Reactive Oxygen Species Scavenging Effects Research Articles

Hyaluronic acid methacrylate/Pluronic F127 hydrogel enhanced with spermidine-modified mesoporous polydopamine nanoparticles for efficient synergistic periodontitis treatment

Bacterial infection, reactive oxygen species (ROS) accumulation, and persistent inflammation pose significant challenges in the treatment of periodontitis. However, the current single-modal strategy makes achieving the best treatment effect difficult. Herein, we developed a double-network hydrogel composed of Pluronic F127 (PF-127) and hyaluronic acid methacrylate (HAMA) loaded with spermidine-modified mesoporous polydopamine nanoparticles (M@S NPs). The PF-127/HAMA/M@S (PH/M@S) hydrogel was injectable and exhibited thermosensitivity and photocrosslinking capabilities, which enable it to adapt to the irregular shape of periodontal pockets. In vitro, the PH/M@S displayed multiple therapeutic effects, such as photothermal antibacterial activity, a high ROS scavenging capacity, and anti-inflammatory effects, which are beneficial for the multimodal treatment of periodontitis. The underlying anti-inflammatory mechanism of this hydrogel involves suppression of the extracellular regulated protein kinase 1/2 and nuclear factor kappa-B signalling pathways. Furthermore, in lipopolysaccharide-stimulated macrophage conditioned media, the PH/M@S effectively restored the osteogenic differentiation potential. In a rat model of periodontitis, the PH/M@S effectively reduced the bacterial load, relieved local inflammation and inhibited alveolar bone resorption. Collectively, these findings highlight the versatile functions of the PH/M@S, including photothermal antibacterial activity, ROS scavenging, and anti-inflammatory effects, indicating that this hydrogel is a promising multifunctional filling material for the treatment of periodontitis.

Silk-enriched hydrogels with ROS-scavenging dendrimers for advanced wound care

This study explores the development of novel hydrogel composites for wound care, incorporating silk fibroin and reactive oxygen species (ROS)-scavenging dendrimers into a polyvinyl alcohol (PVA) matrix. Utilizing ionizing gamma radiation, we fabricated pristine PVA, silk-PVA (SPVA) binary, and dendrimer-silk-PVA (DSPVA) ternary hydrogel composites, with their composition confirmed via UV–visible absorption spectroscopy. Fourier-transform infrared (FTIR) and Raman spectroscopy analyses indicated complex interactions between the hydrogel components, enhancing their structural and biocompatible properties. Scanning electron microscopy (SEM) analysis revealed that dendrimer integration in DSPVA hydrogels significantly increased surface porosity, vital for tissue regeneration. The DSPVA hydrogels demonstrated effective ROS scavenging, reducing hydrogen peroxide (H2O2) concentrations by approximately 70 % within 24 h. In vivo wound healing studies in a diabetic mouse model showed enhanced wound closure in the DSPVA group, with a relative wound area reduction to 30 ± 4.3 % on day 10, compared to 56.5 ± 2.7 % in the control group. By the 16th day, the treated group exhibited near-complete wound contraction, markedly outperforming the control group. These findings underscore the potential of DSPVA hydrogels in diabetic wound management, combining silk fibroin's mechanical support, dendrimers' antioxidative properties, and PVA's structural benefits. Thus, DSPVA hydrogels are promising candidates for advanced wound care applications.

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.

Curcumin loaded hydrogel with double ROS-scavenging effect regulates microglia polarization to promote poststroke rehabilitation

Cyclodextrins are used to include curcumin to form complex, which is subsequently loaded into a reactive oxygen species (ROS) responsive hydrogel (Cur gel). This gel exhibits a dual ROS scavenging effect. The gel can neutralize extracellular ROS to lead to a ROS-sensitive curcumin release. The released curcumin complex can eliminate intracellular ROS. Furthermore, the Cur gel effectively downregulates the expression of CD16 and IL-1β while upregulating CD206 and TGF-β in oxygen and glucose-deprived (OGD) BV2 cells. Additionally, it restores the expression of synaptophysin and PSD95 in OGD N2a cells. Upon injection into the stroke cavity, the Cur gel reduces CD16 expression and increases CD206 expression in the peri-infarct area of stroke mice, indicating an in vivo anti-inflammatory polarization of microglia. Colocalization studies using PSD95 and VGlut-1 stains, along with Golgi staining, reveal enhanced neuroplasticity. As a result, stroke mice treated with the Cur gel exhibit the most significant motor function recovery. Mechanistic investigations demonstrate that the released curcumin complex scavenges ROS and suppresses the activation of the ROS-NF-κB signaling pathway by inhibiting the translocation of p47-phox and p67-phox to lead to anti-inflammatory microglia polarization. Consequently, the Cur gel exhibits promising potential for promoting post-stroke rehabilitation in clinics.

