Reactive Oxygen Species Scavenger Research Articles

Orally Deliverable Microalgal-Based Carrier with Selenium Nanozymes for Alleviation of Inflammatory Bowel Disease.

Excessive reactive oxygen species (ROS) is a hallmark of both the onset and progression of inflammatory bowel disease (IBD), where a continuous cycle of ROS and inflammation drives the progression of diseases. The design of oral antioxidant nanoenzymes for scavenging ROS has emerged as a promising strategy to intervene in IBD. However, the practical application of these nanoenzymes is limited due to their single catalytical property and significantly impacted by substantial leakage in the upper gastrointestinal tract. This study introduces a novel oral delivery system, SP@CS-SeNPs, combining natural microalgae Spirulina platensis (SP), which possesses superoxide dismutase (SOD)-like activity, with chitosan-functionalized selenium nanoparticles (CS-SeNPs) that exhibit catalase-like activity. The SP@CS-SeNPs system leverages the dual catalytic capabilities of these components to initiate a cascade reaction that first converts superoxide anion radicals (O2•-) into hydrogen peroxide (H2O2), and then catalyzes the decomposition of H2O2 into water and oxygen. This system not only utilizes the resistance of the microalgae carrier to gastric acid and its efficient capture by intestinal villi, thereby enhancing intestinal distribution and retention but also demonstrates significant anti-inflammatory effects and effective repair of the damaged intestinal barrier in a colitis mice model. These results demonstrate that this oral delivery system successfully combines the features of microalgae and nanozymes, exhibits excellent biocompatibility, and offers a novel approach for antioxidant nanozyme intervention in IBD.

Enhanced degradation of exogenetic citrinin by glycosyltransferases in the oleaginous yeast Saitozyma podzolica zwy-2-3

The contamination by the toxin citrinin (CIT), produced by fungi, has been reported in agricultural foods and is known to be nephrotoxic to humans. In this study, we found that CIT could be effectively degraded by the oleaginous yeast Saitozyma podzolica zwy-2-3. Four genes encoding glycosyltransferases (GTs) in S. podzolica zwy-2-3 (SPGTs) were identified by evolutionary and structural analyses. The overexpression of SPGTs enhanced CIT degradation to 0.56 mg/L/h in S. podzolica zwy-2-3 by increasing ATP and glutathione (GSH) contents to oxidize CIT and scavenge reactive oxygen species (ROS). Besides, SPGTs promoted lipid synthesis by 9.3 % of S. podzolica zwy-2-3 under CIT stress. These results suggest that SPGTs in oleaginous yeast play a pivotal role in enhancing CIT degradation and lipid accumulation. These findings provide a valuable basis for the application of GTs in oleaginous yeast to alleviate CIT contamination in agricultural production, which may contribute to food safety.

Hydrogel Microsphere-Encapsulated Bimetallic Nanozyme for Promoting Diabetic Bone Regeneration via Glucose Consumption and ROS Scavenging.

The healing of bone defects among diabetic patients presents a critical challenge due to the pathological microenvironment, characterized by hyperglycemia, excessive reactive oxygen species (ROS) production, and inflammation. Herein, multifunctional composite microspheres, termed GMAP are developed, using a microfluidic technique by incorporating Au@Pt nanoparticles (NPs) and GelMA hydrogel to modulate the diabetic microenvironment for promoting bone regeneration. The GMAP enables the sustained release of Au@Pt NPs, which function as bimetallic nanozymes with dual enzyme-like activities involving glucose oxidase and catalase. The synergistic effect allows for efficient glucose consumption and ROS elimination concurrently. Thus, the GMAP effectively protects the proliferation of bone marrow mesenchymal stem cells (BMSCs) under adverse high-glucose conditions. Furthermore, it also promotes the osteogenic differentiation and paracrine capabilities of BMSCs, and subsequently inhibits inflammation and enhances angiogenesis. In vivo diabetic rats bone defect model, it is demonstrated that GMAP microspheres significantly improve bone regeneration, as verified by micro-computed tomography and histological examinations. This study provides a novel strategy for bone regeneration by modulating the diabetic microenvironment, presenting a promising approach for addressing the complex challenges associated with bone healing in diabetic patients.

