Search Results (16,726)

Polynucleotide (PN), a high-molecular-weight DNA fragment derived from salmon and other fish sources, shows promising anti-aging and regenerative effects on the skin. This study investigated how PN enhances collagen synthesis, focusing on its effect on phosphoenolpyruvate carboxykinase 1 (PCK1) in senescent macrophages and its downstream effects on fibroblasts. Using in vitro senescent cell models and in vivo aged animal models, PN significantly upregulated the adenosine 2A receptor (A2AR), adenylate cyclase (AC), cyclic AMP (cAMP), protein kinase A (PKA), and cAMP response element-binding protein (CREB) in senescent macrophages. This led to increased PCK1 expression, which reduced oxidative stress and promoted M2 macrophage polarization, associated with elevated levels of interleukin-10 and tumor growth factor-β. Conditioned media from PN-treated macrophages enhanced SMAD family member 2 and signal transducer and activator of transcription 3 phosphorylation in senescent fibroblasts, increasing collagen I and III synthesis and reducing nuclear factor-κB activity. In vivo, PN administration elevated expression of the A2AR/AC/PKA/CREB/PCK1 pathway, reduced oxidative stress, increased M2 macrophage markers, and significantly improved collagen density and skin elasticity over time. Use of a PCK1 inhibitor attenuated these effects, highlighting the pivotal role of PCK1. Overall, PN modulates macrophage-fibroblast interactions via the CREB/PCK1 axis, enhancing collagen synthesis and counteracting age-related skin changes. PN has emerged as a promising therapeutic agent for skin rejuvenation by targeting cellular senescence and promoting extracellular matrix restoration. Full article

Bacterial antibiotic resistance (AR) has become a critical global health threat. AR is mainly driven by adaptive resistance mutations and the horizontal gene transfer of resistance genes, both of which are enhanced by genome recombination. We previously discovered that genome recombination-mediated tRNA upregulation is important for AR, especially in the early stages. RecA is a crucial bacterial factor mediating genome recombination and the DNA damage response. Therefore, RecA inhibitors should be effective in reducing AR. In this study, we found that BRITE-338733 (BR), a RecA inhibitor, can prevent ciprofloxacin (CIP) resistance in subculturing Escherichia coli strain BW25113 in the early stages (up to the 7th generation). In the presence of BR, the tRNA was decreased, so the bacteria cannot evolve resistance via the tRNA upregulation-mediated AR mechanism. The RecA expression level was also not increased when treated with BR. Transcriptome sequencing revealed that BR could inhibit oxidative phosphorylation, the electron transport chain process, and translation, thereby reducing the bacterial energy state and protein synthesis. Also, the effective concentrations of BR do not harm human cell viability, indicating its clinical safety. These findings demonstrate that BR effectively delays the emergence of spontaneous AR by targeting RecA-mediated pathways. Our findings shed light on a new strategy to counteract clinical AR: applying BR with the antibiotics together at the beginning. Full article

Hypoxia at altitudes above 3000 m poses a significant threat to organ health and physiological homeostasis, particularly in metabolically active tissues such as the brain. Many of the cellular alterations induced by hypoxia are associated with the excessive generation of reactive oxygen species (ROS) and the resulting oxidative stress. In this study, we investigated the effects of exposure duration and altitude levels on oxidative homeostasis in the rat hypothalamus, cortex, hippocampus, and striatum. We assessed ROS production, malondialdehyde (MDA) levels, the antioxidant activities of superoxide dismutase (SOD), and catalase, as well as molecular biomarkers of oxidative stress, cell death, and inflammation. Our findings demonstrated that ROS, MDA and SOD levels increased across all brain regions, particularly in response to higher altitude exposure. Conversely, catalase activity decreased under the same conditions. At the molecular level, we observed overexpression of key biomarkers related to oxidative stress, cell death, and inflammation, especially at extreme altitudes. Furthermore, these effects were most pronounced in the hippocampus, cortex, and striatum. In conclusion, our data indicate that hypoxic exposure at higher altitudes significantly contributes to the oxidative disruption of brain homeostasis in rats. Full article

