Search Results (496)

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterized by impaired mucociliary clearance due to defects in motile cilia. This study investigates the impact of loss-of-function mutations in the CFAP300 gene on the ciliary structure and function in three PCD patients. Using a multimodal approach, we integrated molecular genetic testing, transmission electron microscopy, the high-speed video microscopy assay and immunofluorescence staining to analyze ciliary motility and protein expression in both ex vivo and in vitro-obtained ciliary cells. Our results revealed that the pathogenic variant c.198_200delinsCC (p.Phe67ProfsTer10) in CFAP300 led to the absence of the functional CFAP300 protein, the complete loss of outer and inner dynein arms and immotile cilia. Air–liquid interface (ALI)-cultured cells from patients exhibited no ciliary beating, contrasting with healthy controls. Immunostaining confirmed the absence of CFAP300 in patient-derived cilia, underscoring its critical role in dynein arm assembly. These findings highlight the diagnostic utility of ALI cultures combined with functional and protein analyses for PCD, offering a clinically actionable framework that can be readily incorporated into standard diagnostic workflows. Full article

Cigarette smoking is acknowledged as the most preventable risk factor for thrombogenesis-associated cardiovascular disease. Mice prenatally exposed to the thirdhand smoke (THS) form of tobacco exhibited a higher tendency to develop occlusive thrombosis, along with enhancement of several platelet functional responses. Our objective was to investigate whether prenatal (in utero) THS exposure impacts the platelet transcriptome, resulting in enhanced platelet functional responses, thereby underlying THS-associated thrombogenicity. Blood samples obtained from twenty male mice prenatally exposed to THS, along with an equal number of age-matched male mice exposed to clean air (CA) as a control, were divided into pools of five animals and used to prepare leukocyte and red blood cell-depleted platelets. RNA sequencing for mRNA and microRNA (miRNA) was utilized to analyze and compare the platelet expression profiles of the two exposure groups. RNA seq analyses revealed distinct changes in both gene expression and miRNA profiles, with 448 coding genes and 18 miRNAs significantly altered between the two groups. miRNA–mRNA interaction analysis highlighted 14 differentially expressed miRNAs that potentially target 120 of the differentially expressed genes in our data set. Interestingly, altered genes in miRNA–mRNA pairs were functionally enriched into pathways associated with platelet physiology, including platelet activation, signaling and aggregation, and cellular response to chemical stimuli. Our findings establish—for the first time—that prenatal exposure to THS modifies the platelet transcriptome, thereby rendering platelets hypersensitive to stimuli and more prone to thrombogenicity. Additionally, we illuminate the coordinated function of platelet miRNA and mRNA targets in mediating this response. Full article

Systemic sclerosis (SSc) is an autoimmune connective tissue disorder characterized by vascular abnormalities, immune dysfunction, and progressive fibrosis. One of the most common manifestations of SSc is interstitial lung disease (ILD), known by a progressive course leading to significant morbidity and mortality. Aim: to investigate autoantibodies, cytokines, and genetic markers in SSc-ILD through a systematic review and analysis of a Kazakh cohort of SSc-ILD patients. Methods: A PubMed search over the past 10 years was performed with “SSc-ILD”, “autoantibodies”, “cytokines”, and “genes”. Thirty patients with SSc were assessed for lung involvement, EScSG score, and modified Rodnan skin score. IL-6 was measured by ELISA, antinuclear factor on HEp-2 cells by indirect immunofluorescence, and specific autoantibodies by immunoblotting. Genetic analysis was performed using a 120-gene AmpliSeq panel on the Ion Proton platform. Results: The literature review identified 361 articles, 26 addressed autoantibodies, 20 genetic variants, and 12 cytokine profiles. Elevated levels of IL-6, TGF-β, IL-33, and TNF-α were linked to SSc. Based on the results of the systemic review, we created a preliminary immunogenic panel for SSc-ILD with following analysis in Kazakh patients with SSc (n = 30). Fourteen of them (46.7%) demonstrated signs of ILD and/or lung hypertension, with frequent detection of antibodies such as Scl-70, U1-snRNP, SS-A, and genetic variants in SAMD9L, REL, IRAK1, LY96, IL6R, ITGA2B, AIRE, TREX1, and CD40 genes. Conclusions: Current research confirmed the presence of the broad range of autoantibodies and variations in IRAK1, TNFAIP3, SAMD9L, REL, IRAK1, LY96, IL6R, ITGA2B, AIRE, TREX1, CD40 genes in of Kazakhstani cohort of SSc-ILD patients. Full article

