Search Results (150)

Background/Objectives: Chronic obstructive pulmonary disease (COPD) is increasingly viewed as a disorder of impaired cellular adaptation to chronic stress, involving oxidative injury, mitochondrial dysfunction, and accelerated cellular senescence. We investigated whether genetic variation in these pathways contributes to disease susceptibility, lung function impairment, and polygenic risk prediction. Methods: Thirty-three single-nucleotide variants were analysed in 747 patients with COPD and 703 controls. Associations with disease susceptibility and lung function parameters were assessed using regression models with correction for multiple testing. Weighted and unweighted polygenic scores were constructed from associated variants and evaluated using receiver operating characteristic and net reclassification improvement analyses. Results: Significant associations were identified in genes involved in antioxidant defence (NFE2L2, HMOX1, GSR), PI3K/AKT/mTOR signalling (PIK3R1, PTEN), mitochondrial function (TOMM40), cellular stress responses (FOXO3A), and long non-coding RNA regulation (MEG3, CDKN2B-AS1). The strongest association was observed for PIK3R1 rs831125 (OR = 2.31, p = 2.53 × 10⁻¹⁰). Variants in NFE2L2, PIK3R1, MEG3, MALAT1, and SIRT3 were additionally associated with pulmonary function parameters. The weighted polygenic score demonstrated good discriminative ability (AUC 68.8%, 95% CI 65.9–71.7%) and substantially improved prediction when combined with age, sex, and smoking exposure (AUC 88.1%, 95% CI 86.3–89.8%; NRI = 0.62, p = 2.21 × 10⁻²⁸). Conclusions: The identified loci converge on interconnected pathways involved in cellular stress adaptation, mitochondrial homeostasis, and senescence, supporting their contribution to chronic obstructive pulmonary disease susceptibility and functional decline. Full article

Alternate wetting and drying (AWD) is a crucial water-saving irrigation strategy in rice production, yet its regulatory mechanisms during drought–rewatering cycles remain unclear, particularly across recovery stages. Using a polyethylene glycol (PEG-6000) hydroponic system, we analyzed physiological, metabolomic, and transcriptomic responses of Oryza sativa L. ssp. japonica under control, continuous drought, and rewatering treatments. The net photosynthetic rate (P_n) recovered within one day after rewatering, and subsequently exceeded control levels, indicating a photosynthetic compensatory effect. In contrast, instantaneous water-use efficiency (WUE) showed only a transient increase before declining thereafter and remaining lower than under continuous drought, revealing an asynchronous recovery in which carbon assimilation precedes the recovery of transpiration. Metabolomic analysis indicated a shift from drought-induced accumulation to recovery-driven metabolic reprogramming, with coordinated up-regulation of central carbon metabolism and chlorophyll biosynthesis. Decreases in citrate, malate, and glutamate suggested their sustained utilization to support nitrogen assimilation and chlorophyll synthesis. Transcriptomic data further revealed large-scale reprogramming during late recovery, including up-regulation of nitrogen assimilation genes (e.g., NIA, NiR), linking carbon–nitrogen coordination with photosynthetic compensation. Overall, these results demonstrate that stage-specific integration of physiological recovery, metabolic restructuring, and transcriptional regulation underlies AWD-induced efficiency and identify early rewatering as a critical window for optimizing WUE. Full article

Osteoporosis is a major global health challenge, particularly among aging populations, underscoring the need for safe and effective nutritional interventions. Probiotics and their metabolites have emerged as promising candidates for modulating bone health via the gut-bone axis. In this study, we investigated the effects of a cell-free culture supernatant (CFS) from the food-grade bacterium Limosilactobacillus fermentum GBE18 on the proliferation, differentiation, and mineralization of MC3T3-E1 pre-osteoblasts. GBE18 CFS exhibited no cytotoxicity at concentrations ranging from 1% to 4% (v/v). Notably, 2% (v/v) CFS significantly enhanced alkaline phosphatase (ALP) activity and extracellular matrix mineralization (p < 0.05). Transcriptomic profiling revealed that differentially expressed genes were enriched in osteoblast-related processes and two key signaling pathways: Wnt/β-catenin and PI3K/Akt. Subsequent qRT-PCR and Western blot analyses confirmed the upregulation of critical regulators (Rspo2, Pdpk1, Malat1) and demonstrated coordinated activation of Akt phosphorylation, β-catenin stabilization, and Runx2 protein expression. Our findings indicate that GBE18 CFS promotes osteogenic differentiation through coordinated modulation of the PI3K/Akt and Wnt/β-catenin pathways. Consequently, this study provides mechanistic evidence supporting the potential application of L. fermentum GBE18-derived metabolites as functional food ingredients or dietary interventions for bone health and osteoporosis management. Full article