ERF family transcription factors are crucial regulators in plants, playing a central role in abiotic stress responses and serving as important targets for stress-tolerant crop breeding. Populus davidiana × P. bolleana, an elite hybrid poplar cultivar artificially selected in northern China, holds significant research value encompassing ecological restoration, economic industries, genetic resource development, and environmental adaptability. This study identified that PdbERF109 expression was significantly upregulated in P. davidiana × P. bolleana response to salt treatment. Furthermore, transgenic poplar lines overexpressing PdbERF109 (OE) were generated. Salt stress assays demonstrated that PdbERF109 overexpression significantly enhanced salt tolerance in transgenic poplar. Compared to wild-type (WT) plants, PdbERF109-OE lines exhibited a significant enhancement in the activities of antioxidant enzymes, with increases of 2.3-fold, 1.2-fold, and 0.5-fold for superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), respectively, while the levels of malondialdehyde (MDA) and hydrogen peroxide (H₂O₂) were markedly reduced by 39.89% and 40.03%, indicating significantly enhanced reactive oxygen species (ROS) scavenging capacity and reduced oxidative damage. Concurrently, PdbERF109 overexpression reduced the natural leaf relative water loss (%). Meanwhile, yeast one-hybrid assays confirmed that the PdbERF109 protein specifically binds to GCC-box and DRE cis-acting elements. This study established PdbERF109 as a positive regulator of salt stress responses, highlighting its potential as a target gene for improving plant tolerance to high salinity, providing a promising candidate gene for the molecular breeding of salt-tolerant crops. Full article

Ilex paraguariensis (yerba mate), a culturally and economically important South American species, faces significant challenges in vitro, including contamination, phenolic oxidation, and low regeneration rates. Nanoparticles have recently emerged as promising tools to overcome such limitations. This study evaluated silver (AgNPs) and chitosan nanoparticles (ChNPs) in eight experiments using nodal, leaf, and internodal explants. Surface disinfection with 1% colloidal silver solution 20 ppm significantly reduced contamination (17.2% and 15%) while maintaining viability (62.1%). However, supplementation of culture media with AgNPs (4–75 mg·L⁻¹) or ChNPs (5–120 mg·L⁻¹) did not improve nodal segment responses. In leaf explants, 4 mg·L⁻¹ AgNPs proved most effective, reducing contamination and markedly decreasing callus oxidation from 63.3% to 10.0%. Callogenesis was enhanced when AgNPs were combined with growth regulators, with the highest induction at 6 mg·L⁻¹ AgNPs + zeatin (38.1%) and 4 mg·L⁻¹ AgNPs + BAP (42.9%). Conversely, in internodal segments, AgNPs combined with BAP completely inhibiting callus formation. The resulting calli exhibited compact and friable morphologies but no signs of somatic embryogenesis. Overall, the effectiveness of AgNPs depends on their formulation, explant type, and interaction with cytokinins. Optimization of nanoparticle formulation and hormonal balance remains essential to maximize efficacy while minimizing toxicity. Full article

Background: Major depressive disorder (MDD) is a prevalent and disabling psychiatric illness with complex etiologies involving both genetic and environmental factors. While environmental stress is a known risk factor of MDD, the molecular mechanisms linking stress exposure to persistent depressive phenotypes remain incompletely understood. Methods: We established a 24-hour restraint stress-induced depression model in mice and performed integrated transcriptomic and proteomic analyses of the medial prefrontal cortex (mPFC) to investigate stress-related molecular alterations. Results: Behavioral assessments confirmed persistent depression-like phenotypes, including anhedonia and behavioral despair, lasting up to 35 days post-stress. RNA sequencing identified differentially expressed genes related to dopaminergic signaling and oxidative stress. Proteomic analysis identified 105 differentially expressed proteins involved in immune response and energy metabolism. Integrated multi-omics analysis highlighted convergent disruptions in immune regulation, metabolism, and epigenetic processes. Notably, clemastine exerts its antidepressant-like effects in part by mitigating neuroinflammation and preserving mitochondrial function. Conclusions: These findings provide novel insights into the molecular basis of stress-induced depression and suggest that clemastine is a potential therapeutic candidate. Full article

Introduction: Vatiquinone is a first-in-class, small molecule designed to maintain mitochondrial function in the disorders like Friedreich’s ataxia (FA). Vatiquinone inhibits 15-lipoxygenase, consequently decreasing oxidative stress and neuroinflammatory response pathways. Methods: Population pharmacokinetic modeling analysis was conducted to characterize vatiquinone pharmacokinetic profiles in healthy volunteers and patients and explore the effects of covariates on vatiquinone exposures. Results: A two-compartment model with parallel zero- and first-order absorption was developed and verified. The values of essential parameters were: absorption fraction through the first-order process, 74.4%; absorption rate constant, 0.20 h⁻¹; delay time, 2.79 h; zero-order absorption duration, 6.03 h; apparent volume of distribution, 180.75 L for the central and 4852.69 L for the peripheral compartment; and apparent clearance, 162.72 L/h. Strong CYP3A4 inducers could reduce exposure by 50%; strong CYP3A4 inhibitors could increase it by 252%. Vatiquinone exposure was 19% lower in patients with Friedreich’s ataxia versus healthy volunteers. A medium-fat meal increased exposure up to 25-fold versus a fasted status. Body weight and body mass index had significant clinical relevance to exposures. Conclusions: A two-compartment model effectively described the pharmacokinetic profiles of vatiquinone after oral administration. Covariates significantly impacted exposures, including body weight, meals, disease status, comedications and body mass index. Full article