Polyphosphazene Microparticles with High Free Radical Scavenging Activity for Skin Photoprotection.

Ultraviolet (UV) filters are the core ingredients in sunscreens and protect against UV-induced skin damage. Nevertheless, their safety and effectiveness have been questioned in terms of their poor photostability, skin penetration, and UV-induced generation of deleterious reactive oxygen species (ROS). Herein, an organic UV filter self-framed microparticle sunblock was exploited, in which quercetin (QC) and hexachlorocyclotriphosphazene (HCCP) were self-constructed into microparticles (HCCP-QC MPs) by facile precipitation polymerization without any carriers. HCCP-QC MPs could not only significantly extend the UV shielding range to the whole UV region but also remarkably reduce UV-induced ROS while avoiding direct skin contact and the resulting epidermal penetration of small-molecule QC. Meanwhile, HCCP-QC MPs possess a high QC-loading ability (697 mg g-1) by QC itself as the microparticles' building blocks. In addition, there is no leakage issue with small molecules due to its covalently cross-linked structure. In vitro and vivo experiments also demonstrated that the HCCP-QC MPs have excellent UV protection properties and effective ROS scavenging ability without toxicity. In summary, effective UV-shielding and ROS scavenging ability coupled with excellent biocompatibility and nonpenetration of small molecules make it a broad prospect in skin protection.

Glycopeptide-based multifunctional nanofibrous hydrogel that facilitates the healing of diabetic wounds infected with methicillin-resistant Staphylococcus aureus

Diabetic wound management remains a significant challenge in clinical care due to bacterial infections, excessive inflammation, presence of excessive reactive oxygen species (ROS), and impaired angiogenesis. The use of multifunctional wound dressings has several advantages in diabetic wound healing. Moreover, the balance of macrophage polarization plays a crucial role in promoting skin regeneration. However, few studies have focused on the development of multifunctional wound dressings that can regulate the inflammatory microenvironment and promote diabetic wound healing. In this study, an extracellular matrix-inspired glycopeptide hydrogel composed of glucomannan and polypeptide was proposed for regulating the local microenvironment of diabetic wound sites. The hydrogel network, which was formed via Schiff base and hydrogen bonding interactions, effectively inhibited inflammation and promoted angiogenesis during wound healing. The hydrogels exhibited sufficient self-healing ability and had the potential to scavenge ROS and to activate the mannose receptor (MR), thereby inducing macrophage polarization toward the M2 phenotype. The experimental results confirm that the glycopeptide hydrogel is an effective tool for managing diabetic wounds by showing antibacterial, ROS scavenging, and anti-inflammatory effects, and promoting angiogenesis to facilitate wound repair and skin regeneration in vivo. Statement of Significance•The designed wound dressing combines the advantage of natural polysaccharide and polypeptide.•The hydrogel promotes M2-polarized macrophages, antibacterial, scavenges ROS, and angiogenesis.•The multifunctional glycopeptide hydrogel dressing could accelerating diabetic wound healing in vivo.

ROS Scavenging Effect of Selected Isoflavones in Provoked Oxidative Stress Conditions in Human Skin Fibroblasts and Keratinocytes.

Isoflavones, belonging to polyphenolic compounds, show structural similarity to natural estrogens, and in this context, they have been extensively studied. Some of them are also applied as cosmetic additives; however, little is known regarding their effects on skin cells. In this investigation, common isoflavones, including genistein, daidzein, glycitein, formononetin, and biochanin A, as well as coumestrol, were evaluated for antioxidant activity and their impact on human skin fibroblasts and keratinocytes. Antioxidant effects were assessed using DPPH, ABTS, and FRAP tests, and the ability to scavenge reactive oxygen species (ROS) was tested in cells with H2O2-provoked oxidative stress. The impact on the activity of antioxidant enzymes (SOD, CAT, GSH) and lipid peroxidation (MDA) was also explored. As shown by Alamar Blue and neutral red uptake assays, the compounds were not toxic within the tested concentration range, and formononetin and coumestrol even demonstrated a stimulatory effect on cells. Coumestrol and biochanin A demonstrated significant antioxidative potential, leading to a significant decrease in ROS in the cells stimulated by H2O2. Furthermore, they influenced enzyme activity, preventing depletion during induced oxidative stress, and also reduced MDA levels, demonstrating protection against lipid peroxidation. In turn, genistein, daidzein, and glycitein exhibited low antioxidant capacity.

