The development of novel detection methods is essential for total antioxidant capacity (TAC) assay in the quality of foods and dietary pharmaceuticals. Herein, a series of cobalt-modified boron-doped metal‑nitrogen‑carbon nanoparticles (Co-BCN) were prepared through high-temperature pyrolysis of the precursors. The Co-BCN shows an outstanding activity of oxidase mimics, and can activate dissolved oxygen to generate a large amount of reactive oxygen species (ROS). These ROS oxidize luminol anions rapidly and emits intense chemiluminescent (CL) radiation. The antioxidants, ascorbic acid, glutathione and cysteine can scavenge the generated ROS, thus sharply reducing the CL signal. The reduction in the CL signals show good linear relationships in the concentration range of 0.1-1.0 μmol·L-1 ascorbic acid, 1.0-10.0 μmol·L-1 glutathione, and 10.0-80.0 μmol·L-1 cysteine, respectively. The method was employed for the TAC determination in eight commercially available fruits and beverages, and the results show good agreement with those of the CUPRAC method.

An imbalance between the generation of reactive oxygen species (ROS) and antioxidant defense systems is known as oxidative stress, and it is a major factor in diseases like atherosclerosis, vascular inflammation, endothelial dysfunction, and others that are largely caused by elevated oxidative stress. Interestingly, oxidative stress has also been implicated in the progression of prediabetes to type 2 diabetes (T2DM). Prediabetes, characterized by increased blood glucose levels than the diabetes threshold, impacts a substantial portion of the global population. In India alone, the estimated prevalence of prediabetes by 2023 is approximately 15.3 %. Hyperglycaemia, a hallmark of prediabetes, can promote vascular dysfunction by increasing ROS formation and upregulating chronic inflammatory markers. Additionally, oxidative stress contributes to insulin resistance and impaired beta cell function. Various risk factors of oxidative stress are associated with prediabetes development. This review focuses on ROS's role in prediabetes pathogenesis and its risk factors increasing the effect of oxidative stress. Various ROS scavengers were used as oxidative stress indicators, and ROS scavenging has a deleterious impact on disease progression. Lack of study has reported on role of oxidative stress in prediabetes development and this will be the first review covers pathogenesis and impact of oxidative stress biomarker in prediabetes. This review comprises managing the risk factors of oxidative stress would pave the way for the management of prediabetes progression to T2DM.

Chronic exposure to reactive carbonyl species such as glyoxal and methylglyoxal, along with hydroxyl radicals (•OH), leads to glycative and oxidative damage, contributing to insulin resistance and diabetic complications. Pyridoxamine (PM) is known to counteract these effects, but its potential synergy with mannitol (MN), a hydroxyl radical scavenger, remains unexplored. This study investigates the combined efficacy of MN and PM in preventing glycation and oxidative damage in vitro. Calf thymus DNA was subjected to glycation using 10 mM glyoxal, oxidation via the Fenton reaction, and sequential glycoxidation (glycation followed by oxidation). The inhibitory effects of MN, PM, and their combination were assessed using NBT reduction for early glycation, GK-ribose for AGEs, TBARS for hydroxyl radicals, and spectroscopic analyses for AGEs formation. A clinical study also examined autoantibody prevalence in diabetes and diabetic retinopathy (DR). Results showed that glycoxidated DNA exhibited structural alterations, with MN and PM individually reducing ketoamine content. Their combination further enhanced glycation and glycoxidation inhibition. Additionally, MN-PM co-administration synergistically reduced AGEs and hydroxyl radicals. Autoantibody levels were elevated in diabetes and DR. These findings suggest PM-MN co-administration as a promising strategy to mitigate diabetic complications.

Cuproptosis-a novel cell death mechanism-is an innovative strategy for tumor therapy. However, the insufficient efficacy of cuproptosis, primarily owing to the low sensitivity of tumor cells to Cu ions, remains a major challenge. In this study, we design TiCuMOF@PEG@l-Arg@TPP (TCPAT) nanoparticles to facilitate self-sensitized cuproptosis for anti-tumor therapy through the dual upregulation of p53. TiMOF serves as a microwave sensitizer by generating reactive oxygen species (ROS). Notably, the uniformly distributed Cu ions within the MOF serve as co-catalysts to provide reactive sites that enhance ROS generation. Additionally, the ROS generated are utilized to oxidize l-arginine, thus resulting in the release of nitric oxide (NO), which has a long half-life and diffusion distance, thereby enabling it to penetrate deep into the tumor regions that are typically inaccessible to ROS. Furthermore, TCPAT not only induces cuproptosis but also leverages the efficiently generated ROS and cascade-released NO for the dual upregulation of p53. This upregulation subsequently inhibits glycolysis, increases cellular sensitivity to Cu ions, and facilitates self-sensitized cuproptosis. Consequently, the self-sensitized cuproptosis strategy, dependent on the efficient generation of ROS, presents a promising avenue for tumor therapy based on cuproptosis mechanisms.

Neuronal nitric oxide synthase (nNOS) is a promising target for addressing various neurological disorders and melanoma. Our discovery of a series of truncated pyridinylbenzylamines has yielded potent, selective, and membrane permeable inhibitors of human neuronal nitric oxide synthase. By implementing an efficient synthetic procedure using the Suzuki-Miyaura cross-coupling reaction, we were able to rapidly identify a potent inhibitor. This new inhibitor (18, 6-(2,3-difluoro-5-((methylamino)methyl)phenyl)-4-methylpyridin-2-amine dihydrochloride) exhibits excellent potency, with Ki values of 30 nM for human nNOS and 40 nM for rat nNOS. It also demonstrates high isoform selectivity, showing an 821-fold preference for human nNOS over human endothelial NOS (eNOS) and a 75-fold selectivity over human inducible NOS (iNOS). Additionally, inhibitor 18 displays high permeability (Pe = 10.7 × 10-6 cm s-1) in an artificial membrane permeability assay. The crystal structures of several NOS-inhibitor complexes provide valuable structural insights into the potency and selectivity of this series of novel inhibitors. A particularly notable finding is the unexpected role of a Cl- anion bound to heNOS, which contributes to the high isoform selectivity of these inhibitors and explains why heNOS binds Cl-, while hnNOS does not. This unique Cl- binding site could be important in future inhibitor design, opening new avenues for the development of more selective NOS inhibitors. Additionally, the presented crystal structures reveal the key factors required to maintain both high potency and selectivity in the simplified inhibitors discussed in this study. Abbreviations: NO, nitric oxide; nNOS, neuronal nitric oxide synthase; iNOS, inducible nitric oxide synthase; eNOS, endothelial nitric oxide synthase; rnNOS, rat neuronal nitric oxide synthase; hnNOS, human neuronal nitric oxide synthase; hiNOS, human inducible nitric oxide synthase; heNOS, human endothelial nitric oxide synthase; l-Arg, l-arginine; NADPH, reduced nicotinamide adenine dinucleotide phosphate; CaM, calmodulin; H4B, (6R)-5,6,7,8-tetrahydrobiopterin; FAD, flavin adenine dinucleotide; FMN, Flavin mononucleotide, BBB, blood-brain barrier; CNS, central nervous system; PAMPA, parallel artificial membrane permeability assay; P-gp, P-glycoprotein; ER, efflux ratio; Pe, effective permeability; Papp, apparent permeability; Caco-2, cancer coli-2; TLC, thin layer chromatography; TBAF, tetra-n-butylammonium fluoride; TFA, trifluoroacetic acid.