X. fastidiosa subsp. pauca (Xfp) is the etiological agent of “Olive Quick Decline Syndrome” (OQDS). Cellina di Nardò (Olea europaea L., Oleaceae), one of the major Salento cultivars, is highly susceptible to Xfp, usually showing acute symptoms after infection. NuovOlivo^® a plant-derived formulation made with vegetal oils and water infusion from multi botanical species has been reported as effective against OQDS in plants affected by Xfp. A non-targeted ¹H NMR (Nuclear Magnetic Resonance) fingerprinting approach, with unsupervised and supervised analysis, was applied to observe the possible changes in the metabolic profile in leaf samples of cultivars Cellina di Nardò naturally affected by Xfp treated with NuovOlivo^® compared to untreated plants. The major differences were observed for the content of quinic acid, malate, mannitol, glucose, oleuropein, and aldehyde derivatives in treated compared to untreated samples. The resulting data indicated a season-dependent plant response to both disease and treatment. Moreover, the overall differences observed between the two investigated years, suggest a general decrease in the differences for the discriminating metabolites over time. The protocol NuovOlivo^® was demonstrated to promote changes in the metabolic profile of olive leaves, suggesting a possible role of this treatment, integrated with good agricultural practices, against Xfp and OQDS. Full article

Plant-derived nanovesicles (PDNVs) are increasingly recognized as mediators of intercellular communication in plants, where they play roles in defense, signaling, and cell wall remodeling. In addition, PDNVs are gaining increasing attention for their biomedical potential, both as natural delivery systems and as bioactive entities, with promising applications in inflammatory disorders and cancer. In this study, we isolated carob nanovesicles (CbNVs) from the apoplastic fluid of carob pods (Ceratonia siliqua L.) using vacuum infiltration centrifugation followed by tangential flow filtration and size-exclusion chromatography. Morphological and biophysical analyses revealed spherical vesicles, while proteomic profiling identified 197 proteins, including suggested PDNV markers such as annexin, HSP70, GAPDH, elongation factors, malate dehydrogenase, and TET-8. These proteins were enriched in metabolic processes, stress responses, and cell wall modification pathways. Protein–protein interaction analysis further linked HSP70 to pectinesterases, reinforcing their role in cell wall remodeling and stress adaptation. Functionally, CbNVs were non-cytotoxic to human macrophages, keratinocytes, and intestinal cells. Notably, CbNVs significantly reduced LPS-induced NF-κB expression in macrophages and promoted wound closure in keratinocytes, with superior efficacy compared to the carob bioactive compound D-pinitol. These findings suggest that CbNVs harbor a synergistic cargo of bioactive molecules with anti-inflammatory and wound-healing properties, highlighting their potential as natural nanotherapeutics. Full article

Foxtail millet (Setaria italica L.) possesses characteristics such as strong stress tolerance and high yield. However, weeds compete with foxtail millet, leading to reduced crop yield, degraded quality, and even the promotion of pest and disease spread. Chemical weed control is currently the most practical and feasible method for preventing weed damage in foxtail millet production, but herbicides can harm the main crop, resulting in reduced yield. To investigate the effects of sethoxydim on the growth and development of foxtail millet, this experiment adopted a pot design, setting four concentration gradients for foliar spraying: 0.75, 1.5 (recommended dosage), 3 and 6 L of active ingredient per hectare (L ai ha⁻¹). Sethoxydim treatment hindered electron transport in photosynthesis, leading to a decrease in adenosine triphosphate synthesis and consequently a decline in the photosynthetic parameters of both photosystem I and photosystem II. Meanwhile, the activities and related gene expression of phosphoenolpyruvate carboxylase (PEPC), NADP-malate dehydrogenase (NADP-MDH) and pyruvate phosphate dikinase (PPDK) all showed a decreasing trend. In contrast, the activities and related gene expression of NADP-malic enzyme (NADP-ME) and ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco); the contents of soluble protein and soluble sugar; and the activities of antioxidant enzymes including malondialdehyde (MDA), superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), along with their related gene expression, exhibited a trend of first increasing and then decreasing, reaching their peak at a dosage of 1.5 L ai ha⁻¹ (T2 treatment group). Meanwhile, the continuous rise in O₂^·− and H₂O₂ contents indicated enhanced accumulation of reactive oxygen species (ROS) in plants under herbicide stress. These results show that at the recommended dosage, although sethoxydim causes certain damage to foxtail millet, the plant can maintain certain photosynthetic functions and physiological stability through self-regulation and gradually return to normal. Full article