HDAC/H3K27ac-mediated transcription of NDUFA3 exerts protective effects on high glucose-treated human nucleus pulposus cells through improving mitochondrial function

Diabetes mellitus (DM) is a well-documented risk factor of intervertebral disc degeneration (IVDD). The current study was aimed to clarify the effects and mechanisms of NADH: ubiquinone oxidoreductase subunit A3 (NDUFA3) in human nucleus pulposus cells (HNPCs) exposed to high glucose. NDUFA3 was overexpressed in HNPCs via lenti-virus transduction, which were co-treated with high glucose and rotenone (a mitochondrial complex I inhibitor) for 48 h. Cell activities were assessed for cell viability, cell apoptosis, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP) ratio, oxygen consumption rate (OCR) and mitochondrial complexes I activities. High glucose decreased cell viability, increased apoptotic cells, increased ROS production, decreased MMP levels and OCR values in HNPCs in a dose-dependent manner. Rotenone co-treatment augmented the high glucose-induced injuries on cell viability, apoptosis, ROS production and mitochondrial function. NDUFA3 overexpression counteracted the high glucose-induced injuries in HNPCs. HDAC/H3K27ac mechanism was involved in regulating NDUFA3 transcription. NDUFA3 knockdown decreased cell viability and increased apoptotic cells, which were reversed by ROS scavenger N-acetylcysteine. HDAC/H3K27ac-mediated transcription of NDUFA3 protects HNPCs against high glucose-induced injuries through suppressing cell apoptosis, eliminating ROS, improving mitochondrial function and oxidative phosphorylation. This study sheds light on candidate therapeutic targets and deepens the understanding of molecular mechanisms behind DM-induced IVDD.

Promoting salt tolerance, growth, and phytochemical responses in coriander (Coriandrum sativum L. cv. Balady) via eco-friendly Bacillus subtilis and cobalt

In plant production, evaluation of salt stress protectants concerning their potential to improve growth and productivity under saline stress is critical. Bacillus subtilis (Bs) and cobalt (Co) have been proposed to optimize salt stress tolerance in coriander (Coriandrum sativum L. cv. Balady) plants by influencing some physiological activities. The main aim of this work is to investigate the response of (Bs) and (Co) as eco-safe salt stress protectants to resist the effect of salinity, on growth, seed, and essential oil yield, and the most important biochemical constituents of coriander produced under salt stress condition. Therefore, in a split-plot factorial experiment design in the RCBD (randomized complete block design), four levels of salinity of NaCl irrigation water (SA) were assigned to the main plots; (0.5, 1.5, 4, and 6 dS m−1); and six salt stress protectants (SP) were randomly assigned to the subplots: distilled water; 15 ppm (Co1); 30 ppm (Co2); (Bs); (Co1 + Bs); (Co2 + Bs). The study concluded that increasing SA significantly reduced coriander growth and yield by 42.6%, which could be attributed to ion toxicity, oxidative stress, or decreased vital element content. From the results, we recommend that applying Bs with Co (30 ppm) was critical for significantly improving overall growth parameters. This was determined by the significant reduction in the activity of reactive oxygen species scavenging enzymes: superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) and non-enzyme: proline by 5, 11.3, 14.7, and 13.8% respectively, while increasing ascorbic acid by 8% and preserving vital nutrient levels and enhancing plant osmotic potential to buffer salt stress, seed yield per plant, and essential oil yield increased by 12.6 and 18.8% respectively. The quality of essential oil was indicated by highly significant quantities of vital biological phytochemicals such as linalool, camphor, and protein which increased by 10.3, 3.6, and 9.39% respectively. Additional research is suggested to determine the precise mechanism of action of Bs and Co's dual impact on medicinal and aromatic plant salt stress tolerance.

