Search Results (4,032)

Saline–alkali stress is one of the important abiotic stresses, which affect plant growth and development. However, the understanding of miRNA pathways in different saline–alkali stress is still limited. In order to better understand the salt–alkali stress response mechanism of wheat, we analyzed miRNA transcription levels in two wheat varieties differing in saline–alkali tolerance (Qingmai 6, QM, tolerant; Meisheng 0308, MS, sensitive) under mixed saline–alkali stress (150 mmol·L¹ and 300 mmol·L¹) for 7 days. High-throughput sequencing identified 11,368 miRNAs (106 conserved, 11,262 non-conserved), among which four miRNAs (miR9653b, miR5384-3p, miR9777, and miR531) exhibited a consistent expression trend across both varieties and all stress concentrations. Additionally, a potential miRNA-mediated regulatory network (including miR408 and miR1135) was predicted to regulate reactive oxygen species (ROS) metabolism via cytochrome P450, plant hormone signal transduction, and MAPK pathways. Saline–alkali-tolerant and sensitive wheat cultivars exhibited distinct miRNA expression patterns under stress. QM maintained higher contents of non-enzymatic antioxidants (ascorbic acid, AsA; reduced glutathione, GSH) and activities of key antioxidant enzymes (ascorbate peroxidase, APX; glutathione reductase, GR), which contributed to balanced ROS homeostasis and enhanced saline–alkali tolerance. Full article

Air-dried pork coppa is highly favored for its unique organoleptic and flavor characteristics. However, the traditional long processing cycle and uncontrollable environmental conditions lead to unstable product quality. Staphylococcus mediates the reduction in nitrite to nitric oxide via nitrite reductase; the resulting nitric oxide then binds to myoglobin, forming nitrosylmyoglobin that endows meat products with a characteristic bright red. It could also improve the activity of lipase and protease, promoting the flavor. In this study, Staphylococcus carnosus and Staphylococcus xylosus as starter cultures have been applied to air-dried coppa. After Staphylococcus inoculation, the water activity and pH value of coppa significantly decreased compared with those of naturally fermented coppa (p < 0.05). Meanwhile, it improved the color and increased the hardness and chewiness, which in turn enhanced the overall taste of organoleptic acceptability. The ¹H NMR spectra showed that the main taste metabolites were free amino acids and organic acids. Citrulline, formic acid, isobutyric acid, and isovaleric acid might be the key metabolites distinguishing between those with or without Staphylococcus inoculation. This study suggested that inoculation with Staphylococcus xylosus and Staphylococcus carnosus played an important role in improving the physicochemical properties and taste development of coppa. Full article

Background/Objectives: Environmental exposure to heavy metals is an established risk factor for breast cancer development; however, the molecular mechanisms underlying the contribution of lead (Pb) to disease progression remain unclear. This study aimed to investigate the effects of Pb exposure on breast cancer cells and to delineate the associated mechanisms. Methods: We examined Pb-induced migration and invasion of breast cancer cells using wound-healing and Transwell assays; assessed cell proliferation by flow cytometry and MTT assay; identified potential target genes via RNA sequencing; and further elucidated the underlying mechanisms using integrated molecular biology approaches (including immunofluorescence, Western blotting, and ELISA), functional cellular assays, and bioinformatics analysis. Results: Pb exposure significantly enhanced the migratory and invasive capabilities of breast cancer cells by upregulating aldo-keto reductase family 1 member C3 (AKR1C3), without markedly affecting cell proliferation. Mechanistically, AKR1C3 promoted migration and invasion through activation of NF-κB signaling, leading to upregulated expression of MMP-2 and MMP-9. Conclusions: This study reveals a novel molecular axis—Pb exposure promotes breast cancer cell migration and invasion via the AKR1C3–NF-κB–MMP-2/MMP-9 pathway—and identifies AKR1C3 as a potential therapeutic target for breast cancer associated with environmental heavy metal exposure. Full article

Hair loss is a prevalent condition with various causes, and effective treatments are in high demand. Cacumen Platycladi (Platycladus orientalis leaves), a traditional Chinese medicine, has been historically used to prevent hair loss. This study aimed to evaluate the efficacy and mechanisms of Cacumen Platycladi extract (CPE) in preventing hair loss. Using a gradient extraction method with 1,3-butanediol, ethanol, and water, bioactive compounds like quercitrin, myricetin, and myricitrin were enriched and identified via Liquid Chromatography–Mass Spectrometry (LC-MS). The results showed that CPE inhibited 5α-reductase activity, enhanced the antioxidant capacity of human dermal papilla cells (HDPCs), and upregulated the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway to promote vascular endothelial growth factor (VEGF) and collagen type XVII (COL17) expression. A 12-week clinical trial demonstrated that CPE significantly reduced hair loss and increased local hair density compared to placebo, with no adverse effects. These findings support the potential of CPE as a safe and effective natural alternative for hair loss prevention. Full article

