Aging-related diseases, which are associated with the senescence of endothelial progenitor cells (EPCs), are consistently accompanied by elevated levels of circulating trimethylamine-N-oxide (TMAO), a marker predictive of poor prognosis. Lycopene (Lyc) deficiency has been demonstrated to be linked to these age-related diseases. The AMPK/SIRT1 pathway plays a pivotal role in cellular senescence. In this study, we hypothesize that lycopene could mitigate TMAO-induced EPCs senescence, with involvement of the AMPK/SIRT1 pathway. EPCs were subjected to treatment with TMAO, Lyc, small interfering RNA targeting AMP-activated protein kinase (siAMPK), or sirtin-1 (siSIRT1). The biological functions of EPCs were evaluated through, CCK-8, transwell and tube formation assays, while their senescence was assessed via SA-β-gal activity assay and Western blotting. ROS generation was measured using dichlorodihydrofluorescein diacetate staining. TMAO-induced suppression of EPCs' functionality was alleviated by Lyc, but this effect was reversed by siAMPK and siSIRT1. TMAO increased SA-β-gal-positive cell number and ROS production, while reducing the expression of AMPK and SIRT1. These effects were attenuated by Lyc. However, the protective effects were diminished by siAMPK and siSIRT1. In conclusion, Lyc ameliorates TMAO-induced EPCs senescence through the AMPK/SIRT1 pathway.

Insect protein-derived peptides are gaining attention for their potential bioactivities. This study aimed to evaluate the antioxidant ability of peptides derived from gastrointestinal digestion and assess their absorption through transepithelial transport. Results indicate an increase of antioxidant properties from G. mellonella (W) and A. diaperinus (B) proteins, including reducing power (Fe2+, Cu2+) and radical scavenging (ABTS, DPPH) with enhanced antioxidant activities in gastrointestinal digestates compared to gastric digestates. The inhibition of intracellular Reactive Oxygen Species (ROS) confirmed these findings, the inhibition rates of 40.2 % (W) and 58.5 % (B), respectively. Transepithelial transport analysis demonstrated that peptide absorption primarily occurred between 6 h and 24 h, with W exhibiting a higher apparent permeability coefficient (6.10 × 10-6 cm/s) compared to B (5.91 × 10-7 cm/s). The results highlight the antioxidant potential and absorption capability of insect-derived peptides, with W demonstrating superior antioxidant activity in most assays, whereas B proved more effective in inhibiting intracellular ROS. These findings support the potential of both W and B as bioactive ingredients with functional applications.

Intervertebral disc degeneration (IVDD) is a leading contributor to spinal degenerative diseases; however, its pathogenesis remains only partially elucidated. Recent studies have highlighted that the diminished activity of SIRT1 and the aberrant activation of the NF-κB signaling pathway are critical pathogenic factors in IVDD. DBC1 has been identified as a regulator of SIRT1 activity and the NF-κB signaling pathway. This study aimed to investigate the role of DBC1 in IVDD.

The expression levels of DBC1 in the nucleus pulposus of aging rats were quantified. Both overexpression and knockdown of DBC1 were utilized to explore their effects on the extracellular matrix (ECM) of the nucleus pulposus. Furthermore, the influence of DBC1 on cellular senescence, apoptosis, and ECM regulation in nucleus pulposus cells was assessed using Western blot (WB), cellular fluorescence assays, and histological staining techniques.

Our results demonstrate that DBC1 expression is significantly upregulated in IVDD. Moreover, DBC1 appears to contribute to IVDD by promoting apoptosis, senescence, and ECM degradation in nucleus pulposus cells. Mechanistic investigations revealed that DBC1 activates the NF-κB signaling pathway while suppressing SIRT1 expression in nucleus pulposus cells, suggesting that these two mechanisms underlie its effects on IVDD.

In summary, this study provides evidence that DBC1 may play a pivotal role in the pathogenesis of IVDD by inhibiting SIRT1 activity and activating the NF-κB signaling pathway. Consequently, targeting DBC1 suppression could represent a promising therapeutic strategy for managing IVDD.

Age-related diseases imposed heavy burdens to the healthcare systems globally, while cell senescence served as one fundamental molecular/cellular basis for these diseases. How to tackle the senescence-relevant problems is a hotspot for biomedical research. In this review article, the hallmarks and molecular pathways of cell senescence were firstly discussed, followed by the introduction of the current anti-senescence strategies, including senolytics and senomorphics. With suitable physical or chemical properties, multiple types of nanomaterials were used successfully in senescence therapeutics, as well as senescence detection. Based on the accumulating knowledges for senescence, the rules of how to use these nanoplatforms more efficiently against senescence were also summarized, including but not limited to surface modification, material-cargo interactions, factor responsiveness etc. The comparison of these "senescence-selective" nanoplatforms to other treatment options (prodrugs, ADCs, PROTACs, CART etc.) was also given. Learning from the past, nanotechnology can add more choice for treating age-related diseases, and provide more (diagnostic) information to further our understanding of senescence process.

Alzheimer's disease (AD) presents a significant challenge to global health. It is characterized by progressive cognitive deterioration and increased rates of morbidity and mortality among older adults. Among the various pathophysiologies of AD, mitochondrial dysfunction, encompassing conditions such as increased reactive oxygen production, dysregulated calcium homeostasis, and impaired mitochondrial dynamics, plays a pivotal role. This review comprehensively investigates the mechanisms of mitochondrial dysfunction in AD, focusing on aspects such as glucose metabolism impairment, mitochondrial bioenergetics, calcium signaling, protein tau and amyloid-beta-associated synapse dysfunction, mitophagy, aging, inflammation, mitochondrial DNA, mitochondria-localized microRNAs, genetics, hormones, and the electron transport chain and Krebs cycle. While lecanemab is the only FDA-approved medication to treat AD, we explore various therapeutic modalities for mitigating mitochondrial dysfunction in AD, including antioxidant drugs, antidiabetic agents, acetylcholinesterase inhibitors (FDA-approved to manage symptoms), nutritional supplements, natural products, phenylpropanoids, vaccines, exercise, and other potential treatments.