Antimicrobial resistance (AMR) has emerged as a planetary health emergency, driven not only by the clinical misuse of antibiotics but also by diverse environmental dissemination pathways. This review critically examines the role of environmental compartments—water, soil, and air—as dynamic reservoirs and transmission routes for antibiotic-resistant bacteria (ARB) and resistance genes (ARGs). Recent metagenomic, epidemiological, and mechanistic evidence demonstrates that anthropogenic pressures—including pharmaceutical effluents, agricultural runoff, untreated sewage, and airborne emissions—amplify resistance evolution and interspecies gene transfer via horizontal gene transfer mechanisms, biofilms, and mobile genetic elements. Importantly, it is not only highly polluted rivers such as the Ganges that contribute to the spread of AMR; even low concentrations of antibiotics and their metabolites, formed during or after treatment, can significantly promote the selection and dissemination of resistance. Environmental hotspots such as European agricultural soils and airborne particulate zones near wastewater treatment plants further illustrate the complexity and global scope of pollution-driven AMR. The synergistic roles of co-selective agents, including heavy metals, disinfectants, and microplastics, are highlighted for their impact in exacerbating resistance gene propagation across ecological and geographical boundaries. The efficacy and limitations of current mitigation strategies, including advanced wastewater treatments, thermophilic composting, biosensor-based surveillance, and emerging regulatory frameworks, are evaluated. By integrating a One Health perspective, this review underscores the imperative of including environmental considerations in global AMR containment policies and proposes a multidisciplinary roadmap to mitigate resistance spread across interconnected human, animal, and environmental domains. Full article

Military personnel deployed to Iraq and Afghanistan were exposed to emissions from open-air burn pits, where plastics, metals, and medical waste were incinerated. These exposures have been linked to deployment-related respiratory diseases (DRRD) and may also impact neurological health via the lung–brain axis. To investigate molecular mechanisms, adult male rats were exposed to filtered air, naphthalene (a representative volatile organic compound), or a combination of naphthalene and carbon black (surrogate for particulate matter; CBN) via whole-body inhalation (six hours/day, three consecutive days). Lung, brain, and plasma samples were collected 24 h after the final exposure. Pro-inflammatory biomarkers were assessed using multiplex electrochemiluminescence and western blot. Differentially expressed genes (DEGs) were identified by RNA sequencing, and elastic net modeling was used to define exposure-predictive gene signatures. CBN exposure altered inflammatory biomarkers across tissues, with activation of nuclear factor kappa B (NF-κB) signaling. In the lung, gene set enrichment revealed activated pathways related to proliferation and inflammation, while epithelial–mesenchymal transition (EMT) and oxidative phosphorylation were suppressed. In the brain, EMT, inflammation, and senescence pathways were activated, while ribosomal function and oxidative metabolism were downregulated. Elastic net modeling identified a lung gene signature predictive of CBN exposure, including Kcnq3, Tgfbr1, and Tm4sf19. These findings demonstrate that inhalation of a surrogate burn pit mixture induces inflammatory and metabolic gene expression changes in both lung and brain tissues, supporting the utility of this animal model for understanding systemic effects of airborne military toxicants and for identifying potential biomarkers relevant to DRRD and Veteran health. Full article

Background: As a well-known environmental hazard, ambient fine particulate matter (PM_2.5, aerodynamic diameter ≤ 2.5 µm) has been positively correlated with an increased risk of digestive system diseases, including appendicitis, inflammatory bowel disease, and gastrointestinal cancer. Additionally, PM_2.5 exposure has been shown to alter microbiota composition and diversity in human and animal models. However, its impact on goblet cells and gut mucus barrier integrity remains unclear. Methods: To address this, 8-week-old male and female interleukin-10 knockout (IL10^−/−) mice, serving as a spontaneous colitis model, were exposed to concentrated ambient PM_2.5 or filtered air (FA) in a whole-body exposure system for 17 weeks. Colon tissues from the PM_2.5-exposed mice and LS174T goblet cells were analyzed using H&E staining, transmission electron microscopy (TEM), and transcriptomic profiling. Results: The average PM_2.5 concentration in the exposure chamber was 100.20 ± 13.79 µg/m³. PM_2.5 exposure in the IL10^−/− mice led to pronounced colon shortening, increased inflammatory infiltration, ragged villi brush borders, dense goblet cells with sparse enterocytes, and lipid droplet accumulation in mitochondria. Similar ultrastructure changes were exhibited in the LS174T goblet cells after PM_2.5 exposure. Transcriptomic analysis revealed a predominantly upregulated gene expression spectrum, indicating an overall enhancement rather than suppression of metabolic activity after PM_2.5 exposure. Integrated enrichment analyses, including GO, KEGG, and GSEA, showed enrichment in pathways related to oxidative stress, xenobiotic (exogenous compound) metabolism, and energy metabolism. METAFlux, a metabolic activity analysis, further substantiated that PM_2.5 exposure induces a shift in cellular energy metabolism preference and disrupts redox homeostasis. Conclusions: The findings of exacerbated gut barrier impairment and goblet cell dysfunction following PM_2.5 exposure provide new evidence of environmental factors contributing to colitis, highlighting new perspectives on its role in the pathogenesis of colitis. Full article