The total cavopulmonary anastomosis (Fontan procedure), a palliative procedure for single-ventricle congenital heart disease, improves survival but is associated with progressive multiorgan complications and high long-term morbidity. Prior blood-based proteomic studies in adults have been limited to targeted antibody-based panels or focused on methodological comparisons. Systemic molecular alterations in younger, clinically heterogeneous patients, particularly in untargeted pathways, remain incompletely characterized. Serum samples from 48 Fontan patients and 48 age- and sex-matched healthy controls were analyzed using mass spectrometry with TMT labeling. 2228 proteins were quantified, of which 124 were significantly differentially abundant (fold change > 1.5 or <0.67, FDR-adjusted p < 0.05). Network analysis identified three major functional clusters: extracellular matrix (ECM) organization (predominantly increased), actin cytoskeleton organization, and platelet-related pathways (both predominantly decreased). Stratified analyses showed reduced ECM protein abundance in high-risk patients, suggesting a shift from active remodeling toward a more established fibrotic state, and uniquely elevated cytochrome b5 reductase 3 (CYB5R3), implicating altered redox homeostasis, nitric oxide metabolism, and cellular aging. Overall, our findings extend prior targeted analyses, reveal potential biomarkers such as CYB5R3 and underscore the complexity of the Fontan circulation, with implications for risk stratification and therapeutic targeting. Full article

Sustainable agriculture increasingly relies on biostimulants like protein hydrolysates (PHs) to enhance crop resilience. This study characterized and compared three plant-derived PHs (PH1, PH2, and PH3) from the Malvaceae, Brassicaceae, and Fabaceae families, respectively, under optimal (40 µM Fe³⁺-EDTA) and iron (Fe)-deficient (4 µM Fe³⁺-EDTA) conditions. Initial assays demonstrated that the PHs possessed significant antioxidant capacity and influenced biological activity: PH2 and PH3 promoted pollen germination, while PH1 exhibited a weaker stimulatory effect. In vivo experiments on tomato plants revealed that PH application effectively modulated root architecture and biomass accumulation. Moreover, PH2 and PH3 significantly mitigated Fe deficiency’s impact, by maintaining biomass and preventing chlorosis. Interestingly, while Fe deficiency typically triggers massive root Fe³⁺-chelate reductase activity, PH treatments, particularly PH2, significantly down-regulated this response. This suggests that PHs may improve internal Fe use efficiency or facilitate alternative uptake pathways. Overall, these findings establish a link between the intrinsic bioactive properties of PHs and their biostimulant action, highlighting their potential as innovative tools for improving nutrient use efficiency and crop resilience in sustainable farming systems. Full article

Mycobacterium tuberculosis (M. tuberculosis) relies on the thioredoxin (Trx)–thioredoxin reductase (TrxR) system to maintain intracellular redox homeostasis and to support Trx-dependent DNA synthesis and repair, making TrxR a potential target for anti-tuberculosis therapy. Gold nanoclusters have been reported to inhibit human TrxR and suppress tumor growth, suggesting that gold-based nanomaterials can modulate TrxR activity. In this study, we report a previously uncharacterized oxidized crystal structure of M. tuberculosis TrxR containing two dimers in the asymmetric unit and use this structure to investigate inhibition by a glutathione-coated gold nanocluster (GSH-AuNC). Biolayer interferometry and enzymatic assays show that GSH-AuNC binds directly to M. tuberculosis TrxR and efficiently inhibits its catalytic activity at the purified enzyme level. Molecular dynamics simulations indicate that GSH-AuNC can occupy a surface pocket proximal to the active site, providing a plausible structural basis for enzyme engagement. AlphaFold3 modeling of the M. tuberculosis TrxR-Trx heterodimeric complex defines the interaction interface required for productive electron transfer and provides a structural hypothesis for how GSH-AuNC disrupts this process. Together, these results provide structural and mechanistic insights into the biochemical modulation of M. tuberculosis TrxR by GSH-AuNC, while the antimycobacterial activity of GSH-AuNC remains to be evaluated in future studies. Full article

