Severe Oxidative Stress Research Articles

Tannic Acid-Based Biomimetic Nanomedicine with Pathological Reactive Oxygen Species-Responsive Cargo Release for Relieving Inflammation in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic disease characterized by immune cell infiltration and cartilage damage. The local lesion of RA shows severe oxidative stress and proinflammatory cytokine secretion. For drug therapy, the efficacy of agents, such as methotrexate (MTX), may be greatly limited, resulting from the low bioavailability, immune clearance, and toxic side effects. A nanocarrier (TA-PBA NPs) was developed with anti-inflammatory and antioxidant activities, combined with MTX to prepare nanomedicine (MTX NPs) for synergistic treatment of RA. Moreover, inspired by the biological functions homing to inflammation lesion of macrophages, the biomimetic nanomedicine camouflaged with macrophage membrane (MM@MTX NPs) was constructed. TA-PBA NPs could timely promote MTX release in response to the overaccumulated ROS to exhibit high anti-inflammatory and antioxidant activities for alleviating RA progression. The experimental results confirmed that MM@MTX NPs could significantly reduce the secretion of proinflammatory cytokines (TNF-α) while significantly increasing the typical anti-inflammatory cytokines (IL-10), promote the phenotype transformation of macrophages from M1 to M2, and up-regulate the Nrf2-keap1 pathway-related proteins (HO-1 and NRF2) to positively regulate the local inflammation for effectively inhibiting RA development. Thus, MM@MTX NPs represent a possible candidate as a safe and efficient nanotherapy platform for RA management.

Drug conjugates crosslinked bioresponsive hydrogel for combination therapy of diabetic wound

Basic fibroblast growth factor (bFGF) has proved to be effective for wound healing, yet its effectiveness is extremely retarded in diabetic wounds due to the severe oxidative stress in wound beds. To solve this issue, herein a novel combination therapy of bFGF and N-acetylcysteine (NAC, antioxidant) was devised for improved diabetic wound repair. To avoid rapid loss of both drugs in the wound beds, a bioresponsive hydrogel (bFGF-HSPP-NAC) was engineered by incorporating bFGF and NAC into polymer-drug conjugates (HSPP) via thiol-disulfide exchange reactions. In response to oxidative stress (e.g., reactive oxygen species), the disulfide bonds (SS) within the hydrogel are broken into thiol groups (-S-H), thereby promoting hydrogel degradation and enabling controlled drug release. Initially, NAC is released to scavenge free radicals and ameliorate oxidative damage. Subsequently, bFGF is released to expedite tissue regeneration. This combinatorial strategy is tailored to the specific characteristics of the wound microenvironment at various stages of diabetic wound healing, thereby achieving therapeutic efficacy. The results indicate that the bFGF-HSPP-NAC hydrogel markedly enhances re-epithelialization, collagen deposition, hair follicle regeneration, and neovascularization. In conclusion, the bioresponsive bFGF-HSPP-NAC hydrogel demonstrates significant potential for application in combinatorial therapeutic approaches for diabetic wound healing.

Uncovering the toxic effects and adaptive mechanisms of aminated polystyrene nanoplastics on microbes in sludge anaerobic digestion system: Insight from extracellular to intracellular

The impacts of polystyrene nanoplastics (PS NPs) with amino functional groups on sludge anaerobic digestion process and the underlying microbial feedbacks remains unclear. Herein, PS NPs coated with and without amino functional groups were employed to explore their impacts on the sludge digestion performance. Experimental results showed that aminated PS NPs (PS-NH2) deteriorated the methane yield and hydrolysis rate. The Derjaguin-Landau-Verwey-Overbeek theory analysis suggested that the PS-NH2 decreased the interaction energy barrier, making it easier to contact with sludge and disrupting the structure of extracellular polymeric substances. Metagenomic analysis showed that the abundance of functional microbes (e.g., Longilinea, Leptolinea, and Methanosarcina) decreased, accompanied with lower network complexity and fewer keystone taxa. Molecular docking revealed that PS-NH2 occupy the antioxidant enzyme active binding sites through hydrogen bonding and hydrophobic interactions, impairing degradation of reactive oxygen species. The severe intracellular oxidative stress up-regulated genes associated with quorum sensing (e.g., luxI and luxR) and protein biosynthesis (e.g., algA, trpG and trpE), and further inducing compact tryptophan-like proteins as a defense against NPs. These findings provide new understanding of the toxic effects from PS-NH2 in biological systems and offer valuable insights into the regulation strategies aimed at alleviating NPs inhibition.

