Search Results (9,072)

Lead (Pb) and cadmium (Cd) are common environmental pollutants. Our previous population study revealed a significant positive association between Pb and Cd exposure and the micronuclei frequency among lead smelting workers. However, the underlying mechanisms remain unclear. In this study, human lymphoblastoid TK6 cells were used to investigate the genotoxicity and its mechanisms induced by individual or combined exposure to Pb and Cd. Our results showed that Pb and Cd exposure, alone or in combination, triggered oxidative stress, as evidenced by reduced antioxidant enzyme activity (GSH, SOD and CAT) and increased content of ROS and GSSG. Both metals induced pronounced DNA damage, as shown by elevated Tail DNA% in the Comet assay and γ-H2AX fluorescence intensity. Furthermore, Pb and/or Cd exposure caused inhibition of the DNA repair proteins, including BRCA1, CtIP, RAD52, and XRCC2, indicating impaired DNA repair capacity; and upregulated Bax expression and the Bax/Bcl-2 ratio and Caspase-3 with downregulation of Bcl-2. Notably, Pb and Cd co-exposure produced an antagonistic effect, modulating oxidative stress indicators, cell-cycle arrest, DNA damage markers, DNA repair and apoptosis-related proteins. These findings demonstrate that Pb and Cd induce oxidative stress, DNA damage, inhibition of DNA repair, and apoptosis in TK6 cells. Our study provides new insights into the mechanisms of heavy metal combined exposure–induced genotoxicity and identifies potential molecular targets for intervention. Full article

Muskmelon (Cucumis melo L.) is an economically important crop that remains highly susceptible to destructive fungal diseases, including gummy stem blight, downy mildew, Fusarium wilt, and anthracnose. Although fungicides and resistant cultivars are widely used, reliance on chemical control raises concerns regarding environmental safety, food quality, and the emergence of fungicide-resistant pathogen populations. Consequently, microbial biopesticides, particularly Bacillus species, have attracted increasing attention as sustainable alternatives. In this study, muskmelon plants exhibiting leaf wilting, chlorosis, and stem yellowing were collected from Guangming Farm in Wufeng, Taichung, Taiwan, and associated pathogens were isolated from stem tissues and identified to determine the causal agent of these symptoms. In addition, the biocontrol efficacy of Bacillus subtilis strain MCLB2 against melon fruit rot, as well as its underlying mechanisms, was evaluated. Pathogenicity assays confirmed that isolate F01 was the causal agent. Based on morphological characteristics and internal transcribed spacer (ITS) sequence analysis, this isolate showed 99.8% identity to Fusarium pernambucanum URM 7559 (GenBank accession no. NR_163754), and phylogenetic analysis further placed it within the Fusarium incarnatum–equiseti species complex (FIESC). Antagonistic assays demonstrated that B. subtilis MCLB2 significantly inhibited mycelial growth and suppressed the spore germination of F. pernambucanum. In addition, culture filtrates of strain MCLB2 effectively reduced Fusarium-induced fruit rot in melon and disrupted fungal cellular respiration. Liquid chromatography–tandem mass spectrometry (LC–MS/MS) analysis revealed that the strain produced surfactin-family lipopeptides. In conclusion, B. subtilis MCLB2 exhibits potential as a sustainable biocontrol agent for managing Fusarium fruit rot in melon, likely through surfactin-mediated disruption of fungal cellular respiration. Full article

