Cell Membrane Rupture Research Articles

Ferroptosis: mechanisms and therapeutic targets.

Ferroptosis is a nonapoptotic form of cell death characterized by iron-dependent lipid peroxidation in membrane phospholipids. Since its identification in 2012, extensive research has unveiled its involvement in the pathophysiology of numerous diseases, including cancers, neurodegenerative disorders, organ injuries, infectious diseases, autoimmune conditions, metabolic disorders, and skin diseases. Oxidizable lipids, overload iron, and compromised antioxidant systems are known as critical prerequisites for driving overwhelming lipid peroxidation, ultimately leading to plasma membrane rupture and ferroptotic cell death. However, the precise regulatory networks governing ferroptosis and ferroptosis-targeted therapy in these diseases remain largely undefined, hindering the development of pharmacological agonists and antagonists. In this review, we first elucidate core mechanisms of ferroptosis and summarize its epigenetic modifications (e.g., histone modifications, DNA methylation, noncoding RNAs, and N6-methyladenosine modification) and nonepigenetic modifications (e.g., genetic mutations, transcriptional regulation, and posttranslational modifications). We then discuss the association between ferroptosis and disease pathogenesis and explore therapeutic approaches for targeting ferroptosis. We also introduce potential clinical monitoring strategies for ferroptosis. Finally, we put forward several unresolved issues in which progress is needed to better understand ferroptosis. We hope this review will offer promise for the clinical application of ferroptosis-targeted therapies in the context of human health and disease.

Integrating widely targeted and oxylipin-targeted lipidomics unravels lipid characteristic evolution and oxidation markers in walnuts during deterioration

The susceptibility of walnut lipids to deterioration constitutes challenges for industry development, and the oxylipins formed during this process remain to be explored. This study employed lipidomics to reveal the dynamic evolution of lipid characteristics and identify oxidation markers from oxylipins in walnuts during accelerated storage. Glycerophospholipid (GP) content continuously declined in the initial and severe deterioration stages. The accumulation of diglycerides and partial lysophospholipids characterized initial deterioration. Triglycerides were prone to direct oxidation, while GPs tended to be first hydrolyzed. GP metabolism especially phosphatidylethanolamine degradation triggered walnut deterioration. Moreover, ten oxylipins derived from linoleic acids were identified in walnuts. Trans-EKODE-(E)-Ib, 13-HODE, 9-HODE, and 9(S),12(S),13(S)-TriHOME were screened as oxidation markers. The cellular structure exhibited the cell membrane and oil body membrane rupture during deterioration. Potential mechanisms of lipid deterioration were proposed, providing a scientific basis and guidance in optimizing quality control strategies and assessing practical deterioration degrees of walnuts.

Pyroptosis in Endothelial Cells and Extracellular Vesicle Release in Atherosclerosis via NF-κB-Caspase-4/5-GSDM-D Pathway

Background: Pyroptosis, an inflammatory cell death, is involved in the progression of atherosclerosis. Pyroptosis in endothelial cells (ECs) and its underlying mechanisms in atherosclerosis are poorly understood. Here, we investigated the role of a caspase-4/5-NF-κB pathway in pyroptosis in palmitic acid (PA)-stimulated ECs and EVs as players in pyroptosis. Methods: Human umbilical vein endothelial cells (HUVECs) were cultured in an endothelial cell medium, treated with Ox-LDL, PA, caspase-4/5 inhibitor, NF-κB inhibitor, and sEV release inhibitor for 24 h, respectively. The cytotoxicity of PA was determined using an MTT assay, cell migration using a scratch-wound-healing assay, cell morphology using bright field microscopy, and lipid deposition using oil red O staining. The mRNA and protein expression of GSDM-D, CASP4, CASP5, NF-κB, NLRP3, IL-1β, and IL-18 were determined with RT-PCR and Western blot. Immunofluorescence was used to determine NLRP3 and ICAM-1 expressions. Extracellular vesicles (EVs) were isolated using an exosome isolation kit and were characterized by Western blot and scanning electron microscopy. Results: PA stimulation significantly changed the morphology of the HUVECs characterized by cell swelling, plasma membrane rupture, and increased LDH release, which are features of pyroptosis. PA significantly increased lipid accumulation and reduced cell migration. PA also triggered inflammation and endothelial dysfunction, as evidenced by NLRP3 activation, upregulation of ICAM-1 (endothelial activation marker), and pyroptotic markers (NLRP3, GSDM-D, IL-1β, IL-18). Inhibition of caspase-4/5 (Ac-FLTD-CMK) and NF-κB (trifluoroacetate salt (TFA)) resulted in a significant reduction in LDH release and expression of caspase-4/5, NF-κB, and gasdermin D (GSDM-D) in PA-treated HUVECs. Furthermore, GW4869, an exosome release inhibitor, markedly reduced LDH release in PA-stimulated HUVECs. EVs derived from PA-treated HUVECs exacerbated pyroptosis, as indicated by significantly increased LDH release and augmented expression of GSDM-D, NF-κB. Conclusions: The present study revealed that inflammatory, non-canonical caspase-4/5-NF-κB signaling may be one of the crucial mechanistic pathways associated with pyroptosis in ECs, and pyroptotic EVs facilitated pyroptosis in normal ECs during atherosclerosis.