Drug- and alcohol-induced liver injury involves impaired bile acids or bilirubin secretion, but it is not known how senescence influences the secretion of hepatocytes exposed to drugs and alcohol. In this study, the toxic effects of ritonavir, lopinavir, and alcohol on hepatocyte transporters and the secretion of bile acids and bilirubin were investigated in hydrogen peroxide-induced senescent HepG2 and doxorubicin-induced senescent primary human hepatocytes. In HepG2, intracellular conjugated bilirubin increased upon senescence and extracellular conjugated bilirubin in culture medium was decreased by ritonavir and lopinavir treatment. In the primary hepatocytes, intracellular bile acids or medium bilirubin were not significantly changed upon senescence. However, intracellular bile acids were increased, and medium conjugated bilirubin were decreased in senescent primary hepatocytes treated with alcohol and the two drugs. Transcriptional expressions of adenosine triphosphate (ATP)-binding cassette (ABC) transporters (ABCB4, ABCC6, ABCB11, and ABCD3) were decreased whereas UDP-glucuronosyltransferase (UGT1A1) was increased by ritonavir and lopinavir in senescent HepG2. In senescent primary hepatocytes, expressions of ABCB11, ABCC1, ABCC2, ABCC3, ABCC4, and ABCC6 were apparently reduced whereas UGT1A1 and the cytochrome P450 enzyme CYP7A1 were markedly increased by alcohol combined with ritonavir and lopinavir. Selective ABCC6 knockdown in the primary hepatocytes altered expressions of two senescence markers, Lamin A/C and cyclin-dependent kinase inhibitor CKI (p21), increased expressions of CYP7A1 and hydroxy methyl glutaryl-CoA reductase (HMGCR), and increased intracellular bile acids. Further, anti-cholestasis agents, ursodeoxycholic acid and glycyrrhizin, significantly ameliorated the impaired secretions of bile acids and bilirubin as well as reducing intracellular lipid accumulation and cell death caused by ritonavir, lopinavir, and alcohol in the primary hepatocytes with ABCC6 knockdown. These results indicate that senescence moderately impairs the ABC transporters of hepatocytes and secretion of bile acids or bilirubin, which become worse in the presence of the drugs and alcohol but could be improved by anti-cholestasis agents. Full article

Pre-sowing seed treatment (priming) is a strategic tool for programming future crop yield, aimed at improving early plant development and enhancing stress resilience. This study investigated the effects of priming wheat seeds with 100 µM ibuprofen on early ontogeny under optimal conditions and salt stress (100 mM NaCl). An evaluation of germination energy, growth parameters, phytohormone levels (abscisic acid, indolylacetic acid, and cytokinins) and the status of the antioxidant system in 7-day-old seedlings demonstrated that ibuprofen treatment stimulates wheat growth and tolerance, despite its absence of accumulation in plant tissues. Modulation of hormonal balance plays a key role in these protective effects: under optimal conditions, ibuprofen elevates abscisic acid and indolylacetic acid levels, while under salt stress, it prevents excessive abscisic acid accumulation and mitigates the stress-induced decline in indolylacetic acid and cytokinins. Furthermore, ibuprofen promotes a coordinated increase in glutathione, ascorbate, and H₂O₂ levels, concomitant with the activation of key enzymes (glutathione reductase and ascorbate peroxidase), thereby enhancing the plants’ antioxidant potential. Under saline conditions, ibuprofen pretreatment also reduces stress-induced dysregulation of this system. Therefore, ibuprofen acts as a hormetic preconditioning agent that improves seedling vigor and stress tolerance by fine-tuning hormonal signaling and redox metabolism. Full article

Eutrema salsugineum is a model species for studying stress resistance, particularly extreme salinity, and is often compared with Arabidopsis thaliana. Previous research has shown that basal salicylic acid (SA) levels are significantly lower in E. salsugineum than in A. thaliana. In this study, subtractive hybridization revealed that SA-related genes were extensively induced in Arabidopsis but not in Eutrema. Using exogenous SA and the biosynthesis inhibitor paclobutrazol (PBZ), we further demonstrated that the low endogenous SA level in Eutrema significantly upregulates dehydroascorbate reductase (DHAR) and glutathione reductase (GR) gene expression, doubling the pools of total ascorbic acid and total glutathione. While SA treatment decreased the ratios of reduced ascorbic acid (ASA) to dehydroascorbate (DHA) and reduced glutathione (GSH) to oxidized glutathione (GSSG), PBZ treatment increased them, correspondingly modulating DHAR and GR activities and gene expression. The resulting enhancement of these key non-enzymatic antioxidants is a critical mechanism underpinning the superior salt tolerance of Eutrema. Full article