Phenalenyl chemistry has flourished for decades but currently faces bottlenecks related to synthetic challenges and stability issues. In this study, we introduced an iterative protection-oxidation-protection (POP) strategy to synthesize stabilized phenalenyl radicals (PRs) with multiple substitutions at the α-positions. The applicability of this POP strategy was verified using triisopropylsilylthyl and phenyl substituents to generate trisubstituted PR1 and hexasubstituted PR2. In particular, both oxidation and dimerization were observed during the synthesis involving phenyl substituents. Both PR1 and PR2 were bench-stable, with half-lives in solution of up to 46 d and thermal decomposition temperatures of up to 300 °C. X-ray crystallographic analysis revealed that PR1 existed as a distinct 12-center-2-electron π-dimer, whereas PR2 existed as a monomer. The properties associated with monomer-dimer equilibrium both in the solid state and in solution were systematically investigated via variable-temperature spectroscopy, and the results revealed a small singlet-triplet energy gap and concentration-dependent absorption and electrochemical behaviors. Remarkably, both PR1 and PR2 formed biocompatible nanoparticles, with the latter capable of depleting reactive oxygen species in liver cells. This study thus demonstrated the applicability of the POP strategy for the construction of stable, functionalized PR derivatives with practical applications as spin functional materials.

Life's Essential 8 (LE8) is known to have a negative correlation with biological aging, while the relationship between the Life's Crucial 9 (LC9) score, which includes mental health, and biological aging remains to be further investigated.

We obtained data from two national cohorts, the UK Biobank and National Health and Nutrition Examination Survey (NHANES), to analyze the association between LC9 and biological aging. Biological aging was assessed using PhenoAge and KDMAge, with gender, race, and other indicators included as covariates. We applied linear regression models and restricted cubic splines (RCS) to analyze and describe the relationship. Furthermore, we explored the mediating role of oxidative stress and inflammation in the association between LC9 and biological aging. Subgroup analyses were conducted using multiple linear regression models, and differences between subgroups were assessed through interaction p-value tests. Sensitivity analyses were subsequently performed, followed by an exploration of the underlying mechanisms.

In this study, the UK Biobank cohort included 46,599 participants, with 44,973 participants having complete data for all covariates, LC9, and the necessary calculations for PhenoAge and KDMage. In the NHANES cohort, these numbers were 11,726 and 5,936, respectively. In the UK Biobank cohort, a significant association was found between the LC9 score and PhenoAge (β = -2.484, p < 0.001), with similar results observed for KDMage (β = -7.987, p < 0.001). Similar findings were observed in the NHANES cohort, with significant associations between the LC9 score and both PhenoAge (β = -5.327, p < 0.001) and KDMAge (β = 11.826, p < 0.001). These findings align with previous research suggesting that higher LC9 scores are associated with slower biological aging. After multivariable adjustment, an "inverse L-shaped" relationship was observed (non-linear P < 0.001). In the mediation analysis, oxidative stress and inflammation showed significant mediating effects between LC9 and both PhenoAge and KDMage (p < 0.001 for both). In the subgroup analysis, the LC9 score showed broad applicability, particularly among male participants aged over 60 years.

This cohort study suggests that higher LC9 scores are associated with slower biological aging. In addition to emphasizing diet and lifestyle habits, the role of mental health in biological aging should not be overlooked.

Frailty is a common symptom in Multiple Sclerosis (MS), yet its precise mechanism remains elusive, and the clinical implications of frailty in MS are uncertain. Moreover, inflammation is closely linked to frailty. This study aims to assess serum cytokine levels in individuals with MS and explore their correlation with frailty.

A case-control study included 83 primary MS patients and 100 healthy individuals undergoing health check-ups. Serum cytokine levels were measured, and MS severity was determined using the Expanded Disability Status Scale (EDSS) score. Additionally, a comprehensive frailty index (FI) was calculated based on health deficits from various domains following standardized procedures.

Serum IL-6 and TNF-α levels were significantly higher in the frail group than in the non-frail group, with a statistically significant difference (P < 0.05). After adjusting for disease duration, sex, age, BMI, SBP, and DBP, serum IL-6 independently correlated with frailty in MS patients (OR = 1.46; 95 % CI = 1.02-1.93; P = 0.003). Moreover, increased serum IL-6 levels were associated positively with the frailty index (β = 0.123, P = 0.008).

Our initial findings suggest elevated levels of pro-inflammatory cytokines in MS patients with frailty, with IL-6 showing a positive correlation with frail indices. These results underscore the potential impact of inflammatory responses on frailty development in MS.

This study aimed to determine the paraoxonase activity and prooxidant-antioxidant balance in the brain tissue of Wistar rats following subacute treatment with selected K-oximes. Each K-oxime was administered intramuscularly (0.1 LD50/kg) twice per week for four weeks, and 7 days after the last treatment, the paraoxonase activity (PON1), the prooxidant-antioxidant balance (PAB), the levels of superoxide anion radical (O2•-), the concentration of nitrite (NO2-) and the content of free protein thiol groups in the brain homogenates were evaluated. The PON1 and PAB activity were significantly reduced in almost all oxime-treated groups (p < 0.01 and p < 0.001, respectively). The concentrations of O2•- were significantly increased in the obidoxime-, K048-, K074- and K075-treated groups (p < 0.001), while the levels of NO2- was significantly decreased in asoxime-, obidoxime-, K074 and K075-treated rats (p < 0.01, p < 0.001, respectively). The content of Thiol groups was significantly elevated in all oxime-treated groups (p < 0.001). Continuing our previously published data, these results confirmed that applied K-oximes improved the oxidative status and further harmful systemic effects of rats after subacute administration.

Senescence impacts plant growth and yields in tetraploid potatoes (Solanum tuberosum L.). Because of their homogenous tetraploid features, it is a major challenge to understand the genetic basis and molecular mechanisms of senescence. Here, we identified a novel central senescence regulator (Nicotinate-nucleotide pyrophosphorylase QPT/StNADC) through map-based cloning. Overexpression of StNADCZ3 accelerated senescence in the late-senescence variety, with NAD content declining by around 40%. CRISPR/Cas9-induced StNADC mutant cr2-11 exhibited extremely early senescence, and the NAD content was reduced by 87% along with reduced chlorophyll content and photosynthesis. Moreover, the downstream products of the NAD synthesis pathway, such as NaMN, NAD, or niacin, can refresh the cr2-11 mutant to grow normally. Further, the transcriptomics and metabolomics data unveiled that the disrupting of StNADC impairs NAD metabolism, accelerating plant senescence through multiple biological levels. Our results show that StNADC is indispensable for NAD synthesis, and targeting the StNADC-mediated NAD synthesis pathway could be a useful strategy to regulate senescence in potato breeding preprograms.