Air pollution acts as a pervasive oxidative stressor, disrupting global crop production and ecosystem health through the overproduction of reactive oxygen species (ROS). Hazardous pollutants impair critical physiological processes—photosynthesis, respiration, and nutrient uptake—triggering oxidative damage and yield losses. This review synthesizes current knowledge on plant defense mechanisms, emphasizing the integration of enzymatic (SOD, POD, CAT, APX, GPX, GR) and non-enzymatic (polyphenols, glutathione, ascorbate, phytochelatins) antioxidant systems to scavenge ROS and maintain redox homeostasis. We highlight the pivotal roles of transcription factors (MYB, WRKY, NAC) in orchestrating stress-responsive gene networks, alongside MAPK and phytohormone signaling (salicylic acid, jasmonic acid, ethylene), in mitigating oxidative stress. Secondary metabolites (flavonoids, lignin, terpenoids) are examined as biochemical shields against ROS and pollutant toxicity, with evidence from transcriptomic and metabolomic studies revealing their biosynthetic regulation. Furthermore, we explore biotechnological strategies to enhance antioxidant capacity, including overexpression of ROS-scavenging genes (e.g., TaCAT3) and engineering of phenolic pathways. By addressing gaps in understanding combined stress responses, this review provides a roadmap for developing resilient crops through antioxidant-focused interventions, ensuring sustainability in polluted environments. Full article

Background/Objective: Dysbiosis is implicated in the pathogenesis of ulcerative colitis. Hydrogen has been reported to promote intestinal microbiota diversity and suppress ulcerative colitis progression in mice models. In this study, we investigated changes in the intestinal microbiota, therapeutic effects, and safety of hydrogen inhalation in patients with ulcerative colitis. Methods: In this randomised, double-blind, placebo-controlled trial, 10 active patients with ulcerative colitis (aged ≥20 years; Lichtiger’s clinical activity index, 3–10; and Mayo endoscopic subscores ≥1) participated, and they were assigned to either a hydrogen or air inhalation group (hydrogen and placebo groups, respectively). All patients inhaled gas for 4 h every day for 8 weeks. Subsequently, we performed clinical indices and microbiota analyses using the metagenomic sequencing of stool samples before and after inhalation. Results: There was significant difference in the sum of the Mayo endoscopic subscores before and after inhalation in the clinical assessment indices. The hydrogen group showed higher α-diversity (p = 0.19), and the variation in β-diversity was markedly different, compared to the placebo group, in intestinal microbiota analysis (p = 0.02). Functional gene analysis revealed 115 significant genetic changes in the hydrogen group following treatment. No inhalation-related adverse events were observed. Conclusions: Hydrogen inhalation appeared to improve intestinal microbiota diversity; however, no clear therapeutic effect on ulcerative colitis was observed. Further studies are needed, and hydrogen inhalation may possibly lead to a logical solution combined with microbiome therapy, such as faecal microbiota transplantation, with fewer adverse events. Full article

