Amount Of ROS Research Articles

Effect of Combination of Blue and Red Light with Terbinafine on Cell Viability and Reactive Oxygen Species in Human Keratinocytes: Potential Implications for Cutaneous Mycosis

Cutaneous mycoses are common infections whose treatment has become more complex due to increasing antifungal resistance and the need for prolonged therapies, hindering patient adherence and increasing the incidence of adverse effects. Consequently, the use of physical therapies, especially photodynamic therapy (PDT), has increased for the treatment of onychomycosis due to its antimicrobial capacity being mediated by the production of reactive oxygen species. This study investigates the in vitro effect of applying blue light (448 nm) or red light (645 nm), alone or together with terbinafine, on the viability of human keratinocytes and the production of reactive oxygen species. The combination of terbinafine and blue light significantly increases ROS production and caspase-3 expression, while red light together with terbinafine increases catalase, superoxide dismutase (SOD) and PPARγ expression, which reduces the amount of ROS in the cultures. The effect of both treatments could be useful in clinical practice to improve the response of cutaneous mycoses to pharmacological treatment, reduce their toxicity and shorten their duration.

4-Methyl-N-(Piperidin-1-Ylmethylene) Benzenesulfonamide (PMSA) Promotes Ferroptosis of Tumor Cells by Targeting the KEAP1-NRF2-GPX4 Axis.

We aimed to investigate the effect of 4-methyl-N-(piperidin-1-ylmethylene) benzenesulfonamide (PMSA) on tumor cell proliferation, migration, ferroptosis, and the potential molecular mechanism of ferroptosis in tumor cells. PMSA was produced in the marine biomedical research institute of Guangdong Medical University (Zhanjiang, China) and used for tumor cells treatment. MTT and cell colony formation assays were used to measure the inhibition of tumor cell proliferation, the scratch assay was used to identified the suppression of tumor cell migration, the death of tumor cells was measured by Annexin-V-FITC/PI staining, the level of ferroptosis-relative lipid ROS in tumor cells was measured by flow cytometry and MDA detection kit, and the expression of ferroptosis-relative protein was measured by Western blot. The Discovery Studio system was used for molecular docking and the binding ability was measured by cellular thermal shift assay. The PMSA we produced inhibited tumor cell proliferation, colony formation, migration and triggered cell death, and Fer-1 could reverse these effects. The amount of ROS and MDA levels in tumor cells was also markedly raised by PMSA. PMSA treatment significantly reduced the expression of SLC7A11/XCT, NRF2, and GPX4 in tumor cells. The phosphorylation level of NRF2 was also decreased. Through molecular docking, it was discovered that PMSA could bind to NRF2 and thereby block its activity. The KEAP1-NRF2-GPX4 axis was the target of PMSA's anti-tumor action, which results in ferroptosis of tumor cells. This demonstrated that the compound has the potential to be used as a candidate for anti-tumor drugs.

An added value of Azithromycin: mitigation of Doxorubicin associated oxidative damage and genotoxicity in normal human bronchial epithelium cells.

Doxorubicin, a well-known and widely used antineoplastic agent with direct ROS-accumulating activity, has proven effective in treating various cancer types. However, its non-specific cytotoxicity towards non-cancerous cells prompts concerns regarding potential adverse effects. Azithromycin is an antibiotic for treating bacterial infections and an anti-inflammatory agent, particularly beneficial in managing respiratory conditions like bronchitis and sinusitis. Despite azithromycin's well-documented antibacterial properties, its potential cellular/genomic protective effects remain unexplored. As an in vitro model, BEAS-2B cells (normal human bronchial epithelium cells) were employed in the present study to assess whether azithromycin possesses any protective properties against doxorubicin-induced cellular toxicity. Cells in pre-treatment culture were treated to various amounts of azithromycin (3.125, 6.25, 12.5, 25, and 50 μg/mL) in combination with doxorubicin at IC50 (0.08 μg/mL). Doxorubicin at 0.08 μg/mL highlighted cytotoxicity, oxidative stress, and genotoxicity. Azithromycin at 25 and 50 μg/mL markedly modulated oxidative stress and genomic damage by decreasing the ROS and LPO amounts, and suppressing DNA fragmentation in the comet assay parameters. Consequently, azithromycin may be regarded as a cytomodulating, antigenotoxic, and antioxidant agent.