Volcanic ash is a significant source of micronutrients including iron (Fe), copper (Cu), and zinc (Zn) in oligotrophic tropical waters. These bioactive metals enhance primary productivity, influencing local and global biogeochemical cycles. This study explores how volcanic ash exposure affects trace metal uptake and photophysiological response, and how redox-sensitive metal stable isotope measurements in the tissues of the scleractinian coral Stylophora pistillata can provide crucial information on coral health. Controlled coral culture experiments were conducted in which coral nubbins were exposed to varying intensity and duration of volcanic ash. Throughout the experiment, coral symbionts showed enhanced photosynthetic performance irrespective of intensity or duration of ash exposure. Stable isotopes, such as δ65Cu and δ56Fe, in the coral tissue are marked by systematic variations, not associated with intensity or duration of ash exposure. Instead, we suggest biologically modulated redox-sensitive fractionation associated with ash exposure, linked to the coral host's oxidative stress state. This is evidenced by significant correlations between δ65Cu in coral hosts and photophysiology, with lighter Cu isotope ratios associated with higher photosynthetic performances. Hence, we propose that δ65Cu, and more generally redox-sensitive isotopic ratios (i.e. δ56Fe), in coral hosts serves as an indicator of the physiological state of symbiotic corals.

The incidence of osteonecrosis is increasing annually due to the widespread use of glucocorticoids. Recent evidence suggests a significant association between glucocorticoid-induced osteonecrosis and oxidative stress. Youguiyin (YGY) decoction, a classic formula of traditional Chinese medicine, has been widely used for the prevention of glucocorticoid-induced osteonecrosis. However, its underlying pharmacological mechanisms are still not fully understood.

UPLC-Q-TOF-MS and network pharmacology were used to elucidate the material basis of YGY decoction and its mechanism for the treatment of glucocorticoid-induced osteonecrosis. The anti-oxidative stress and bone-enhancing effects in vivo were detected by hematoxylin-eosin (HE) staining, serum metabolomics, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), and Western Blot (WB). Rat bone marrow mesenchymal stem cells (BMSCs) were induced with dexamethasone (DXMS) for 24 h, followed by YGY medicated serum for 24 h. Significantly up- and down-regulated genes were detected by RNA sequencing. Oxidative stress levels were detected by ROS fluorescence. Alizarin red S staining was used to detect osteogenic effects. WB and ELISA were used to detect the expression of proteins related to the ROS/PHD2/HIF-1a pathway.

The application of YGY decoction significantly promoted bone repair and antagonized excess reactive oxygen species (ROS) generation in glucocorticoid-associated osteonecrosis of the femoral head (GA-ONFH) rats. In addition, YGY medicated serum antagonized DXMS-induced ROS production and promoted osteogenic differentiation in BMSCs. We also found that YGY medicated serum attenuated excess ROS generation while PHD2 expression was significantly increased, HIF-1α expression was significantly decreased and RUNX2 expression was significantly increased.

These results provide compelling in vivo and in vitro evidence that YGY decoction may play a role in promoting glucocorticoid-induced osteonecrosis bone repair by targeting the mediation of the ROS/PHD2/HIF-1α oxidative stress signaling pathway, thus providing a new theoretical basis for the clinical application of YGY decoction to glucocorticoid-induced osteonecrosis.

Superoxide anion contributes significantly in the pathological process of acute liver injury. Therefore, real-time in vivo imaging of superoxide anion is of great significance for understanding the pathogenesis. Nevertheless, developing superoxide anion probes that possess high sensitivity and resolution continues to be a challenge. Herein, we report the design of BODIPY-based molecule probes (BDPOS1-2) for fluorescence and photoacoustic dual-modality imaging of superoxide anion. The probes exhibited exceptional selectivity and specificity towards superoxide anion, with a "turn-on" photoacoustic and "turn-off" fluorescence response. They maintained good stability and demonstrated the response behavior to superoxide anion within the pH range of 5-10. BDPOS1-2 can be used for fluorescence imaging endogenous and exogenous superoxide anion in HepG2 cells with detection in the 670-750 nm channel. Notably, galactose-modified BDPOS2 demonstrated selective hepatocyte-targeting capability and achieved dual-modality imaging of superoxide anions during acute liver injury in live mice via capturing photoacoustic signals at 715 nm and fluorescence signals in the 650-690 nm channel. Our findings offer a powerful approach for high-sensitivity and high-resolution in vivo imaging, with considerable potential for early and precise diagnosis of liver injury.

This study contributes to develop and evaluate the biological applications of eco-friendly synthesized silver nanoparticles using Amphilophium paniculatum leaf ethanol extract via. solar irradiation method. The synthesized silver nanoparticles were characterized using UV, FTIR, FESEM and EDS. UV spectrum of silver nanoparticles showed the surface plasma resonance at 431 nm, which confirms the formation of silver nanoparticles. FTIR revealed the presence of functional groups in the extract which helps in the formation of silver nanoparticles. XRD pattern revealed the crystallite nature of nanoparticles. FESEM images showed spherical morphology with average size of 26-28 nm. Biological evaluations of silver nanoparticles exhibited higher antioxidant (IC50- 57.76 μg/mL) compared to extract (IC50- 100.09 μg/mL). The synthesized silver nanoparticles possess good antibacterial activities against clinical isolates such as Staphylococcus aureus (ZOI- 18 mm) and Klebsiella pneumonia (ZOI- 14 mm). Further, in vitro antidiabetic potential of silver nanoparticles revealed greater alpha amylase inhibition compared with standard drugs. The cytotoxic assessment on A549 cell lines revealed lower IC50 value (26.34 μg/mL) for silver nanoparticles, compared to extract (224 μg/mL), suggesting significant cytotoxicity. In silico screening of selected bioactive compounds from Amphilophium paniculatum evaluated for their physicochemical properties, toxicity and docking studies. Molecular docking studies revealed that (+)-lyoniresinol-3-alpha-O-beta-D-glucopyranoside and linarin exhibits better binding interactions with 2RIP-DPPIV receptor, suggesting a potent therapeutic agent for type 2 diabetes mellitus. Therefore, the synthesized silver nanoparticles act as multi therapeutic potential based novel drugs to combat multi-drug resistant pathogens, lung cancer, and diabetes mellitus.