There is a growing concern about the impact of environmental contamination by metals on insects owing to their biodiversity and important ecological roles. We investigated the neurobehavioral traits, cellular responses, and levels of metals in tissues of Nauphoeta cinerea nymphs exposed, separately and in ternary mixtures, to arsenic (15 and 7.5 mg/L), copper (15 and 7.5 mg/L), and zinc (100 and 50 µg/L), in drinking water for 35 consecutive days. Results showed that the diminutions in locomotor parameters (maximum speed, motility time, and distance traveled), motor and turning capabilities (path efficiency, turn angle, and body rotation) and the increase in anxiety-like behavior (total time freezing and freezing episodes) were more pronounced in individual metal exposure than triple metal mixtures groups. Barring zinc alone group, acetylcholinesterase activity decreased significantly in all the treatment groups compared to the control. The diminutions in glutathione level and antioxidant enzyme activities were partially attenuated in the fat body, midgut, and head of insects in the triple metal mixtures groups. Further, the levels of nitric oxide, hydrogen peroxide, lipid peroxidation, and reactive oxygen and nitrogen species were higher in individual metal exposed insects than the ternary mixture groups. The concentrations of arsenic, copper, and zinc in the fat body, midgut, and head of insects were significantly higher in individual metal exposure groups than the ternary metal mixtures groups. Collectively, the detrimental effects of elevated ecological concentrations of arsenic, copper, and zinc were more pronounced in insects exposed to individual metal than those in ternary mixtures groups.

Gestational chronic hypoxia impacts prenatal development, leading to fetal growth restriction (FGR), defined as the fetus's failure to reach its genetic growth potential. Postnatal hypoxia in the cerebral tissue can induce a redox imbalance and mitochondrial dysfunction, consequently increasing neuronal death. However, these data cannot necessarily be extrapolated to prenatal hypoxia. In this regard, this study aims to describe the effect of gestational hypoxia on redox balance and apoptosis cell death mechanisms in the prefrontal cortex of guinea pigs. Ten Guinea pig (Cavia porcellus) pregnant dams were utilized in this study; five gestated in normoxia (Nx; three newborn males, and two females) and five gestated under chronic hypobaric hypoxia (Hx; two newborn males, and three females). We monitored the pregnancies by ultrasound examinations from gestational days 20 to 65 (term ~ 70). At birth, pups were euthanized, and the fetal brain was collected for cellular redox measurement, mitochondrial enzyme expression, and apoptosis assay. Gestation under hypoxia induced an imbalance in the expression of anti- and pro-oxidant enzymes, resulting in increased oxidative stress. Additionally, a decrease in cytochrome I and III expression and neuronal density in the neonatal prefrontal cortex was observed. Finally, DNA fragmentation was increased by the TUNEL assay in the brain tissue of newborns gestated under chronic hypoxia. Our findings demonstrate the association of gestational hypoxia with oxidative stress and neuronal death in newborns, which may predispose to neuronal dysfunction in adulthood.

Cellular senescence is a stable, pro-inflammatory cell cycle arrest that has been recently implicated in the persistent memory deficits experienced with repetitive mild traumatic brain injury (rmTBI). Testosterone (T) treatment immediately following traumatic brain injury (TBI) mitigates cognitive deficits and cellular dysfunction known to induce cellular senescence. However, it has yet to be elucidated whether the therapeutic window for T treatment can be extended to a subacute time post-injury. This study examined the progression of hippocampal cellular senescence after rmTBI and evaluated the effects of subacute T on persistent memory deficits and cellular senescence post-injury. Changes in senescence-associated markers in the hippocampus were quantified at 5- and 9-weeks post-injury (WPI). An age-independent progressive increase in senescence-associated gene expression was observed for Cdkn2a, Cdkn1a, and p53 protein levels, along with a decrease in Sirt1 gene expression. Acute and persistent cognitive deficits were observed in the rmTBI rats as compared to sham rats. Serum T levels were significantly decreased at 4 WPI. Testosterone administration at 5 WPI ameliorated these persistent memory deficits. Moreover, subacute T treatment reduced rmTBI-induced levels of Cdkn2a 4 weeks post-treatment. This study indicates that rmTBI results in a progressive cellular senescence pathology that may contribute to the underlying mechanisms of persistent cognitive symptoms. Therapeutically targeting cellular senescence within this extended temporal window holds implications for patients dealing with the chronic cognitive ramifications of rmTBI.

Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasia characterized by the BCR::ABL1 fusion gene, which codifies the BCR-ABL protein with increased tyrosine kinase activity. Despite the clinical results for the outstanding tyrosine kinase inhibitors (TKIs), drug resistance is a problem in CML management. Genetic variants that alter redox homeostasis by changing antioxidant enzyme expression or activity may influence patient responses and could enhance patient stratification. We aimed to assess the association of SOD2, CAT GPX1, NRF2, and KEAP1 genetic variants with TKI response and disease prognosis. For this purpose, we genotyped the variants rs4880 (SOD2), rs1050450 (GPX1), rs1001179 (CAT), rs6721961, rs4893819, rs35652124, rs6706649, rs13001694 (NFE2L2), and rs113540846 (KEAP1) via PCR in 187 CML patients. Our results show that variants in genes related to oxidative stress influence the development and degree of TKI resistance (allele G and GG genotypes of GPX1 and CT genotype of NFE2L2 rs4893819), the appearance of mutations in the BCR::ABL1 gene (AG genotype of NFE2L2 rs13001694 and genetic profile GGCTTCCCGG of the NFE2L2/KEAP1 axis), disease evolution (AG genotype of SOD2 and CT genotype of NFE2L2 rs4893819), and overall survival (CC genotype of CAT and GG genotype of NFE2L2 rs13001694) of CML patients. Our study found that variants in oxidative stress-related genes impact treatment response and outcomes in CML.

Animal-derived traditional Chinese medicines have a long-standing history in Chinese medicine, which exhibit unique efficacy due to similar structure and function with human tissue. As the major types of constituents that accounted for a relatively high proportion of animal-derived TCMs, peptides with molecular weight between 100 Da and hundreds of thousands of kDa have caught wide attention due to their outstanding bioavailability and excellent specificity.

This review aims to comprehensively delve into the up-to-date research progress in their pharmacology, mechanism, sequence composition, and therapeutic application, laying a solid foundation for future clinical treatment and scientific research.

Relevant information on the peptides from animal-derived TCMs was collected from scientific literature databases including PubMed, CNKI, literature sources (Ph.D. and M.Sc. dissertations), and Web of Science by using the keywords "Peptides", "Animal", and "TCMs" for gradual screening in the past 30 years.

To date, the peptides from 27 kinds of animal-derived TCMs have been systematically combed. Their pharmacological activity and underlying mechanisms on multiple systems (nervous, circulatory, skeletal, and immune), as well as anti-tumor, antioxidative, and antimicrobial effects, have been sorted out. Besides, the potential safety issues and deficiencies (low bioavailability, imperfect quality management, and toxicity of raw materials) have also been pointed out.