A ferrocene-based hydrogel as flexible electrochemical biosensor for oxidative stress detection and antioxidation treatment

Real-time sensing of reactive oxygen species (ROS) and timely scavenging of excessive ROS in physiological environments are critically important in the diagnosis and prevention of ROS-related diseases. To solve the mismatch problem between conventional rigid ROS biosensors and biological tissues in terms of both modulus and composition, here, we present a flexible ferrocene-based hydrogel biosensor designed for oxidative stress detection and antioxidation treatment. The hydrogel was fabricated through a supramolecular assembly of ferrocene-grafted polyethylenimine (PEI-Fc), sodium alginate (SA), and polyvinyl alcohol (PVA). Multiple non-covalent interactions, including electrostatic interactions between PEI-Fc and SA, hydrophobic interactions and π–π stacking among ferrocene groups, and the PVA crystalline domain, synergistically improve the mechanical properties of the PVA/SA/PEI-Fc hydrogel. The flexible PVA/SA/PEI-Fc hydrogel biosensor exhibited a broad detection range for hydrogen peroxide (H2O2), from 0 to 120 μM, using the differential pulse voltammetry method. Furthermore, the hydrogel demonstrated effective ROS scavenging and oxygen generation performance, desirable biocompatibility, and satisfactory antibacterial activity, making it suitable for biological interfaces. In vitro studies revealed that the PVA/SA/PEI-Fc hydrogel could monitor H2O2 concentration in the proximity of inflammatory cells, and effectively scavenge ROS to protect cells from oxidative stress damage. This all-in-one multifunctional hydrogel, integrating both sensing and treatment functions, holds great promise for clinical applications in the diagnosis and management of ROS-related diseases.

Immunomodulatory poly(L-lactic acid) nanofibrous membranes promote diabetic wound healing by inhibiting inflammation, oxidation and bacterial infection.

Given the significant impact on human health, it is imperative to develop novel treatment approaches for diabetic wounds, which are prevalent and serious complications of diabetes. The diabetic wound microenvironment has a high level of reactive oxygen species (ROS) and an imbalance between proinflammatory and anti-inflammatory cells/factors, which hamper the healing of chronic wounds. This study aimed to develop poly(L-lactic acid) (PLLA) nanofibrous membranes incorporating curcumin and silver nanoparticles (AgNPs), defined as PLLA/C/Ag, for diabetic wound healing. PLLA/C/Ag were fabricated via an air-jet spinning approach. The membranes underwent preparation and characterization through various techniques including Fourier-transform infrared spectroscopy, measurement of water contact angle, X-ray photoelectron spectroscopy, X-ray diffraction, scanning electron microscopy, assessment of in vitro release of curcumin and Ag+, testing of mechanical strength, flexibility, water absorption and biodegradability. In addition, the antioxidant, antibacterial and anti-inflammatory properties of the membranes were evaluated in vitro, and the ability of the membranes to heal wounds was tested in vivo using diabetic mice. Loose hydrophilic nanofibrous membranes with uniform fibre sizes were prepared through air-jet spinning. The membranes enabled the efficient and sustained release of curcumin. More importantly, antibacterial AgNPs were successfully reduced in situ from AgNO3. The incorporation of AgNPs endowed the membrane with superior antibacterial activity, and the bioactivities of curcumin and the AgNPs gave the membrane efficient ROS scavenging and immunomodulatory effects, which protected cells from oxidative damage and reduced inflammation. Further results from animal studies indicated that the PLLA/C/Ag membranes had the most efficient wound healing properties, which were achieved by stimulating angiogenesis and collagen deposition and inhibiting inflammation. In this research, we successfully fabricated PLLA/C/Ag membranes that possess properties of antioxidants, antibacterial agents and anti-inflammatory agents, which can aid in the process of wound healing. Modulating wound inflammation, these new PLLA/C/Ag membranes serve as a novel dressing to enhance the healing of diabetic wounds.