In this study, we evaluated the nitrous oxide production potential of denitrifying bacterial strains isolated from sediments of the urban wetland Santa María del Lago under anaerobic and aerobic conditions to determine their potential role in mitigating anthropogenic N₂O emissions, which have increased by approximately 40% since 1980, and if these emissions could be related to the absence of the nitrous oxide reductase gene (nosZ). The results demonstrated that denitrifying bacteria belonging to the genus Bacillus were able to generate nitrous oxide in high concentrations under both aerobic (up to 83 nM/h) and anaerobic (up to 3865.5 nM/h) conditions in cultures with optimal concentrations of nitrate and carbon. The amplification of the nosZ gene as marker of denitrifying microorganisms showed that only 50% of strains possess this gene, and its presence did not correlate with nitrous oxide reduction under anoxic conditions. Interestingly, one strain was able to reduce nitrous oxide in the presence of air, which is promising for its potential use in aerobic bioremediation systems that require microorganisms with a high affinity for this greenhouse gas to reduce emissions into the atmosphere. Full article

Nocardia spp. are opportunistic pathogens of humans, domestic animals, and wildlife that can cause high levels of morbidity and mortality. Here, we present a unique case of nocardial airsacculitis in a free-ranging mallard (Anas platyrhynchos) from Arizona, USA, and compare it to the hosts, geographic distribution, diagnostic methodology, and infection site of known nocardiosis cases in birds. A gross necropsy, histopathology, and bacterial culture were performed. There were no gross findings associated with the nocardiosis. Histopathology showed multiple granulomas expanding the air sac with intralesional filamentous bacteria that were Grocott’s methenamine silver-positive, Fite–Faraco and Ziehl–Neelsen acid-fast, positive with the Periodic acid–Schiff reaction, and variably Gram-positive. The organism was isolated in culture and identified as Nocardia cyriacigeorgica based on the sequencing of a 463 bp portion of the 16S rRNA gene. While reports of nocardiosis in the class Aves are rare and some are possibly misdiagnosed due to limited diagnostics, cases are reported globally, sometimes resulting in epizootics. More information is needed to understand whether immunosuppression plays a role in disease development in birds. Known to be an emerging pathogen in humans, N. cyriacigeorgica can be considered as a differential diagnosis for pulmonary and potentially cutaneous or disseminated infections in birds. Full article

Nicotine-induced oxidative stress contributes significantly to vascular endothelial dysfunction. While negative air ions (NAIs) demonstrate potential blood-pressure-regulating and antioxidant properties, their mechanistic role remains unclear. This study examined the effects of NAIs against nicotine-induced oxidative damage and vascular endothelial injury in spontaneously hypertensive rats (SHRs). Western blotting was used to detect the expression levels of the α7nAChR/MAPK/AP1 pathway. Transcriptomic sequencing was performed to identify the differentially expressed genes after treatment with nicotine or NAIs. Furthermore, reactive oxygen species (ROS), endothelin-1 (ET-1), and [Ca²⁺]_i levels were detected in human aortic endothelial cells (HAECs) treated with nicotine, and the relationship between transcription factor activator protein 1 (AP1) and the target genes was further elucidated through ChIP–qPCR. Nicotine exposure in SHRs elevated blood pressure and induced oxidative damage through α7nAChR/MAPK/AP1 pathway activation, causing endothelial structural disruption. These effects manifested as decreased NO/eNOS and increased ET-1/ET_ab expression, while these changes were reversed by NAIs. In HAECs, nicotine impaired proliferation while increasing oxidative stress and [Ca²⁺]_i levels. This endothelial damage was markedly attenuated by either NAIs or fibronectin 1 (Fn1)/secreted phosphoprotein 1 (Spp1) knockdown. Mechanistically, we identified AP1 as the transcriptional regulator of FN1 and SPP1. NAIs attenuate nicotine-induced endothelial dysfunction in hypertension by inhibiting AP1-mediated FN1 and SPP1 activation, providing novel insights for smoking-associated cardiovascular risk. Full article

Air pollution is a known contributor to cancer risk, although its specific impact on endometrial cancer (EC) remains unclear. This study integrates network toxicology, transcriptomics, molecular docking, and machine learning to investigate pollutant–gene interactions in EC. We identify 83 air pollution-associated EC genes (APECGs), with TNF, ESR1, IL1B, NFKB1, and PTGS2 as the hub genes. A 13-gene RSF-SuperPC model, including CCNE1, SLC2A1, AHCY, and CDC25C, shows effective prognostic stratification. Molecular docking reveals strong binding between pollutants (e.g., benzene, toluene, and ethylbenzene) and key APECGs. The enrichment and SHAP analyses suggest that pollutant-driven EC progression involves DNA damage, metabolic reprogramming, epigenetic dysregulation, immune suppression, and inflammation. These findings reveal potential mechanisms linking air pollution to EC and support the development of biomarkers for high-exposure populations. Further experimental and epidemiological validation is needed to enable clinical translation. Full article