Non-enzymatic oxylipin production in a mudflat microphytobenthic biofilm: evidence of a diatom response to light

Microphytobenthos (MPB) are a diatom-dominated microbial community of primary producers that inhabit mudflat sediments. The benthic diatoms display photo-protective strategies to face extreme light variations susceptible to generate cellular oxidative stress. However, oxidative stress induces the production of reactive oxygen species (ROS) that generate oxylipins—oxygenated metabolites of polyunsaturated fatty acids (PUFAs) —which are among the known chemical mediators in diatoms. Non-enzymatically generated oxylipins known as “isoprostanoids” or “isofuranoids” are poorly studied in diatoms. To better understand the roles of the latter in migrational MPB light response, we investigated the effect of different irradiances corresponding to dark (D), low light (LL, 50 and 100 μmol. photons. m−2. s−1PAR), medium light (ML, 250 μmol. photons. m−2. s−1 PAR), and high light (HL, 500, 750, and 1000 μmol. photons. m−2. s−1 PAR) on isoprostanoid production by the biofilm’s organisms. The PUFA precursors of the varying oxylipins evidenced a diatom response to irradiance. Under 1000 PAR, the total amount of isoprotanoids increased, indicating an oxidative stress response. Isoprostanes (IsoPs) and prostaglandins (PGs) characterized HL conditions and evidenced lipid peroxidation, probably linked to the higher generation of ROS by photosynthesis. In contrast, phytoprostanes (PhytoPs) characterized LL and ML, where the ROS scavengers were probably not overwhelmed. This first investigation of non-enzymatic oxylipin production by a microphytobenthic biofilm under different irradiances highlighted the potential of exploring their possible signaling roles related to MPB light responses.

Thiostrepton as a Potential Therapeutic Agent for Hepatocellular Carcinoma.

Due to limited drug efficacy and drug resistance, it is urgent to explore effective anti-liver cancer drugs. Repurposing drugs is an efficient strategy, with advantages including reduced costs, shortened development cycles, and assured safety. In this study, we adopted a synergistic approach combining computational and experimental methods and identified the antibacterial drug thiostrepton (TST) as a candidate for an anti-liver cancer drug. Although the anti-tumor capabilities of TST have been reported, its role and underlying mechanisms in hepatocellular carcinoma (HCC) remain unclear. TST was found here to inhibit the proliferation of HCC cells effectively, arresting the cell cycle and inducing cell apoptosis, as well as suppressing the cell migration. Further, our findings revealed that TST induced mitochondrial impairment, which was demonstrated by destroyed mitochondrial structures, reduced mitochondria, and decreased mitochondrial membrane potential (MMP). TST caused the production of reactive oxygen species (ROS), and the mitochondrial impairment and proliferation inhibition of HCC cells were completely restored by the ROS scavenger N-acetyl-L-cysteine (NAC). Moreover, we discovered that TST induced mitophagy, and autophagy inhibition effectively promoted the anti-cancer effects of TST on HCC cells. In conclusion, our study suggests TST as a promising candidate for the treatment of liver cancers, and these findings provide theoretical support for the further development and potential application of TST in clinical liver cancer therapy.