Background: Cardiac involvement represents a major determinant of morbidity and mortality in patients with muscular dystrophies (MDs). Evidence supporting guideline-directed heart failure (HF) therapy in this population remains limited. We aimed to retrospectively assess the effectiveness and tolerability of sodium–glucose co-transporter 2 inhibitors (SGLT2i) in patients with MDs and a previous history of HFrEF, HFpEF and HFmrEF and/or echocardiographic evidence of an LVEF < 50% Methods: In this retrospective, single-center study, we enrolled consecutive patients with MD treated with empagliflozin or dapagliflozin between October 2021 and October 2024. Comprehensive clinical, laboratory, echocardiographic, and functional data were collected at a baseline (V1) and at follow-up (V3) visit to evaluate longitudinal changes. Results: Twenty-four patients (mean age 42 ± 16 years; 92% male) were included, with a median follow-up of 418 ± 104 days. SGLT2i therapy was well tolerated; one patient discontinued treatment due to a urinary tract infection. LVEF significantly improved from 41 ± 5% to 44 ± 6% (p = 0.005). FSS decreased from 36 to 30 (p < 0.001), indicating improved functional capacity. Background HF therapy was intensified over time, with increased prescription of mineralocorticoid receptor antagonists (21% vs. 52%; p = 0.039) and β-blockers (67% vs. 91%). The interval between MD diagnosis and cardiomyopathy onset independently predicted LVEF improvement (β = 0.17; p = 0.012). Conclusions: In patients with MDs and HF, SGLT2i therapy was safe and associated with a modest but significant improvement in LVEF, reduced fatigue, and enhanced prescription of guideline-directed HF therapy. These findings support the potential role of SGLT2i in this high-risk population and warrant confirmation in larger prospective studies. Full article

Polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (B[a]P), are major risk factors for lung cancer and other diseases, acting through the aryl hydrocarbon receptor (AHR). Alveolar macrophages (AMs) help regulate the lung microenvironment by responding to inhaled toxicants and resident microbiota. Although small extracellular vesicles (sEVs, aka exosomes) released by AMs mediate intercellular communication and immune responses, the influence of lung microbiota on sEV biogenesis and the mechanisms underlying sEV dysregulation during PAH exposure remain unknown. Here, we investigated the interplay between AMs, B[a]P, and lung microbiota, focusing on sEV-associated miRNAs (exo-miRNAs). Murine AMs (MH-S) were exposed to varying B[a]P concentrations in the presence or absence of murine lung microbiota with or without an AHR antagonist. sEVs from each condition were characterized and profiled for miRNA. Distinct miRNA signatures emerged: high-dose B[a]P enriched miRNAs linked to cancer progression, whereas lung microbiota alone or with low-dose B[a]P induced tumor-suppressor miRNAs that limit proliferation and metastasis and promote apoptosis, an effect enhanced by AHR antagonism. Lung microbiota appeared to counteract high-dose B[a]P by modulating tumor-suppressive exo-miRNAs. This study demonstrates that lung microbiota-induced exo-miRNAs critically shape AM-derived sEV-miRNA signaling during PAH exposure. The identified exosomal miRNAs could serve as important exposure biomarkers and therapeutic targets for mitigating B[a]P-induced toxicity and cancer development. Full article

Background: The clinical outcomes of patients with intracranial haemorrhage (ICH) whilst using direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) are uncertain. This study aimed to assess outcomes and management in patients receiving DOACs compared with those receiving VKAs. Methods: In this retrospective study, patients hospitalised during the period from 1 January 2017 to 31 December 2023 for traumatic and non-traumatic ICH and using oral anticoagulants (OACs) were included. The primary outcomes were mortality and functional outcomes, as measured by the modified Rankin Scale (mRS) during admission and 90-day follow-up. ICH management and complications were studied and compared between the two OAC groups. Results: A total of 171 eligible patients were included, comprising 24 patients on DOACs and 147 patients on VKAs. Patients receiving DOACs were older (79.1 vs. 66.8, p < 0.001) and had a higher proportion of traumatic ICH (75.0% vs. 46.3%, p = 0.009) than those receiving VKAs. In-hospital and 90-day outcomes were not statistically different between the two groups, with an adjusted odds ratio (aOR) of 1.30 (0.39–4.36) for in-hospital mortality, p = 0.67, and an aOR of 0.89 (0.33–2.41) for mRS 0–2 at 90 days, p = 0.83. In total, 81.3% of patients received at least one reversal agent; fresh frozen plasma was commonly used in the VKA group (78.9% vs. 33.3%, p < 0.001), whereas prothrombin complex concentrate was significantly prescribed in patients with DOAC-associated ICH (29.2% vs. 3.4%, p < 0.001). Conclusions: Patients with DOAC-associated ICH had comparable in-hospital and long-term clinical outcomes to those with VKA use. Full article