Aging is associated with a gradual decline in cellular function, largely driven by oxidative stress, which leads to cellular senescence. These processes contribute to tissue degeneration and age-related dysfunction. Human dermal fibroblasts (HDFs), critical for maintaining skin structure, are highly vulnerable to oxidative damage, making them key contributors to skin aging. Umbilical cord blood plasma (UCBP), rich in growth factors and regenerative molecules, has shown potential in preventing cellular senescence and addressing key mechanisms of tissue aging. Based on findings from heterochronic parabiosis experiments that demonstrated the rejuvenating effect of young blood, we investigated the effects of UCBP on hydrogen peroxide (H2O2) induced oxidative stress in HDFs and compared its efficacy with adult blood plasma (ABP). Our results indicate that although both UCBP and ABP reduce reactive oxygen species (ROS), UCBP is more effective in suppressing cellular senescence and maintaining fibroblast proliferation. These findings suggest that UCBP's protective effects extend beyond ROS reduction, potentially by modulating the senescence-associated secretory phenotype and the enhancement of tissue repair mechanisms.

Understanding the biological mechanisms underlying extreme lifespan variation within species remains a fundamental challenge in aging research. Here, we investigated the role of gut microbiota and age in honey bee (Apis mellifera) queens combining 16S rRNA gene sequencing and transcriptomics. Analysis of 40 queen hindguts revealed that Commensalibacter melissae (Alpha 2.1) relative abundance was significantly higher in young queens compared to old queens. Using queens with the highest and lowest C. melissae relative abundance, RNA sequencing identified 1451 differentially expressed genes associated with C. melissae abundance, twice the number associated with age alone (719 genes). Queens with high C. melissae abundance showed distinct transcriptional profiles related to stress response, protein homeostasis, and longevity-regulating pathways, particularly genes involved in oxidative stress response and cellular maintenance. Our analysis revealed complex relationships between age, C. melissae abundance, and gene expression patterns, suggesting that multiple interacting factors contribute to queen quality. These findings contribute to our understanding of host-microbe interactions in honey bee queens and highlight the intricate relationship between gut microbiota composition and host physiology in honey bees.

For a potential resource to improve healthspan, polysaccharides present unique advantages in terms of side effects and long-term use owing to their low cytotoxicity. In this study, we demonstrate that a glucomannogalactan (PGP) derived from Pleurotus geesteranus extends the healthspan of both naturally senescent and therapy-induced senescence (TIS) mice. Daily treatment of naturally senescent mice with PGP resulted in a reduced accumulation of senescent cells and alleviation of senescence-related parameters, including metabolic dysfunction, underlying lesions in multiple organs, and oxidative damage. PGP treatment also attenuated senescence in TIS mice. Furthermore, in an in vitro model of oxidative stress-induced senescence using a human cell line, we discovered that PGP alleviated senescence by promoting the nuclear translocation of NRF2. This study suggests that PGP may extend the healthspan of senescent mice by facilitating the nuclear translocation of NRF2.

Maintaining microbiota balance and enhancing the antioxidant performance of nanozyme-based probiotic systems are crucial for effective inflammatory bowel disease (IBD) therapy. Despite significant advancements, developing a green and safe coating technology that functionalizes probiotics with nanozymes while preserving the activity of both components remains a challenge. To address this, chitosan-modified epigallocatechin gallate (EGCG-CS, EC)is synthesized, leveraging the intrinsic adhesive and coordination properties of polyphenols to capture gold nanozymes (AuNPs), forming ECA complexes that enhance nanozyme activity. When coated onto Escherichia coli Nissle 1917 (EcN), the resulting ECA@EcN system effectively scavenged reactive oxygen species (ROS), improving probiotic viability and promoting colon accumulation. Mechanistically, ECA protected EcN by suppressing the activation of the Flagellar Assembly and Branched-Chain Amino Acid Synthesis pathways, ultimately alleviating inflammation and modulating intestinal microbial communities to relieve IBD symptoms. Given the biocompatibility of its components and the environmentally friendly assembly approach, this polyphenol-nanozyme-armored probiotic system represents a promising platform for IBD treatment.

Vascular dementia (VD) is one of the most prevalent forms of dementia, yet effective treatments remain limited. Our previous research identified hippocampal neural stem cells (hNSCs) senescence as a key contributor to VD progression and suggested that reducing hNSC senescence could help reverse cognitive impairment. In this study, we investigated whether Oleracein E (OE), a phenolic antioxidant alkaloid, could alleviate hNSC senescence and improve cognitive function in VD. Using a two-vessel occlusion mouse model of VD, we found that OE treatment significantly reduced hNSCs senescence, restored proliferation and neuronal differentiation capacities, and improved cognitive performance. Mechanistically, OE exerted its effects by inhibiting ERK1/2 phosphorylation and suppressing mTOR activation. Furthermore, pharmacological activation of mTOR with MHY1485 partially abolished the antisenescence effects of OE in hNSCs. These findings suggest that OE may counteract senescence-related neurogenesis dysfunction and cognitive decline in VD, highlighting its potential as a therapeutic intervention.

Oxidative stress is widely recognized as a key contributor to the pathogenesis of Alzheimer's disease (AD). While not the sole factor, it is closely linked to critical pathological features, such as the formation of senile plaques and neurofibrillary tangles. The development of agents with antioxidant properties has become an area of growing interest in AD research. Between 2015 and 2024, several antioxidant-targeted drugs for AD progressed to clinical trials, with increasing attention to the evaluation of antioxidant properties during their development. Oxidative stress plays a pivotal role in linking various AD hypotheses, underscoring its importance in understanding the disease mechanisms. Despite this, comprehensive reviews addressing advancements in AD drug development from the perspective of antioxidant capacity remain limited, hindering the design of novel compounds. This review aims to explore the mechanistic relationship between oxidative stress and AD, summarize methods for assessing antioxidant capacity, and provide an overview of antioxidant compounds with anti-AD properties reported over the past decade. The goal is to offer strategies for identifying effective antioxidant-based therapies for AD and to deepen our understanding of the role of oxidative stress in AD pathology.

In this study, we demonstrate that a highly efficient colorimetric sensor prepared from carbon-shielded Co-Ce Prussian blue analog (PBA) nanopetals (CoOx/CeO2@C) by green chemical deposition method and thermal annealing processes for detection of ascorbic acid (AA) in cerebral microdialysis fluids. The synthesized CoOx/CeO2@C showed high dual-mimetic activity, i.e., peroxidase- and catalase-like activity, and great catalytic stability. The combination of carbon film and Co-Ce PBA nanopetals (1) greatly enhances the interfacial electron transfer rate of the nanopetals due to excellent electrical conductivity of carbon, and (2) protects nanopetals from acidic chemical environments during the catalytic process, which greatly reduces loss of the catalytic activity of the cobalt-cerium (hydroxide) oxides. Based on the peroxidase-like property of CoOx/CeO2@C nanopetals, this sensor has a good linear range from 0.1 to 150 μM with a low detection limit of 0.04 μM, i.e., improved sensitivity for AA colorimetric measurement. The developed colorimetric strategy with a green synthetic pathway, catalytic stability and wide linear range confirms the monitoring of AA in brain systems during calm/ischemic processes.