In Vitro Investigation of Antioxidant and Antidiabetic Properties of Phenolic-Rich Extract from Stingless Bee Honey (Heterotrigona itama)

Introduction: The increase of Type 2 diabetes mellitus has prompted numerous research toward finding an alternative to manage the disease through the oxidant-antioxidant balance, mainly through bioactive compounds in natural products. This study explored the antioxidant and antidiabetic properties of phenolic-rich extract (PRE) from Stingless bee honey (SBH) (Heterotrigona itama) as therapeutic agent to restore the redox balance. Methods: The total phenolic content (TPC), total flavonoid content (TFC) and antioxidant assays of PRE and SBH, were determined to provide preliminary insight into the sample’s antioxidant properties, followed by high-performance liquid chromatography analysis of PRE. The antidiabetic potential of PRE and SBH were determined based on their inhibition against α-amylase and α-glucosidase enzymes. The cytotoxicity analysis of PRE was conducted on 3T3-L1 adipocytes and L6 muscle cells before the glucose uptake and cellular antioxidant analyses were performed on both cell lines, respectively. Results: PRE yielded higher TPC, TFC and antioxidant activities than SBH. The phytochemical profile of PRE comprises gallic acid, myricetin, kaempferol, epicatechin, chlorogenic acid, quercetin, syringic acid, and cinnamic acid. The results from carbohydrate enzymatic inhibitory assays collectively suggested that PRE exhibited more robust antidiabetic activities than SBH. PRE showed good glucose uptake stimulating and reactive oxygen species scavenging effects in those cell lines. Conclusion: Overall, PRE from SBH showed higher carbohydrate enzymatic inhibition, glucose uptake, and protection against intracellular oxidative stress, primarily due to its high antioxidant content and may serve as an alternative therapeutic agent for managing T2DM.

Synergistic action of Pseudomonas fluorescens with melatonin attenuates salt toxicity in mustard by regulating antioxidant system and flavonoid profile

AbstractSalt stress is an alarming abiotic stress that reduces mustard growth and yield. To attenuate salt toxicity effects, plant growth‐promoting rhizobacteria (PGPR) offers a sustainable approach. Among the various PGPR, Pseudomonas fluorescens (P. fluorescens NAIMCC‐B‐00340) was chosen for its salt tolerance (at 100 mM NaCl) and for exhibiting various growth‐promoting activities. Notably, P. fluorescens can produce auxin, which plays a role in melatonin (MT) synthesis. Melatonin is a pleiotropic molecule that acts as an antioxidant to scavenge reactive oxygen species (ROS), resulting in stress reduction. Owing to the individual role of PGPR and MT in salt tolerance, and their casual nexus, their domino effect was investigated in Indian mustard under salt stress. The synergistic action of P. fluorescens and MT under salt stress conditions was found to enhance the activity of antioxidative enzymes and proline content as well as promote the production of secondary metabolites. This led to reduced oxidative stress following effective ROS scavenging, maintained photosynthesis, and improved growth. In mustard plants treated with MT and P. fluorescens under salt stress, eight flavonoids showed significant increase. Kaempferol and cyanidin showed the highest concentrations and are reported to act as antioxidants with protective functions under stress. Thus, we can anticipate that strategies involved in their enhancement could provide a better adaptive solution to salt toxicity in mustard plants.In conclusion, the combination of P. fluorescens and MT affected antioxidant metabolism and flavonoid profile that could be used to mitigate salt‐induced stress and bolster plant resilience.

Functionalized Cerium Dioxide Nanoparticles with Antioxidative Neuroprotection for Alzheimer's Disease.