Background/Objectives: While standard antiemetic regimens have evolved, breakthrough symptoms and anticipatory nausea persist. Lorazepam has historically been used as an adjunct, yet a comprehensive re-evaluation of its efficacy across historical trials is lacking. This study provides a synthesis of clinical evidence to re-evaluate the adjunctive therapeutic value of lorazepam, potentially addressing persistent gaps in emesis control, such as anticipatory and refractory symptoms. Methods: Following PRISMA guidelines, we analyzed eight randomized controlled trials (n = 864) published between 1989 and 1997. Primary endpoints included complete and improved responses for emesis and nausea. Results: Eight trials (n = 864), published between 1989 and 1997, met the inclusion criteria. Lorazepam-containing regimens significantly increased the complete response rate for overall emesis (OR = 1.55; 95% CI, 1.12–2.14; p = 0.008) and improved the response rate (OR = 1.50; 95% CI, 1.03–2.19; p = 0.04). Subgroup analysis of acute emesis showed consistent benefits (complete response OR = 1.77; 95% CI 1.23–2.55; p = 0.002). Nausea control also favored lorazepam, although the differences were not statistically significant. Sedation was more frequent with lorazepam (RR = 2.67; 95% CI 1.54–4.63), although no serious adverse events were reported. Conclusions: By revisiting decades of clinical evidence, this meta-analysis confirms that lorazepam provides a significant therapeutic advantage in controlling chemotherapy-related vomiting, particularly during the acute phase. While its direct efficacy alongside modern agents like NK1 receptor antagonists remains to be fully elucidated, the anxiolytic and amnestic properties of lorazepam remain a potential adjunct for managing complex CINV profiles. Careful dose titration is necessary to balance efficacy with sedation. Full article

Background and Objectives: Venous thromboembolic disease (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a major cause of morbidity and mortality worldwide and imposes a substantial financial burden on health systems due to both the direct and indirect costs of acute management and long-term complications. This systematic review aimed to assess patient satisfaction with anticoagulation therapy for VTE and to highlight potential differences according to the type of anticoagulant. The review focused on factors influencing the patient experience, such as perceived efficacy, ease of use, adverse effects, and health-related quality of life. Materials and Methods: A systematic review, without quantitative meta-analysis, was conducted in accordance with PRISMA 2020 guidelines. Articles were identified through searches in major databases (PubMed, Scopus, Cochrane Library and others) using keywords including “patient satisfaction”, “anticoagulation”, “venous thromboembolic disease”, and “quality of life”. In total, 21 studies published between 2009 and 2025 met the inclusion criteria. The studies assessed patient satisfaction with different types of anticoagulation, including vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs), and low-molecular-weight heparin (LMWH) injections. Results: Across the included studies, patients generally reported higher levels of treatment satisfaction with DOACs compared with VKAs, mainly due to the absence of routine laboratory monitoring and fewer dietary restrictions. However, satisfaction varied according to age, sex, and clinical status. In specific patient populations, such as those with cancer-associated thrombosis, factors including fewer drug–drug interactions and perceptions of safety with LMWH appeared to influence treatment choice and satisfaction. Adverse effects, particularly bleeding, were identified as major drivers of dissatisfaction. Several studies suggested that higher treatment satisfaction was associated with better adherence, while quality of life appeared to improve in patients treated with DOACs in comparison with VKAs. Conclusions: Patient satisfaction is a critical component of successful VTE management. Overall, DOACs appear to be associated with higher treatment satisfaction than traditional therapies such as VKAs, although further high-quality research is needed to individualise anticoagulation strategies. Systematic incorporation of patient-reported satisfaction into clinical decision-making and into international guidelines may improve adherence, enhance quality of life, and ultimately increase the effectiveness of anticoagulation therapy. Full article