Bitter gourd (Momordica charantia L.) is widely consumed worldwide due to its unique flavor and medicinal value. In subtropical regions, low spring temperatures limit bitter gourd growth, leading to plant mortality and yield loss. Thus, elucidating the mechanisms of cold tolerance in bitter gourd could facilitate the development of cold-resistant cultivars via genetic engineering or molecular breeding. In this study, a cold-tolerant (CT) and a cold-sensitive (CS) inbred line of bitter gourd were used to investigate proteomic differences under cold stress. Before cold stress, 504 differentially accumulated proteins (DAPs) were identified, with 123 up-accumulated in CT plants compared to CS plants. Upon exposure to cold stress, these numbers changed to 388 DAPs (259 up-accumulated in CT) at 6 h and further to 649 DAPs (415 up-accumulated in CT) at 24 h. K-means cluster analysis identified 65 cold-stress response proteins that may contribute to cold tolerance in CT plants, including evm.TU.chr4.3733 (Proline dehydrogenase 1), evm.TU.chr10.115 (Delta(1)-pyrroline-2-carboxylate reductase), and evm.TU.chr10.815 (Calcium-dependent protein kinase 3). Glucose and starch levels remained stable in both CS and CT plants during cold stress, and the baseline concentration of glucose was consistently and significantly higher in CT plants than in CS plants. Before cold stress, proline content was similar in both CT and CS plants. Following 6 h of cold stress, CS plants accumulated significantly higher proline levels than CT plants. This trend, however, reversed after 24 h, with proline content becoming significantly lower in CS plants. Differential protein accumulation between CT and CS plants under cold stress reflects their distinct responses, with core DAPs serving as key functional determinants of enhanced cold tolerance in the CT genotype. This study revealed important proteomic data underlying the cold stress response in bitter gourd. Full article

Diabetic retinopathy (DR) is a major microvascular complication of type 2 diabetes (T2D) and is strongly associated with chronic inflammation. Neutrophils contribute to this inflammatory milieu, and the hyperosmolar stress-responsive transcription factor NFAT5 and its downstream effector aldose reductase (AR) may play crucial roles in this process. NFAT5 regulates AR, which converts glucose to sorbitol; excessive sorbitol accumulation promotes endothelial and retinal cell damage. Given the links between NFAT5, metabolic stress and immune activation, dysregulation of the NFAT5–AR axis in neutrophils may contribute to DR pathophysiology. This study evaluated NFAT5 and AR expression in peripheral blood neutrophils from 150 individuals classified as nondiabetic (n = 50), T2D without DR (n = 50), or T2D with DR (n = 50). Clinical, metabolic, and ophthalmic assessments were performed, and neutrophils were isolated to quantify NFAT5 and AR via ELISA. Associations with renal function, plasma osmolarity (pOSM), and hematological inflammatory ratios (NLR, NMR, NPAR, and SII) were analyzed. T2D-DR subjects presented impaired renal parameters, increased pOSM, reduced eGFR, and elevated NLR and NPAR. NFAT5 and AR levels were significantly increased in T2D-DR neutrophils and correlated positively with pOSM and the inflammatory ratios, whereas NFAT5 correlated inversely with the eGFR. These findings suggest that activation of the NFAT5–AR pathway contributes to neutrophil-driven inflammatory and hyperosmolar dysregulation in T2D and may influence DR progression. Full article

Ascorbic acid (AsA) is a key antioxidant and nutrient in plants, regulating reactive oxygen species (ROS) levels and maintaining cellular redox homeostasis. The AsA recycling pathway sustains AsA pools by restoring its oxidized forms, ensuring intracellular balance. Among the enzymes involved, monodehydroascorbate reductase (MDHAR) is important for the regeneration of AsA from monodehydroascorbate. In this study, we analyzed the four MDHAR paralogs in Lactuca sativa using CRISPR/Cas9 to determine whether disruption of individual MDHAR genes could alter AsA levels in lettuce leaves. Unexpectedly, none of the knockouts caused long-term changes in leaf AsA content. Transcriptomic analyses at 14 and 28 days showed minimal effects on AsA recycling or biosynthesis genes, except MDHAR genes. However, several other genes indirectly implicated in AsA regulation displayed differential expression in all mutants compared to the wild type, suggesting the presence of a complex regulatory network. In particular, genes encoding transcription factors (TFs), such as mTERF15, COL9, UPBEAT1, NAC28, and NAC42, were differentially regulated in all MDHAR mutants compared to the wild type at 28 days. These findings indicate that, although AsA content remains unchanged, MDHAR single knockouts alter expression of other genes through which the plants may indirectly compensate to maintain redox homeostasis. Full article