Attenuation of TNF-α and Iron Levels in Renal Hemosiderosis by Phaleria macrocarpa (Scheff.) Boerl Extract in a Rat Iron Overload Model

Regular blood transfusions are typically used to treat the genetic anemia known as thalassemia, which can lead to an increase in the body's total iron levels. The condition of excess iron can be toxic to the body due to the formation of free radicals that are harmful and can damage cells and tissues. So the availability of free iron will form the basis of iron toxicity because it accelerates the Fenton reaction to produce an increase in the amount of ROS that cannot be suppressed so that saturation of the antioxidant system can occur. Excess iron has been known to be a risk factor for organ dysfunction and damage that results in various organ diseases such as liver, heart and kidney, diabetes mellitus, and neurodegenerative diseases. Mangiferin is an active compound has been shown to act as an iron chelating agent by forming complexes with iron. The complex formed can reduce iron accumulation in thalassemia patients who receive blood transfusions on a regular basis. Mahkota Dewa (Phaleria macrocarpa) is a well-known medicinal plant native to Papua, Indonesia, and it also includes the active ingredient mangiferin. This study aims to determine the effectiveness of the ethanolic extract of Phaleria macrocarpa fruit as an iron chelating agent observed in the kidneys in a rat model of excess iron

Monocarbonyl curcuminoids as potential photosensitizers in photodynamic therapy against skin cancer

Two monocarbonyl dimethylamino curcuminoids, one derived from acetone (C3) and the second one from cyclohexane (C6), were synthesized aiming to study their photophysical properties and anticancer photodynamic potential. Compound C6 exhibited lower absorbance and fluorescence than C3. Photobleaching studies showed that C3 and C6 photostability behavior in DMSO differ significantly. C3 was completely photoconverted into a new species absorbing at lower wavelength than the parent compound, whereas, C6, upon a 30 min irradiation at λ = 440 nm with 15 mW/cm2 reached a photostationary phase where a smaller amount of the initial compound coexists with some photoproducts of higher and lower absorbance. Both compounds were able to generate significant amounts of ROS upon irradiation in an aqueous environment and exhibited successful intracellular localization in skin cancer cells (A431 cells). After dark cytotoxicity studies the concentrations of 5 μM and 1 μM for C3 and C6, respectively, were selected for the PDT assessment. C3 presented light dose-dependent photodynamic activity against A431 cells, resulting in 40 % cell viability after 12 min of light irradiation (440 nm, 15 mW/cm2). On the other side, C6 showed a biphasic light dose PDT effect with cell viability gradually decreasing up to 50 % after 5 min of light exposure, and then increasing again after 8 and 12 min of light exposure. The photodynamic performance of C6 may provide a new insight into the development of PSs with reduced prolonged photosensitivity.

Crosstalk between ROS-inflammatory gene expression axis in the progression of lung disorders.

A significant number of deaths and disabilities worldwide are brought on by inflammatory lung diseases. Many inflammatory lung disorders, including chronic respiratory emphysema, resistant asthma, resistance to steroids, and coronavirus-infected lung infections, have severe variants for which there are no viable treatments; as a result, new treatment alternatives are needed. Here, we emphasize how oxidative imbalance contributes to the emergence of provocative lung problems that are challenging to treat. Endogenic antioxidant systems are not enough to avert free radical-mediated damage due to the induced overproduction of ROS. Pro-inflammatory mediators are then produced due to intracellular signaling events, which can harm the tissue and worsen the inflammatory response. Overproduction of ROS causes oxidative stress, which causes lung damage and various disease conditions. Invasive microorganisms or hazardous substances that are inhaled repeatedly can cause an excessive amount of ROS to be produced. By starting signal transduction pathways, increased ROS generation during inflammation may cause recurrent DNA damage and apoptosis and activate proto-oncogenes. This review provides information about new targets for conducting research in related domains or target factors to prevent, control, or treat such inflammatory oxidative stress-induced inflammatory lung disorders.

Lysosome-Targeted and pH-Activatable Phototheranostics for NIR-II Fluorescence Imaging-Guided Nasopharyngeal Carcinoma Phototherapy.