In Vitro Screening of Trehalose Synbiotics and Their Effects on Early-Lactating Females and Offspring Mice.

Activities such as childbirth and breastfeeding can cause severe oxidative stress and inflammatory damage to the mother during early lactation, and can affect animal milk production, and the growth and development of offspring. Trehalose alleviates damage to the body by endowing it with stress resistance. In this study, we used trehalose combined with Lactobacillus plantarum, Bifidobacterium longum, Bacillus subtilis, and Saccharomyces cerevisiae to explore whether dietary intervention can alleviate oxidative stress and inflammatory damage in early lactation and to evaluate the growth ability, acid production ability, antioxidant ability, non-specific adhesion ability, antibacterial ability, and other parameters to determine the optimal combinations and proportions. The results showed that the synbiotics composed of 2.5% trehalose and 1 × 107 cfu/g of Bifidobacterium longum could regulate the gut microbiota, and promote mammary gland development in dams by reducing progesterone (PROG) content in the blood, increasing prolactin (PRL) and insulin-like growth factor-1 (IGF-1) content, enhancing their antioxidant and immune abilities, and effectively increasing the weight and lactation of early lactating dams. In addition, it can also affect the growth of offspring and the development of the intestinal barrier. These results indicate that trehalose synbiotics have great potential in alleviating oxidative stress and inflammatory damage in early lactation.

EFFICACY OF CHROMOLAENA ODORATA SUPPLEMENTATION ON METHOTREXATE -INDUCED NEPHROPATHY AND OXIDATIVE STRESS

We carried out this research to investigate nephro-protective efficacy of Chromolaena odorata aqueous leaf extract on kidney toxicity in Methotrexate (MTX)-induced albino male rats. Thirty (30) wistar male rats spread into five study groups were used. Group I: orally administered normal saline daily and was the normal control. Group II: received C. odorata extract (250 mg/kg B.W.) orally once daily for ten days. Group III: received MTX (7mg/kg B.W.) intraperitoneally from 8th day for three days consecutively. Group IV: received C. odorata extract (250 mg/kg B.W.) orally once daily for ten days and then administered MTX (7 mg/kg B.W.) intraperitoneally from 8th day for three days consecutively. Group V: received Vitamin C (100 mg/kg B.W.) orally once daily for ten days and then administered MTX (7 mg/kg BW) intraperitoneally from 8th day for three days consecutively. 24hours after last treatment and administration, all rats were sacrificed and blood collected in EDTA bottles for hematology or in plain tubes for biochemical analysis. Creatinine and Urea were analyzed in serum. Superoxide Dismutase (SOD), Catalase, Malondialdehyde (MDA) and histopathological analysis was assessed using the kidney tissues. The obtained results revealed that three days of consecutive Methotrexate administration caused a significant rise in kidney function activity as well as severe oxidative damage and oxidative stress shown by a significant rise in Creatinine and Urea, increased level of MDA and a significant drop in SOD and CAT. However, C. odorata attenuated Methotrexate-induced biochemical alterations and oxidative stress in kidney. Also, C. odorata alone or in combination with Methotrexate showed an increase in Packed Cell Volume (PCV), Red Blood Cells (RBC), Haemoglobin (HB), White Blood Cells (WBC) and Platelets level compared to the group administered Methotrexate alone which showed degenerative levels in the analyzed hematological parameters. Showing corroboration, histopathological analysis showed deterioration and collapse of the kidney tubules in rats administered Methotrexate alone whereas C. odorata groups showed considerable nephro-protection and restoration towards normalcy. The results from this study revealed that the C. odorata have a nephro-protective efficacy against Methotrexate-induced kidney toxicity and damage via scavenging of free radicals and stabilization/enhancement of endogenous antioxidant status