Podocyte injury is a characteristic feature of focal segmental glomerulosclerosis (FSGS) that leads to the development of nephrosis as its loss causes proteinuria and progressive glomerulosclerosis. The physiological function of podocytes is critically dependent on proper intracellular calcium levels; an excess or shortage of calcium influx in these cells may result in foot process effacement, apoptosis, and nephron degeneration. A key protein responsible for the regulation of calcium flux is the canonical transient receptor potential 6 (TRPC6) expressed in podocytes. Several mutations in the TRPC6 gene have been associated with FSGS. Here we present a systematically optimized inducible FSGS model system in human induced pluripotent stem cells (hiPSCs). We generated and phenotypically characterized three transgenic hiPSC lines with regulatable overexpression of TRPC6 wild-type and FSGS-associated gain-of-function (GoF, P112Q) and loss-of-function (LoF, G757D) mutations. Moreover, these cell lines were differentiated into induced podocytes (ipodocytes). We assessed the impact of TRPC6 GoF and LoF mutants on calcium influx in combination with TRPC6 agonists and antagonists. Our data showed relative calcium responses consistent with the GoF and LoF phenotypes. Transgenic iPSC-based models, like the one presented here, are instrumental to studying disease mechanisms in vitro and investigating the outcomes of, and possible therapeutic interventions for, this complex disease. Full article

Background/Objectives: Several recent human studies have associated the use of certain medicines, such as antibiotics and antacids, with allergic conditions, potentially through microbiome disruption. In contrast, probiotics which may prevent dysbiosis, could have protective effects. Our meta-analysis aimed to evaluate the impact of these drugs (consumed during pregnancy or early life) on the risk of childhood food allergy, based on the available literature. Methods: Literature searches were conducted in the EMBASE, PubMed, Cochrane, and Web of Science databases using predefined PICO criteria. Overall, our meta-analysis included 25 studies involving 1,662,861 mothers and 5,164,280 children. Results: Using the random-effects model, we found that prenatal and early life antibiotic use (up to 2 years of age) was associated with higher odds of food allergy in childhood (OR: 1.34; 95% CI [1.10, 1.63], OR: 1.53; 95% CI [1.18, 1.98], respectively). Proton pump inhibitors were also associated with a risk of food allergies (OR: 2.65; 95% CI [1.22–5.77]), whereas the impact of H2-receptor antagonists was non-significant (OR: 2.07; 95% CI [0.96–4.45]). Probiotic use during the first two years of life was not associated with decreased risk for food allergy in children (OR: 1.25; 95% CI [0.46, 3.38]). Conclusions: These findings suggest an association between microbiome-disrupting medications during pregnancy and early childhood and an increased risk of childhood food allergy, especially those with a family history of food allergy. However, due to the predominantly observational design of the included studies, causality cannot be established. These results highlight the need for cautious and judicious use of such medications in these populations. Full article