This study investigates the 96 hr toxicity and physiological effects of eight azole fungicides on Raphidocelis subcapitata (R. subcapitata). The findings revealed significant differences in toxicity levels among these fungicides, with the hierarchy of toxicity as follows: difenoconazole ≈ tetraconazole ≈ fuberidazole > metconazole > terrazole ≈ triflumizole > flutriafol > hymexazol. Increased concentrations of azole fungicides corresponded with decreased cellular activity and inhibited algal growth, highlighting the concentration-dependent nature of toxicity. The toxicological mechanisms involved include reduced levels of chlorophyll (Chla, Chlb) and carotenoids, disrupting the photosynthetic process. Additionally, exposure to these fungicides resulted in decreased total protein levels, increased reactive oxygen species and malondialdehyde, and elevated activity of antioxidant enzymes such as superoxide dismutase and catalase. Consequently, there was a significant rise in apoptosis rates among algal cells. These findings provide important insights for assessing the ecological impact of azole fungicides on aquatic ecosystems and aquatic life.

Exopolysaccharides (EPS) produced by Bacillus species display various biological activities and characteristics such as anti-oxidant, immunomodulatory, anti-bacterial, and bioadhesive effects. These attributes confer Bacillus species broad potential applications in diverse fields such as food, medicine, environment, and agriculture. Moreover, Bacillus-derived EPS are easier to produce and yield higher quantities than plant-derived polysaccharides. Despite these advantages, Bacillus-derived EPS still encounter numerous obstacles in industrial production and commercial applications, including elevated costs, the absence of mature fermentation tank production procedures, and the lack of systematic in vivo and in vitro activity and metabolic evaluation. Therefore, it is essential to gain insight into the current status of structure, production, and applications of Bacillus-derived EPS for facilitating their future broader application. This paper provides a comprehensive overview of the current research on the production, separation, characteristics and applications of these related biological products. Furthermore, this paper summarizes the current challenges impeding industrial production of Bacillus-derived EPS, along with potential solutions, and their prospective applications in enhancing the attributes of beneficial biofilms, laying a solid scientific foundation for the applications of Bacillus-derived EPS in industry and agriculture.

Osteoarthritis (OA) is an age-related degenerative disease that affects bones and joints. The hallmark pathogenesis of OA is associated with chondrocyte senescence. Surfactant protein D (SP-D) is a member of the innate immune proteins family, which can inhibit the immune inflammatory response of chondrocytes. However, the effect of SP-D on chondrocyte senescence phenotype is poorly studied. The present study investigated the phenotypic regulation of OA chondrocyte senescence mediated by SP-D and explored the underlying molecular mechanism.

In this study, an in vitro senescence chondrocyte model was generated by subjecting chondrocytes to IL-1β treatment. Furthermore, the expression of aging-related biomarkers and mitochondrial functions in SP-D overexpressing chondrocytes was observed. Co-immunoprecipitation was conducted to verify the association between SP-D and the identifed proteins within chondrocytes. Moreover, a rat OA model was established by destabilization of the medial meniscus surgery, and the effect of SP-D on reversing the aging phenotype of OA cartilage was investigated.

The results indicated that SP-D significantly decreased senescence and enhanced mitochondrial functions in senescent chondrocytes. The RNA-sequencing analysis revealed that the SIRT3/SOD2 pathway predominantly modulated the effect of SP-D on alleviating senescence. In addition, SP-D overexpression mitigated chondrocyte senescence, suppressed senescence-associated secretory phenotype (SASP) secretion and ameliorated mitochondrial damage. In the rat OA model, SP-D inhibited aging-related pathological changes by upregulating SIRT3/SOD2 pathway, thereby protecting the cartilage tissue integrity.

These findings indicate that SP-D modulates the inhibition of chondrocyte senescence by upregulating SIRT3/SOD2 pathway. These data indicate that targeting SP-D and the SIRT3/SOD2 pathway might be a promising therapeutic strategy for OA.

Mammals exhibit an unusual variation in their maximum lifespan potential, measured as the longest recorded longevity of any individual in a species. Evidence suggests that lifespan increases follow expansion in brain size relative to body mass. Here, we found significant gene family size expansions associated with maximum lifespan potential and relative brain size but not in gestation time, age of sexual maturity, and body mass in 46 mammalian species. Extended lifespan is associated with expanding gene families enriched in immune system functions. Our results suggest an association between gene duplication in immune-related gene families and the evolution of longer lifespans in mammals. These findings explore the genomic features linked with the evolution of lifespan in mammals and its association with life story and morphological traits.

Sickle cell disease (SCD) is a monogenic blood disorder characterized by abnormal hemoglobin S production, which polymerizes under hypoxia conditions to produce chronic red blood cell hemolysis, widespread organ damage, and vasculopathy. As a result of vaso-occlusion and ischemia-reperfusion injury, individuals with SCD have recurrent pain episodes, infection, pulmonary disease, and fall victim to early death. Oxidative stress due to chronic hemolysis and the release of hemoglobin and free heme is a key driver of the clinical manifestations of SCD. The net result is the generation of reactive oxygen species that consume nitric oxide and overwhelm the antioxidant system due to a reduction in enzymes such as superoxide dismutase and glutathione peroxidase. The primary mechanism for handling cellular oxidative stress is the activation of antioxidant proteins by the transcription factor NRF2, a promising target for treatment development, given the significant role of oxidative stress in the clinical severity of SCD. In this review, we discuss the role of oxidative stress in health and the clinical complications of SCD, and the potential of NRF2 as a treatment target, offering hope for developing effective therapies for SCD. This task requires our collective dedication and focus.