Currently, clinical therapeutic strategies for nasopharyngeal carcinoma (NPC) confront insurmountable dilemmas in which surgical resection is incomplete and chemotherapy/radiotherapy has significant side effects. Phototherapy offers a maneuverable, effective, and noninvasive pattern for NPC therapy. Herein, we developed a lysosome-targeted and pH-responsive nanophototheranostic for near-infrared II (NIR-II) fluorescence imaging-guided photodynamic therapy (PDT) and photothermal therapy (PTT) of NPC. A lysosome-targeted S-D-A-D-S-type NIR-II phototheranostic molecule (IRFEM) is encapsulated within the acid-sensitive amphiphilic DSPE-Hyd-PEG2k to form IRFEM@DHP nanoparticles (NPs). The prepared IRFEM@DHP exhibits a good accumulation in the acidic lysosomes for facilitating the release of IRFEM, which could disrupt lysosomal function by generating an amount of heat and ROS under laser irradiation. Moreover, the guidelines of NIR-II fluorescence enhance the accuracy of PTT/PDT for NPC and avoid damage to normal tissues. Remarkably, IRFEM@DHP enable efficient antitumor effects both in vitro and in vivo, opening up a new avenue for precise NPC theranostics.

Ganoderma lucidum Polysaccharides Ameliorate Acetaminophen-Induced Acute Liver Injury by Inhibiting Oxidative Stress and Apoptosis along the Nrf2 Pathway.

The excessive employment of acetaminophen (APAP) is capable of generating oxidative stress and apoptosis, which ultimately result in acute liver injury (ALI). Ganoderma lucidum polysaccharides (GLPs) exhibit hepatoprotective activity, yet the protective impact and potential mechanism of GLPs in relation to APAP-induced ALI remain ambiguous. The intention of this research was to scrutinize the effect of GLPs on APAP-induced ALI and to shed light on their potential mechanism. The results demonstrated that GLPs were capable of notably alleviating the oxidative stress triggered by APAP, as shown through a significant drop in the liver index, the activities of serum ALT and AST, and the amounts of ROS and MDA in liver tissue, along with an increase in the levels of SOD, GSH, and GSH-Px. Within these, the hepatoprotective activity at the high dose was the most conspicuous, and its therapeutic efficacy surpassed that of the positive drug (bifendate). The results of histopathological staining (HE) and apoptosis staining (TUNEL) indicated that GLPs could remarkably inhibit the necrosis of hepatocytes, the permeation of inflammatory cells, and the occurrence of apoptosis induced by APAP. Moreover, Western blot analysis manifested that GLPs enhanced the manifestation of Nrf2 and its subsequent HO-1, GCLC, and NQO1 proteins within the Nrf2 pathway. The results of qPCR also indicated that GLPs augmented the expression of antioxidant genes Nrf2, HO-1, GCLC, and NQO1. The results reveal that GLPs are able to set off the Nrf2 signaling path and attenuate ALI-related oxidative stress and apoptosis, which is a potential natural medicine for the therapy of APAP-induced liver injury.

Isomolar high-entropy engineering and Ac-coordination regulated nanocubic hydroxystannate for synergistic adsorption-photocatalytic acetaldehyde abatement under anoxic conditions

High-entropy materials have attracted increasing attention in many applications due to their unusual properties, yet little is known about the effects of cationic ratios and anionic ligands on their catalytic activity. Herein, a novel isomolar high-entropy and Ac-coordinated hydroxystannate nanocube (iHEOH-Ac) is fabricated using NaOH as precipitant and acetate anion as ligand in one step. The unique strategy simultaneously employing isomolar high-entropy engineering and Ac coordination in iHEOH-Ac synergistically facilitates the formation of oxygen vacancies and acid sites and significantly enhances optical absorption, charge separation and acetaldehyde activation, leading to the highest amount of ROS (•OH and •O2– and h+). The synergistic adsorption-photocatalytic performance of iHEOH-Ac in acetaldehyde abatement outperforms its net photocatalytic mode and other counterparts, with maximum removal ratio up to ∼ 100% under anoxic conditions and reversible deactivation of ∼ 10% over 360 min. This work not only sheds light on the enhancement mechanism on the acetaldehyde oxidation performance through isomolar high-entropy and Ac-coordinated strategy, but also successfully regulates the acetaldehyde oxidation pathways by the reaction mode and anionic coordination environment, providing a new route for the design of high-performance acetaldehyde oxidation photocatalysts under anoxic environments.

A Hydrogen-Bonded Organic Framework-Based Mitochondrion-Targeting Bioorthogonal Platform for the Modulation of Mitochondrial Epigenetics.