Comprehensive analysis showed that low development and resource waste accompanied by the inadequate report about the pharmacological activity of most peptides from animal-derived TCMs make it have good research prospects. Although a breakthrough in the field of healthcare products has been made, the development potential for clinical products that bring surprising turnaround will be obtained if the above-mentioned confusions and current needs (improve identification technology and design reasonable dosage forms) are implemented.

Oxidative stress (OS), arising from an imbalance between reactive oxygen species (ROS) production and antioxidant defenses, plays a pivotal role in cellular dysfunction and the pathogenesis of numerous diseases. This study evaluates the impact of oxidative stress induced by hydrogen peroxide on the metabolomic profiles of the human embryonic kidney (HEK-293) and African green monkey kidney (COS-7) cell lines. Viability (MTT) and free radical accumulation (DCF-DA) assays confirmed a dose-dependent cytotoxic effect of hydrogen peroxide, with COS-7 cells exhibiting greater resistance and producing lower levels of intracellular ROS compared to HEK-293. Metabolomic profiling was conducted using nuclear magnetic resonance spectroscopy (1H NMR) to identify and quantify metabolic changes. Exposure to a free radical inducer significantly altered both intracellular and extracellular metabolites compared to control H2O2-free samples. The analysis revealed common changes in intracellular metabolites between the two lines, including glutamate, NAD+, glutathione, ATP/ADP, AMP, and pyruvate - key molecule for mitochondrial function, as well as extracellular metabolites such as glutamate, glutamine, acetate, lactate, and pyruvate. Metabolomic differences observed in COS-7 cells suggest a potentially greater capacity for metabolic adaptation to oxidative stress. These included elevated levels of branched-chain amino acids (BCAA), supporting energy production, and increased formate production, which may aid purine synthesis and cellular resilience. These findings highlight the distinct metabolic adaptations of COS-7 cells to oxidative stress in comparison to the HEK-293 cell line. They also provide insights into the direct cellular responses to altered redox potential, offering possible therapeutic strategies aimed at targeting metabolic pathways to mitigate oxidative stress.

Functioning corpora lutea (CL) are required for establishment and maintenance of pregnancy in pigs. Disruptions of pregnancy and reproductive cyclicity due to heat stress (HS) result in substantial economic losses for the swine industry. The objectives of this study were to characterize the CL proteome during early pregnancy establishment, and identify differentially abundant proteins during pregnancy establishment affected by HS and altrenogest supplementation. Following synchronization and estrus detection, gilts (n = 41) were assigned to one of six treatment groups enabling comparisons to evaluate the effects of pregnancy (cyclic (C) or pregnant (P)), thermal environment (thermal neutral (TN) or HS), and within pregnant gilts, supplementation with altrenogest 15 mg/d (ALT) or without (CON). Gilts were exposed to the thermal treatment at 2 days post estrus (dpe) and began receiving ALT supplementation 3dpe. At 12dpe, animals were euthanized, CL (n = 3-4) from each gilt were collected, protein extracted, and subjected to label free liquid chromatography - tandem mass spectrometry (LC-MS/MS). Two separate analyses, one focused on the effect of pregnancy and environment, and the other on the effect of environment and ALT supplementation, were conducted that identified 1470 and 907 differentially abundant proteins, respectively. Differences between treatments identified that pregnancy, HS and ALT supplementation alter the CL proteome in ways that may influence CL function and regression. These included proteins involved in oxidoreductase activity (SOD1), translation and ribosomal activity, and metal ion binding (PGMRC1 and CYCS). An understanding of these effects could help improve reproductive performance in swine production.

Polymersomes, which are polymer vesicles containing an aqueous cavity enclosed in a polymer membrane, hold enormous potential for biomedical applications. In recent years, enzyme-loaded polymersomes, serving as therapeutic nanoreactors, have drawn substantial interest. A crucial requirement for effective catalytic function is to impart semipermeability to the vesicular membrane while maintaining its role as a protective barrier for encapsulated enzymes. However, achieving both long-term stability and optimal membrane permeability for sustained functionality remains a challenge in many reported examples. In this study, we introduce ROS-responsive polyion complex vesicles (PICsomes) loaded with antioxidant enzymes (catalase) as antioxidative nanoreactors. The intrinsic semipermeability and crosslinked network structure of the membrane enable long-lasting catalytic function of catalase. The nanoreactor exhibits inherent cell-protective properties against oxidative stress in fibroblasts due to the ROS-scavenging ability of polymers. Notably, triggered by ROS, the nanoreactor demonstrates autoregulatory control of redox homeostasis. This is because the cysteamine released by PICsomes not only acts as a free radical scavenger but also facilitates the transport of L-cysteine into cells, thereby enhancing glutathione (GSH) biosynthesis. The results further demonstrate significant long blood circulation of PICsomes loaded with catalase and strong protection effects against bloodstream oxidative stress, paving the way for the further development of truly effective in vivo therapeutics. These findings underscore the potential of the engineered antioxidative nanoreactor with durable functionality as synthetic organelles for cellular protection against oxidative stress.

Antioxidants are vital in skincare for neutralizing reactive oxygen species (ROS), which impact key cellular structures, such as cell nuclei and elastic fibres and can contribute to skin ageing. Oxidative stress, compounded by processes such as glycation, therefore leads to impaired cellular renewal and reduced skin elasticity. The effectiveness of antioxidants depends on their concentrations, making it essential to investigate their dosage-related benefits to optimize skincare formulations. This raises an important question regarding the reciprocal effects of antioxidants on glycation and whether their protective effects against macromolecular damage are dose-dependent.

This study evaluated the antioxidant and anti-glycation effects of three concentrations of butylated hydroxytoluene (BHT), vitamin E and vitamin C. Using the established quantitative assays and immunofluorescence, total antioxidant capacities, the intracellular ROS production, glycation levels and expression of cellular biomarkers were measured in dermal fibroblasts and three-dimensional skin models cultured with methylglyoxal (MGO).

All three antioxidants showed a significant ability to inhibit the formation of intracellular ROS and glycation products induced by MGO. Notably, there were differences in the concentrations required to defend against glycation-induced damage. Whilst the linear dose responses were observed for ROS and glycation inhibition, the protective effect against cellular damage was moderate. The inverse dose-response relationships, particularly in terms of collagen fibre preservation, suggested that higher total antioxidant capacity could have enhanced protective effects. Vitamin C, in particular, exhibited the most pronounced benefits at lower concentrations, suggesting its potential as a key player in combating glycation damage.

The potentially novel aspect of this research lies in the synergistic relationship between the modulation of oxidative stress and glycation. This relationship significantly depends on the concentration of the molecules involved and their antioxidant properties. These findings may lead to more refined approaches in formulating active ingredients tailored to individual needs in personalized skincare.