Guanidinium-Functionalized Carbon Dots: An Efficient Antibacterial Agent against Multidrug-Resistant ESKAPE Pathogens.

The rise of multidrug-resistant (MDR) bacteria poses a substantial challenge in clinical settings, particularly with the increasing prevalence of ESKAPE pathogens (E. faecium, S. aureus, K. pneumoniae, A. baumannii, P. aeruginosa, and E. coli) as critical MDR bacteria. These ESKAPE pathogens have the capability to undermine antibiotic treatments, leading to a high incidence of drug resistance. However, the development of efficient antibacterial agents against ESKAPE pathogens is still in the bottleneck. Herein, the first example of antibacterial carbon dots against ESKAPE pathogens was reported. Onion powder-based carbon dots were melted with poly(hexamethylene biguanide) hydrochloride (PHMB) to obtain guanidinium-functionalized carbon dots (GCDs), which exhibited satisfactory antibacterial activity against all the tested bacteria, including both Gram-positive and Gram-negative bacteria, and even ESKAPE pathogens. The efficient antibacterial ability of GCDs derives from the rupture of the bacterial cell membrane and elevated ROS levels. Safety assessments revealed that GCDs neither trigger detectable drug resistance nor exhibit any cytotoxic effects. Furthermore, GCDs effectively promoted wound healing without observable adverse reactions of mixed MDR bacteria-infected wounds in rats. The GCDs also showed excellent long-term stability. These findings indicate that GCDs hold promise as an efficient antibacterial agent for the treatment of MDR strain-caused clinical infected-wound healing.

The Values-Based Psychopathology of Antoni Kępiński (1918-1972).

The question of the role of personal values in the constitution of and recovery from mental illness is a divisive subject discussed in contemporary psychopathology. This article criti-cally examines the psychopathological theories and contributions of Antoni Kępiński - a seminal yet internationally under-recognized Polish psychiatrist. Drawing upon a multi-layered framework incorporating biological, affective-emotional, and socio-cultural dimensions, Kępiński posited mental disorders as disturbances in the energy and information metabolism with the environment leading to an increase in entropy. Kępiński's work also contributes to a richer understanding of schizophrenia (whose essence he metaphorically de-scribed as the plasma membrane rupture) and the complexities inherent in the decision-making processes of patients. In a quasi-phenomenological vein, Kępiński encouraged to re-evaluate delu-sions and hallucinations as opportunities to access unfiltered insights into reality. He also argued for the potential for moral growth within psychiatric treatment. Kępiński's theories anticipated many concepts now foundational in neuroscientific research and clinical psychiatry, showcasing his role as a forward-thinking figure in the history of the profession.

Pyroptosis in asthma: inflammatory phenotypes, immune and non-immune cells, and novel treatment approaches.