Bioorthogonal chemistry represents a powerful tool in chemical biology, which shows great potential in epigenetic modulation. As a proof of concept, the epigenetic modulation model of mitochondrial DNA (mtDNA) is selected because mtDNA establishes a relative hypermethylation stage under oxidative stress, which impairs the mitochondrion-based therapeutic effect during cancer therapy. Herein, we design a new biocompatible hydrogen-bonded organic framework (HOF) for a HOF-based mitochondrion-targeting bioorthogonal platform TPP@P@PHOF-2. PHOF-2 can activate a prodrug (pro-procainamide) in situ, which can specifically inhibit DNA methyltransferase 1 (DNMT1) activity and remodel the epigenetic modification of mtDNA, making it more susceptible to ROS damage. In addition, PHOF-2 can also catalyze artemisinin to produce large amounts of ROS, effectively damaging mtDNA and achieving better chemodynamic therapy demonstrated by both in vitro and in vivo studies. This work provides new insights into developing advanced bioorthogonal therapy and expands the applications of HOF and bioorthogonal catalysis.

Dual pH- and ATP-Responsive Antibacterial Nanospray: On-Demand Release of Antibacterial Factors, Imaging Monitoring, and Accelerated Healing of Bacteria-Infected Wounds under NIR Activation.

The prevalence of pathogenic bacterial infections with high morbidity and mortality poses a widespread challenge to the healthcare system. Therefore, it is imperative to develop nanoformulations capable of adaptively releasing antimicrobial factors and demonstrating multimodal synergistic antimicrobial activity. Herein, an NIR-activated multifunctional synergistic antimicrobial nanospray MXene/ZIF-90@ICG was prepared by incorporating ZIF-90@ICG nanoparticles onto MXene-NH2 nanosheets. MXene/ZIF-90@ICG can on-demand release the antimicrobial factors MXenes, ICG, and Zn2+ in response to variations in pH and ATP levels within the bacterial infection microenvironment. Under NIR radiation, the combination of MXenes, Zn2+, and ICG generated a significant amount of ROS and elevated heat, thereby enhancing the antimicrobial efficacy of PDT and PTT. Meanwhile, NIR excitation could accelerate the further release of ICG and Zn2+, realizing the multimodal synergistic antibacterial effect of PDT/PTT/Zn2+. Notably, introducing MXenes improved the dispersion of the synthesized antimicrobial nanoparticles in aqueous solution, rendering MXene/ZIF-90@ICG a candidate for application as a nanospray. Importantly, MXene/ZIF-90@ICG demonstrated antimicrobial activity and accelerated wound healing in the constructed in vivo subcutaneous Staphylococcus aureus infection model with NIR activation, maintaining a favorable biosafety level. Therefore, MXene/ZIF-90@ICG holds promise as an innovative nanospray for adaptive multimodal synergistic and efficient antibacterial applications with NIR activation.

Multispectral-responsive Cu7S4@rGO bio-heterojunction for rapid sterilization through bacterial cuproptosis-like death

Bacterial infection is a significant challenge in the realm of wound healing, particularly in burn and trauma cases, as it delays wound healing, threatens patient health, and promotes the development of drug-resistant bacteria. Although phototherapy is widely employed in the field of antimicrobial therapy, these methods are typically applied in broad spectrum approach to treat various types of infectious diseases. Their selectivity is often limited, which may lead to an increased risk of tissue damage, thereby diminishing clinical applicability and specificity in particular contexts. To address this daunting issue, we have designed a multispectral-responsive bio-heterojunction (bio-HJ) (Cu7S4@rGO bio-HJ) to induce bacteria cuproptosis-like death. Cu7S4@rGO bio-HJ catalytically generates a considerable amount of ROS which assaults the membrane of extracellular bacteria under near infrared (NIR) or visible light. Additionally, Cu7S4@rGO bio-HJ can effectively kill bacteria by inducing localized hyperthermia under NIR. As a result, the multispectral antibacterial properties of Cu7S4@rGO bio-HJ has significantly enhanced its applicability and feasibility in medical settings. Cu7S4@rGO bio-HJ demonstrates potential for utilization in the treatment of oral infections, cutaneous infections (such as acne and herpes), and other superficial infections through its responsiveness to visible light, facilitating photodynamic therapy. Furthermore, in the context of deep-seated tissue infections, Cu7S4@rGO bio-HJ responsiveness to NIR renders it viable for the implementation of combined photodynamic and photothermal therapy. This study reveals the potential of Cu7S4@rGO bio-HJ in multispectral responsiveness and bacterial sterilization, providing new insights for novel biomedical applications.