Parkinson's disease (PD) is an aging-related neurodegenerative disease characterized by a progressive loss of dopamine (DA)-secreting neurons in the substantia nigra. Most of the currently available treatments attempt to alleviate the disease symptoms by increasing DA transmission in the brain and are associated with unpleasant side effects. Since there are no treatments that modify the course of PD or regenerate DA neurons, identifying therapeutic strategies that slow, stop, or reverse cell death in PD is of critical importance. Here, factors that confer vulnerability of substantia nigra DA neurons to cell death and the primary mechanisms of PD pathogenesis, including cellular senescence, a cellular stress response that elicits a stable cell cycle arrest in mitotic cells and profound phenotypic changes including the implementation of a pro-inflammatory secretome, are reviewed. Additionally, a discussion of the characteristics, mechanisms, and markers of cellular senescence and the development of approaches to target senescent cells, referred to as senotherapeutics, is included. Although the senotherapeutics curcumin, fisetin, GSK-650394, and astragaloside IV had disease-modifying effects in in vitro and in vivo models of PD, the potential long-term side effects of these compounds remain unclear. It remains to be elucidated whether their beneficial effects will translate to non-human primate models and/or human PD patients. The enhanced selectivity, safety, and/or efficacy of next generation senotherapeutic strategies including senolytic peptides, senoreverters, proteolysis-targeting chimeras, pro-drugs, immunotherapy, and nanoparticles will also be reviewed. Although these next generation senotherapeutics may have advantages, none have been tried in models of PD.

Background and Objective: Alcoholic liver disease (ALD) is a major health burden caused by chronic alcohol consumption, leading to oxidative stress, inflammation, and fibrosis. Current treatments are limited, highlighting the need for novel therapeutic agents. This study investigated the hepatoprotective effects of 'Terpinen-4-ol (T4OL)', a natural monoterpene from tea tree oil, against ethanol-induced liver injury, focusing on its molecular and cellular mechanisms. Materials and Methods: Network pharmacology and molecular docking were employed to predict T4OL's interaction with ALD-associated targets. Human HepG2 cells were used to validate the in silico findings. Cells were exposed to ethanol (8%) prior to treatment with T4OL or silymarin (SIL), and cytotoxicity was assessed through MTT, crystal violet, and trypan blue assays. Moreover, ELISA and qPCR were conducted to evaluate antioxidant, inflammatory, and fibrotic markers. Results: Network pharmacology analysis suggested that T4OL exerts its hepatoprotective effects by suppressing inflammatory and fibrotic mediators (HIF-1α, TGF-β1, and TNF-α). Docking studies also exhibited a strong binding affinity of T4OL to key ALD targets, with docking scores comparable to SIL. In addition, T4OL (13-1300 µM) dose-dependently protected HepG2 cells from ethanol-induced damage, restoring viability by up to 80% at 650 µM. It significantly elevated antioxidant levels (GSH by 2.5-fold, SOD by 1.8-fold) and suppressed pro-inflammatory and fibrotic markers (IL-6, COL1A1, TIMP-1) by 40-60%. At higher concentrations (650-1300 µM), T4OL outperformed SIL in cytoprotection and anti-fibrotic effects. Conclusions: T4OL mitigates ethanol-induced liver injury by targeting oxidative stress, inflammation, and fibrosis pathways, demonstrating superior efficacy to SIL at optimal doses. Its multi-target action supports its potential as a therapeutic candidate for ALD.

The therapeutic efficacy of intravesical agents for bladder cancer (BCa) is frequently constrained by their clearance via urine flushing and periodic bladder emptying, as well as the absence of tumor-targeting capabilities. Consequently, an effective drug delivery system must possess both tumor-targeting and adhesion properties to overcome these limitations.

In this study, we investigated a tumor-selective hydrogel as a potential vehicle for BCa treatment. For the first time in the field of intravesical therapy, we introduced the concept of pre-targeting, sequentially instilling modified polyarginine and membrane nanoparticles into the bladder to achieve selective gelation on the tumor surface. We comprehensively evaluated tumor selectivity, endocytosis pathways, organelle localization, and osmotic capacity, and demonstrated in vivo and in vitro degradation following drug delivery.

The pre-targeted hydrogel exhibited superior tumor selectivity. The drug-loaded membrane nanoparticles released during hydrogel degradation were internalized by tumor cells at levels exceeding those in normal cells by more than eightfold. Our findings indicated that this internalization process was energy-dependent and mediated by caveolin. Post-internalization, the drug-loaded membrane nanoparticles localized to the endoplasmic reticulum and Golgi apparatus, with minimal colocalization with lysosomes. Moreover, the hydrogel demonstrated profound penetration into tumor tissue. In terms of antitumor efficacy, the hydrogel loaded with gemcitabine exhibited significantly enhanced therapeutic effects compared to free gemcitabine.

Our dual-functional hydrogel system exhibits robust anti-tumor activity against BCa, presenting a promising alternative for intravesical therapy. This innovative approach addresses key limitations of current treatments by combining tumor targeting with sustained drug adhesion, offering a novel strategy for the management of BCa.

Glycation of nucleic acids secondary to hyperglycemia can lead to structural alterations and the formation of neoantigens. These molecular changes may elicit an early immune response. This study investigates the interaction between serum autoantibodies from prediabetic individuals and fructose-glycated human placental DNA, aiming to assess DNA glycation as a potential early indicator of glycemic stress.

and Methods: To investigate structural modifications in DNA produced by glycation, purified placental DNA was incubated with fructose (25 mM) at 37 °C for 5, 10, and 15 days, followed by spectrophotometric analysis. Peripheral blood samples were collected from 50 normoglycemic (mean age: 39.70 ± 6.63 years; 26 males, 24 females) and 50 prediabetic (mean age: 40.84 ± 5.44 years; 23 males, 27 females) adult patients, matched for age, sex, body mass index, and socio-economic conditions. The presence of circulating antibodies against glycated DNA was evaluated using direct and competitive ELISA.

Fructose-mediated glycation of DNA resulted in hyperchromicity and a new absorbance peak at 360 nm, indicating structural modification. Direct ELISA revealed significantly higher levels of anti-DNA autoantibodies in prediabetic sera (0.367 ± 0.225) compared to controls (0.239 ± 0.118; p = 0.003). Competitive ELISA showed that these antibodies had greater specificity for glycated DNA, with maximum inhibition by fructose-modified DNA at 37.86 ± 2.57 %, versus 23.01 ± 2.33 % for native DNA (p < 0.01).

The study concludes that DNA glycation occurs in prediabetic patients with intermediate hyperglycemia as a result of high blood glucose. This suggests that glycated DNA may serve as an early molecular indicator of glycemic stress, with potential applications in risk assessment and early detection strategies for individuals at risk of progressing to type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by impaired glucose regulation. This study evaluated the antioxidant and antidiabetic potential of aqueous extracts from four plant species from the southern Algarve: Aristolochia baetica, Chelidonium majus, Dittrichia viscosa, and Lavandula viridis, using non-cellular in vitro assays. HPLC/PDA was used to identify active compounds. Antioxidant activity was assessed by using TAA, FRAP, RP, and DPPH assays; antidiabetic potential through α-glucosidase and α-amylase inhibition; and wound healing relevance through elastase, collagenase, and lipoxygenase inhibition. D. viscosa showed the highest antioxidant activity (FRAP: 1132.99 ± 19.54 mg TE/g dw; DPPH IC50 = 25.85 ± 0.75 μg/mL) and total phenolic/flavonoid content, with a diverse profile including caffeic and chlorogenic acids, isoquercetin, and quercetin. It also exhibited potent α-glucosidase inhibition (IC50 = 0.61 ± 0.06 mg/mL), outperforming acarbose. L. viridis had the highest total phenolic content (39.04 mg/g), while A. baetica demonstrated the strongest anti-elastase, anti-collagenase, and lipoxygenase activity, suggesting wound-healing potential. C. majus showed the weakest effects. A strong correlation was observed between phenolic content and antioxidant/antidiabetic activity. These findings support further in vivo studies on D. viscosa and A. baetica for potential use in T2DM management and diabetic wound healing.