Background: Cardiovascular disease (CVD) is the leading cause of mortality in obese patients with type 2 diabetes mellitus (T2DM). Conventional biomarkers often fail to detect early endothelial dysfunction and oxidative stress. Haptoglobin (Hp), an acute-phase protein with antioxidant and hemoglobin-binding properties, may indicate vascular injury. While plasma Hp (pl-Hp) reflects systemic inflammation, urinary Hp (u-Hp) could signal renal and microvascular damage. We hypothesize that elevated u-Hp and altered pl-Hp levels are associated with increased oxidized LDL and may serve as sensitive indicators of early vascular injury, thereby identifying obese patients with T2DM at higher cardiovascular risk. This study aims to investigate the associations between u-Hp, pl-Hp, and oxidized LDL (ox-LDL) in obese patients with T2DM, and to evaluate the potential role of Hp as an early biomarker of cardiovascular risk in this high-risk population. Methods and Results: The study included 57 patients with T2DM (mean age 61 ± 10 years, HbA1c 8.66 ± 1.60%, and BMI 35.15 ± 6.65 kg/m²). Notably, 95% of the patients had hypertension, 82% had dyslipidemia, and 59% had an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m². Pl-Hp and u-Hp concentrations, as well as ox-LDL levels, were assessed using an enzyme-linked immunosorbent assay (ELISA). Correlations and multivariate regression analyses were employed to investigate the associations between Hp, ox-LDL, and clinical cardiovascular risk factors. Pl-Hp was positively correlated with ox-LDL (r = 0.358, p < 0.006) and negatively correlated with C-reactive protein (CRP) (r = −0.364, p < 0.013), while u-Hp correlated positively with HbA1C and apoB levels (r = 0.298, p < 0.030 and r = 0.310, p < 0.021, respectively). Multivariate analysis indicated that pl-Hp, but not u-Hp, was independently associated with ox-LDL (β = 0.536, p < 0.027) after adjusting for potential confounding factors, including age, gender, BMI, HbA1c, liver enzymes, hs-CRP and creatinine. The Stepwise analysis identified IL-6 as the most significant predictor of cardiovascular disease risk, suggesting its pivotal role in subclinical vascular inflammation among obese individuals with T2DM. Furthermore, the significant positive association between pl-Hp and ox-LDL was stronger in patients with declining renal function as expressed by the estimated glomerular filtration rate (eGFR) (eGFR < 30 mL/min/1.73 m²: β = 2.173, p < 0.031 and eGFR 30–59 mL/min/1.73 m²: β = 1.318, p < 0.002). This association also appeared in early and low-normal ranges of serum albumin: creatinine ratio (s-ACR) (s-ACR < 0.2714 mg/mmol: β = 2.304, p < 0.005 and s-ACR 0.2714–0.3649 mg/mmol: β = 1.000, p < 0.041), suggesting that pl-Hp and ox-LDL rise before overt kidney damage. Elevated IL-6 (≥32.93 pg/mL) further strengthened this link (β = 1.037, p < 0.005), highlighting the role of inflammation in amplifying oxidative stress and acute-phase responses. Conclusions: Taken together, these findings emphasize the interconnected contributions of renal impairment, inflammation, and oxidative stress to vascular injury. While these results need to be confirmed in larger prospective longitudinal studies, monitoring pl-Hp levels in conjunction with inflammatory and kidney function markers could be a sensitive and non-invasive way to identify early CVD risk in high-risk groups, such as obese patients with T2DM. Full article

Mitochondrial quality control (MQC) mechanisms, including proteostasis, mitophagy, mitochondrial dynamics, and biogenesis, are essential for maintaining mitochondrial function and overall cellular health. Dysregulation of these systems is a common feature of both neurodegenerative diseases and cancer, but the outcomes differ. Neurons depend strongly on healthy mitochondria and are easily damaged when MQC fails, resulting in organellar dysfunction and oxidative stress. By contrast, cancer cells often adapt by using MQC pathways to sustain survival and resist cell death. The mitochondrial unfolded protein response (mtUPR) and mitophagy are central to these processes, yet their roles are context-dependent. In neurodegeneration, activation of these pathways may help neurons survive, yet persistent stimulation can shift towards harmful effects. In cancer, these same pathways enhance metabolic flexibility, promote resistance to treatment, and support tumor progression. Although therapeutic strategies targeting MQC are being explored, their translation to the clinic is difficult, partly due to opposite effects in different diseases. The observed inverse epidemiological link between cancer and neurodegeneration may also reflect the distinct regulation of MQC pathways. A clearer understanding of these mechanisms is needed to identify new treatment strategies for disorders that are clinically distinct but share common mitochondrial defects. Full article