Highly aligned electroactive ultrafine fibers promote the differentiation of mesenchymal stem cells into Schwann-like cells for nerve regeneration

This study investigates the efficacy of a novel tissue-engineered scaffold for nerve repair and functional reconstruction following injury. Utilizing stable jet electrospinning, we fabricated aligned ultrafine fibers from dopamine and poly(L-lactic acid) (PLLA), further developing a biomimetic, oriented, and electroactive scaffold comprising poly(pyrrole) (PPy), polydopamine (PDA), and PLLA through dual in situ polymerizations. The scaffold demonstrated enhanced cell adhesion and reactive oxygen species (ROS) scavenging capabilities and promoted the differentiation of mesenchymal stem cells (MSCs) into Schwann-like cells, essential for nerve regeneration. In vivo assessments revealed significant peripheral nerve regeneration in 10 mm sciatic nerve defects in rats, with observations made 12 weeks post-transplantation. This included facilitated myelination and increased muscle density on the injured side, leading to improved motor function recovery. Our results suggest that the aligned PPy/PDA/PLLA fibrous scaffold offers a promising approach for promoting the differentiation of MSCs into Schwann-like cells conducive to nerve regeneration and represents a significant advancement in nerve repair technologies. This study provides a foundational basis for future research into tissue-engineered solutions for nerve damage, potentially impacting clinical strategies for nerve reconstruction.

Exploring the potential of nanoparticles-based polydopamine for effective treatment of refractory keratitis: Mild photothermal loop therapy

Keratitis is the leading cause of blindness worldwide. In refractory cases, it can even lead to eyeball enucleation. The critical challenges of refractory keratitis are the drug-resistant bacteria and bacterial biofilms formation. Therefore, we established an innovative therapeutic approach for keratitis based on mild photothermal loop (MPL) therapy. First, we analyzed the bactericidal effect of methicillin-resistant Staphylococcus aureus (MRSA) under various loops and temperature durations to determine the optimal condition. Then, RAN-seq was applied to explore the underlying mechanisms. Additionally, we formulated a dual-purpose polyvinyl alcohol-polydopamine (PDA/PVA) hydrogel system and explored its effects on the reactive oxygen species (ROS) scavenging capability, antibacterial properties, and anti-inflammatory properties in vitro, as well as its effect in vivo. The results indicated substantial bactericidal properties after exposure in four loops, each lasting 10 min at 45 °C. RNA-seq revealed the altered genes related to virulence and biofilm formation. In addition to good photothermal performance, the PDA/PVA system could effectively eliminate MRSA, reduce ROS, inhibit biofilm formation, and decrease inflammatory factors expression. Moreover, the in vivo results demonstrated the potential of MPL for bacterial keratitis. This study serves as the first attempt to use MPL therapy for refractory keratitis, offering a new approach for clinical practice.

Two-step emulsification for the fabrication of homogeneous PCL microspheres encapsulating geniposidic acid with antioxidant properties

The mortality rate of neurological disorders is increasing globally, and natural antioxidant geniposidic acid (GPA) holds great potential in the treatment of neuronal oxidative damage. Nevertheless, its inherent instability constrains its pragmatic utilization. Herein, we introduced a drug delivery system capable of protecting unstable natural active compounds from degradation. Among the various methods for preparing drug-loaded microspheres, the emulsification-solvent evaporation technique is one of the most commonly employed due to its efficiency and simplicity. Nevertheless, this method results in microspheres with heterogeneous particle sizes. To address this limitation, we developed a two-step emulsification method involving stirring and homogenization. Using the biocompatible, synthetic, biodegradable polymer polycaprolactone (PCL) as the drug delivery carrier, we prepared GPA-loaded PCL microspheres via the two-step emulsification method. The results demonstrated that the microspheres possessed uniform particle size (polydispersity index = 0.12), excellent drug loading capacity (∼4.86%), sustained drug release profiles (∼68.55% in 264 h), and biocompatibility (cell viability >85%). The in vitro tests showed that the microspheres exerted antioxidant effects by scavenging reactive oxygen species (ROS) induced by oxidative stress, thereby protecting neuronal cells from oxidative damage. This work presents a promising new approach for the treatment of neuronal oxidative damage.

Enhancing Growth in Vigna radiata through the Inhibition of Charcoal Rot Disease: A Strategic Approach Using Plant Growth-Promoting Rhizobacteria.