2-Aryl-1H-imidazo[4,5-f][1,10]phenanthroline-Based Binuclear Ru(II)/Ir(III)/Re(I) Complexes as Mitochondria Targeting Cancer Stem Cell Therapeutic Agents.

A series of novel Ru(II)/Ir(III)/Re(I)-based organometallic complexes [Ru2L1, Ru2L2, Ir2L1, Ir2L2, Re2L1, and Re2L2] have been synthesized to assess their potency and selectivity against multiple cancer cells A549, HCT-116, and HCT-116 colon CSCs. The cytotoxic screening of the synthesized complexes has revealed that complex Ru2L1 and Ir2L2 are two proficient complexes among all, but Ru2L1 is the most potent complex. A significant binding constant value was observed for DNA and BSA in all complexes. Significant lipophilic properties allow them to penetrate cancer cell membranes, and substantial quantum yield (ϕf) values support bioimaging potential. Again, these complexes are particular for mitochondrial localization and produce a profuse amount of ROS to damage the mitochondrial DNA and then G1 phase cell-cycle arrest. Protein expression analysis unveiled that pro-apoptotic Bax protein overexpressed in Ru2L1-treated cells, whereas antiapoptotic Bcl-2 protein was expressed twofold in Ir2L2-treated cells, which correlated with autophagy reticence.

Designing multi-functional MoS2/rGO piezocatalysts based on bacteria-catalyst topological interactions and electron pump effects for efficient water disinfection

In catalytic technology, the capability of nanocatalysts to generate reactive species (ROS) and the rapid contact between ROS and target pollutants are critical for the catalytic reaction. Herein, we proposed an effective strategy to construct multi-functional MoS2/rGO piezocatalysts based on bacteria-catalyst topological interactions and electron pump effects, which possessed high carrier separation ability and adhesion to bacteria, ensuring the effective utilization of ROS. Attributed to the unique 3D heterogeneous structure and interface electronic structure, MoS2/rGO could completely inactivate 6.21 log10 cfu mL−1 of E. coli K-12 within 30 min under ultrasonic conditions, significantly faster than pure MoS2. It was demonstrated experimentally and theoretically that the introduction of rGO led to the generation of a large amount of ROS by enhancing the piezoelectric properties and conductivity of MoS2/rGO, while the topological interactions between MoS2/rGO and bacteria facilitated effective bacteria capture, improving the utilization of ROS. Additionally, Kelvin Probe Force Microscopy texting confirmed that rGO acts as an electron pump, effectively attracting electrons from bacterial cells, which disrupted bacterial metabolic processes, increased oxidative stress, and further enhanced the bactericidal effect. The mechanisms of topological interactions and electron pump effects elucidated in this work offer new insights into the design and understanding of efficient bactericidal materials in water purification applications.

Chemical composition of Artemisia argyi essential oil and its antifungal activity against dermatophytes by inhibiting oxidative phosphorylation and causing oxidative damage

Ethnopharmacological relevanceDermatophytes are notorious pathogens capable of infecting various mammals skin, posing serious threats to human health and overall life quality worldwide. Artemisia argyi has been recorded and applied for over a thousand years to treat skin itching. Although it has the potential to be developed as a plant-based antifungal agent, it’s antifungal activity and action mechanism of active ingredients are still unclear. Aim of the studyThe aim of this study was to investigate the chemical composition, antifungal activity against skin fungi, and potential mechanisms of Artemisia argyi essential oil (AEO). Materials and methodsThe chemical composition of AEO was analyzed by gas chromatography-mass spectrometry (GC-MS) firstly. Flat growth restraint and double half dilution tests was performed to evaluate AEO antifungal activity against Microsporum gypseum, Trichophyton mentagrophytes, and Trichophyton rubrum. And then, the physiological mechanism of AEO inhibiting dermatophytes was systematically explored through scanning electron microscopy, relative conductivity, membrane leakage, ROS content, and antioxidant enzyme activity. Finally, the main pathways were screened through transcriptome sequencing, while the related genes expression levels and enzyme activity were validated. ResultsMonoterpenes and sesquiterpenoids were the most highly representative class of AEO. AEO had powerful antifungal activity against M. gypseum, T. mentagrophytes, and T. rubrum, with minimum inhibitory concentration (MIC) values of 0.6, 1.2, and 1.2 μL/mL, respectively. Moreover, AEO can also damage the cell membrane integrity of T. mentagrophytes, resulting in cellular extravasation of intracellular substances. Transcriptome analysis revealed that the main target of AEO is to inhibit electron transfer and oxidative phosphorylation during respiration, ultimately leading to obstruction of normal ATP synthesis and energy metabolism in mitochondria. And a large amount of ROS will generate due to the incompletely catalysis of oxygen under mitochondrial complexes. Coupled with the decrease of antioxidant enzyme (SOD, POD) activity, excessive accumulation of ROS will cause serious oxidative damage to cells and eventually exhibiting antifungal activity against dermatophytes. ConclusionsThe present study demonstrated that Artemisia argyi was a valuable source of active compounds with antifungal activity. These findings support AEO as a potential agent to inhibit dermatophytes and prevent related dermatophytoses.