Pyroptosis is a form of inflammatory programmed cell death, and is activated by pathogen infections or endogenous danger signals. The canonical pyroptosis process is characterized by the inflammasome (typically NLRP3)-mediated activation of caspase-1, which in turn cleaves and activates IL-1β and IL-18, as well as gasdermin D, which is a pore-forming executor protein, leading to cell membrane rupture, and the release of proinflammatory cytokines and damage-associated molecular pattern molecules. Pyroptosis is considered a part of the innate immune response. A certain level of pyroptosis can help eliminate pathogenic microorganisms, but excessive pyroptosis can lead to persistent inflammatory responses, and cause tissue damage. In recent years, pyroptosis has emerged as a crucial contributor to the development of chronic inflammatory respiratory diseases, such as asthma. The present study reviews the involvement of pyroptosis in the development of asthma, in terms of its role in different inflammatory phenotypes of the disease, and its influence on various immune and non-immune cells in the airway. In addition, the potential therapeutic value of targeting pyroptosis for the treatment of specific phenotypes of asthma is discussed.

The interplay between ferroptosis and inflammation: therapeutic implications for cerebral ischemia-reperfusion.

Stroke ranks as the second most significant contributor to mortality worldwide and is a major factor in disability. Ischemic strokes account for 71% of all stroke incidences globally. The foremost approach to treating ischemic stroke prioritizes quick reperfusion, involving methods such as intravenous thrombolysis and endovascular thrombectomy. These techniques can reduce disability but necessitate immediate intervention. After cerebral ischemia, inflammation rapidly arises in the vascular system, producing pro-inflammatory signals that activate immune cells, which in turn worsen neuronal injury. Following reperfusion, an overload of intracellular iron triggers the Fenton reaction, resulting in an excess of free radicals that cause lipid peroxidation and damage to cellular membranes, ultimately leading to ferroptosis. The relationship between inflammation and ferroptosis is increasingly recognized as vital in the process of cerebral ischemia-reperfusion (I/R). Inflammatory processes disturb iron balance and encourage lipid peroxidation (LPO) through neuroglial cells, while also reducing the activity of antioxidant systems, contributing to ferroptosis. Furthermore, the lipid peroxidation products generated during ferroptosis, along with damage-associated molecular patterns (DAMPs) released from ruptured cell membranes, can incite inflammation. Given the complex relationship between ferroptosis and inflammation, investigating their interaction in brain I/R is crucial for understanding disease development and creating innovative therapeutic options. Consequently, this article will provide a comprehensive introduction of the mechanisms linking ferroptosis and neuroinflammation, as well as evaluate potential treatment modalities, with the goal of presenting various insights for alleviating brain I/R injury and exploring new therapeutic avenues.

Exploring the lipids, carotenoids, and vitamins content of Rhodotorula glutinis with selenium supplementation under lipid accumulating and growth proliferation conditions

BackgroundRhodotorula glutinis, a specific type of yeast, has been recognised as a superior resource for generating selenium-enriched biomass that possesses exceptional nutritional and functional attributes. The purpose of this investigation was to assess the effect of sodium selenite at different concentrations on lipid and carotenoid synthesis, as well as the growth of R. glutinis.MethodsThe lipid’s fatty acid composition was determined using gas chromatography (GC). The vitamins were detected by high-performance liquid chromatography (HPLC). Transmission electron microscopy was used to detect the structural modification of yeast cells caused by the addition of sodium selenite to the growth medium, as well as the accumulation of elemental selenium in the yeast cells.ResultsThe yeast cells demonstrated the ability to endure high concentrations of sodium selenite under lipid accumulation (LAM) and growth-promoting (YPD) conditions. 25.0 mM and 30.0 mM, respectively, were published as the IC50 values for the LAM and YPD conditions. In both growth media, 1 mM sodium selenite boosted lipid synthesis. Lipid accumulation increased 26% in LAM to 11.4 g/l and 18% in YPD to 4.3 g/l. Adding 1 mM and 3 mM sodium selenite to YPD medium increased total and cellular carotenoids by 22.8% (646.7 µg/L and 32.12 µg/g) and 48.7% (783.3 µg/L and 36.43 µg/g), respectively. Palmitic acid was identified as the most abundant fatty acid in all treatments, followed by oleic acid and linoleic acid. The concentrations of water soluble vitamins (WSV) and fat soluble vitamins (FSV) were generally significantly increased after supplementation with 1.0 mM sodium selenite. TEM examination revealed a significant reduction in lipid bodies accumulation in the yeast cells when sodium selenite was added to lipid-promoting environments. This decline is accompanied by an augmentation in the formation of peroxisomes, indicating that selenium has a direct impact on the degradation of fatty acids. In addition, autophagy appears to be the primary mechanism by which selenium ions are detoxified. Additionally, intracellular organelles disintegrate, cytoplasmic vacuolization occurs, and the cell wall and plasma membrane rupture, resulting in the discharge of cytoplasmic contents, when a high concentration of sodium selenite (20.0 mM) is added. Also, the presence of numerous electron-dense granules suggests an intracellular selenium-detoxification pathway.ConclusionThis study proposes the use of YPD with 1 mM sodium selenite to cultivate selenium-enriched biomass from R. glutinis. This approach leads to heightened lipid levels with higher accumulation of oleic, linoleic and linolenic acids, carotenoids, and vitamins. Hence, this biomass has the potential to be a valuable additive for animal, fish, and poultry feed. Furthermore, explain certain potential factors that indicate the impact of selenium in reducing the accumulation of lipid droplets in R. glutinis during lipogenesis, as detected through TEM examination.