A Literature-Based Study of Tardive Dyskinesia- From Pathogenesis to Treatment

: Tardive dyskinesia (TD) is induced by antipsychotic drugs that have dopamineantagonising properties. It frequently causes physical and mental anguish in individuals, lowering their quality of life. Recent research on the aetiology and pathogenesis of TD indicates that genetic predisposition, treatment options, age, sex, and lifestyle factors are among the key risk factors contributing to the development of TD. Various genetic polymorphisms along with severe oxidative stress and other diseased conditions help to precipitate TD while on antipsychotic medications or other dopamine receptor blockers. Individuals diagnosed with schizophrenia are at a higher likelihood of developing TD. The current piece of literature aims to review the probable underlying mechanisms of TD, explore its pathophysiology, address the diagnostic challenges, and present the available treatment options. This comprehensive analysis draws from a range of published peerreviewed publications, presenting the information in a clear and accessible manner.

Ascorbic Acid Enhances the Inhibitory Effect of Theasaponins against Candida albicans

Candida albicans (C. albicans) is a main cause of hospital-acquired fungal infections. Combination therapy is promising as a novel anti-C. albicans strategy because of its better efficacy. Theasaponins are pentacyclic triterpenes in the Camellia genus with multiple biological activities. Our previous studies prove that theasaponins display inhibitory activity against C. albicans. Ascorbic acid (VC) is a vitamin found in many plants that shows potential in combination therapy. However, whether VC enhances the activity of theasaponins remains unclear. In this study, the checkerboard micro-dilution method was used to assess the effect of VC (0–80 mmol/L) on the anti-C. albicans effect of theasaponins (0–1000 μg/mL). Then, the effects of theasaponins (31.25 μg/mL), VC (80 mmol/L), and theasaponins (31.25 μg/mL) + VC (80 mmol/L) on C. albicans planktonic cells and different stages of biofilm formation were assessed. Transcriptomic analysis was conducted to investigate the molecular mechanisms. According to the results, VC enhanced the anti-planktonic and anti-biofilm effect of theasaponins against C. albicans. The minimum inhibitory concentration of theasaponins was significantly decreased and the fungicidal efficiency was increased with the addition of VC. VC remarkably aggravated the suppression of theasaponins with regard to various virulence factors of C. albicans, including adhesion, early biofilm formation, mature biofilm, cell surface hydrophobicity, and phospholipase activity. Compared with the theasaponins or VC groups, the level of intracellular reactive oxygen species was higher, while the levels of mitochondrial membrane potential and adenosine triphosphate were lower in the combination group, suggesting more severe oxidative stress, mitochondrial injury, and energy deficiency. Transcriptomic analysis revealed that the combination predominantly suppressed the pathways of glycolysis, glycerophospholipid metabolism, glutathione metabolism, and cysteine and methionine metabolism. This implied that energy deficiency and redox imbalance were associated with the anti-C. albicans activity of the combination. These results prove that VC enhances the inhibitory effect of theasaponins against C. albicans and that the combination has the potential to be used as a topical antifungal therapy or disinfectant.

An efficient polyaluminum lanthanum silicate coagulant for phosphorus removal and algal bloom control

Due to the advantages of convenient operation and low cost, the use of coagulants is considered a promising method for algae bloom harvesting. However, large dosages, poor algal bloom control rates, and limited phosphorus removal efficiency restrict the usage of most coagulants. In this study, a novel polyaluminum lanthanum silicate (PALS) coagulant was used to remove phosphorus and control algal bloom. The results of isotherm study showed that phosphorus adsorption on PALS fitted Freundlich model, indicating chemisorption and heterogeneous multilayer adsorption were the mechanisms of phosphorus adsorption by PALS. The maximum phosphorus adsorption capacity of PALS by Langmuir model was 485.30mg/g. According to the algal bloom control experiments, the removal of algae and phosphorus was slight at low dosages of PALS (2mg/L and 5mg/L). Short-term control of the algal bloom was observed within 2 days in PALS-10 group, but the bloom recovered afterward, while phosphorus and algae were almost completely removed in PALS-15 and PALS-20. When the dosage of PALS was ≤ 10mg/L, PALS coated the algal cell surfaces and induced mild oxidative stress, showing a little damage to cell integrity. However, the PALS dose over 15mg/L could effectively capture algal cells through charge neutralization, cause severe oxidative stress, strongly upregulate the expression of selected five genes, significantly damage cell integrity, and lead to algae lysis. These findings demonstrated that PALS is a promising coagulant for phosphorus removal and algal bloom control in eutrophic waters, and the minimum threshold of its usage was 15mg/L.

