides derived from elder Polygonatum cyrtonema exhibit superior health benefits remains unclear. This study systematically compared the in vitro fermentation characteristics, gut microbiota-modulating effects, and short-chain fatty acid (SCFA) production of PCPs extracted from three-year-old (TPP), five-year-old (FPP), and eight-year-old (EPP) plants using a human fecal fermentation model. The fermentation dynamics were evaluated by monitoring pH, OD₆₀₀, and the consumption of total and reducing sugars, while the structural degradation and compositional differences in PCPs were tracked via molecular weight distribution and monosaccharide composition analysis. The results showed that all three PCPs were degraded and utilized by gut microbiota, accompanied by decreased pH, increased OD₆₀₀, and enhanced antioxidant activities. High-throughput 16S rDNA sequencing revealed that, at the phylum level, all PCPs increased the Firmicutes/Bacteroidetes ratio. At the genus level, they reduced the abundance of harmful bacteria such as Sutterella and increased beneficial bacteria including Bifidobacterium and Megasphaera. Furthermore, gas chromatography (GC) analysis demonstrated that, compared with FPP, TPP and EPP significantly promoted the production of SCFAs. In summary, this study indicates that the in vitro fermentation characteristics and prebiotic properties of PCPs vary with growth years, and a comprehensive evaluation suggests that three-year-old Polygonatum cyrtonema Hua represents a promising raw material for the development of functional foods. Full article

The global emergence of multidrug-resistant fungal pathogens, including Candida auris, Candida albicans, Aspergillus fumigatus, Cryptococcus neoformans, and Pneumocystis jirovecii, poses a growing threat to public health, particularly among immunocompromised individuals. The limited number of available antifungal drug classes and the rapid evolution of resistance mechanisms, including target-site mutations, efflux pump activation, biofilm formation, metabolic adaptation, and stress-response signaling, have substantially reduced treatment efficacy. This review provides a comprehensive overview of current antifungal therapies, their limitations, and emerging molecular targets for next-generation antifungal drug discovery. We highlight promising targets involved in fungal cell wall biosynthesis, membrane integrity, mitochondrial metabolism, virulence regulation, and host–pathogen interactions, emphasizing their interconnected roles within adaptive resistance networks. Attention is given to small-molecule isothiazolone-based inhibitors, including phosphoglucomutase-targeting compounds, as novel candidates capable of disrupting multiple fungal survival pathways. We further discuss advances in combination therapies, anti-virulence approaches, nanotechnology-based delivery systems, and artificial intelligence-driven drug discovery pipelines that integrate multi-omics data, structural modeling, molecular docking, and virtual screening to accelerate therapeutic development. These advances support a transition from conventional single-target strategies toward systems-level, precision-guided antifungal therapies, providing a framework for overcoming multidrug resistance and improving clinical outcomes in invasive fungal infections. Full article

Background/Objectives: Microplastics (MPs) and nanoplastics (NPs) have emerged as ubiquitous environmental contaminants resulting from the extensive production, use, and degradation of plastic materials. Human exposure occurs primarily through contaminated food and drinking water, with inhalation representing an additional important route. Growing concern has focused on the ability of these particles, particularly NPs, to cross biological barriers, enter the systemic circulation, and reach human tissues. The aim of this review was to summarize current evidence on dietary exposure to MPs and NPs, their gastrointestinal bioavailability and toxicokinetics, and their potential systemic health effects, with particular emphasis on organ-specific responses, underlying biological mechanisms, and the strength and limitations of the available evidence. Methods: A comprehensive narrative review of the scientific literature published between 2000 and 2026 was conducted using PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar. Original research articles and review papers addressing dietary exposure, occurrence in food and drinking water, migration from food-contact materials, gastrointestinal absorption, translocation, biodistribution, bioaccumulation, elimination, molecular mechanisms, and potential organ-specific or systemic health effects were included. Publications without full-text availability, conference proceedings, editorials, commentaries, duplicate publications, and studies without relevance to human exposure or health were excluded. Results: Food, drinking water, beverages, and food-contact materials represent important sources of human exposure to MPs and NPs. Following ingestion, most larger particles are eliminated through the gastrointestinal tract, whereas smaller MPs and particularly NPs may cross biological barriers and potentially reach the systemic circulation and distant tissues. Experimental studies consistently identify interconnected biological responses involving oxidative stress, inflammation, mitochondrial dysfunction, barrier impairment, immune dysregulation, genotoxicity, apoptosis, and endocrine disruption. These mechanisms have been associated with alterations in the gastrointestinal, respiratory, cardiovascular, nervous, urinary, reproductive, endocrine, and skeletal systems and with biological processes relevant to carcinogenesis. However, most mechanistic evidence derives from in vitro and animal models, whereas human evidence remains limited and predominantly observational. Consequently, the extent to which these experimental findings translate into clinically significant effects in humans remains uncertain. Conclusions: Current evidence supports the biological plausibility of systemic effects associated with MNP exposure but is insufficient to establish causal relationships between chronic dietary exposure and specific human diseases. The detection of MNPs in human tissues and reported associations with pathological conditions should therefore be interpreted cautiously. Standardized analytical methods, improved characterization of realistic human exposure, and well-designed longitudinal epidemiological studies integrating quantitative exposure assessment with validated clinical outcomes are required to clarify dose–response relationships, long-term health effects, and the clinical significance of MNP exposure. Full article