Parkinson's disease (PD) is a complex neurodegenerative disorder marked by the progressive loss of dopaminergic neurons in the substantia nigra. While current treatments primarily manage symptoms, there is increasing interest in alternative approaches, particularly the use of phytochemicals from medicinal plants. These natural compounds have demonstrated promising neuroprotective potential in preclinical studies by targeting key pathological mechanisms such as oxidative stress, neuroinflammation, and protein aggregation. However, the clinical translation of these phytochemicals is limited due to a lack of robust clinical trials evaluating their safety, efficacy, and pharmacokinetics. This review provides a comprehensive overview of the neuroprotective potential of phytochemicals in PD management, examining the mechanisms underlying PD pathogenesis and emphasizing neuroprotection. It explores the historical and current research on medicinal plants like Mucuna pruriens, Curcuma longa, and Ginkgo biloba, and discusses the challenges in clinical translation, including ethical and practical considerations and the integration with conventional therapies. It further underscores the need for future research to elucidate mechanisms of action, optimize drug delivery, and conduct rigorous clinical trials to establish the safety and efficacy of phytochemicals, aiming to shape future neuroprotective strategies and develop more effective, personalized treatments for PD.

Photo-oxidation is recognized as a contributor to the deterioration of milk quality, posing potential safety hazards to human health. However, there has been limited investigation into the impact of consuming photo-oxidized milk on health.

This study employs multi-omics analysis techniques to elucidate the mechanisms by which photo-oxidized milk induces oxidative stress in the liver.

Mouse model was used to determine the effect of the gavage administration of milk with varying degrees of photo-oxidation on the mouse liver. The damage degree was established by measuring serum markers indicative of oxidative stress, and with a subsequent histopathological examination of liver tissues. In addition, comprehensive metabolome, lipidome, and transcriptome analyses were conducted to elucidate the underlying molecular mechanisms of hepatic damage caused by photo-oxidized milk.

A significant elevation in the oxidative stress levels and the presence of hepatocellular swelling and inflammation subsequent to the gavage administration of photo-oxidized milk to mice. Significant alterations in the levels of metabolites such as lumichrome, all-trans-retinal, L-valine, phosphatidylglycerol, and phosphatidylcholine within the hepatic tissue of mice. Moreover, photo-oxidized milk exerted a pronounced detrimental impact on the glycerophospholipid metabolism of mice liver. The peroxisome proliferator-activated receptors (PPAR) signaling pathway enrichment appreciated in the animals that consumed photo-oxidized milk further supports the substantial negative influence of photo-oxidized milk on hepatic lipid metabolism. Gene set enrichment and interaction analyses revealed that photo-oxidized milk inhibited the cytochrome P450 pathway in mice, while also affecting other pathways associated with cellular stress response and lipid biosynthesis.

This comprehensive study provides significant evidence regarding the potential health risks associated with photo-oxidized milk, particularly in terms of hepatic oxidative damage. It establishes a scientific foundation for assessing the safety of such milk and ensuring the quality of dairy products.

Actin is an extraordinarily complex protein whose functions are essential to cell motility, division, contraction, signaling, transport, tissular structures, DNA repair, and many more cellular activities critical to life for both animals and plants. It is one of the most abundant and conserved proteins and it exists in either a soluble, globular (monomeric, G-actin) or an insoluble, self-assembled (polymerized or filamentous actin, F-actin) conformation as a key component of the cytoskeleton. In the early 1990's little, if anything, was known about the impact of reactive oxygen species (ROS) on the biology of actin except that ROS could disrupt the actin cytoskeleton. Instructively, G-actin is susceptible to alteration by ROS, and thus, purification of G-actin is typically performed in the presence of strong antioxidants (like dithiothreitol) to limit its oxidative degradation. In contrast, F-actin is a more stable conformation and thus actin can be kept relatively intact in purified preparations as filaments at low temperature for extended periods of time. Both G- and F-actin interact with a myriad of intracellular proteins and at least with a couple of extracellular proteins, and these interactions are essential to the many actin functions. This review will show how, over the past 30 years, our understanding of the role of ROS for actin biology has evolved from noxious denaturizing agents to remarkable regulators of the actin cytoskeleton in cells and consequent cellular functions.

Arsenolipid (AsL) is a complex lipid-soluble organic arsenic compound, which is usually found in marine organisms. Among them, arsenic-containing hydrocarbons (AsHCs) are a common type. At present, the toxic effects of different AsHCs have not been elucidated due to their different hydrocarbon chain lengths and large numbers. A model Caenorhabditis elegans (C.elegans) was used to study the reproductive toxicity and mechanism of AsHC 332, AsHC 346 and AsHC 360, which are commonly found in seafood. The results showed that three different molecular weights of AsLs reduced the number of offspring and gonadal area of C. elegans, prolonged the generation time. Meanwhile, the three AsLs regulated the expression levels of oxidative stress genes (isp-1, mev-1, sod-3, gas-1), resulting in changes in the expression of apoptosis-related genes (ced-3, ced-4, ced-9) and DNA damage-related genes (hus-1, clk-2, cep-1 and egl-1). In addition, the mechanism of arsenolipid-induced nematode reproductive toxicity was further elucidated through the HUS-1-CEP-1-EGL-1-CED-9-CED-4-CED-3 signaling pathway. Therefore, our results suggest that AsHC 332 is more exposed to reproductive toxicity than AsHC 346 and AsHC 360, which is related to changes in physicochemical properties and DNA damage-induced germ cell apoptosis.

Numerous studies have shown that inappropriate regression of corpus luteum would lead to adverse pregnancy outcomes during gestation. However, the detailed mechanisms and types of programmed cell death involved in the regression of pregnant corpus luteum are largely unknown. Here, we investigated whether ferroptosis and ferritinophagy were involved in luteal regression during parturition in mice and related mechanisms. The results showed that ferroptosis and ferritinophagy were both involved in luteal regression during mice peri-parturition in vivo. Erastin (ferroptosis agonist) treatment significantly accelerated luteal regression and induced premature labor in pregnant mice. PGF2α treatment induced the ferroptosis and ferritinophagy of luteal cells in vitro. Nevertheless, inhibition or promotion of ferroptosis significantly altered the states of PGF2α-induced luteal cell viability and ferroptosis. Furthermore, inhibition of autophagy (3-methyladenine co-treatment) alleviated PGF2α-induced ferritinophagy and ferroptosis of luteal cells, and knockdown of NCOA4 reduced the degradation of FTH1 and the level of ferroptosis of luteal cells induced by PGF2α. In summary, our current data demonstrated that the ferroptosis associated with NCOA4-mediated ferritinophagy was a novel way of luteal regression during peri-parturition in mice. Targeting ferroptosis in the corpus luteum may be a therapeutic strategy for preventing luteal insufficiency in the future.