Cinnamon essential oil causes cell membrane rupture and oxidative damage of Rhizopus stolonifer to control soft rot of peaches

Cinnamon essential oil causes cell membrane rupture and oxidative damage of Rhizopus stolonifer to control soft rot of peaches

A type VI secretion system in Burkholderia species cenocepacia and orbicola triggers distinct macrophage death pathways independent of the pyrin inflammasome.

The Burkholderia cepacia complex contains opportunistic pathogens that cause chronic infections and inflammation in the lungs of people with cystic fibrosis. Two closely related species within this complex are Burkholderia cenocepacia and the recently classified Burkholderia orbicola. B. cenocepacia and B. orbicola encode a type VI secretion system and the effector TecA, which is detected by the pyrin/caspase-1 inflammasome, and triggers macrophage inflammatory death. We previously showed that the pyrin inflammasome was dispensable for lung inflammation in mice infected with B. orbicola AU1054, indicating this species activates an alternative pathway of macrophage inflammatory death. Notably, B. cenocepacia strains J2315 and K56-2 can damage macrophage phagosomes, and K56-2 triggers activation of the caspase-11 inflammasome, which detects cytosolic lipopolysaccharide. Here, we investigated inflammatory cell death in pyrin- (Mefv-/-) or caspase-1/caspase-11- (Casp1/11-/-) deficient mouse macrophages infected with B. cenocepacia J2315 or K56-2 or B. orbicola AU1054 or PC184. Macrophage inflammatory death was measured by cleavage of gasdermin D protein, the release of cytokines IL-1α and IL-1β, and plasma membrane rupture. We found that J2315 and K56-2 are detected by the caspase-11 inflammasome in Mefv-/- macrophages, resulting in IL-1β release. By contrast, inflammasome activation was not detected in Mefv-/- macrophages infected with AU1054 or PC184. Instead, AU1054 triggered an alternative macrophage inflammatory death pathway that required TecA and resulted in plasma membrane rupture and IL-1α release. Structural modeling of TecA orthologs in B. cenocepacia and B. orbicola suggested that amino acid changes in the latter may underlie its ability to trigger a non-inflammasome macrophage death pathway.