This study evaluated the effects of dietary supplementation with N-Carbamylglutamate (NCG) on growth performance, immune function, intestinal metabolites, and microbiota in Danzhou chickens. In a 35-day feeding trial, a total of 480 one-day-old female chicks were randomly assigned to a control group (basal diet) and three experimental groups supplemented with 400, 800, or 1200 mg/kg NCG, with 120 chicks in each group (n = 120). The results demonstrated that NCG, particularly at 400 mg/kg, significantly improved growth parameters, including average daily gain and feed conversion ratio, while enhancing immune function by increasing serum levels of immunoglobulins (IgA, IgY) and malate dehydrogenase (p < 0.05). Metabolomic analysis revealed that NCG modulated key pathways such as sphingolipid metabolism and mTOR signaling pathway, leading to significant changes in metabolites including L-arginine, ceramide, and docosahexaenoic acid (p < 0.05). 16S rDNA sequencing indicated that NCG induced structural shifts in the gut microbiota, primarily affecting Bacteroidota and Firmicutes, with several bacterial genera showing strong correlations with the observed metabolic changes (p < 0.05). Mechanistically, NCG promotes growth by facilitating arginine synthesis via the urea cycle and activating the mTOR signaling pathway, while its regulation of sphingolipid metabolism enhances immunomodulatory capacity. In conclusion, NCG enhances feed efficiency and immune competence by orchestrating the gut microbiota-metabolite network, demonstrating its potential for poultry production. Full article

Lung cancer remains the most prevalent and deadliest malignancy worldwide. According to the European Society for Medical Oncology guidelines for non-oncogene-addicted metastatic non-small-cell lung cancer (NSCLC), patients with metastatic squamous-cell carcinoma (LUSC) or metastatic non-squamous NSCLC with performance status 2 and PD-L1 < 50% may receive single-agent chemotherapy with gemcitabine (GEM), docetaxel (DOC), or vinorelbine. Herein, we investigated the cellular effects of GEM/DOC as monotherapies in NSCLC cell lines—lung adenocarcinoma, A549 and CALU6; LUSC, H520 and H1703. Treatment with GEM/DOC may induce apoptotic cell death in all NSCLC cell lines at 48 h. GEM/DOC can affect cancer cell migration assessed by scratch assay. Both GEM/DOC may produce distinct effects on cell cycle arrest, consistent with their particular pharmacodynamic effects. Furthermore, GEM/DOC induced signals consistent with autophagic activity in LUSC cell lines, but only GEM triggered signals consistent with autophagic activity in the CALU6 cell line. Analysis of three key long non-coding RNAs (lncRNAs)—MALAT1, NEAT1, and HOTAIR—showed variable expression in the studied cell lines as a potential response to DOC and GEM treatment. Our findings indicate different cellular effects of GEM and DOC in NSCLC cell lines and provide an overview of how currently used chemotherapeutics may influence the expression of lncRNAs. Full article