Background: Gold (Au) complexes have emerged as promising anticancer candidates due to their distinct coordination chemistry and ability to modulate thiol-dependent and redox-regulated cellular pathways, particularly thioredoxin reductase (TrxR). In recent years, structurally diverse Au(I) and Au(III) complexes have been reported with potent in vitro anticancer activity; however, cross-study comparability and design principles remain unclear. Aim: This systematic review critically evaluates anticancer Au(I/III) complexes reported since 2016, with the specific aim of identifying how oxidation state, coordination geometry, and ligand class influence in vitro potency, selectivity, and translational potential. Methods: A PRISMA-guided literature search was performed in Scopus, Web of Science, PubMed, and ScienceDirect for studies published between January 2016 and March 2025. Two independent reviewers screened titles/abstracts and full texts according to predefined inclusion criteria. Only original studies reporting anticancer activity of structurally characterized Au(I/III) complexes in human cancer models were included. After the removal of duplicates, 1100 records were screened at the title and abstract level. Of these, 240 articles were assessed in full text for eligibility. Ultimately, 128 studies reporting anticancer activity of structurally characterized Au(I/III) complexes met the inclusion criteria and were included in the qualitative synthesis. Biological potency data were harmonized to μM units where applicable, and results were synthesized qualitatively due to heterogeneity in experimental design. Results: A total of 128 studies met the inclusion criteria. Au(I) complexes—particularly phosphine- and N-heterocyclic carbene (NHC)-based compounds—consistently showed sub-micromolar cytotoxicity in TrxR-dependent cancer cell lines, whereas Au(III) complexes displayed greater structural diversity but variable stability and redox behavior. In vivo efficacy was reported for a limited subset of compounds and was frequently constrained by solubility, systemic toxicity, or metabolic instability. Conclusions: The available evidence indicates that anticancer activity of gold complexes is strongly dependent on oxidation state, ligand environment, and redox stability. While Au(I) scaffolds show more reproducible in vitro potency, successful translation to in vivo models remains limited. This review defines structure–activity and structure–liability relationships that can guide the rational design of next-generation gold-based anticancer agents. Full article

Nanotechnology has emerged as a transformative tool in animal production, offering novel strategies to enhance productivity, health, and product quality. Among trace elements, selenium (Se) plays an essential role in antioxidant defence, immune regulation, and redox balance through its incorporation into selenoproteins. Selenium nanoparticles (SeNPs), synthesized via chemical, physical, or biological methods, have shown superior bioavailability, stability, and lower toxicity compared to traditional organic and inorganic selenium forms. This review explores the synthesis, physicochemical properties, and metabolic fate of SeNPs, emphasizing their advantages in poultry production systems. In poultry, SeNPs exhibit potent antioxidant and anti-stress effects by enhancing the activity of glutathione peroxidase, superoxide dismutase, and thioredoxin reductase, thereby mitigating lipid peroxidation and oxidative tissue damage. Their immunomodulatory effects are linked to improved lymphocyte proliferation, cytokine regulation, and increased immunoglobulin levels under normal and stress conditions. SeNP supplementation has been associated with enhanced growth performance, feed efficiency, carcass quality, and reproductive outcomes in broilers, layers, and quails. Furthermore, selenium nanoparticles have demonstrated therapeutic potential in preventing or alleviating chronic diseases such as cancer, diabetes, cardiovascular dysfunction, and neurodegenerative disorders. SeNPs also serve as biofortification agents, increasing selenium deposition in poultry meat and eggs, thus improving their nutritional value for human consumption. However, selenium’s narrow safety margin requires careful dose optimization to avoid potential toxicity. This review highlights the multifaceted benefits of selenium nanoparticles in poultry nutrition and health, while underscoring the need for further studies on grey SeNPs, long-term safety, and regulatory frameworks. Integrating SeNPs into poultry production represents a promising strategy to bridge animal health, food security, and public nutrition. Full article