The rapid and sensitive detection of regulatory elements within transgenic constructs of genetically modified organisms (GMOs) is essential for effective monitoring and control of their distribution. In this study, we present several innovative electrochemical biosensing platforms for the detection of regulatory sequences in genetically modified (GM) plants, combining the loop-mediated isothermal amplification (LAMP) method with electrodes functionalized by two-dimensional (2D) nanomaterials. The sensor design exploits the high surface area and excellent conductivity of reduced graphene oxide, Ti₃C₂T_x, and molybdenum disulfide (MoS₂) to enhance signal transduction. Furthermore, we used a “green synthesis” method for Ti₃C₂T_x preparation that eliminates the use of hazardous hydrofluoric acid (HF) and hydrochloric acid (HCl), providing a safer and more sustainable approach for nanomaterial production. Within this framework, the performance of various custom-fabricated electrodes, including laser-patterned gold leaf films, physical vapor deposition (PVD)-deposited gold electrodes, and screen-printed gold electrodes, is evaluated and compared with commercial screen-printed gold electrodes. Additionally, gold and carbon electrodes were electrochemically covered by gold nanoparticles (AuNPs), and their properties were compared. Several electrochemical methods were used during the DNA detection, and their importance and differences in excitation signal were highlighted. Electrochemical properties, sensitivity, selectivity, and reproducibility are characterized for each electrode type to assess the influence of fabrication methods and material composition on sensor performance. The developed biosensing systems exhibit high sensitivity, specificity, and rapid response, highlighting their potential as practical tools for on-site GMO screening and regulatory compliance monitoring. This work advances electrochemical nucleic acid detection by integrating environmentally-friendly nanomaterial synthesis with robust biosensing technology. Full article

During periodontitis, Porphyromonas gingivalis and its lipopolysaccharides (LPS) may translocate into the bloodstream and alter adipocyte function, aggravating obesity-related disorders. This study aimed to evaluate the inflammatory and metabolic effects of P. gingivalis in obese db/db mice, and to decipher the molecular mechanisms targeted by P. gingivalis or its LPS in 3T3-L1 adipocytes. Then, we determined the ability of three major dietary polyphenols, namely caffeic acid, quercetin and epicatechin, to protect adipocytes under LPS conditions. Results show that obese mice exposed to P. gingivalis exhibited an altered lipid profile with higher triglyceride accumulation, an enhanced pro-inflammatory response and a reduced antioxidant SOD activity in the adipose tissue. In adipose cells, P. gingivalis and LPS induced the TLR2-4/MyD88/NFκB signaling pathway, and promoted IL-6 and MCP-1 secretion. Bacterial stimuli also increased ROS levels and the expression of NOX2, NOX4 and iNOS genes, while they deregulated mRNA levels of Cu/ZnSOD, MnSOD, catalase, GPx and Nrf2. Interestingly, caffeic acid, quercetin and epicatechin protected adipose cells via antioxidant and anti-inflammatory effects. Overall, these findings show the deleterious impact of P. gingivalis on inflammation, oxidative stress and lipid metabolism in obese mice and adipose cells, and highlight the therapeutic potential of polyphenols in mitigating periodontal bacteria-mediated complications during obesity. Full article

Thermal oxidative aging failure of high-temperature vulcanized silicone rubber (HTV) in high-voltage insulators is the core hidden danger of power grid security. In this study, terahertz time domain spectroscopy (THz-TDS) and attenuated total reflection infrared spectroscopy (ATR-FTIR) were combined to reveal the quantitative structure–activity relationship between dielectric response and chemical group evolution of HTV during accelerated aging at 200 °C for 80 days. In this study, HTV flat samples were made in the laboratory, and the dielectric spectrum of HTV in the range of 0.1 THz to 0.4 THz was extracted by a terahertz time–domain spectrum platform. ATR-FTIR was used to analyze the functional group change trend of HTV during aging, and the three-stage evolution of the dielectric real part (0.16 THz), the dynamics of the carbonyl group, the monotonic rise of the dielectric imaginary part (0.17 THz), and the linear response of silicon-oxygen bond breaking were obtained by combining the double Debye relaxation theory. Finally, three aging stages of HTV were characterized by dielectric loss angle data. The model can warn about the critical point of early oxidation and main chain fracture and identify the risk of insulation failure in advance compared with traditional methods. This study provides a multi-scale physical basis for nondestructive life assessment in a silicon rubber insulator. Full article