PROTOCOLOS TERAPÊUTICOS PARA O TRATAMENTO DA ESPOROTRICOSE FELINA REFRATÁRIA E INOVAÇÕES DECORRENTES DAS PESQUISAS

Sporotrichosis in felines is much more pathogenic than in other animals or in humans, even if immunocompetent, which makes treatment a challenge in clinical medicine, as many of them are refractory to the preferred therapy such as Itraconazole or Ketoconazole. This situation also arises from the prolonged oral administration of the medication, the animal's reluctance to take the drug and the guardian's abandonment of the prescription when he notices an improvement in the lesions caused by the disease, which generates relapses and resistance to the antifungals available on the market. Itraconazole, as well as Ketoconazole, act by causing permeability of the plasma membrane and cell necrosis, however, they have adverse effects such as nausea and vomiting in the first and liver disease as relevance in the second. Terbinafine works by interrupting the synthesis of ergosterol and as a consequence the cell membrane ruptures and death, however, it also has side effects such as gastrointestinal and skin problems. Potassium iodide can be used in combination with azoles or Terbinafine, although the literature does not agree with the issue, as not all felines respond to treatment, adverse effects are due to iodism such as depression, anorexia, vomiting and diarrhea. There are also alternative treatments that can enhance oral medication, such as laser therapy, ozone therapy, cryotherapy and cryosurgery. Due to the issue of non-responsive felines, there is research being developed aiming to provide new therapeutic horizons for these animals, such as the use of intranasal infusion of 1% Clotrimazole spray associated with Itraconazole added with Potassium iodide or not, with good results, no relapses and no side effects. NikZ, the result of a substance produced by the bacterium Streptomyces tendae, called Nikkomycin Z, also appears as a new therapeutic potential for the treatment of Sporotrix spp., with a blocking effect on chitin synthase present in the cell wall of fungi, were maide research with dogs, rats and is in Phase 1 of experiments on humans. NikZ represents a new form of prescription, as it can be placed in the animals' drinking water, avoiding the desertion of those responsible for the felines, it has no observable adverse effects in the analyzes carried out and represents an alternative for cats refractory to existing medical protocols in veterinary.

Quercetin suppresses pyroptosis in mouse fibroblasts by inhibiting the NLRP3/caspase-1/GSDMD pathway

To investigate whether quercetin inhibits pyroptosis of mouse fibroblast NIH-3T3 cells by regulating the NLRP3/caspase-1/GSDMD signaling pathway. NIH-3T3 cells were treated with quercetin or MCC950 (a specific inhibitor of NLRP3) before stimulation with lipopolysaccharide (LPS) and ATP to induce cell pyroptosis. The optimal quercetin concentration and duration were screened using the CCK-8assay after testing various concentrations and times. Morphological changes of the treated cells was observed, and the levels of IL-18 and IL-1β in the cell culture supernatant were detected with ELISA; the protein expressions of NLRP3, cleaved caspase-1, and GSDMD-N and the mRNA levels of NLRP3, caspase-1 and GSDMD were detected using Western blotting and qRT-PCR. The changes in cell pyroptosis were examined with TUNEL staining and LDH release assay. The CCK-8 assay indicated that 24-hour treatment with 20 μmol/L quercetin yielded the most favorable results. LPS and ATP stimulation of NIH-3T3 cells induced obvious swelling, cell membrane rupture and leakage of cell contents, significantly increased IL-18 and IL-1β levels, and enhanced protein expressions of NLRP3, cleaved caspase-1 and GSDMD-N and mRNA levels of NLRP3, caspase-1 and GSDMD. LPS and ATP stimulation also caused a significant increment of TUNEL-positive cell counts and LDH release in NIH-3T3 cells. Treatment with quercetin or MCC950 significantly reduced cell pyroptosis induced by LPS and ATP, lowered the concentrations of IL-18 and IL-1β, decreased the expression levels of NLRP3, caspase-1/cleaved caspase-1, GSDMD/GSDMD-N, and reduced the number of TUNEL-positive cells and LDH release. Quercetin suppresses pyroptosis of mouse fibroblasts stimulated with LPS and ATP and reduces secretion of inflammatory cytokines by inhibiting the NLRP3/caspase-1/GSDMD pathway.

NINJ1 regulates ferroptosis via xCT antiporter interaction and CoA modulation.

Ninjurin-1 (NINJ1), initially identified as a stress-induced protein in neurons, recently emerged as a key mediator of plasma membrane rupture (PMR) during apoptosis, necrosis, and pyroptosis. However, its involvement in ferroptosis is less well elucidated. Here, we demonstrate that NINJ1 also plays a crucial role in ferroptosis, but through a distinct mechanism. NINJ1 knockdown significantly protected cancer cells against ferroptosis induced only by xCT inhibitors but no other classes of ferroptosis-inducing compounds (FINs). Glycine, known to inhibit canonical NINJ1-mediated membrane rupture in other cell deaths, had no impact on ferroptosis. A compound screen revealed that the ferroptosis protective effect caused by NINJ1 knockdown can be abolished by pantothenate kinase inhibitor (PANKi), buthionine sulfoximine (BSO), and diethylmaleate (DEM). These results suggest that this ferroptosis protection is mediated via Coenzyme A (CoA) and glutathione (GSH), both of which were found to be elevated upon NINJ1 knockdown. Furthermore, we discovered that NINJ1 interacts with the xCT antiporter, which is responsible for cystine uptake for the biosynthesis of CoA and GSH. The removal of NINJ1 increased xCT levels and stability, enhancing cystine uptake and thereby providing protection against ferroptosis. Conversely, NINJ1 overexpression reduced xCT levels and sensitized ferroptosis. These findings reveal that NINJ1 regulates ferroptosis via a non-canonical mechanism, distinct from other regulated cell deaths.