Oxidative stress induced reactive oxygen species (ROS) and aggregation of amyloid β (Aβ) in the nervous system are significant contributors to Alzheimer's disease (AD). Cerium dioxide and manganese oxide are known as to be effective and recyclable ROS scavengers with high efficiency in neuroprotection. A hollow-structured manganese-doped cerium dioxide nanoparticle (LMC) was synthesized for loading Resveratrol (LMC-RES). The LMC-RES were characterized by TEM, DLS, Zeta potential, and X-ray energy spectrum analysis. We also tested the biocompatibility of LMC-RES and the ability of LMC-RES to cross the blood-brain barrier (BBB). The antioxidant effects of LMC-RES were detected by SH-SY5Y cells. Small animal live imaging was used to detect the distribution of LMC-RES in the brain tissue of AD mice. The cognitive abilities of mice were tested by water maze and nesting experiments. The effects of LMC-RES in reducing oxidative stress and protecting neurons was also explored by histological analysis. The results showed that LMC-RES had good sustained release effect and biocompatibility. The drug release rate of LMC-RES at 24 hours was 80.9 ± 2.25%. Meanwhile, LMC-RES could cross the BBB and enrich in neurons to exert antioxidant effects. In Aβ-induced SH-SY5Y cells, LMC-RES could inhibits oxidative stress through the Nrf-2/HO-1 signaling pathway. In AD model mice, LMC-RES was able to reduce ROS levels, inhibit Aβ-induced neurotoxicity, and protect neurons and significantly improve cognitive deficits of AD mice after drug administration. LMC-RES can effectively across the BBB, reduce oxidative stress, inhibit Aβ aggregation, and promote the recovery of neurological function.

Macrophage-Derived Extracellular Vesicles-Coated Palladium Nanoformulations Modulate Inflammatory and Immune Homeostasis for Targeting Therapy of Ulcerative Colitis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease mainly involving the colon and rectum, which features recurrent mucosal inflammation. The excessive production of reactive oxygen species (ROS) is a trigger for pathological changes such as cell apoptosis and disordered immune microenvironments, which are crucial for the progression of UC and can be a promising therapeutic target. Nowadays, the development of targeted therapeutic strategies for UC is still in its infancy. Thus, developing effective therapies based on ROS scavenging and elucidating their molecular pathways are urgently needed. Herein, a biomimetic nanoformulation (Pd@M) with cubic palladium (Pd) as the core and macrophage-derived extracellular vesicles (MEVs) as the shell is synthesized for the treatment of UC. These Pd@M nanoformulations exhibit multienzyme-like activities for effective ROS scavenging, excellent targeting ability as well as good biocompatibility. It is verified that Pd@M can regulate the polarization state of macrophages by inhibiting glycolysis, and decrease neutrophil infiltration and recruitment. In this way, the colonic inflammatory and immune microenvironment is remodeled, and apoptosis is prevented, ultimately improving colonic mucosal barrier function and alleviating colitis in the mouse model. This finding provides a promising alternative option for the treatment of UC patients.

Polypropylene composite mesh modified by polyurethane gel with ROS scavenging and anti-inflammatory effects for pelvic floor repair.

Development of an inflammation modulating polypropylene (PP) mesh in pelvic floor repair is an urgent clinical need. This is because PP mesh for pelvic floor repair can cause a series of complications related to foreign body reactions (FBR) in postoperative period. Therefore, we successfully prepared PP composite mesh that can scavenge reactive oxygen species (ROS) and inhibit inflammation to moderate FBR by a simple method. First, a pregel layer was formed on PP mesh by dip coating. Among them, polyurethane with polythioketal (PTK) is an excellent ROS scavenger, and dopamine methacrylamide (DMA) improves the stability of the coating and synergistically scavenges ROS. Then, a composite mesh (optimal PU50-PP) was obtained by photopolymerization. The results showed that the polyurethane gel layer was able to scavenge more than 90% of free radicals and about 75% of intracellular ROS. In vitro, PU50-PP mesh significantly scavenged ROS and resisted macrophage adhesion. After implantation in the posterior vaginal wall of rats, PU50-PP eliminated 53% of ROS, inhibited inflammation (decreased IL-6, increased IL-10), and dramatically reduced collagen deposition by about 64%, compared to PP mesh. Thus, the composite PP mesh with ROS scavenging and anti-inflammatory properties provides a promising approach for mitigating FBR.

Encapsulation of Selenium Nanoparticles and Metformin in Macrophage-Derived Cell Membranes for the Treatment of Spinal Cord Injury.