Macrophomina phaseolina is a vital seed and soil-borne phytopathogen responsible for substantial crop yield losses. Although various methods exist for managing soil-borne pathogens, such as agronomic practices, chemical treatments, and varietal tolerance, biological control utilizing plant growth-promoting rhizobacteria (PGPR) or their secondary metabolites presents promising avenues. In this study, a screening of 150 isolates from the rhizosphere of Vigna radiata L. was conducted to identify strains capable of promoting host growth and controlling charcoal rot disease. Among the tested isolates, only 15 strains demonstrated the ability to produce plant growth-related metabolites, including indole acetic acid, hydrogen cyanide, ammonia, and lytic enzymes, and solubilize inorganic phosphate. Subsequently, these potent strains were evaluated for their antifungal activity against Macrophomina phaseolina in vitro. Three strains, namely MRP-7 (58% growth inhibition), MRP-12 (55% growth inhibition), and MRP-8 (44% growth inhibition), exhibited the highest percent growth inhibition (PGI.). Furthermore, a pot experiment demonstrated that the selected strains acted as effective growth promoters and ROS (reactive oxygen species) scavengers, and served as potential biocontrol agents, significantly reducing the incidence of charcoal rot disease and improving various agronomic attributes of the host plant. These findings highlight the potential of these strains to be utilized as biofertilizers and biocontrol agents for sustainable agricultural practices.

EP4 receptor agonist CAY10598 upregulates ROS-dependent Hsp90 cleavage in colorectal cancer cells

Prostaglandin E2 (PGE2) interacts with four specific G protein-coupled receptors, namely EP1, EP2, EP3, and EP4, playing a pivotal role in determining the fate of cells. Our previous findings highlighted that stimulating the EP4 receptor with its agonist, CAY10598, triggers apoptosis in colon cancer HCT116 cells via the production of reactive oxygen species (ROS). This process also reduces the phosphorylation of the oncogenic protein JAK2 and leads to its degradation in these cells. In this study, our goal was to explore the pathways through which CAY10598 leads to JAK2 degradation. We focused on Hsp90, a heat shock protein family member known for its role as a molecular chaperone maintaining the stability of several key proteins including EGFR, MET, Akt, and JAK2. Our results show that CAY10598 decreases the levels of client proteins of Hsp90 in HCT116 cells, an effect reversible by pretreatment with the ROS scavenger N-acetyl cysteine (NAC) or the proteasome inhibitor MG132, indicating that the degradation is likely driven by ROS. Furthermore, we observed that CAY10598 cleaves both α and β isoforms of Hsp90, the process inhibited by NAC. Inhibition of EP4 with the antagonist GW627368x not only prevented the degradation of Hsp90 client proteins but also the cleavage of Hsp90 itself in CAY10598-treated HCT116 cells. Additionally, CAY10598 suppressed the growth of HCT116 cells implanted in mice. Our findings reveal that CAY10598 induces apoptosis in cancer cells by a novel mechanism involving the ROS-dependent cleavage of Hsp90, thereby inhibiting the function of crucial Hsp90 client proteins.

Prolonged, staged, and self-regulated methotrexate release coupled with ROS scavenging in an injectable hydrogel for rheumatoid arthritis therapy