Numerous types of environmental toxicants alter human metabolomics, directly or indirectly, through gut microbial dysbiosis, upsetting immune homeostasis. Environmental toxicants capable of these direct and indirect effects have included heavy metals, pesticides, herbicides, polychlorinated biphenyl (PCB) congeners, and endocrine-disrupting chemicals. The cell and molecular events induced by some diverse toxicants are reviewed, along with their potential additive, synergistic, and antagonistic effects on immune homeostasis (increasing proinflammatory immune cell activation and suppressing immunoregulation), which leads to systemic oxidative stress (OS). As people are exposed in varying degrees to countless chemicals and environmental factors over a lifetime, it is challenging to correlate specific diagnoses to any single toxicant or exposure, which is often a key challenge in linking environmental exposure to health outcomes. However, many toxicants have the common mechanistic effect of OS. The effects of toxicants are more pronounced with aging due to cumulative exposures and immunoaging (immunosenescence), with chronic low-grade inflammation referred to as “inflammaging”. The cell and molecular mechanisms of toxicants include altered calcium flux, mitochondrial dysfunction, and increased levels of damage-associated molecular patterns (alarmins) that trigger an inflammatory response and possibly promote autoimmune and neurological disorders. OS skews type-1 immunity for defenses against pathogens and cancers more toward type-2 immune responses to self-antigens (autoimmunity). The toxicants may directly affect the innate and adaptive immune cells inducing this skewing, or they may modify portions of gut microbial species and strains and their production of metabolites that indirectly affect systemic immunity. These latter toxicant influences require metabolomic analysis of the differential structures and activities of the microbial metabolites. The damaging effects of OS and inflammation disrupting immune homeostasis and leading to disorders are reviewed and discussed. The need for well-designed studies that allow for standardized comparison of exposures and related effects are emphasized, and their real-world limitations noted. Full article

Enterocytozoon bieneusi is a major zoonotic pathogen causing human microsporidiosis, with small ruminants serving as crucial reservoir hosts. Hu sheep and local goats are pillar livestock breeds in Zhejiang Province, yet no parallel comparative epidemiological data on E. bieneusi exist for sympatric small ruminants in southern Zhejiang, and the infection status in Hu sheep remains entirely uncharacterized. Here, a total of 297 fecal samples (159 Hu sheep, 138 goats) were collected from four administrative regions in southern Zhejiang from 2021 to 2023 and screened via nested PCR targeting the ribosomal internal transcribed spacer (ITS) region of the E. bieneusi genome. Overall, the total E. bieneusi prevalence reached 18.18%, and Hu sheep exhibited a significantly higher infection rate (24.53%, 39/159) than sympatric goats (10.87%, 15/138; χ² = 9.27, p = 0.002). Obvious geographical and age-dependent disparities were observed in Hu sheep, with pre-weaning lambs (<3 months) showing the highest prevalence (60.42%), while adult sheep (>1 year) had the lowest rate (4.48%). No significant age or regional differences were detected in goats. Five genotypes were identified from Hu sheep: CM7 (n = 25), BEB6 (n = 10), CHG1 (n = 2), Type IV (n = 1), and CHG5 (n = 1). Five genotypes were detected from goats: CHG1 (n = 9), BEB6 (n = 3), Type IV (n = 1), CHG3 (n = 1), and CYG-2 (n = 1). BEB6, Type IV, and CHG1 were shared by both hosts. All genotypes belonged to zoonotic Group 1 and Group 2. This study provides the first systematic parallel survey of E. bieneusi in sympatric Hu sheep and goats in eastern China. It identifies distinct host-specific infection patterns potentially associated with divergent rearing systems, provides molecular data consistent with potential inter-species circulation and shared environmental exposure, and highlights the need for breed-tailored biosecurity strategies within a One Health framework. Full article