Biofilms rapidly form on medical devices such as urinary catheters and surgical materials. These biofilms compromise patient safety and undermine infection prevention and control (IPC). Biofilms also reduce the effectiveness of antibiotics and disinfectants. As a result, they increase healthcare-associated infections and increase costs through device failure and the need for maintenance or replacement. Researchers are increasingly exploring biosurfactants (BSs) as surface coatings and cleaning additives to prevent microbial attachment and disrupt early biofilm formation on medical devices and healthcare-related surfaces. This review examines the translational potential of biosurfactants as preventive, disruptive, and adjunctive antibiofilm agents for medical devices and healthcare-related surfaces. Literature evidence on glycolipids (rhamnolipids, sophorolipids) and lipopeptides (surfactin) from static, flow-based, and microfluidic in vitro models that used clinically relevant materials, such as silicone and polydimethylsiloxane (PDMS), were examined. In our literature search, we focused on pathogens central to IPC, such as Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus spp., and Candida spp., and it was generally noted that BSs reduced microbial adhesion and delayed early biofilm formation on medical devices and healthcare-related surfaces. Significant evidence also suggests that they partially disrupt biofilms and improve antimicrobial penetration when co-applied, mainly through membrane disruption, destabilization of extracellular substances, interfering with quorum sensing, and synergistic and/or antagonistic interactions with other molecules. Their performance varied with class, formulation, hydrodynamic conditions, and microbial composition. BSs function better as preventive and adjunctive IPC tools than stand-alone antimicrobial agents and can help to reduce biofilm formation on devices and improve surface disinfection. However, translating this promise into practice demands more robust data on long-term safety, stability, and product quality. Full article

Mango (Mangifera indica L.), a major tropical fruit crop, suffers severe anthracnose damage caused by Colletotrichum spp., and traditional chemical control has environmental and food safety risks, with plant-microbe interaction-based biological control as a sustainable alternative. However, the regulatory role of phyllosphere microbiota in the tripartite interactions among mango, beneficial microbes and Colletotrichum remains unclear. This study explored phyllosphere microbiota’s function in mango resistance to Colletotrichum and clarified the biocontrol mechanism of key beneficial isolates. We found Colletotrichum infection significantly reshaped mango leaf endophytic and epiphytic microbial communities, enriching Burkholderia, Acinetobacter, Bacillus and other dominant genera. We isolated a B. subtilis strain L-1 from the epiphytic microbiota that was 18-fold enriched in Colletotrichum-infected mango leaves. This strain exhibited potent antagonistic activity against Colletotrichum siamense with a relative inhibition rate of 82.10%, and delivered 79.77% biocontrol efficacy on mango leaves via two synergistic pathways: inhibiting pathogen spore germination and penetration by producing antimicrobial secreted metabolites and volatile organic compounds, and enhancing host disease resistance. Our findings advance the understanding of plant-phyllosphere microbiota-pathogen tripartite interactions and provide elite microbial resources for sustainable anthracnose management. Full article

Background/Objectives: Burning mouth syndrome (BMS) is a chronic idiopathic orofacial pain disorder characterized by persistent intraoral burning in the absence of detectable mucosal alterations. Diagnosis is challenging due to the lack of specific biomarkers and the need to exclude numerous systemic and local conditions that can mimic oral burning. This literature review aims to summarize current and emerging therapeutic strategies for BMS. Methods: A structured and filtered search of PubMed, Scopus, and Web of Science identified studies evaluating pharmacological, phytotherapeutic, and non-pharmacological interventions. Results: Various antidepressants, anticonvulsants, benzodiazepines, H2 receptor antagonists, and low-dose naltrexone have demonstrated varying degrees of symptom reduction, while alpha lipoic acid (ALA) and phytomedicines such as capsaicin, Hypericum perforatum, Catuama, lycopene, crocin, and melatonin show mixed clinical benefits. Non-pharmacological approaches, including photobiomodulation (PBM), oral cryotherapy, neuromodulation techniques, and cognitive behavioral therapy, also provide meaningful symptom improvement in many patients. Conclusions: Across all modalities, therapeutic responses remain heterogeneous and generally incomplete, underscoring the absence of a universally effective treatment. Current evidence supports an individualized and multidisciplinary approach that integrates pharmacological, psychological, and adjunctive therapies to address the multifactorial nature of BMS. Full article