NINJ1 regulates plasma membrane fragility under mechanical tension.

Plasma membrane integrity is vital not only for cell survival but also nearly all aspects of cell functioning1. Mechanical stress can cause plasma membrane damage2, but it is not known whether there are large molecules (proteins) that control plasma membrane integrity. Here we constructed a 384-well cellular stretch system that delivers precise, reproducible mechanical strain to adherent cells. Using the system, we screened 10,843 siRNAs targeting 2,726 multi-pass transmembrane proteins for stretch-induced membrane permeability changes. The screen identified NINJ1, a protein recently proposed to regulate pyroptosis and other lytic cell death3,4, as the top hit. We demonstrate that NINJ1 is a critical regulator for mechanical force-induced plasma membrane rupture (PMR), without the need of stimulating any cell death programs. Low NINJ1 expression renders the membrane more resistant to stretching, while high expression of NINJ1 lowers the threshold of PMR under mechanical strain. NINJ1 level on the plasma membrane is inversely correlated to tension required to rupture the membrane. In the pyroptosis context, NINJ1 on its own is not sufficient to fully rupture the membrane, and additional mechanical stress is required for full PMR. Our work establishes that NINJ1 functions as a bona fide determinant of membrane biomechanical properties. Our study also suggests that PMR across tissues of distinct mechanical environments is subjected to fine tuning by differences in NINJ1 expression and external mechanical forces.

The Release of Platelet DAMPs is Regulated by NINJ1-Mediated Plasma Membrane Rupture

The Release of Platelet DAMPs is Regulated by NINJ1-Mediated Plasma Membrane Rupture

Selenomethionine Mitigates Effects of Nocardia cyriacigeorgica-Induced Inflammation, Oxidative Stress, and Apoptosis in Bovine Mammary Epithelial Cells

Nocardia cyriacigeorgica causes bovine mastitis, reduces milk quantity and quality, and is often resistant to antimicrobials. Selenomethionine (SeMet) is a form of selenium, which reduces reactive oxygen species (ROS)-mediated apoptosis and intramammary infections. However, the protective effects of SeMet on N. cyriacigeorgica-infected bovine mammary epithelial cells (bMECs) are unclear. The objective of this study was to evaluate whether SeMet mitigated N. cyriacigeorgica-induced inflammatory injury, oxidative damage and apoptosis in bMECs. Cells were cultured with or without being pretreated with 40 µM of SeMet for 12 h, then challenged with N. cyriacigeorgica (multiplicity of infection = 5:1) for 6 h. Although N. cyriacigeorgica was resistant to lincomycin, erythromycin, enrofloxacin, penicillin, amoxicillin, cephalonium, cephalexin, and ceftriaxone, 40 μM SeMet increased cell viability and inhibited lactate dehydrogenase release in infected bMECs. Furthermore, N. cyriacigeorgica significantly induced mRNA production and protein expression of TNF-α, IL-1β, IL-6, and IL-8 at 6 h. Cell membrane rupture, cristae degeneration and mitochondria swelling were evident with transmission electron microscopy. Superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) activities were down-regulated after 3, 6, or 12 h, whereas malondialdehyde (MDA) and ROS contents were significantly upregulated, with cell damage and apoptosis rapidly evident (the latter increased significantly in a time-dependent manner). In contrast, bMECs pretreated with 40 μM SeMet before infection, SOD, and GSH-px activities were upregulated (p < 0.05); MDA and ROS concentrations were downregulated (p < 0.05), and apoptosis was reduced (p < 0.05). In conclusion, 40 μM SeMet alleviated inflammation, oxidative stress and apoptosis induced by N. cyriacigeorgica in bMECs cultured in vitro.