Selenomethionine and Allicin Synergistically Mitigate Intestinal Oxidative Injury by Activating the Nrf2 Pathway.

Oxidative stress frequently contributes to intestinal barrier injury in animals and humans. It was reported that both Selenomethionine (SeMet) and allicin exhibit protective effects against a range of diseases caused by oxidative stress. This study aimed to investigate the synergistic antioxidant effects and underlying mechanisms of SeMet and allicin on a H2O2-induced intestinal barrier injury model using IPEC-J2 cells and mice. The results showed that H2O2 induced severe oxidative stress, including a decrease in cell viability, antioxidant level, migration capacity, and cell integrity. SeMet and allicin exhibited significant synergistic anti-oxidative effects on intestinal epithelial cells. The combined use of SeMet and allicin increased SOD activity, GSH content, and GSH/GSSG ratio while decreasing MDA, NO, and ROS content levels. Furthermore, we found that SeMet and allicin synergistically activated the nuclear factor erythroid-related factor 2 (Nrf2)-NAD(P)H dehydrogenase [quinone] 1 (NQO1) signaling pathway and down-regulated endoplasmic reticulum stress (ER stress)-related proteins. However, the synergistic antioxidative and intestinal barrier protective effects of SeMet and allicin were abolished by Nrf2 inhibitor ML385 in vitro and in vivo. In conclusion, SeMet and allicin synergistically attenuate intestinal barrier injury induced by excessively oxidative stress through the activation of the Nrf2 signaling pathway and inhibition ER stress. These findings support that the combined use of SeMet and allicin could enhance antioxidative properties and alleviate intestinal injury in further clinical practice.

Study on the mechanism of ROS-induced oxidative stress injury and the broad-spectrum antimicrobial performance of nickel ion-doped V6O13 powder

In this study, pure V6O13 and nickel ion-doped V6O13 powders were synthesized by a simple hydrothermal-calcination method, and their broad-spectrum antimicrobial properties and mechanisms were investigated. The crystal structure, morphology, and chemical state of the powders were thoroughly analyzed by XRD, SEM, TEM, XPS, and UV–Vis. Their antimicrobial properties and mechanisms were evaluated by the ring of inhibition, bio-SEM, live-dead cell staining, ROS detection, and protein leakage experiments. The results showed that nickel ion doping modulated the oxygen defects of V6O13, generating more reactive oxygen species and leading to more severe oxidative stress, resulting in a broad-spectrum and highly efficient antimicrobial effect. This study also revealed the antimicrobial mechanism based on oxygen defect -induced ROS production, which caused cellular oxidative stress damage, leading to leakage of intracellular substances and cell death. This study not only demonstrates the potential of V6O13 as an efficient antimicrobial agent but also provides a strong experimental basis and theoretical support for the engineering design and optimization of novel antimicrobial materials by modulating material defects through ion doping.

Mechanism of biochar in alleviating the inhibition of anaerobic digestion under ciprofloxacin press