Angiotensin-converting enzyme (ACE) inhibitors (ACEis) are one of the most successful drug classes for the treatment of hypertension and the prevention of its cardiovascular complications. ACE activates the pressor hormone angiotensin but also inactivates the vasodilator peptide bradykinin (BK). A rare side effect of ACEis, angioedema (AE), has been proposed to result from pro-inflammatory effects of BK. Novel considerations are offered in this debate: (1) the bradykinin B2 receptor antagonist icatibant has had an inconsistent effect on ACEi-associated AE, but its potency and duration of action are much inferior to those of a novel nonpeptide antagonist of this receptor, deucrictibant. (2) Tissue kallikrein (KLK-1) is an effective kininogenase, particularly abundant in the salivary glands, possibly related to orofacial presentation of ACEi-induced AE. (3) The strongly regulated human kinin B1 receptor, optimally responsive to Lys-des-Arg⁹-BK, is functionally compartmentalized with KLK-1 which produces Lys-BK from kininogens. Chronic treatment with ACEi drugs in laboratory animals induces the expression of vascular B1R that mediates vasodilation. Therefore, ACEi-AE may be largely or completely initiated by KLK-1. Inhibitors of this protease or combined antagonists of both kinin receptor subtypes may be useful for the management of this condition. Full article

Astragalus membranaceus is an important perennial medicinal plant whose roots constitute its primary medicinal organ; however, its cultivation is severely constrained by root rot caused by Fusarium oxysporum. This study aimed to characterize differences in the rhizosphere microbiome between healthy and diseased plants, identify antagonistic microorganisms from healthy rhizosphere soils, and investigate their suppressive effects on F. oxysporum and the associated host metabolic responses. High-throughput sequencing was used to compare bacterial and fungal communities in the rhizospheres of healthy and diseased plants. Microorganisms were isolated from healthy rhizosphere soils and screened for antagonistic activity against F. oxysporum, followed by validation in pot experiments. Metabolomic analysis was further conducted to assess host metabolic responses to microbial treatment. Root rot disease significantly altered the dominant composition of rhizosphere microbial communities and was associated with reduced fungal diversity and lower bacterial richness in diseased soils. Co-occurrence network analysis revealed increased complexity in bacterial networks and strengthened positive correlations among fungal taxa under diseased conditions. A total of 81 microbial strains were isolated from healthy rhizosphere soils, among which Penicillium halotolerans exhibited the strongest inhibitory activity against the mycelial growth of F. oxysporum. Pot experiments further supported its suppressive effect on Astragalus root rot. Metabolomic analysis indicated that P. halotolerans treatment was associated with changes in host metabolic profiles related to energy metabolism, defense-associated protein synthesis, and nutrient uptake. Overall, this study identified P. halotolerans as a fungal strain with antagonistic activity against F. oxysporum and provided initial evidence for its association with the suppression of Astragalus root rot. These findings offer candidate microbial resources and mechanistic insights for understanding rhizosphere-associated disease suppression in Astragalus membranaceus. Full article

Mastitis is a common inflammatory disease that harms mammary gland health. Its development is closely linked to dysregulated inflammatory signaling. Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, has potential anti-inflammatory effects. However, its molecular mechanism in mastitis prevention remains unclear. In this study, we used both in vivo and in vitro models to evaluate how EPA pretreatment regulates mastitis-related inflammatory signaling. Transcriptome analysis showed that differentially expressed genes after EPA treatment were mainly enriched in the peroxisome proliferator-activated receptor (PPAR) signaling pathway. In an LPS-induced mastitis model, EPA restored the LPS-reduced PPARγ protein level and suppressed NF-κB p65 activation, consistent with reduced nuclear translocation of p65. Similar effects were observed in mammary epithelial cells, where EPA inhibited NF-κB activation at 50 and 100 μM. Functional experiments further showed that a PPARγ agonist mimicked the inhibitory effect of EPA on p65, whereas PPARγ antagonist partially abrogated EPA-mediated inhibition of p65. Collectively, these data indicate that EPA attenuates mastitis-associated inflammation at least in part through the PPARγ–NF-κB axis. Full article