Rheumatoid arthritis (RA) remains a formidable healthcare challenge due to its chronic nature and potential for irreversible joint damage. Methotrexate (MTX) is a cornerstone treatment for RA but carries significant risks of adverse effects with repeated administration, necessitating the exploration of alternative delivery methods. Injectable hydrogels loaded with MTX for intra-articular injection present a promising solution, allowing sustained drug release directly into affected joints. However, current hydrogel systems often lack extended therapeutic periods and the ability to self-regulate drug release according to disease state. Furthermore, RA is associated with excessive production of reactive oxygen species (ROS), which exacerbates inflammation and joint damage. Herein, we developed an advanced injectable hydrogel (MPDANPs/MTX HA-PEG gel) based on “bio-orthogonal chemistry”, combining hyaluronic acid and polyethylene glycol (PEG) matrices co-loaded with mesoporous polydopamine nanoparticles (MPDANPs) and MTX. MPDANPs/MTX HA-PEG gel achieved prolonged, staged, and self-regulated MTX release, coupled with ROS scavenging capabilities for enhanced therapeutic efficacy. Due to its optimized MTX release behavior and significant ROS scavenging function, MPDANPs/MTX HA-PEG gel exhibited potent anti-inflammatory effects in collagen-induced arthritis (CIA) rats following a single intra-articular injection. Our findings highlight the potential of MPDANPs/MTX HA-PEG gel as a highly effective treatment strategy for RA, offering a promising avenue for improving patient outcomes.

Rhodium nanozyme mitigates RPE degeneration and preserves vision in age-related macular degeneration via antioxidant and anti-inflammatory mechanisms

Age-related macular degeneration (AMD) is the leading cause of blindness among elderly people worldwide. However, there are currently no effective treatments for AMD. Oxidative stress-induced retinal pigment epithelium (RPE) degeneration and the inflammatory response are the main causes of AMD. In this study, a polyethylene glycol (PEG)-coated rhodium nanozyme (PEG-RhZ) with excellent reactive oxygen species (ROS) and reactive nitrogen species (RNS) elimination capability was synthesized for the treatment of AMD. PEG-RhZs protected RPE cell viability and barrier function upon exposure to oxidative stress stimuli. Additionally, microglial migration and iNOS, IL-1β and TNF-α expression were inhibited by PEG-RhZs. In the acute phase of the AMD model, PEG-RhZs significantly alleviated RPE oxidative damage and inhibited microglial activation. In the late stage of the AMD model, PEG-RhZs reduced photoreceptor loss and improved vision impairment. Furthermore, PEG-RhZs showed good biocompatibility and stability both in vitro and in vivo. Collectively, our findings suggest the therapeutic potential of PEG-RhZs for AMD treatment.STATEMENT OF SIGNIFICANCE: AMD is a kind of retinal degenerative disease that poses heavy health burden globally. PEG-RhZs exhibiting robust ROS and RNS scavenging capabilities have shown promise in safeguarding retinal pigment epithelium (RPE) from oxidative stress, suppressing microglia activation and the secretion of pro-inflammatory molecules, mitigating loss of retinal photoreceptor cells, and ameliorating visual impairment. The commendable antioxidant properties, biological safety, and biostability of PEG-RhZs offer valuable insights for the clinical management of AMD.

TUBB4A Inhibits Glioma Development by Regulating ROS-PINK1/Parkin-Mitophagy Pathway.

Glioma is a refractory malignant tumor with a powerful capacity for invasiveness and a poor prognosis. This study aims to investigate the role and mechanism of tubulin beta class IVA (TUBB4A) in glioma progression. The differential expression of TUBB4A in humans was obtained from databases and analyzed. Glioma cells U251-MG and U87-MG were intervened by pcDNA3.1(+) and TUBB4A overexpression plasmid. MTT, CCK8, LDH, wound healing, transwell, and western blotting were used to explore whether TUBB4A participates in the development of glioma. Reactive oxygen species (ROS) were detected by the DCFH-DA probe. Mitochondrial membrane potential (MMP) was examined by JC-1. It was found thatTUBB4A expression level correlated with tumor grade, IDH1 status,1p/19q status, and poor survival in glioma patients. In addition, TUBB4A overexpression inhibited the proliferation, migration, and invasion of U251-MG and U87-MG, while increasing the degree of apoptosis. Notably, TUBB4A overexpression promotes ROS generation and MMP depolarization, and induces mitophagy through the PINK1/Parkin pathway. Interestingly, mitochondria-targeted ROS scavenger reversed the effect of TUBB4A overexpression on PINK1/Parkin expression and mitophagy, whereas mitophagy inhibitor did not affect ROS production. And the effect of TUBB4A overexpression on mitophagy and glioma progression was consistent with that of PINK1/Parkin agonist. In conclusion,TUBB4A is a molecular marker for predicting the prognosis of glioma patients and an effective target for inhibiting glioma progression by regulating ROS-PINK1/Parkin-mitophagy pathway.