Nanoparticles (NPs) have actively contributed to nanotechnologies advancement over the last years, due to the unique properties they possess compared to their pristine counterparts. Consequently, NPs found wide applications in various fields such as the medical, biomedical, chemical, agro-food industries, and cosmetology. NP's extensive uses could lead to their release into the environment, especially in the marine ecosystems, considered as NPs sink, resulting in harmful effects on organisms. Concerns regarding NPs' toxicity in aquatic organisms have emerged, however, several points remain unexplored. In the present study, the toxicity of chromium oxide (Cr2O3 = 42 nm) and aluminum oxide (Al2O3 = 38 nm) NPs (1 mg/L, 2.5 mg/L, and 5 mg/L) in the gills of the marine gastropod Stramonita haemastoma was assessed through time (7, 14, and 28 days) by a multi-biomarker, Integrated biomarkers response (IBR), and Histological analysis. Both NPs induced varied changes in the antioxidant system, suggesting the onset of oxidative stress marked by superoxide dismutase (SOD), catalase (CAT), acetylcholinesterase (AChE), metallothionein (MT), and malondialdehyde (MDA) levels imbalance. Varied histological alterations in the gills of S. haemastoma were also observed including inflammation, hypertrophy, and lamellar fusion, IBR proved to be a promising tool for assessing NPs toxicity in gastropods. In this study results indicated the co-response of reduced glutathione (GSH), glutathione S-transferase (GST), glutathione peroxidase (GPx), CAT, SOD, and MT after 28 days of exposure. S. haemastoma showed sensitivity to all exposure concentrations of NPs thus validating this species as a suitable indicator of NPs contamination and toxicity.

Chinese olive (CO; Canarium album L.) fruits are rich in phytochemicals with known physiological benefits. However, most studies evaluating the effects of CO have used ethyl acetate, acetone, and chloroform as the extraction solvents, which do not accurately reflect real dietary conditions. Moreover, research on CO leaves and pits remains limited. This study investigated the functional properties of extracts derived from CO leaves, fruits, and pits, prepared under simulated conventional culinary and dietary conditions (including solvents, extract combinations, and heat treatment), referred to as cooking-mimicking extracts. Our results revealed that most CO extracts reduced the production of nitric oxide in lipopolysaccharide-stimulated RAW264.7 macrophages and inhibited the proliferation of HCT116 colorectal cancer cells. Combinations of water-soluble CO extracts exerted a synergistic effect, suppressing cancer cell proliferation. To the best of our knowledge, this study is the first to identify methylellagic acid deoxyhexoside, vitexin 2-O-rhamnoside, and isovitexin 2-O-rhamnoside in CO extracts. Molecular docking predicted strong interactions with phosphofructokinase (PFK), a key glycolytic enzyme implicated in cancer cell proliferation. Treatment with CO extracts, including heat-treated forms, markedly reduced PFK activity and cell viability in HCT116 cells. These findings provide new insights into the bioactive constituents and physiological functions of CO extracts, supporting their potential application in dietotherapy.

Quaternary ammonium salts of chitosan have been widely used in the development of anti-microbial biomaterials for their important role in inhibiting the growth of microorganisms. However, it is important to modify its structure to obtain more efficient and biologically active derivatives. Herein, a series of chitosan derivatives with antibacterial, antifungal, antioxidant, and non-cytotoxic properties was synthesized. These four quaternary ammonium salts of chitosan were prepared by incorporating 2-thiophenecarboxaldehyde, 2-furancarboxaldehyde, 2-pyridinecarboxaldehyde and benzaldehyde to form Schiff bases, followed by a reductive amination to obtain the chitosan N-derivatives, and quaternized by iodomethane. The inhibition rate of thiophenecarboxaldehyde chitosan trimethyl ammonium iodide (TpTMC) to B. cinerea could reach 93.78 % and the inhibition ability of pyridinecarboxaldehyde chitosan trimethyl ammonium iodide (PyTMC) to F. graminearum could reach 98.08 % at the concentration of 1.0 mg/mL. Furthermore, furancarboxaldehyde chitosan trimethyl ammonium iodide (FrTMC) exhibited a strong ability to scavenge hydroxyl radicals and DPPH radicals, especially the DPPH radicals scavenging ability was comparable to that of l-ascorbic acid at the concentration of 1.6 mg/mL. The B3LYP/6-311++G (d,p) basis set was employed to determine electronic properties, including HOMO-LUMO energies, and to analyze the chemical reactivity of the compounds. L929 cells were used to evaluate the cytotoxicity of the compounds at different concentrations (1-1000 μg/mL). The results demonstrated the diverse applications of aromatic ring-modified quaternary ammonium salts of chitosan, along with their significant antioxidant and antifungal effects against plant fungi. Therefore, these compounds have potential applications in the preparation of agricultural, biological, and medical materials.

As a complex chronic gynecological disorder characterized by multifaceted etiology involving genetics, environment, immunity and inflammation, endometriosis (EM) has long been a significant concern for women of reproductive age worldwide. This review aimed to comprehensively examine the interplay between epigenetics and oxidative stress (OS) in the pathogenesis of EM. Through the integration of cutting-edge research, the response of OS signals to epigenetic modifications was explored. The microbiome exerts an influence on this causal regulatory relationship, and these mechanisms collectively contribute to the pathophysiology of EM. Specifically, this article highlighted the roles of epigenetics and OS in EM and underscored the importance of the microbiome as a regulatory link. A discussion was also held on the future directions of biomarkers and precision medicine, including the application prospects of epigenetic and OS markers in the diagnosis and treatment decision-making of EM, and innovations in therapeutic strategies like targeting epigenetic modifications and antioxidant therapies. Moreover, this review emphasized the potential of multi-omics integrated analysis to deepen the understanding of the disease, guide future therapeutic strategies and promote personalized medicine.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) disrupts innate immunity by inducing necroptosis in polymorphonuclear neutrophils (PMNs), a process linked to excessive inflammation and tissue damage. CA-MRSA releases virulence factors that enhance its pathogenicity by disrupting the host's innate immune response, particularly impairing the phagocytic function of PMNs. Steamed Panax notoginseng (S-PN), a traditional Chinese medicine (TCM), has demonstrated immune-regulatory and anti-inflammatory properties, showing promising therapeutic effects in alleviating the severe inflammatory responses induced by pathogenic microbial infections.

This study aims to investigate the pharmacological effects and mechanisms of S-PN alleviating CA-MRSA-induced PMN necroptosis by suppressing MRSA virulence factors and inhibiting the RIPK1/RIPK3/MLKL signaling pathway, thereby attenuating inflammatory damage.

A co-culture model of MRSA USA300 strain and PMNs isolated from healthy human blood was established to observe the changes in necroptosis marker HMGB1, PMNs counts, ROS, chemokine MCP-1 and pro-inflammatory cytokines IL-1β, IL-8, TNF-α. RNA-seq was employed to analyze the effects of S-PN on the transcriptional expression of pathogenesis-related genes of MRSA. RT-PCR was utilized to validate the expression of S-PN on MRSA virulence factors and PMNs necroptosis related genes.

S-PN significantly inhibited HMGB1, ROS, MCP-1, IL-1β and IL-8 in MRSA-PMN co-cultures, the PMN count in the S-PN group was higher than that in the model group. S-PN downregulated MRSA pathogenic-associated S. aureus infection and quorum sensing signaling pathways, and significantly reduced the virulence factors PSM and PVL. S-PN suppressed the expression of genes associated with necroptosis ripk1, ripk3, and mlkl in PMNs.

S-PN alleviates CA-MRSA infection-induced immune damage through dual mechanisms: suppression of bacterial virulence factors (PSM and PVL) and inhibition of PMNs necroptosis. These findings underscore its potential as a complementary therapeutic strategy against CA-MRSA infections, providing a theoretical foundation for integrating TCM into adjuvant treatments for drug-resistant bacterial infections.