Oxidative stress (OS) occurs when there is an imbalance between the production of reactive oxygen species (ROS) and the body's antioxidant defenses, causing damage to lipids, proteins, and DNA. In marine mammals, physiological adaptation to aquatic life conditions, such as prolonged and repeated dives resulting in cycles of hypoxia followed by reperfusion, is associated with increased production of ROS. This study examines the relationship between oxidative stress, muscular stress, and metabolic damage in the blood serum of eleven captive bottlenose dolphins (Tursiops truncatus), six males and five females. This relationship is investigated using oxidative stress markers (d-ROMs, OXY, and Oxidative Stress index, OSi) and biochemical parameter measurements, including glucose (GLU), aspartate aminotransferase (AST), creatine kinase (CK), and lactate dehydrogenase (LDH). Pearson's sex correlation was performed, and males exhibited significantly higher pro-oxidant levels than females, suggesting a potential protective role of female hormones. Also, a positive correlation between pro-oxidants and antioxidants has been observed in relation to age, as older dolphins produced more ROS but also exhibited higher antioxidant capacity, likely to compensate for oxidative damage. Results show no significant correlation between biochemical parameters and oxidative stress markers. However, a moderately positive correlation between LDH and antioxidant (OXY) capacity was observed (r = 0.458), suggesting a possible association between tissue turnover and antioxidant defenses. The results indicate that the biochemical markers analyzed are not strong predictors of oxidative stress in bottlenose dolphins. However, the correlation between LDH and antioxidant capacity suggests that tissue turnover may affect antioxidant defenses. This is a preliminary study, and further research is needed to clarify these relationships in order to better understand physiological adaptations in dolphins and their implications for management, health, and welfare.

Aging-induced testicular inflammation impairs male fertility. The purpose of this study was to investigate the effectiveness and mechanism of C. pilosula water extract (CPWE) in preventing testicular inflammation in D-galactose-induced aging mice.

The "The Plant List" database (www.theplantlist.org) provided verified plant taxonomy. D-galactose was intraperitoneally injected to induce an aging mice model, with high, medium, and low dosages of CPWE used as pharmacological interventions. The concentrations of superoxide dismutase (SOD), malondialdehyde (MDA), testosterone and in mouse serum or testicle samples after CPWE treatment were quantified using biochemical method. Hematoxylin and eosin (HE) staining was employed to assess the morphological features of testicular tissues, whereas immunohistochemical (IHC) analysis and enzyme-linked immunosorbent assay (ELISA) were conducted to evaluate the presence and levels of inflammatory cytokines interleukin-6 (IL-6) and interleukin-1β (IL-1β) within testicular samples of mice. Differentially expressed genes were identified using transcriptome sequencing; the genes and pathways regulated by CPWE, as well as immune cell infiltration, were examined using bioinformatics analysis. The expression of target gene and pathway-related protein was confirmed using real-time quantitative PCR and Western blotting.

Treatment with CPWE alleviated the pathological alterations in the testicular tissues of aged mice, increased the concentrations of SOD and testosterone in the serum, and decreased the levels of MDA, IL-6 and IL-1β in the testes. The expression of C-C motif chemokine ligand 21a (Ccl21a) and C-C motif chemokine ligand 27b (Ccl27b) genes was downregulated after treatment with CPWE. The protein levels associated with the C-type lectin domain family 7, member A (CLEC7A)/inflammasome signaling pathway, including IL-1β, Caspase 8 (CASP8), and nuclear factor-kappa B (NF-κB), were found to be downregulated after treatment with CPWE. T cells, B cells, and macrophages showed a strong association with aging and the modulatory effects of CPWE.

The results indicate that CPWE regulates the CLEC7A/inflammasome pathway, thereby inhibiting inflammasomes activation and reducing the expressions of proinflammatory cytokines such as IL-6 and IL-1β, as well as chemokines such as Ccl21a and Ccl27b, providing substantial protection against age-related testicular inflammatory injury.

Reactive oxygen species (ROS) are natural by-products of cellular metabolism and are also formed in response to environmental stressors such as pollution, extreme temperatures, and ultraviolet radiation exposure. Physiological factors such as intense activity, growth, reproduction, nutrient deficiency, captivity, and disease also contribute to ROS production. While ROS, including free radicals, play a key role in cell physiology, including immune defense, their excessive accumulation can damage cellular components and cause oxidative stress when antioxidant defenses are overwhelmed. To regulate ROS levels, wild birds rely on enzymatic (e.g., catalase, superoxide dismutase, glutathione peroxidase) and non-enzymatic antioxidants (e.g., vitamins C and E, carotenoids). Oxidative stress affects important aspects of wild bird biology, including health, reproduction, and survival, and is closely linked to overall fitness. It is also linked to physiological challenges such as migration and the progression of various diseases affecting wild bird populations. The study of oxidative stress in wild birds requires the use of appropriate biomarkers to assess its role in disease development. A deeper understanding of the balance between ROS production and antioxidant defenses is essential to determine how wild birds cope with environmental and physiological challenges. In this review, we summarize the mechanisms of oxidative stress in wild birds and the role of antioxidants in maintaining health and promoting longevity in wild bird populations.

Cellular senescence may predominantly drive the progression of early subclinical injury under conditions of low-dose, long-term occupational exposure. However, previous research has largely overlooked the cellular senescence induced by hexavalent chromium [Cr(VI)]. To bridge the gap, 304 workers from a chromate facility were enrolled, and a mouse model was used to confirm the effects of Cr(VI) on cellular senescence. A 2.7-fold increase in blood Cr was related to the changes of p53 [23.19 (13.06, 34.23)%], serum α-Klotho [11.45 (6.13, 17.04)%], adipsin [-14.11(-22.16, -5.24)%], leptin [-4.32(-6.99, -1.58)%] and resistin [-3.29(-5.54, -0.98)%]. There were significant correlations of blood Cr with DNA methylation of ELOVL2 and hTERT genes. Furthermore, methylation at hTERT Pos1, Pos2, Pos6, and Pos8 significantly mediated the relationship between blood Cr and p53. In the mouse model, we observed significantly higher mRNA expression levels of key genes in the p53/p21 and Rb/p16 pathways and senescence-associated β-galactosidase positive cell ratio in the exposed group. In conclusion, we found that p53 in human peripheral blood cells serves as a Cr(VI)-induced senescence biomarker, with α-Klotho upregulation and adipokines (adipsin, leptin, and resistin) downregulation indicating compensatory responses, as well as hTERT methylation partially mediating Cr(VI)-senescence association.

Electrochemistry has become a key technique for studying biomolecular reactions and dynamics of living systems by using electron-transfer reactions to probe the complex interactions between biological redox molecules and their surrounding environments. To enable such measurements, redox mediators such as ferro/ferricyanide, ferrocene methanol, and tris(bipyridine) ruthenium(II) chloride are used. However, the impact of these exogeneous redox mediators on the health of cell cultures remains underexplored. Herein, we present the effects of three common redox mediators on the health of four of the most commonly used cell lines (Panc1, HeLa, U2OS, and MDA-MB-231) in biological studies. Cell health was assessed using three independent parameters: reactive oxygen species quantification by fluorescence flow cytometry, cell migration through scratch assays, and cell growth via luminescence assays. We show that as the concentration of mediator exceeds 1 mM, ROS increases in all cell types while cell viability plumets. In contrast, cell migration was only hindered at the highest concentration of each mediator. Our observations highlight the crucial role that optimized mediator concentrations play in ensuring accuracy when studying biological systems by electrochemical methods. As such, these findings provide a critical reference for selecting redox mediator concentrations for bioanalytical studies on live cells.