Sphingosine kinase 2 suppresses neutrophil responses while attenuating immune pathology during a persistent viral infection

Abstract During chronic virus infections, the functions of immune cells are often suppressed which may restrict immune pathology but lead to viral persistence. However, the underlying mechanisms are incompletely understood. Sphingosine kinase 2 (SphK2) generates sphingosine 1-phosphate, a bioactive lipid mediator, and mediates diverse cellular processes. We have recently found that SphK2-deficient mice succumb to infection by lymphocytic choriomeningitis virus (LCMV) clone 13 (Cl 13) due to immune pathology associated with nephropathy. Heightened T cell immunity was crucial for infection-induced mortality of SphK2 KO mice. However, in addition to T cell immunity, a notable increase of neutrophils was observed in multiple tissues as well as blood of LCMV-infected SphK2 KO mice. Importantly, SphK2-deficient neutrophils expressed substantially lower levels of the immune suppressive marker CD244 and produced higher amounts of ROS compared to SphK2-sufficient neutrophils upon infection. Depletion of neutrophils from SphK2 KO mice increased the viability of infected mice. Further, adoptively transferred SphK2-deficient neutrophils improved virus-specific T cell responses in wild type mice when compared to the transferred SphK2-sufficient neutrophils. The results indicate that SphK2 inhibits neutrophil expansion and function, contributing to the immune regulation during a persistent virus infection. The study may help to design new immune therapeutics to control viral diseases.

Cold Atmospheric Pressure Plasma-Activated Medium Modulates Cellular Functions of Human Mesenchymal Stem/Stromal Cells In Vitro.

Cold atmospheric pressure plasma (CAP) offers a variety of therapeutic possibilities and induces the formation of reactive chemical species associated with oxidative stress. Mesenchymal stem/stromal cells (MSCs) play a central role in tissue regeneration, partly because of their antioxidant properties and ability to migrate into regenerating areas. During the therapeutic application, MSCs are directly exposed to the reactive species of CAP. Therefore, the investigation of CAP-induced effects on MSCs is essential. In this study, we quantified the amount of ROS due to the CAP activation of the culture medium. In addition, cell number, metabolic activity, stress signals, and migration were analyzed after the treatment of MSCs with a CAP-activated medium. CAP-activated media induced a significant increase in ROS but did not cause cytotoxic effects on MSCs when the treatment was singular and short-term (one day). This single treatment led to increased cell migration, an essential process in wound healing. In parallel, there was an increase in various cell stress proteins, indicating an adaptation to oxidative stress. Repeated treatments with the CAP-activated medium impaired the viability of the MSCs. The results shown here provide information on the influence of treatment frequency and intensity, which could be necessary for the therapeutic application of CAP.

A potent and selective activator of large-conductance Ca2+-activated K+ channels induces preservation of mitochondrial function after hypoxia and reoxygenation by handling of calcium and transmembrane potential.