Apple vacuolar sugar transporters regulated by MdDREB2A enhance drought resistance by promoting accumulation of soluble sugars and activating ABA signaling

Abstract Soluble sugars are not only an important contributor to fruit quality, but also serve as the osmotic regulators in response to abiotic stresses. Early drought stress promotes sugar accumulation, while specific sugar transporters govern the cellular distribution of the sugars. Here, we show that apple plantlets accumulate soluble sugars in leaf tissues under drought stress. Transcriptional profiling of stressed and control plantlets revealed differential expression of several plasma membrane- or vacuolar membrane-localized sugar transporter genes. Among these, four previously identified vacuolar sugar transporter (VST) genes (MdERDL6–1, MdERDL6–2, MdTST1 and MdTST2) showed higher expression under drought, suggesting their roles in response to drought stress. Promoter cis-elements analyses, yeast one-hybrid and dual-luciferase tests confirmed that the drought-induced transcription factor MdDREB2A could promote the expression of MdERDL6–1/−2 and MdTST1/2 by binding to their promoter regions. Moreover, overexpressing of each of these four MdVSTs alone in transgenic apple or Arabidopsis plants accumulated more soluble sugars and abscisic acid, and enhanced drought resistance. Furthermore, apple plants overexpressing MdERDL6–1 also showed reduced water potential, facilitated stomatal closure and reactive oxygen species scavenging under drought condition compared to control plants. Overall, our results suggest a potential strategy to enhance drought resistance and sugar accumulation in fruits through manipulating the genes involved in vacuolar sugar transport.

Copper tannate nanosheets-embedded multifunctional coating for antifouling and photothermal bactericidal applications

Implant-associated infections (IAIs), triggered by pathogenic bacteria, are a leading cause of implant failure. The design of functionalized coatings on biomedical materials is crucial to address IAIs. Herein, a multifunctional coating with good antifouling effect and antibacterial photothermal therapy (aPTT) performance was developed. The copper tannate nanosheets (CuTA NSs) were formed via coordination bonding of Cu2+ ions and tannic acid (TA). The CuTA NSs were then integrated into the TA and poly(ethylene glycol) (PEG) network to form the TCP coating for deposition on the titanium (Ti) substrates via surface adhesion of TA and gravitational effect. The resulting Ti-TCP substrate exhibited good antifouling property, reactive oxygen species (ROS) scavenging capability and cytocompatibility. The TCP coating exhibited antifouling efficacy in conjunction with aPTT, curtailing the surface adhesion and biofilm formation of pathogens, such as Staphylococcus aureus and Escherichia coli. Notably, the Ti-TCP substrate also exhibited the ability to prevent bacterial infection in vivo in a subcutaneous implantation model. The present work demonstrated a promising approach in designing high-performance antifouling and photothermal bactericidal coatings to combat IAIs.

Alginate-based injectable probiotic/squid ink composite hydrogels for accelerated wound healing of MRSA infected abscess through photothermally synergized probiotic therapy