Inflammation plays a key role in various diseases such as pancreatitis, cancer, and rheumatoid arthritis. Acute inflammation involves processes like vasodilation, increased vascular permeability, and leukocyte accumulation, which lead to cellular damage due to reactive oxygen species (ROS). Low-frequency electromagnetic fields (ELF-EMFs) have shown potential in reducing oxidative stress and inflammation. This study assesses the effectiveness of a new wearable device containing graphene quantum dots in reducing inflammation and oxidative stress in Jurkat T cells stimulated by lipopolysaccharide (LPS). The device is evaluated for its impact on ROS production and inflammation.

The results show that the device significantly lowers ROS levels and reduces the inflammatory response by decreasing pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β. Additionally, the device inhibits LPS-induced iNOS and COX-2 activity and modulates NF-κB signaling, indicating its potential as a therapeutic tool for managing inflammation and oxidative stress.

These findings highlight the device's ability to combat inflammation, offering a non-invasive and effective approach for inflammatory diseases.

Aging is characterized by a gradual decline in physiological functions, with brain aging being a major risk factor for numerous neurodegenerative diseases. Given the brain's high energy demands, maintaining an adequate ATP supply is crucial for its proper function. However, with advancing age, mitochondria dysfunction and a deteriorating energy metabolism lead to reduced overall energy production and impaired mitochondrial quality control (MQC). As a result, promoting healthy aging has become a key focus in contemporary research. This review examines the relationship between energy metabolism and brain aging, highlighting the connection between MQC and energy metabolism, and proposes strategies to delay brain aging by targeting energy metabolism.

The Bruch's membrane (BM) is an acellular, extracellular matrix that lies between the choroid and retinal pigment epithelium (RPE). The BM plays a critical role in retinal health, performing various functions including biomolecule diffusion and RPE support. The BM is also involved in many retinal diseases, and insights into BM dysfunction allow for further understanding of the pathophysiology of various chorioretinal pathologies. Thus, characterization of the BM serves as an important area of research to further understand its involvement in retinal disease. In this article, we provide a review of various advancements in characterizing and visualizing the BM. We provide an overview of the BM in retinal health, as well as changes observed in aging and disease. We then describe current state-of-the-art imaging modalities and advances to further visualize the BM including various types of optical coherence tomography imaging, near-infrared reflectance (NIR), and autofluorescence imaging and tissue matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS). Following advances in imaging of the BM, we describe animal, cellular, and synthetic models that have been developed to further visualize the BM. Following this section, we provide an overview of deep learning in retinal imaging and describe advances in computational and artificial intelligence (AI) techniques to provide automated segmentation of the BM and BM opening. We conclude this section considering the clinical implications of these segmentation techniques. Ultimately, the diverse advances aimed to further characterize the BM may allow for deeper insights into the involvement of this critical structure in retinal health and disease.

Tetrabromobisphenol A (TBBPA) is an extensively employed Brominated flame retardant (BFR), but studies have shown that it has a range of toxicities, and it has been banned from use at present. Tetrabromobisphenol S (TBBPS) is increasingly used in industrial production as a substitute for TBBPA. However, up to now, the toxicity and molecular mechanism of TBBPS in the reproductive system have not been fully revealed. Therefore, we investigated the effects of TBBPS on testicular. In vitro, GC-1 cells and TM4 cells were used as models to perform an array of biochemical tests, and the toxicological impacts of TBBPS on testicular cells were evaluated. It was found that TBBPS could induce testicular cells senescence. Additionally, p16, p21, and p53 expression were also increased after TBBPS treatment. TBBPS also induced oxidative stress and inflammation response. Mechanistic studies have revealed that TBBPS causes mitochondrial damage, which leads to mitochondrial ds-DNA leakage into the cytoplasm, the NLRP3 inflammasome was then activated, in turn leading to inflammatory and senescence responses in testicular cells. In vivo, we found that TBBPS caused testicular tissue aging and inflammatory responses by detecting a series of molecular markers. In summary, the current study demonstrates that TBBPS can induce aging damage and inflammatory responses in testis, and this study lays a foundation for further exploring the reproductive toxicity of TBBPS.

Protein kinase A (PKA) is a key regulator of cellular signaling that regulates key physiological processes such as metabolism, cell proliferation, and neuronal function. While its activation by the second messenger 3',5'-cyclic adenosine triphosphate (cAMP) is well characterized, recent research highlights additional regulatory mechanisms, particularly oxidative post-translational modifications, that influence PKA's structure, activity, and substrate specificity. Both the regulatory and catalytic subunits of PKA are susceptible to redox modifications, which have been shown to play important roles in the regulation of key cellular functions, including cardiac contractility, lipid metabolism, and the immune response. Likewise, redox-dependent modulation of PKA signaling has been implicated in numerous diseases, including cardiovascular disorders, diabetes, and neurodegenerative conditions, making it a potential therapeutic target. However, the mechanisms of crosstalk between redox- and PKA-dependent signaling remain poorly understood. This review examines the structural and functional regulation of PKA, with a focus on redox-dependent modifications and their impact on PKA-dependent signaling. A deeper understanding of these mechanisms may provide new strategies for targeting oxidative stress in disease and restoring balanced PKA signaling in cells.

Heat stress (HS) is one of the most important stressors in chickens, and its adverse effects are primarily caused by disturbing the redox homeostasis. An increase in electron leakage from the mitochondrial electron transport chain is the major source of free radical production under HS, which triggers other enzymatic systems to generate more radicals. As a defense mechanism, cells have enzymatic and non-enzymatic antioxidant systems that work cooperatively against free radicals. The generation of free radicals, particularly the reactive oxygen species (ROS) and reactive nitrogen species (RNS), under HS condition outweighs the cellular antioxidant capacity, resulting in oxidative damage to macromolecules, including lipids, carbohydrates, proteins, and DNA. Understanding these detrimental oxidative processes and protective defense mechanisms is important in developing mitigation strategies against HS. This review summarizes the current understanding of major oxidative and antioxidant systems and their molecular mechanisms in generating or neutralizing the ROS/RNS. Importantly, this review explores the potential mechanisms that lead to the development of oxidative stress in heat-stressed chickens, highlighting their unique behavioral and physiological responses against thermal stress. Further, we summarize the major findings associated with these oxidative and antioxidant mechanisms in chickens.