Spinal cord injury is an impact-induced disabling condition. A series of pathological changes after spinal cord injury (SCI) are usually associated with oxidative stress, inflammation, and apoptosis. These pathological changes eventually lead to paralysis. The short half-life and low bioavailability of many drugs also limit the use of many drugs in SCI. In this study, we designed nanovesicles derived from macrophages encapsulating selenium nanoparticles (SeNPs) and metformin (SeNPs-Met-MVs) to be used in the treatment of SCI. These nanovesicles can cross the blood-spinal cord barrier (BSCB) and deliver SeNPs and Met to the site of injury to exert anti-inflammatory and reactive oxygen species scavenging effects. Transmission electron microscopy (TEM) images showed that the SeNPs-Met-MVs particle size was approximately 125 ± 5 nm. Drug release assays showed that Met exhibited sustained release after encapsulation by the macrophage cell membrane. The cumulative release was approximately 80% over 36 h. In vitro cellular experiments and in vivo animal experiments demonstrated that SeNPs-Met-MVs decreased reactive oxygen species (ROS) and malondialdehyde (MDA) levels, increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, and reduced the expression of inflammatory (TNF-α, IL-1β, and IL-6) and apoptotic (cleaved caspase-3) cytokines in spinal cord tissue after SCI. In addition, motor function in mice was significantly improved after SeNPs-Met-MVs treatment. Therefore, SeNPs-Met-MVs have a promising future in the treatment of SCI.

Cryptotanshinone-Doped Photothermal Synergistic MXene@PDA Nanosheets with Antibacterial and Anti-Inflammatory Properties for Wound Healing.

Humans are threatened by bacteria and other microorganisms, resulting in countless pathogen-related infections and illnesses. Accumulation of reactive oxygen species (ROS) in infected wounds activates strong inflammatory responses. The overuse of antibiotics has led to increasing bacterial resistance. Therefore, effective ROS scavenging and bactericidal capacity are essential and the advanced development of collaborative therapeutic techniques to combat bacterial infections is needed. Here, this work developes an MXene@polydopamine-cryptotanshinone (MXene@PDA-CPT) antibacterial nanosystem with excellent reactive oxygen and nitrogen species scavenging ability, which effectively inactivates drug-resistant bacteria and biofilms, thereby promoting wound healing. In this system, the adhesion of polydopamine nanoparticles to MXene produced a photothermal synergistic effect and free radical scavenging activity, presenting a promising antibacterial and anti-inflammatory strategy. This nanosystem causes fatal damage to bacterial membranes. The loading of cryptotanshinone further expanded the advantages of the system, causing a stronger bacterial killing effect and inflammation mitigatory effect with desired biosafety and biocompatibility. In addition, combining nanomaterials and active ingredients of traditional Chinese medicine, this work provides a new rationale for the future development of wound dressings, which contributes to eliminating bacterial resistance, delaying disease deterioration, and alleviating the pain of patients.

Gallium Nitrate Enhances Antimicrobial Activity of Colistin against Klebsiella pneumoniae by Inducing Reactive Oxygen Species Accumulation.

Klebsiella pneumoniae, a pathogen of critical clinical concern, urgently demands effective therapeutic options owing to its drug resistance. Polymyxins are increasingly regarded as a last-line therapeutic option for the treatment of multidrug-resistant (MDR) Gram-negative bacterial infections. However, polymyxin resistance in K. pneumoniae is an emerging issue. Here, we report that gallium nitrate (GaNt), an antimicrobial candidate, exhibits a potentiating effect on colistin against MDR K. pneumoniae clinical isolates. To further confirm this, we investigated the efficacy of combined GaNt and colistin in vitro using spot dilution and rapid time-kill assays and growth curve inhibition tests and in vivo using a murine lung infection model. The results showed that GaNt significantly increased the antimicrobial activity of colistin, especially in the iron-limiting media. Mechanistic studies demonstrated that bacterial antioxidant activity was repressed by GaNt, as revealed by RNA sequencing (RNA-seq), leading to intracellular accumulation of reactive oxygen species (ROS) in K. pneumoniae, which was enhanced in the presence of colistin. Therefore, oxidative stress induced by GaNt and colistin augments the colistin-mediated killing of wild-type cells, which can be abolished by dimethyl sulfoxide (DMSO), an effective ROS scavenger. Collectively, our study indicates that GaNt has a notable impact on the antimicrobial activity of colistin against K. pneumoniae, revealing the potential of GaNt as a novel colistin adjuvant to improve the treatment outcomes of bacterial infections. IMPORTANCE This study aimed to determine the antimicrobial activity of GaNt combined with colistin against Klebsiella pneumoniae in vitro and in vivo. Our results suggest that by combining GaNt with colistin, antioxidant activity was suppressed and reactive oxygen species accumulation was induced in bacterial cells, enhancing antimicrobial activity against K. pneumoniae. We found that GaNt functioned as an antibiotic adjuvant when combined with colistin by inhibiting the growth of multidrug-resistant K. pneumoniae. Our study provides insight into the use of an adjuvant to boost the antibiotic potential of colistin for treating infections caused by multidrug-resistant K. pneumoniae.