The antibiotic ciprofloxacin (CIP), detected in various aqueous environments, has broad-spectrum antimicrobial properties that can severely affect methanogenic performance in anaerobic systems. In this study, a novel strategy to alleviate the inhibition of AD performance under CIP press with the direct addition of biochar (BC) prepared from corn stover was proposed and the corresponding alleviation mechanism was investigated. When the dosage of BC was 5 and 20 g/L, the cumulative methane production in AD could reach 317.9 and 303.0 mL/g COD, and the CIP degradation efficiencies reached 94.1 % and 96.6 %, significantly higher than those of 123.0 mL/g COD and 81.2 % in the Control system. BC avoided excessive reactive oxygen species in anaerobic systems and induced severe oxidative stress response, while protecting the cell membrane and cell wall of microorganisms. Microorganisms could consume and utilize more organic extracellular polymeric substances for their growth and metabolism. When BC was involved in AD, fewer toxic intermediates were generated during CIP biodegradation, reducing acute and chronic toxicity in anaerobic systems. Microbial diversity suggested that BC could enrich functional microorganisms involved in direct interspecies electron transfer like Methanosaeta, norank_f_Bacteroidetes_vadinHA17, JGI-0000079-D21 and Syntrophomonas, thus facilitating the methanogenic process and CIP degradation. Genetic analyses showed that BC could effectively upregulate functional genes related to the conversion of butyrate-to-acetate and acetyl-to-methane under CIP stress, while functional gene abundance associated with CIP degradation enhanced partially, about encoding translocases, oxidoreductases, lyases, and ligases. Therefore, BC can be added to AD under CIP press to address its inhibited methanogenic performance.

Immune response for acute Aeromonas hydrophila infection in two distinct color morphs of northern snakehead, Channa argus

To compare and analyze the differences in immunological response between the two color morphs of Channa argus, a fish cohort was divided into four groups: black C argus + PBS (B-PBS), black C argus + Aeromonas hydrophila (B-Ah), white C. argus + PBS (W-PBS), and white C. argus + A hydrophila (W-Ah). The B-PBS and W-PBS groups received 100 μL PBS, while the B-Ah and W-Ah groups received 3.6 × 105 CFU/mL A. hydrophila in the same volume. The death rate in each group was noted, changes in plasma biochemical indicators and the expression of liver immune-related genes were examined, and transcriptome techniques were used to compare the differences between the two colors of C. argus following stress. No mortality occurred in the B-PBS and W-PBS groups. Mortality in the W-Ah and B-Ah groups showed an upward and then downward trend after A. hydrophila injection. The highest mortality occurred within 24 h and was higher in the W-Ah group than in the B-Ah group. MDA levels in the B-Ah and W-Ah groups increased and then decreased, while SOD and T-AOC showed the reverse tendency. The W-Ah and W-PBS groups differed significantly in MDA at 3, 12, and 24 h, SOD from 6 to 96 h, and T-AOC between 6 and 48 h. Plasma MDA and T-AOC levels at 12 h and SOD levels at 24 and 48 h differed significantly between the B-PBS and B-Ah groups. In both the W-Ah and B-Ah groups, the expression levels of IL-1β and IL-8 in the liver showed a temporal pattern with an initial increase followed by a decrease, reaching peak levels after 24 h, while IL-10 showed the reverse pattern. Transcriptome analysis of the liver revealed significant differences between the two C. argus colors. Differential genes in black C. argus were mainly enriched in steroid biosynthesis, glycolysis/gluconeogenesis, and glutathione and propanoate metabolism pathways 24 h after infection. In contrast, differential genes in white C. argus were mainly enriched in pathways such as oxidative phosphorylation, pancreatic secretion, and protein digestion and absorption 24 h after infection. After A. hydrophila infection, white C. argus had higher mortality, more severe oxidative stress and inflammatory responses, and lower antioxidant capacity than black C. argus.

The bifunctional impact of polylactic acid microplastics on composting processes and soil-plant systems: Dynamics of microbial communities and ecological niche competition