Methicillin-resistant Staphylococcus aureus (MRSA) infections pose great challenges to skin wound care due to the severe drug resistance developed in the clinic. There is an urgent need to exploit next-generation bactericidal therapeutics that are both antibiotic-free and multifunctional for enhanced wound healing. Herein, we designed a Ca2+-crosslinked alginate hydrogel (EcNSIN@Alg) containing two naturally derived bioactive components, probiotics Escherichia coli Nissle1917 (EcN) and Squid ink nanoparticles (SIN), to treat MRSA-infected wounds. The injectable composite hydrogel displayed excellent biocompatibility, photothermal antibacterial activity, and reactive oxygen species (ROS) scavenging property. Importantly, the probiotic EcN can enhance the photothermal SIN to promote immune regulatory activities, shifting pro-inflammatory macrophages (M1) to anti-inflammatory macrophages (M2). In an MRSA-infected abscess model, EcNSIN@Alg can reduce the expression level of wound inflammatory factors and ROS, increase the number of anti-inflammatory macrophages, accelerate collagen deposition and promote wound healing. This work offers a new perspective on developing safe, antibiotic-free, multifunctional bactericides using fully bioderived materials, with potential applications in clinical practice.

PM2.5 Induces Pyroptosis via Activation of the ROS/NF-κB Signaling Pathway in Bronchial Epithelial Cells.

Background and Objectives: Fine particulate matter, PM2.5, is becoming a major threat to human health, particularly in terms of respiratory diseases. Pyroptosis is a recently discovered and distinct form of cell death, characterized by pore formation in the cell membrane and secretions of proinflammatory cytokines. There has been little research on the effect of PM2.5 on pyroptosis, especially in airway epithelium. We investigated whether PM2.5-related oxidative stress induces pyroptosis in bronchial epithelial cells and defined the underlying mechanisms. Materials and Methods: After exposure of a BEAS-2B cell line to PM2.5 concentration of 20 µg/mL, reactive oxygen species (ROS) levels, parameters related to pyroptosis, and NF-κB signaling were measured by Western blotting, immunofluorescence, and ELISA (Enzyme-linked immunosorbent assay). Results: PM2.5 induced pyroptotic cell death, accompanied by LDH (Lactate dehydrogenase) release and increased uptake of propidium iodide in a dose-dependent manner. PM2.5 activated the NLRP3-casp1-gasdermin D pathway, with resulting secretions of the proinflammatory cytokines IL-1β and IL-18. The pyroptosis activated by PM2.5 was alleviated significantly by NLRP3 inhibitor. In PM2.5-exposed BEAS-2B cells, levels of intracellular ROS and NF-κB p65 increased. ROS scavenger inhibited the expression of the NLRP3 inflammasome, and the NF-κB inhibitor attenuated pyroptotic cell death triggered by PM2.5 exposure, indicating that the ROS/NF-κB pathway is involved in PM2.5-induced pyroptosis. Conclusions: These findings show that PM2.5 exposure can cause cell injury by NLRP3-inflammasome-mediated pyroptosis by upregulating the ROS/NF-κB pathway in airway epithelium.

Tcap deficiency impedes striated muscle function and heart regeneration with elevated ROS and autophagy

Telethonin/titin-cap (TCAP) encodes a Z-disc protein that plays important roles in sarcomere/T-tubule interactions, stretch-sensing and signaling. Mutations in TCAP are associated with muscular dystrophy and cardiomyopathy; however, the complete etiology and its roles in myocardial infarction and regeneration are not fully understood. Here, we generated tcap gene knockout zebrafish with CRISPR/Cas9 technology and observed muscular dystrophy-like phenotypes and abnormal mitochondria in skeletal muscles. The stretch-sensing ability was inhibited in tcap‐/‐ mutants. Moreover, Tcap deficiency led to alterations in cardiac morphology and function as well as increases in reactive oxygen species (ROS) and mitophagy. In addition, the cardiac regeneration and cardiomyocyte proliferation ability of tcap‐/‐ mutants were impaired, but these impairments could be rescued by supplementation with ROS scavengers or autophagy inhibitors. Overall, our study demonstrates the essential roles of Tcap in striated muscle function and heart regeneration. Additionally, elevations in ROS and autophagy may account for the phenotypes resulting from Tcap deficiency and could serve as novel therapeutic targets for muscular dystrophy and cardiomyopathy.