Fumarate, succinate, maleate, dihydroxyfumarate, D–tartarate, L–tartarate, DL–tartarate, L-malate, D-malate, oxaloacetate, citrate, and DL-isocitrate in the 5–100 μM concentration range were incubated in 12.5 mM HEPES/25 mM TRIS base containing 200 μM Eu³⁺–tetracycline and 60% (v/v) formamide (pH unadjusted). After 30 min of incubation, they were separated at 4 °C by capillary electrophoresis utilizing laser-induced luminescence detection with 12.5 mM HEPES/25 mM TRIS base containing 60% formamide as the running buffer. All analytes yielded peaks, with the exception of fumarate, succinate, and maleate. L-Malate was detected down to 100 nM. The main component of this study was the analysis of malate. The objective was to develop a stereoselective methodology for the detection of L-malate. This was achieved by varying the formamide concentration and separation temperature. When the temperature was increased to 22 °C and the formamide concentration decreased to 40%, the sensitivity for L-malate was diminished about 10-fold, but that for D-malate was eliminated. This combination of conditions allowed for the stereospecific analysis of L-malate. Full article

Background and Objectives: Fireweed (Chamerion angustifolium L.) possesses antibacterial, antioxidant, anti-inflammatory, and anti-cancer properties. This study evaluated the effects of aqueous fireweed leaf extracts and their major compound, oenothein B, on the viability and mitochondrial function of Caco-2 colon cancer cells, emphasizing the impact of leaf fermentation. Materials and Methods: Cells were treated for 48 h with oenothein B and aqueous extracts from unfermented (NF) and fermented leaves (F 24 h, F 48 h). Cell viability and mitochondrial function were assessed by MTT assay and high–resolution respirometry. Results: IC₅₀ values were 0.843 mg/mL (NF), 1.548 mg/mL (F 24 h), 1.931 mg/mL (F 48 h), and 0.09 mg/mL (57 µM) (oenothein B). Mitochondrial respiration decreased in up to 67% (glutamate/malate) and 61% (succinate) in both fermented and unfermented groups, while oenothein B increased in leak respiration by 34–73% but reduced oxidative respiration by 24%. Conclusions: Aqueous extracts of fireweed from both unfermented and fermented leaves significantly reduced Caco-2 cell viability and mitochondrial function. Oenothein B on its own had a stronger effect on cell viability, but a weaker effect on mitochondrial function, compared to fireweed extracts. Full article

Malolactic fermentation (MLF), a key enological process for wine deacidification and aroma and flavor development, is predominantly mediated by lactic acid bacteria. This study characterized 342 indigenous Lactiplantibacillus plantarum (L. plantarum) isolates, a potential starter species underexploited for MLF, from China’s Jiaodong Peninsula wine regions through polyphasic analysis. Thirty strains with high tolerance to wine stress conditions and efficient malate metabolism were selected. Among these, two high-performance strains, P101 and J43, exhibited superior MLF kinetics. Their applications had almost no effect on the wine’s basic physicochemical parameters, color parameters, and individual phenolic contents. Solid-phase microextraction–gas chromatography–mass spectrometry (SPME-GC-MS) analysis revealed that these strains significantly enhance key aroma compound contents in wines, including ethyl acetate, ethyl lactate, ethyl 2-methylbutyrate, and nerol, contributing more floral and fruity aroma characteristics. These indigenous L. plantarum strains, novel microbial starter cultures, demonstrate dual functionality in enhancing wine quality through controlled fermentation while supporting microbial biodiversity through the development of region-specific strain resources. Full article

The resistance of malaria parasites towards the current antimalarial therapies continues to fuel the search for new antimalarial drugs, preferably from natural sources. This study aimed to investigate the potential of the dichloromethane extract of Acanthospermum australe to inhibit Plasmodium falciparum heat shock protein 70-1 (PfHsp70-1). The plasmodium lactate dehydrogenase (pLDH) assay was used to determine the antiplasmodial activity of the crude extract against the chloroquine-sensitive P. falciparum strain 3D7. The inhibitory effect of the plant extract on the chaperone activity of P. falciparum heat shock protein 70-1 (PfHsp70-1) was determined using the ATPase, thermally induced luciferase and malate dehydrogenase (MDH) assays. The extract showed a significantly high activity against P. falciparum strain 3D7 with an IC₅₀ value of 1.3 µg/mL. A decrease in thermally induced aggregation of MDH and luciferase was observed when each of the proteins was incubated with PfHsp70-1 only. However, an increased protein aggregation was observed when the proteins were incubated with PfHsp70-1 in the presence of the plant extract. The extract also exhibited inhibitory activity on the ATPase activity of PfHsp70-1. The results obtained from this study suggest that A. australe extract contains compounds that could target malaria parasite Hsp70 functions. Full article