Although extensive research has been conducted on the environmental impact of microplastics (MPs), their effects on microorganisms during the composting process and on the compost-soil system remain unclear. Our research investigates the microbial response to polylactic acid microplastics (PLAMPs) during aerobic composting and examines how compost enriched with PLAMPs affects plants. Our findings reveal that PLAMPs play a dual role in the composting process, influencing microorganisms differently depending on the composting phase. PLAMPs reduce the relative abundance of sensitive bacterial ASVs, specifically those belonging to Limnochordaceae and Enterobacteriaceae, during composting, while increasing the relative abundance of ASVs belonging to Steroidobacteriaceae and Bacillaceae. The impact of PLAMPs on microbial community assembly and niche width was found to be phase-dependent. In the stabilization phase (S5), the presence of PLAMPs caused a shift in the core microbial network from bacterial dominance to fungal dominance, accompanied by heightened microbial antagonism. Additionally, these intricate microbial interactions can be transferred to the soil ecosystem. Our study indicates that composting, as a method of managing PLAMPs, is also influenced by PLAMPs. This influence is transferred to the soil through the use of compost, resulting in severe oxidative stress in plants. Our research is pivotal for devising future strategies for PLAMPs management and predicting the subsequent changes in compost quality and environmental equilibrium.

Toxicological effects, absorption and biodegradation of bisphenols with different functional groups in Chromochloris zofingiensis

Bisphenols (BPs) are recognized as endocrine disrupting compounds and have garnered increasing attention due to their widespread utilization. However, the varying biological toxicities and underlying mechanisms of BPs with different functional groups remain unknown. In the present study, the toxic effects of four BPs (BPA, BPS, BPAF, and TBBPA) on a photosynthetic microalgae Chromochloris zofingiensis were compared. Results showed that halogen-containing BPs exhibited higher cellular uptake, leading to more severe oxidative stress, lower photosynthetic efficiency, and greater accumulation of starch and lipids. Specifically, TBBPA with bromine groups showed a greater toxicity than BPAF with fluorine groups, possibly due to the incomplete debromination in C. zofingiensis. Transcriptomic analysis revealed that halogen-containing BPs triggered greater number of differentially expressed genes (DEGs), and only 64 common DEGs were found among different BPs, indicating that the effects of BPs with different functional groups varied greatly. Genes involved in endocytosis, peroxisomes, and endoplasmic reticulum protein processing pathways were mostly upregulated across different BPs, while photosynthesis-related genes showed varied expression, possibly due to their distinct functional groups. Additionally, SIN3A, ZFP36L, CHMP, and ATF2 emerged as potential key regulatory genes. Overall, this study thoroughly explained how functional groups impact the toxicity and biodegradation of BPs in C. zofingiensis.

The preventive effectiveness of Crocus sativus extract in treating lung injuries caused by inhaled paraquat in rats

Ethnopharmacological relevanceThe herbicide paraquat (PQ) is highly toxic, capable of inducing severe lung inflammation and oxidative stress, resulting in lung fibrosis and respiratory failure. Previous research has demonstrated a range of pharmacological effects associated with Crocus sativus. L (Cs) through its anti-inflammatory, antioxidant and immunomodulatory properties. Pharmacological studies support the widespread use of Cs in traditional medicine to treat respiratory disorders such as coughs and asthma. Aim of studyThis study aimed to investigate the preventive impact of Cs extract and pioglitazone (Pio) on lung inflammation, oxidative stress, pathological alterations, and tracheal reactivity induced by inhaled PQ in rats as compared to dexamethasone (Dexa). MethodsThe control (Ctrl) group of rats was administered with saline aerosol, while the remaining six groups received PQ aerosol eight times every other day. The six PQ exposure groups were treated daily during the exposure period to PQ with either; saline alone, low dose Cs, High dose Cs, Pio alone, Pio combined with low dose Cs, or Dexa of 16 days. ResultsIn the PQ group, the levels of superoxide dismutase (SOD), catalase (CAT), and thiol in the bronchoalveolar lavage fluid (BALF) were declined whereas, the levels of MDA, total and differential WBC, and lung tissue levels of tumor necrosis factor (TNF-α) and Interleukin 10 (IL-10), tracheal responsiveness (TR) to methacholine and lung pathological changes were enhanced. The measured variables showed significant improvement in all treated groups, except for a few variables in Cs (L). The combined Cs (L) + Pio showed higher effects than Cs (L) and Pio alone. For all comparisons, p values were <0.05 to <0.001. ConclusionsThe results showed preventive effect of Cs comparable to that of Dexa and the potential additive preventive capabilities of the Cs and Pio indicate that the involvement of the PPARγ receptor is implicated in the effects induced by Cs.