Ischaemic heart disease remains a significant cause of mortality globally. A pharmacological agent that protects cardiac mitochondria against oxygen deprivation injuries is welcome in therapy against acute myocardial infarction. Here, we evaluate the effect of large-conductance Ca2+-activated K+ channels (BKCa) activator, Compound Z, in isolated mitochondria under hypoxia and reoxygenation. Mitochondria from mice hearts were obtained by differential centrifugation. The isolated mitochondria were incubated with a BKCa channel activator, Compound Z, and subjected to normoxia or hypoxia/reoxygenation. Mitochondrial function was evaluated by measurement of O2 consumption in the complexes I, II, and IV in the respiratory states 1, 2, 3, and by maximal uncoupled O2 uptake, ATP production, ROS production, transmembrane potential, and calcium retention capacity. Incubation of isolated mitochondria with Compound Z under normoxia conditions reduced the mitochondrial functions and induced the production of a significant amount of ROS. However, under hypoxia/reoxygenation, the Compound Z prevented a profound reduction in mitochondrial functions, including reducing ROS production over the hypoxia/reoxygenation group. Furthermore, hypoxia/reoxygenation induced a large mitochondria depolarization, which Compound Z incubation prevented, but, even so, Compound Z created a small depolarization. The mitochondrial calcium uptake was prevented by the BKCa activator, extruding the mitochondrial calcium present before Compound Z incubation. The Compound Z acts as a mitochondrial BKCa channel activator and can protect mitochondria function against hypoxia/reoxygenation injury, by handling mitochondrial calcium and transmembrane potential.

Knockdown of KBTBD7 attenuates septic lung injury by inhibiting ferroptosis and improving mitochondrial dysfunction

Lung injury in sepsis is caused by an excessive inflammatory response caused by the entry of pathogenic microorganisms into the body. It is also accompanied by the production of large amounts of ROS. Ferroptosis and mitochondrial dysfunction have also been shown to be related to sepsis. Finding suitable sepsis therapeutic targets is crucial for sepsis research. BTB domain-containing protein 7 (KBTBD7) is involved in regulating inflammatory responses, but its role and mechanism in the treatment of septic lung injury are still unclear. In this study, we evaluated the role and related mechanisms of KBTBD7 in septic lung injury. In in vitro studies, we established an in vitro model by inducing human alveolar epithelial cells with lipopolysaccharide (LPS) and found that KBTBD7 was highly expressed in the in vitro model. KBTBD7 knockdown could reduce the inflammatory response by inhibiting the secretion of pro-inflammatory factors and inhibit the production of ROS, ferroptosis and mitochondrial dysfunction. Mechanistic studies show that KBTBD7 interacts with FOXA1, promotes FOXA1 expression, and indirectly inhibits SLC7A11 transcription. In vivo studies have shown that knocking down KBTBD7 improves lung tissue damage in septic lung injury mice, inhibits inflammatory factors, ROS production and ferroptosis. Taken together, knockdown of KBTBD7 shows an alleviating effect on septic lung injury in vitro and in vivo, providing a potential therapeutic target for the treatment of septic lung injury.

Chitosan‐Stabilized PtAu Nanoparticles with Multienzyme‐Like Activity for Mixed Bacteria Infection Wound Healing and Insights into Its Antibacterial Mechanism

Traditional antibacterial agents are often observed to be ineffective because bacteria evolved to strains with greater antibiotic resistance. Here, vigorous chitosan‐stabilized PtAu nanoparticles (CSPA) with multienzyme‐like activity are successfully fabricated, which serve an effective artificial nanozyme to enhance antibacterial activity for mixed bacterial infection wound treatment. Ultrasmall size CSPA exhibits excellent hydrophilicity and biocompatibility, possesses strong oxidase‐ and peroxidase‐like activity generating a substantial amount of ROS (, 1O2, ·OH) to cause oxidative damage to bacteria, also demonstrates nicotinamide adenine dinucleotide dehydrogenase‐like activity disrupting the bacterial respiratory chains, and subsequently impedes adenosine triphosphate production. CSPA exhibits favorable broad‐spectrum antibacterial activity at very low concentrations, prevents bacterial resistance, and completely inhibits bacterial biofilm formation. Antibacterial Mechanism of CSPA by the transcriptomics is further revealed that CSPA can induce bacterial oxidative stress, hinder bacterial energy metabolism, and disrupt the synthesis and function of bacterial cell walls and cell membranes. In vivo, CSPA inhibits the mixed bacterial population at the wound site and promotes wound healing in rats. This study introduces a novel antibacterial approach, providing important insight into the antibacterial mechanism of CSPA nanozymes and promoting the advancement of nanocatalytic materials in biomedical applications.