The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a key regulator of cellular defense system against oxidative insults. Directly inhibiting the Kelch-like ECH-associated protein 1 (Keap1)-Nrf2 protein-protein interaction (PPI) has emerged as a promising approach to activate Nrf2 for the treatment of diseases associated with oxidative stress. Herein, we identified β-amino acids as privileged structural fragments for designing novel naphthalene sulfonamide-based Keap1-Nrf2 PPI inhibitors. Comprehensive structure-activity relationship (SAR) exploration identified compound 19 as the optimal inhibitor with an IC50 of 0.55 μM for disrupting the Keap1-Nrf2 interaction and a Kd of 0.50 μM for binding to Keap1. Further studies demonstrated that 19 effectively activated the Nrf2-regulated cytoprotective system and provided protective effects against dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in both in vitro and in vivo models. These findings highlight the potential of β-amino acid substituted naphthalene sulfonamide Keap1-Nrf2 inhibitor 19 as a prospective therapeutic agent for UC via Keap1 targeting.

Antioxidants had a growing interest owing to their protective roles in food and pharmaceutical products against oxidative deterioration and in the body and against oxidative stress-mediated pathological processes. Screening of antioxidant properties of plants and plant derived compounds requires appropriate methods, which address the mechanism of antioxidant activity and focus on the kinetics of the reactions including the antioxidants. Many studies have been conducted with evaluating antioxidant activity of various samples of research interest using by different methods in food and human health. These methods were classified methods described and discussed in this review. Methods based on inhibited autoxidation are the most suited for termination-enhancing antioxidants and, for chain-breaking antioxidants while different specific studies are needed for preventive antioxidants. For this purpose, the most commonly methods used in vitro determination of antioxidant capacity of food and pharmaceutical constituents are examined and also a selection of chemical testing methods is critically reviewed and highlighting. In addition, their advantages, disadvantages, limitations and usefulness were discussed and investigated for pure molecules and raw plant extracts. The effect and influence of the reaction medium on performance of antioxidants is also addressed. Hence, this overview provides a basis and rationale for developing standardized antioxidant capacity methods for the food, nutraceuticals, and dietary supplement industries. Also, the most important advantages and shortcomings of each method were detected and highlighted. The underlying chemical principles of these methods have been explained and thoroughly analyzed. The chemical principles of methods of 1,1-diphenyl-2-picrylhydrazyl (DPPH•) radical scavenging, 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulphonate) radical (ABTS·+) scavenging, ferric ions (Fe3+) reducing assay, ferric reducing antioxidant power (FRAP) assay, cupric ions (Cu2+) reducing power assay (Cuprac), Folin-Ciocalteu reducing capacity (FCR assay), superoxide radical anion (O2·-), hydroxyl radical (OH·) scavenging, peroxyl radical (ROO·) removing, hydrogen peroxide (H2O2) decomposing, singlet oxygen (1O2) quenching assay, nitric oxide radical (NO·) scavenging assay and chemiluminescence assay are overviewed and critically discussed. Also, the general antioxidant aspects of the main food and pharmaceutical components were discussed through several methods currently used for detecting antioxidant properties of these components. This review consists of two main sections. The first section is devoted to the main components in food and their pharmaceutical applications. The second general section includes definitions of the main antioxidant methods commonly used for determining the antioxidant activity of components. In addition, some chemical, mechanistic, and kinetic properties, as well as technical details of the above mentioned methods, are provided. The general antioxidant aspects of main food components have been discussed through various methods currently used to detect the antioxidant properties of these components.

Mallotus peltatus (Geiseler) Mull. Arg. (MPMA) is a specialty plant used to make tea in Hainan Province, China. However, its hypolipidemic activity has been rarely studied. In this study, three polyphenol fractions (MPMAP-1, MPMAP-2, and MPMAP-3) were purified from a 60% ethanol extract of MPMA, and the hypolipidemic activities were evaluated by establishing an FFA-induced L02 cell model to determine lipid accumulation, antioxidant enzyme activities, and gene levels related to the Nrf2/ARE pathway and lipid metabolism. In addition, noninduced and high glucose-induced models were established using Caenorhabditis elegans (C. elegans) to evaluate the lipid-lowering activity of MPMAP-1. The results showed that all three polyphenols could significantly inhibit lipid accumulation, reduce intracellular MDA content, and enhance the activities of CAT, SOD, and GPx in FFA-induced L02 cells. The qRT-PCR results indicated that the amount of fat accumulation in L02 cells could be regulated by modulating the relative expression of mRNA in the Nrf2/ARE signaling pathway and lipid metabolism pathway. The noninduced model and high glucose-induced model demonstrated that MPMAP-1 was able to reduce lipid accumulation and ROS levels and increase the activities of antioxidant enzymes in C. elegans. In summary, our results suggested that polyphenol compounds of MPMA may be a promising natural product for lipid-lowering.

Oxidative stress underlies many diabetic complications, including diabetic vasculopathy. It is unclear if oxidative stress has different effects in regionally distant arteries. We compared the contractile function of three arteries from diabetic mice and elucidated the mechanisms underlying their differential adaptation. We examined responses of the aorta, carotid and femoral arteries, isolated from the same diabetic (db/db) or normoglycemic control mice, to different vasoconstrictors in the presence and absence of indomethacin, apocynin, sulfaphenazole, L-NAME or a reactive oxygen species generating system to identify the enzyme(s) contributing to vascular dysfunction. Expression of superoxide dismutase (SOD) isoforms was measured. db/db aortae showed augmented contractile responses to KCl, phenylephrine, A23197 and U-46619 likely due to activated cyclooxygenases and hypersensitivity to thromboxane A2. Contractile responses of db/db carotid arteries were unaltered, likely due to higher SOD3 and SOD1 levels compared to the aortae. Femoral arteries were more vulnerable to oxidative stress, lacked SOD3 expression, and showed higher basal potassium channels activity. Phenylephrine contractions in femoral arteries were dependent on extracellular calcium entry; while contractions in aortae were dependent on extracellular calcium entry and intracellular calcium release. Femoral arteries from db/db mice exhibited higher basal potassium channels activity and attenuated contractility compared to control mice likely due to lower SOD levels. Heterogeneity exists between the three arteries at functional and molecular levels due to different signalling pathways and antioxidant defense mechanisms. Understanding regional differences in vasomotor control coupled with advanced delivery systems can help in developing therapies targeting specific vascular beds.