Quercetin activates autophagy in the distal ischemic area of random skin flaps through Beclin1 to enhance the adaptability to energy deficiency

Random flaps are frequently employed in treating substantial skin abnormalities and in surgical tissue-rebuilding interventions. The random flap technique provides flaps of specific dimensions and contours to fit the surgical incision. However, blood supply deficiency and subsequent ischemia-reperfusion injury can cause severe oxidative stress and apoptosis, eventually leading to distal necrosis, which limits the clinical application of the flap. Quercetin (QUE) is primarily found in the glycoside form in many plant parts, such as stem bark, flowers, leaves, buds, seeds, and fruits. Cellular, animal, and clinical studies have demonstrated the antioxidant, anti-apoptosis, anti-inflammatory, and activation of autophagy properties of QUE. In previous studies, high doses of QUE effectively suppressed the survival of human umbilical vein endothelial cells (HUVECs) stimulated by hydrogen peroxide. However, different concentration gradients of QUE on HUVECs revealed a significant protective effect at a concentration of 10 mM. The protective impact of QUE on HUVECs was evaluated using scratch tests, CCK-8 assays, and EDU assays. Simultaneously, a mouse model of random skin flap was created, and the impact of QUE on skin flap survival was examined by intragastric injection. The QUE group showed a significantly larger survival area of the random flap and higher blood flow intensity compared to the control group. Furthermore, the beneficial effects of QUE were reversed by the autophagy inhibitor 3-MA. Therefore, autophagy plays a significant role in the therapeutic benefits of QUE on flap survival.

Functional analysis of the novel mitochondrial tRNATrp and tRNASer(AGY) variants associated with type 2 diabetes mellitus.

Mutations in mitochondrial tRNA (mt-tRNA) genes that result in mitochondrial dysfunction play important roles in type 2 diabetes mellitus (T2DM). We pre-viously reported a large Chinese pedigree with maternally inherited T2DM that harbors novel mt-tRNA Trp A5514G and tRNA Ser(AGY) C12237T variants, however, the effects of these mt-tRNA variants on T2DM progression are largely unknown. To assess the potential pathogenicity of T2DM-associated m.A5514G and m.C12237T variants at genetic, molecular, and biochemical levels. Cytoplasmic hybrid (cybrid) cells carrying both m.A5514G and m.C12237T variants, and healthy control cells without these mitochondrial DNA (mtDNA) variants were generated using trans-mitochondrial technology. Mitochondrial features, including mt-tRNA steady-state level, levels of adenosine triphosphate (ATP), mitochondrial membrane potential (MMP), reactive oxygen species (ROS), mtDNA copy number, nicotinamide adenine dinucleotide (NAD+)/NADH ratio, enzymatic activities of respiratory chain complexes (RCCs), 8-hydroxy-deo-xyguanine (8-OhdG), malondialdehyde (MDA), and superoxide dismutase (SOD) were examined in cell lines with and without these mt-tRNA variants. Compared with control cells, the m.A5514G variant caused an approximately 35% reduction in the steady-state level of mt-tRNA Trp (P < 0.0001); however, the m.C12237T variant did not affect the mt-tRNA Ser(AGY) steady-state level (P = 0.5849). Biochemical analysis revealed that cells with both m.A5514G and m.C12237T variants exhibited more severe mitochondrial dysfunctions and elevated oxidative stress than control cells: ATP, MMP, NAD+/NADH ratio, enzyme activities of RCCs and SOD levels were markedly decreased in mutant cells (P < 0.05 for all measures). By contrast, the levels of ROS, 8-OhdG and MDA were significantly increased (P < 0.05 for all measures), but mtDNA copy number was not affected by m.A5514G and m.C12237T variants (P = 0.5942). The m.A5514G variant impaired mt-tRNA Trp metabolism, which subsequently caused mitochondrial dysfunction. The m.C12237T variant did not alter the steady-state level of mt-tRNA Ser(AGY), indicating that it may be a modifier of the m.A5514G variant. The m.A5514G variant may exacerbate the pathogenesis and progression of T2DM in this Chinese pedigree.