Vitiligo is an acquired depigmentation disorder characterized by the selective destruction of melanocytes, resulting in the progressive loss of pigment in the skin and hair. This condition frequently leads to significant psychological distress. Its pathogenesis is complex and multifactorial, involving a combination of genetic susceptibility, metabolic derangement related to oxidative stress, defective melanocyte adhesion to the basal epidermis, and dysregulated innate and adaptive immune responses, ultimately converging in the targeted elimination of melanocytes. Despite the availability of several therapeutic modalities, current corrective options are often limited in efficacy and are associated with high relapse rates. There remains a pressing need for novel, safe, and more effective therapeutic strategies to improve patients’ quality of life. Growing evidence indicates that the immune system plays a pivotal role in vitiligo onset and progression, as most triggers converge on inflammatory and autoimmune pathways targeting melanocytes. However, immunosuppressive therapies alone have shown limited effectiveness in halting disease progression and achieving lasting repigmentation. Targeting only immunological processes without addressing the underlying triggers of their activation likely represents a significant limitation in restoring pigmentation. In contrast, interventions aimed at upstream events may help prevent the initiation of the immune response. Consequently, combinatorial therapeutic approaches that target multiple pathogenic pathways and incorporate diverse pharmacological agents are being explored to improve clinical outcomes. This review aims to re-evaluate the intrinsic cellular abnormalities and associated dysregulated signaling pathways in vitiligo, with the goal of identifying novel, effective, nonimmunological treatment strategies. Full article

The increasing use of water-based drilling muds in offshore oil and gas operations has raised concerns about potential ecological risks of their primary components, such as bentonite, on marine organisms. To date, the biological effects of bentonite on benthic species remain poorly understood. This study aimed to evaluate the physiological and oxidative stress responses of Pacific abalone (Haliotis discus hannai) exposed to varying concentrations (20–3000 mg/L) of bentonite over a 10-day period. Short-term exposure (up to 7 days) to bentonite did not result in significant mortality across treatment groups; however, partial mortality was observed in the highest concentration group (3000 mg/L) on day 8. Biochemical analyses revealed elevated levels of hydrogen peroxide and malondialdehyde, particularly in higher concentration groups, indicating oxidative stress. Antioxidant enzyme activities showed concentration- and time-dependent changes, with early activation followed by suppression under prolonged exposure. Total antioxidant capacity also declined over time in high-concentration groups. These findings indicate that while bentonite may not be acutely lethal to abalone, it can trigger sublethal oxidative stress responses, particularly under chronic exposure conditions, underscoring the importance of evaluating long-term physiological impacts of suspended drilling particulates and the need for research on a wider range of marine species. Full article

Alkaline stress, driven by high pH and carbonate accumulation, results in severe physiological damage in plants. While the molecular mechanisms underlying alkaline tolerance have been partially elucidated in many crops, they remain largely unexplored in wheat. We hypothesize that alkaline stress tolerance in wheat is genotype-dependent. This study employed an integrated multi-omics approach to assess alkaline stress responses, combining genome-wide association study (GWAS) and RNA-seq analyses. Systematic phenotyping revealed severe alkaline stress-induced root architecture remodeling—with 57% and 73% length reductions after 1- and 3-day treatments, respectively—across 258 accessions. Analysis of the GWAS results identified nine significant alkaline tolerance QTLs on chromosomes 1A, 3B, 3D, 4A, and 5B, along with 285 associated candidate genes. Using contrasting genotypes—Dingxi 38 (tolerant) and TDP.D-27 (sensitive)—as experimental materials, physiological analyses demonstrated that root elongation was less inhibited in Dingxi 38 under alkaline stress compared to TDP.D-27, with superior root integrity observed in the tolerant genotype. Concurrently, Dingxi 38 exhibited enhanced reactive oxygen species (ROS) scavenging capacity. Subsequent RNA-seq analysis identified differentially expressed genes (DEGs) involved in ion homeostasis, oxidative defense, and cell wall remodeling. Integrated GWAS and RNA-seq analyses allowed for the identification of seven high-confidence candidate genes, including transcription factors (MYB38, bHLH148), metabolic regulators (ATP-PFK3), and transporters (OCT7), elucidating a mechanistic basis for adaptation to alkaline conditions. These findings advance our understanding of alkaline tolerance in wheat and provide candidate targets for molecular breeding of saline- and alkaline-tolerant crops. Full article