A strictly anaerobic bacterium denoted as strain NIT-TF6 of the genus Desulfitobacterium was isolated from a trichloroethene-dechlorinating culture with formate. Cells were straight rods of 1.6–6 µm long and 0.25–0.5 µm in diameter and used H₂, lactate, pyruvate, and malate as electron donors and thiosulfate and Fe (III)-citrate as electron acceptors. The genome of strain NIT-TF6 was 4.8 Mbp in size and included nine 16S rRNA genes. Phylogenetic analysis based on 16S rRNA sequences showed that NIT-TF6 shared the highest sequence similarity (96.39%) with Desulfitobacterium hafniense DCB-2ᵀ, forming an independent clade in the phylogenetic tree. Digital DNA-DNA hybridization (dDDH) and average nucleotide identity (ANI) values between strain NIT-TF6 and other Desulfitobacterium species ranged from 15.9 to 16.9% and from 71.68 to 72.51%, respectively. These are well below the thresholds for species delineation. A distinguishing feature of strain NIT-TF6 was its possession of both L-lactate dehydrogenase (L-LDH) and D-lactate dehydrogenase (D-LDH), in contrast to other Desulfitobacterium strains that exclusively express D-LDH. Based on the dDDH and ANI results, combined with physiological, phylogenetic, morphological, biochemical, genomic, and metabolic iron-related characteristics, strain NIT-TF6 has been proposed as a novel species within the genus Desulfitobacterium. The name Desulfitobacterium elongatum sp. nov. has been proposed for this strain, with NIT-TF6ᵀ designated as the type strain. Full article

In the absence of fully effective therapies and preventive strategies against the development of urosepsis, a deeper understanding of the virulence mechanisms of Uropathogenic Escherichia coli (UPEC) strains is needed. UPEC strains employ a wide range of virulence factors (VFs) to persist in the urinary tract and bloodstream. UPEC strains were isolated from patients with sepsis and a control group without sepsis. PCR was used to detect 36 genes encoding various groups of virulence and fitness factors. Profiling of both intracellular and extracellular bacterial proteins was also included in our approach. Bacterial metabolites were identified and quantified using GC-MS and LC-MS techniques. The UpaG autotransporter, a trimeric E. coli AT adhesin, was significantly more prevalent in urosepsis strains (p = 0.00001). Iron uptake via aerobactin and the Iha protein also appeared to be predictive of urosepsis (p = 0.03 and p = 0.002, respectively). While some studies suggest an association between S fimbriae and the risk of urosepsis, we observed no such correlation (p = 0.0001). Proteomic and metabolomic analyses indicated that elevated levels of bacterial citrate, malate, coenzyme Q10, pectinesterase (YbhC), and glutamate transport proteins, as well as the regulators PhoP two-component system, CpxR two-component system, Nitrate/nitrite response regulator protein NarL, and the Ferrienterobactin receptor FepA, may play a role in sepsis. These genetic biomarkers, proteins, and metabolites derived from UPEC could potentially serve as indicators for assessing the risk of developing sepsis. Full article

Malic enzyme (ME), a key enzyme involved in various metabolic pathways, catalyzes the oxidative decarboxylation of malate to generate pyruvate, CO₂, and NADPH. This enzyme plays essential roles in plant growth, development, and stress responses. In this study, 13 maize ME genes were identified by performing homologous sequence alignment using the sequences of the Arabidopsis ME gene family as references. Chromosomal localization analysis demonstrated that ME genes were not detected on chromosomes 9 and 10, whereas the remaining eight chromosomes exhibited an uneven distribution of these genes. Phylogenetic analysis indicated a high degree of conservation between maize ME genes and their orthologs in teosinte (Zea luxurians L.) throughout the evolutionary history of Poaceae crops. Furthermore, cis-acting element analysis of promoters demonstrated that members of the maize ME gene family harbor regulatory elements associated with stress responses, phytohormones signaling, and light responsiveness, which suggests their potential role in abiotic stress adaptation. Expression profiling under stress conditions revealed differential expression levels of maize ME genes, with ZmME13 emerging as a promising candidate gene for enhancing stress resistance. These results lay a solid foundation for further investigation into the biological functions of the maize ME gene family. Full article