Comparison on stress memory of two Hypnaceae moss species to haze

Abstract Industrialization and the rapid growth of economies have caused severe environmental pollution, which might impact the survival of sensitive species. In this study, we investigated the defense responses of two common mosses with varying anti-haze capacities, Hypnum callichroum and Homomallium incurvatum, in response to simulated haze pollution. Photoprotection and antioxidant mechanisms of both mosses were measured immediately after the first exposure to the haze treatment, followed by the initial recovery stage and again after exposure to secondary stress and secondary recovery. Haze exposure caused severe oxidative stress and photodamage in both H. callichroum and H. incurvatum. Metabolic processes such as photorespiration, the ascorbate–glutathione cycle, and secondary metabolism—which play roles in defense responses—were significantly activated in both moss species after haze treatment. During the recovery following haze stress, H. callichroum exhibited a significant stress memory response, as evidenced by the greater accumulation of several memory substances, including xanthophylls and phenolic acids. However, H. incurvatum did not exhibit a strong stress memory response, which might explain its relatively inferior anti-haze capacity in the natural environment.

Glucose-responsive, self-healing, wet adhesive and multi-biofunctional hydrogels for diabetic wound healing

Diabetic wounds are serious clinical complications which manifest wet condition due to the mass exudate, along with disturbed regulation of inflammation, severe oxidative stress and repetitive bacterial infection. Existing treatments for diabetic wounds remain unsatisfactory due to the lack of ideal dressings that encompass mechanical performance, adherence to moist tissue surfaces, quick repair, and diverse therapeutic benefits. Herein, we fabricated a wet adhesive, self-healing, glucose-responsive drug releasing hydrogel with efficient antimicrobial and pro-healing properties for diabetic wound treatment. PAE hydrogel was constructed with poly(acrylic acid-co-acrylamide) (AA-Am) integrated with a dynamic E-F crosslinker, which consisted of epigallocatechin gallate (EGCG) and 4-(2-acrylamidoethylcarbamoyl)-3-fluorophenylboronic acid (AFPBA). Due to the dynamic crosslinking nature of boronate esters, abundant catechol groups and hydrogen bonding, PAE hydrogel demonstrated excellent mechanical properties with about 1000 % elongation, robust adhesion to moist tissues, fast self-healing, and absorption of biofluids of 10 times of its own weight. Importantly, PAE hydrogel exhibited sustained and glucose-responsive release of EGCG. Together, the bioactive PAE hydrogel had effective antibacterial, antioxidative, and anti-inflammatory properties in vitro, and accelerated diabetic wound healing in rats via reducing tissue-inflammatory response, enhancing angiogenesis, and reprogramming of macrophages. Overall, this versatile hydrogel provides a straightforward solution for the treatment of diabetic wound, and shows potential for other wound-related application scenarios.

Metabolome and Its Mechanism Profiling in the Synergistic Toxic Effects Induced by Co-Exposure of Tenuazonic Acid and Patulin in Caco-2 Cells.

Tenuazonic acid (TeA), usually found in cereals, fruits, vegetables, oil crops, and their products, was classified as one of the highest public health problems by EFSA as early as 2011, but it has still not been regulated by legislation due to the limited toxicological profile. Moreover, it has been reported that the coexistence of TeA and patulin (PAT) has been found in certain agricultural products; however, there are no available data about the combined toxicity. Considering that the gastrointestinal tract is the physiological barrier of the body, it would be the first target site at which exogenous substances interact with the body. Thus, we assessed the combined toxicity (cell viability, ROS, CAT, and ATP) in Caco-2 cells using mathematical modeling (Chou-Talalay) and explored mechanisms using non-targeted metabolomics and molecular biology methods. It revealed that the co-exposure of TeA + PAT (12.5 μg/mL + 0.5 μg/mL) can induce enhanced toxic effects and more severe oxidative stress. Mechanistically, the lipid and amino acid metabolisms and PI3K/AKT/FOXO signaling pathways were mainly involved in the TeA + PAT-induced synergistic toxic effects. Our study not only enriches the scientific basis for the development of regulatory policies but also provides potential targets and treatment options for alleviating toxicities.