Regular consumption of brown rice has been linked to a reduction in the probability of oxidative stress-related diseases, including diabetes, Alzheimer's disease and cancer. The higher abundance of bioactive metabolites, including polyphenols and vitamins, in brown rice relative to white rice may contribute to its associated health benefits. Aflatoxin B1 (AFB1), a kind of mycotoxin widely found in grains, is recognized as a primary risk factor for hepatocellular carcinoma in humans. Therefore, the differential polyphenol metabolites between brown rice and white rice, as natural plant antioxidants, may also be able to mitigate the oxidative damage caused by AFB1. In this work, the differential polyphenol metabolites between brown rice and white rice were identified using ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS). The results showed that 35 differential metabolites were found and classified into phenolic acids, flavonoids, lignans and coumarins. Among them, ferulic acid (FA) was characterized as a kind of differential metabolite that could mitigate AFB1-induced oxidative damage based on the interaction network and cell experiments. Furthermore, results of the mice experiment confirmed that FA mitigated AFB1-induced hepatic injury through a potential mechanism associated with the enhancement of antioxidant capacity, restoration of mitochondrial function and attenuation of AFB1-induced apoptosis. In conclusion, FA, identified between brown rice and white rice, could effectively alleviate AFB1-induced hepatic injury in vitro and in vivo. This study provides important insight into the application of brown rice (abundant in FA) as a functional food.

Acrylamide (ACR), utilized as a precursor for producing polyacrylamide for water purification, has demonstrated neurotoxic properties. However, the mechanisms underlying its neurotoxicity remain inadequately understood. In this investigation, Caenorhabditis elegans were exposed to ACR at concentrations ranging from 250 to 1000 μg/mL and then their locomotor behavior, neuronal development, neurotransmitter concentrations, and gene expression profiles were assessed. Exposure to 250-1000 μg/mL ACR resulted in observable behaviors such as head swiveling and body bending, accompanied by a significant reduction in body size. Furthermore, ACR exposure caused damage to serotonergic, cholinergic, dopaminergic, and glutamatergic neuronal structures. In this context, elevated levels of serotonin, dopamine, acetylcholine, and glutamate were detected, along with notable upregulation of the expression of genes associated with neurotransmitters, including tph-1, cat-4, mod-1, mod-5, cat-1, ser-1, dat-1, dop-1, dop-3, unc-17, cho-1, eat-4, and glr-2. Moreover, ACR exposure elevated reactive oxygen species (ROS), O2, and H2O2 levels while concurrently depleting glutathione (GSH), thereby compromising the antioxidant defense system. This led to a significant upsurge in the expression of genes involved in the nematode ACR detoxification pathway, specifically daf-16, skn-1, mlt-1, sod-3, gst-4, gcs-1, hsf-1, and hsp-16.2. Additionally, Spearman correlation analysis revealed a significant inverse relationship between certain neurotransmitter and antioxidant genes and locomotor activities, highlighting the role of these genes in mediating ACR-induced neurotoxicity in C. elegans. Collectively, this research enhances the understanding of the mechanisms related to ACR neurotoxicity.

Preeclampsia is a pregnancy-specific syndrome, linked to oxidative stress, affecting 5-8% of pregnancies, with no effective treatment available. Here, diaryl-hydrazones have been designed, synthesized, and investigated as mitochondria-targeting antioxidants to reduce placental oxidative stress and mitigate preeclampsia symptoms. The design, based on density functional theory studies, revealed that conjugated electron structure with the NH-motif appeared to explain their effect. Thirty compounds were synthesized and tested in three assays, where they exhibited excellent radical scavenging activity, significantly greater than that of the standard, Trolox. Based on the data, eight compounds were selected for cell-based assays. Oxidative stress was induced in human trophoblast cells and assessed whether the compounds reduced downstream antiangiogenic responses using ascorbic acid and MitoTEMPO as standards. The pretreatment with the hydrazones reduced mitochondrial superoxide and sFLT-1 production in H2O2-exposed trophoblast cells, indicating that mitochondrial oxidative stress and the anti-angiogenic response can be alleviated by these compounds.

ABSTRACTThis study investigated the effect of calcium silicate hydrate (C-S-H) on copper (Cu) uptake, availability, geochemical speciation, and immobilization in the soil-plant system. C-S-H, prepared from coal gangue, was added to Cu-contaminated soil to assess its effect on pakchoi growth. C-S-H application increased soil pH, organic matter content, and cation exchange capacity while reducing electrical conductivity. It also increased soil microbial biomass and enzyme activities while reducing Cu bioavailability, mobility, and leaching toxicity. The possible Cu fixation mechanisms by C-S-H in soil media included ion exchange, complexation, and precipitation. Moreover, fresh biomass, dry biomass, plant height, and root length increased significantly by 5.81-23.74%, 8.48-34.69%, 5.13-29.42%, and 6.78-28.81%, respectively. Cu content in the shoots and roots of pakchoi decreased by 17.30-66.04% and 11.77-58.09%, respectively. These findings demonstrate that C-S-H is an effective soil amendment for reducing Cu accumulation in the pakchoi and enhances Cu solidification ability in contaminated soil.

Background/Objectives: Oral health is a complex concept involving physical, psychological, emotional, and social components. A key factor in maintaining oral tissue integrity is redox balance, which is disrupted by oxidative stress (OS) through an imbalance between reactive oxygen species (ROS) and antioxidant defenses. This study examines the contribution of endogenous and exogenous sources to OS and explores the therapeutic potential of medicinal plants from the Asteraceae and Lamiaceae families in restoring redox homeostasis and improving oral health. Methods: A literature review was conducted, analyzing the role of OS in oral diseases and the antioxidant mechanisms of selected Asteraceae species. Special attention was given to their phytochemical contents-polyphenols, flavonoids, and essential oils-and their biological relevance to oral health. Results: OS plays a critical role in the onset and progression of oral conditions such as caries, periodontitis, gingivitis, aphthous ulcers, abscesses, precancerous lesions, and oral cancers. ROS and reactive nitrogen species (RNS) cause inflammation, tissue breakdown, and salivary gland dysfunction. Asteraceae plants like Matricaria chamomilla, Calendula officinalis, Cichorium intybus, Taraxacum officinale, Arctium lappa, Achillea millefolium, and Solidago virgaurea demonstrate notable antioxidant, anti-inflammatory, and antimicrobial properties that help counteract OS and support oral homeostasis. Conclusions: Asteraceae and Lamiaceae species show high therapeutic potential in addressing OS-related oral disorders. Their bioactive compounds aid in restoring redox balance and protecting oral tissues. These findings support the integration of phytotherapeutic agents into oral healthcare and call for further clinical validation of plant-based strategies for disease prevention and management.