Background/Objectives: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autoimmune disorder caused by mutations in the AIRE gene. Approximately 60% of affected females develop premature ovarian insufficiency (POI) by age 30, often most commonly due to steroidogenic autoantibodies. Although APECED is typically diagnosed in childhood, its reproductive implications are underrecognized. This study reports a case of successful fertility preservation in an adult woman with APECED and reviews the relevant literature. Methods: We describe the clinical course of a 37-year-old woman with genetically confirmed APECED who underwent ovarian stimulation for fertility preservation. A comprehensive PubMed search was also conducted to identify English-language case reports on fertility preservation in APECED-associated POI. Results: The patient experienced menarche at age 13, adrenal insufficiency at 14, and menstrual irregularities from age 18. Genetic analysis confirmed an AIRE mutation (NM_000383: exon 11: c.1400+1G>A). Given her relatively high anti-Müllerian hormone level, she opted for fertility preservation and underwent six cycles of ovarian stimulation, resulting in the cryopreservation of 17 mature oocytes. During ovarian stimulation, multiple follicular developments were observed, but serum E2 levels remained low. The literature review identified fewer than 20 reported cases addressing fertility preservation in APECED, highlighting its rarity and the lack of standardized management. Conclusions: Although APECED frequently leads to early POI due to impaired steroidogenesis, residual ovarian function may persist. Early assessment of ovarian reserve and timely fertility counseling are crucial, even in asymptomatic patients or those diagnosed in childhood. Reproductive planning should be integrated into the long-term care of women with APECED. Full article

Transcriptomic profiling has shown that exposure to PM_2.5, a common air pollutant, can modulate gene expression, which has been linked to negative health effects and diseases. However, there are few population-based cohort studies on the association between PM_2.5 exposure and specific gene set expression. In this study, we used an unbiased transcriptomic profiling approach to examine gene expression in a mouse model exposed to PM_2.5 and to identify PM_2.5-responsive genes. The gene expressions were further validated in both the human cell lines and a population-based cohort study. Two cohorts of healthy older adults (aged ≥ 65 years) were recruited from regions characterized by differing levels of PM_2.5. Logistic regression and decision tree algorithms were then utilized to construct predictive models for PM_2.5 exposure based on these gene expression profiles. Our results indicated that the expression of five genes (FAM102B, PPP2R1B, OXR1, ITGAM, and PRP38B) increased with PM_2.5 exposure in both cell-based assay and population-based cohort studies. Furthermore, the predictive models demonstrated high accuracy in classifying high-and-low PM_2.5 exposure, potentially supporting the integration of gene biomarkers into public health practices. Full article

A 7-week feeding trial was conducted with Nile tilapia juveniles with an average body weight of 143.5 ± 3.1 g in a cage system in order to test the effect of different feed additives on growth performance, antioxidant defense system, and immune status of fish. For this reason, experimental diets were formulated with inclusion of two different additives containing bioactive compounds, namely Nannochlorophsis gaditana in 3.5% (diet EXP-A) and black soldier fly larvae meal (diet EXP-I) in 3.5%, and compared with a diet supplemented with a mixture of two different commercial compounds (Yang and Syrena Boost) in 0.4% (diet EXP-S). As a negative control, a commercially available feed (Nongteng, Laos) for tilapia was selected. At the end of the feeding trial, production parameters and expression of genes related to the antioxidant defense system and innate immune response were studied. Furthermore, following the feeding, air exposure stress for 5 min was administered to the fish, and similar parameters were assessed. Results indicated that all diets promoted adequate fish growth (SGR 1.67–1.81 g day⁻¹) and feed utilization (FCR 1.29–1.57 g g⁻¹) with no significant (p < 0.05) differences in these parameters between the dietary fish groups. Expression of genes sod, cat, and gpx significantly increased in the liver samples of the EXP-A group at the end of feeding. Following air exposure, the EXP-A group maintained a significantly higher level of antioxidant-related gene expression compared to other treatments. Subsequently, gpx upregulation was observed in the EXP-S group in the post-stress stage compared to pre-stress. Based on our results, we recommend the inclusion of any of the tested additives at the evaluated doses to enhance the non-specific immune response of Nile tilapia. Additionally, Nannochloropsis gaditana at a 3.5% inclusion level can be used to further improve antioxidant defense capacity. Full article