Metabolic syndrome (MetS) represents a growing global health burden characterized by obesity, insulin resistance, dyslipidemia, and hypertension. Increasing evidence suggests that gut microbiota-associated mediators may serve as signaling intermediates involved in host metabolic regulation. However, the mechanisms by which these mediators interact with host signaling pathways and influence metabolic responses remain incompletely understood. This review summarizes current advances in gut microbiota-associated mediators, focusing on short-chain fatty acids, bile acids, lipopolysaccharide, trimethylamine N-oxide, and branched-chain amino acids. We discuss their interactions with host metabolic and inflammatory pathways, including pathways implicated in FFAR2/3-mediated signaling, FXR/TGR5 signaling, TLR4/NF-κB-mediated inflammatory signaling, and mTORC1-associated nutrient-sensing. Furthermore, we propose a microbiota–mediator–host signaling network framework as an emerging conceptual model to integrate these molecular interactions and highlight the utility of multi-omics approaches in characterizing complex microbiota–host communication. Despite mechanistic advances, substantial challenges remain, including heterogeneous microbial signatures across populations, limited causal evidence, inter-individual variability in therapeutic responses, and barriers to clinical translation of microbiota-targeted interventions. A better understanding of microbiota-associated signaling networks may provide new insights into metabolic regulation and contribute to the rational development of microbiota-targeted strategies that complement established lifestyle interventions for MetS management. Full article

Togaviridae represents a candidate family for emerging public health emergencies of international concern. Among them, chikungunya virus (CHKIV) has caused recurrent epidemics in the temperate zone of most continents and represents a threat to the safety of blood supplies. The global expansion of vectors (i.e., Aedes mosquitoes) and increasing international travel have contributed to the growing epidemiological importance of this pathogen. In fact, CHIKV has been reported in more than 110 countries across the following four continents: Africa, Asia, Americas, and Europe. Consequently, public health authorities have emphasized the importance of surveillance, vector control programs, outbreak preparedness, and blood safety measures. The aim of this review was to summarize the current knowledge of CHIKV considering virology, molecular epidemiology, transmission mechanisms, clinical features, preventive strategies, and blood safety implications, with particular attention to issues relevant to transfusion services. Full article

Genome-wide association studies (GWASs) have mapped many regions affecting cattle production, health and fertility, yet the lead variant is usually a marker for a linkage-disequilibrium block rather than the molecular lesion. This state-of-the-field review examines how those loci are interpreted at different levels. The literature shows both progress and persistent limits. Colocalization may identify a likely effector transcript without establishing mediation, whereas structural variants missing from SNP-based analyses can account for expression, splicing, or complex-trait signals. Earlier reviews have audited proposed causative variants across cattle and pigs, surveyed causal variants across livestock species, or concentrated on structural variation. Here, these lines of evidence are brought together around a narrower question: Why do cattle complex-trait loci remain resolved at such different biological depths? Coding, regulatory, splicing, and structural examples show where inference is persuasive and where alternatives remain. The evidence is organized as a conceptual landscape, not a validated hierarchy or prescriptive pipeline. The available mechanistic evidence is nevertheless concentrated in commercial taurine, particularly dairy populations, which limits the direct transferability of locus-level conclusions to indicine, African taurine, composite and locally adapted cattle. Priorities include clearer causal terminology, multi-signal and multi-breed analyses, better representation of structural variation, tissue- and cell-state-matched molecular data, native bovine experimental systems and transparent reporting of unresolved explanations. Full article