Effects of Nigella sativa Oil Fractions on Reactive Oxygen Species and Chemokine Expression in Airway Smooth Muscle Cells.

many previous studies have demonstrated the therapeutic potential of N. sativa total oil fractions, neutral lipids (NLs), glycolipids (GLs), phospholipids (PLs), and unsaponifiable (IS) in asthma patients. We therefore tested its effect on airway smooth muscle (ASM) cells by observing its ability to regulate the production of glucocorticoid (GC)-insensitive chemokines in cells treated with TNF-α/IFN-γ, and its antioxidative and reactive oxygen species (ROS) scavenging properties. the cytotoxicity of N. sativa oil fractions was assessed using an MTT assay. ASM cells were treated with TNF-α/IFN-γ for 24 h in the presence of different concentrations of N. sativa oil fractions. An ELISA assay was used to determine the effect of N. sativa oil fractions on chemokine production (CCL5, CXCL-10, and CXCL-8). The scavenging effect of N. sativa oil fractions was evaluated on three reactive oxygen species (ROS), O2•-, OH•, and H2O2. our results show that different N. sativa oil fractions used at 25 and 50 µg/mL did not affect cell viability. All fractions of N. sativa oil inhibited chemokines in a concentration-dependent manner. Interestingly, the total oil fraction showed the most significant effect of chemokine inhibition, and had the highest percentage of ROS scavenging effect. these results suggest that N. sativa oil modulates the proinflammatory actions of human ASM cells by inhibiting the production of GC-insensitive chemokines.

Dihydromyricetin functions as a tumor suppressor in hepatoblastoma by regulating SOD1/ROS pathway.

Hepatoblastoma has an unsatisfactory prognosis, and traditional chemotherapy has strong side effects. Dihydromyricetin is a flavonoid extracted from a woody vine of the genus Serpentine in the family Vitaceae, with effects such as preventing alcoholic liver and reducing the incidence of liver cancer. However, the effect of DHM on hepatoblastoma and its specific pathway are still unclear. The purpose of this study was to investigate the effects of DHM on children's hepatoblastoma and its related mechanisms. CCK-8 assays were used to measure proliferation. Apoptosis and reactive oxygen species (ROS) were analyzed by flow cytometry. Apoptotic cells were observed using Hoechst 33342 staining and fluorescence microscopy. Protein expression levels in HuH-6 and HepG2 cells were determined by western blotting. We found that DHM was able to inhibit the growth and increase cellular mortality in HuH-6 and HepG2 cells. Furthermore, DHM decreased the intracellular ROS level and increased the expression of SOD1. ROS scavenger NAC promoted apoptosis, while the use of SOD1 inhibitor LCS-1 weakened the ROS scavenging effect of DHM , and to some extent reduced the killing effect of DHM on hepatoblastoma cells. These results suggest that regulating SOD1/ROS pathway to induce apoptosis is one of the potential mechanisms of DHM as a tumor suppressor in hepatoblastoma. Therefore, DHM may be a novel candidate for inhibiting hepatoblastoma growth and deserves further study.

Hydrogel with ROS scavenging effect encapsulates BR@Zn-BTB nanoparticles for accelerating diabetic mice wound healing via multimodal therapy

The strategies for eliminating excess reactive oxygen species (ROS) or suppressing inflammatory responses on the wound bed have proven effective for diabetic wound healing. In this work, a zinc-based nanoscale metal-organic framework (NMOF) functions as a carrier to deliver natural product berberine (BR) to form BR@Zn-BTB nanoparticles, which was, in turn, further encapsulated by hydrogel with ROS scavenging ability to yield a composite system of BR@Zn-BTB/Gel (denoted as BZ-Gel). The results show that BZ-Gel exhibited the controlled release of Zn2+ and BR in simulated physiological media to efficiently eliminated ROS and inhibited inflammation and resulted in a promising antibacterial effect. Invivo experiments further proved that BZ-Gel significantly inhibited the inflammatory response and enhanced collagen deposition, as well as to re-epithelialize the skin wound to ultimately promote wound healing in diabetic mice. Our results indicate that the ROS-responsive hydrogel coupled with BR@Zn-BTB synergistically promotes diabetic wound healing.