There is a surplus of byproducts from food processing in the food industry, which has potential nutritional value. The process of transforming these leftover materials into products of higher value or utility is currently referred to as upcycling. The objective of this systematic review was to answer the following question: "Can byproducts from the food industry promote health-related benefits in vivo?". To answer this question, three scientific databases were considered for the literature search: PubMed, Scopus, and Web of Science. The inclusion criteria were outlined by the PICOS, and data analysis was conducted following the PRISMA guidelines. Thirteen studies that used animal models to evaluate the potential benefits of food byproducts were included in this review. These food byproducts demonstrated potential positive effects on overall health. The main results identified are related to the reduction of reactive oxygen species, reduction of enzymes related to liver damage, improvement of cytokines such as IL-6, IL-2, and TNF-α, and improvement of glucose and lipid plasma levels. However, more studies are necessary to better elucidate the activities, mechanisms of action, and potential toxicity of these compounds. PROSPERO (CRD42024576869).

A proper body condition determines the correct functioning of physiological processes and the optimal expression of fitness-related traits. Among these processes, maintaining the redox balance is essential to protect the organism from damage caused by oxidative stress. Yet, the causal link between an impaired body condition and a consequent increase in oxidative stress remains surprisingly far from clear. We experimentally tested such link by imposing a dietary restriction (DR), that is, decreased food availability, to nonreproductive adult red-legged partridges (Alectoris rufa) and measuring a battery of oxidative stress biomarkers. Levels of oxidative status (ratio of reduced to oxidized glutathione [GSH:GSSG] in erythrocytes), oxidative damage in plasma lipids (MDA), and plasma antioxidant capacity (OXY and TEAC assays) were quantified before the DR, twice during the DR, and once after the end of the DR. The GSH:GSSG ratio remained steady throughout the experiment. By contrast, after 19 days under DR, individuals showed an increase in MDA levels and an altered antioxidant capacity (a reduction in OXY and an increase in TEAC) with respect to controls, showing that the worsening of body condition indeed leads to an increase of the oxidative stress. However, these effects were transitory, appearing only by 19 days under DR and disappearing afterwards. These findings suggest that, despite the temporary increase in oxidative damage, individuals adapt their oxidative physiology to overcome resource restriction, possibly by reallocating resources from other physiological processes. This highlights the importance of considering dynamic changes when evaluating the impact of stressful conditions.

Attention-deficit hyperactivity disorder (ADHD), the most prevalent neurodevelopmental disorder, is characterized by inattention, hyperactivity, and impulsivity, manifesting in distinct symptoms and varying degrees of severity among patients. While the cellular processes underlying the neurobiology of ADHD are still being explored, in vitro studies suggest the involvement of certain cellular pathways in its clinical manifestations. Neurodevelopmental disorders such as ADHD are caused by malfunctions in numerous cells in the central nervous system (CNS) throughout development; nevertheless, most of the research focuses on neuronal dysfunction. In the last decade, it has become evident that glia and astrocytes play a crucial role in neurodevelopmental processes, which, if deficient, may result in neurodevelopmental disorders. Besides contributing to homeostatic maintenance of the blood-brain barrier (BBB) and other glial cell types, astrocytes provide neurons with structural, trophic, and metabolic support, which is indispensable for their proper functionality. Emerging evidence implicates that astrocytes are involved in processes associated with the etiopathology of ADHD, including oxidative stress, aberrant synaptic formation, neuroinflammation, and excitatory/inhibitory imbalance. This review will summarize the current knowledge addressing astrocyte dysfunction in ADHD, the remaining caveats in clinical data, and the possibilities for drug therapy. Findings substantiated by in vivo, in vitro, and genetic data will be provided, along with the impact of methylphenidate on astrocyte condition.

Cardiovascular diseases (CVDs) remain a leading global health concern, responsible for substantial morbidity and mortality. In recent years, as our understanding of the multifaceted nature of CVDs has increased, it has become increasingly evident that traditional risk factors alone do not account for the entirety of cardiovascular morbidity and mortality. Environmental toxins, a heterogeneous group of substances ubiquitous in our surroundings, have now entered the spotlight as offenders in the development and progression of CVDs. Environmental toxins include heavy metals, air pollutants, pesticides, and endocrine-disrupting chemicals, among others. Upon exposure, they can elicit oxidative stress, a condition characterized by an imbalance between the production of reactive oxygen species (ROS) and the body's ability to detoxify and repair the resulting damage. Oxidative stress triggers a cascade of events, including inflammation, endothelial dysfunction, lipid peroxidation, and vascular remodeling, which can contribute to the development of atherosclerosis, hypertension, and other cardiovascular pathologies. This article delves into the molecular mechanisms underpinning oxidative stress-mediated cardiovascular damage induced by environmental toxins, emphasizing the role of specific toxins in this process. Further research is necessary to understand how individual susceptibility and genotype influence the impact of environmental toxins on oxidative stress and the risk of CVD.

With low toxicity and good biocompatibility, carbon dots (CDs) are widely used in the fields of biosensing and drug delivery. In recent years, they have demonstrated excellent antimicrobial properties, thus becoming another research hotspot in the antimicrobial field. However, most of the studies showed that CDs were effective in inhibiting Gram-positive bacteria but ineffective against Gram-negative bacteria. In this study, macadamia nutshell (MNS)-CDs were prepared from the hard shells of macadamia nuts by a one-step hydrothermal method, and their appearance, morphology, structural composition, antimicrobial properties, and toxicity were investigated. The results showed that the MNS-CDs were spherical particles with an average diameter of about 4.25 nm, with hydrophilic groups, a hemolysis rate of less than 2%, good biocompatibility, and excellent antimicrobial properties against both Gram-negative and Gram-positive bacteria. The antimicrobial mechanism of these materials was also investigated. The inhibition of Gram-negative bacteria by MNS-CDs was mainly due to electrostatic interactions, while the inhibition of Gram-positive bacteria was mainly based on activated oxygen sterilization. Furthermore, MNS-CDs achieved good antimicrobial effects when applied in the fields of water purification, plates, fabrics, and food packaging, indicating that the prospects of their broad application are good.

The purpose of this study is to evaluate the antimicrobial and therapeutic effects of nebulized-plasma activated saline (N-PAS) on pulmonary infections caused by Escherichia coli in rats. This research highlights the novel therapeutic potential of N-PAS for treating respiratory infection in animal models. Seven groups of four-week-old Wistar rats, each weighing approximately 180 grams, were used. After inducing pulmonary infections with E. coli, the rats inhaled 36 ml of N-PAS for 30 minutes daily over a period of 7 days. Blood samples were analyzed to assess Paraoxonase-1and catalase enzyme activities, malondialdehyde levels, and total antioxidant capacity. Results were compared to those of untreated infected rats, rats treated with non-activated saline, and also healthy rats to evaluate efficacy and potential side effects. N-PAS significantly enhanced antioxidant enzyme activities and reduced oxidative stress compared to controls. histopathological analysis showed minimal lung tissue damage in N-PAS-treated groups. Furthermore, Prolonged exposure up to 17 days revealed no significant side effects. These findings suggest that N-PAS inhalation is a promising and safe therapeutic approach for respiratory infections.

Diabetic kidney disease (DKD) is a common microvascular complication and the main cause of death in diabetic patients. Metabolic disorders can accelerate the occurrence and development of DKD through a variety of ways, Recent studies have found that Clusterin (Clu) levels are associated with renal dysfunction and can be used as a biomarker of renal tubular injury, while preclinical studies reveal its renoprotective function. This article reviews the molecular mechanisms of Clu in the interaction between various cells in DKD. In addition, we discuss the latest research progress of Clu in the field of DKD. This review aims to explore Clu as a potential therapeutic target for DKD and provide some guidance for future clinical treatment.