Silver Nanoparticles in Therapeutics and Beyond: A Review of Mechanism Insights and Applications.

Silver nanoparticles (NPs) have become highly promising agents in the field of biomedical science, offering wide therapeutic potential due to their unique physicochemical properties. The unique characteristics of silver NPs, such as their higher surface-area-to-volume ratio, make them ideal for a variety of biological applications. They are easily processed thanks to their large surface area, strong surface plasmon resonance (SPR), stable nature, and multifunctionality. With an emphasis on the mechanisms of action, efficacy, and prospective advantages of silver NPs, this review attempts to give a thorough overview of the numerous biological applications of these particles. The utilization of silver NPs in diagnostics, such as bioimaging and biosensing, as well as their functions in therapeutic interventions such as antimicrobial therapies, cancer therapy, diabetes treatment, bone repair, and wound healing, are investigated. The underlying processes by which silver NPs exercise their effects, such as oxidative stress induction, apoptosis, and microbial cell membrane rupture, are explored. Furthermore, toxicological concerns and regulatory issues are discussed, as well as the present difficulties and restrictions related to the application of silver NPs in medicine.

FengycinA-M3 Inhibits Listeria monocytogenes by Binding to Penicillin-Binding Protein 2B Targets to Disrupt Cell Structure.

The contamination of food with Listeria monocytogenes threatens food safety and human health, and developing a novel, green, and safe antimicrobial substance will offer a new food preservation strategy. FengycinA-M3 is a novel lipid peptide with low cytotoxicity and resistance and has effective antibacterial activity against L. monocytogenes with a minimum inhibitory concentration (MIC) of 4 µg/mL. Further combined transcriptomics and proteomics analysis yielded 20 differentially expressed genes (DEGs). The MICs of the combined use of FengycinA-M3 and Cefalexin on L. monocytogenes were further determined as FengycinA-M3 (2 µg/mL) and Cefalexin (8 µg/mL) using the checkerboard method. In addition, FengycinA-M3 was found to play a role in delaying pork deterioration. This study explored the inhibitory effect of FengycinA-M3 on L. monocytogenes and its mechanism of action. FengycinA-M3 interacted with penicillin-binding protein 2B on the cell membrane of L. monocytogenes, destroying the permeability of the membrane, causing cell membrane rupture, thereby inhibiting the growth of L. monocytogenes. Overall, FengycinA-M3 is a promising candidate for preventing the emergence and spread of L. monocytogenes with potential applications in food processing.

NINJ1-mediated Macrophage Plasma Membrane Rupture and Neutrophil Extracellular Trap Formation Contribute to Oxalate Nephropathy.

Oxalate nephropathy is characterized by calcium oxalate crystals deposition, which triggers necrosis of renal tubular epithelial cells, initiates an inflammatory cascade characterized by neutrophil and macrophage activation within the renal microenvironment. Despite the close association of immune cells with acute oxalate nephropathy, the underlying mechanisms still remain unclear. Nerve injury-induced protein 1 (NINJ1) plays an essential role in the induction of plasma membrane rupture (PMR), leading to damage-associated molecular patterns (DAMPs) release and triggering inflammation. We hypothesize that NINJ1-mediated high mobility group box 1 (HMGB1) release from macrophage PMR and neutrophil extracellular traps (NETs) formation synergistically contribute to the progression of acute oxalate nephropathy. Using a murine model of acute oxalate nephropathy, myeloid cell-specific deletion of Ninj1 mice (Ninj1fl/flvavcre) and their wild-type littermate control mice (Ninj1wt/wtvavcre) were administered intraperitoneal injection of 100 mg/kg sodium oxalate followed by drinking water with 3% sodium oxalate. Evaluation was conducted on tubular injury and inflammatory cell infiltration. In vitro studies involved isolation and culture of renal proximal tubular epithelial cells (RTECs), bone marrow-derived macrophages, and neutrophils to investigate NETs formation and HMGB1 release. Targeted deletion of Ninj1 in myeloid cells significantly mitigated oxalate-induced acute kidney injury by suppressing both HMGB1 release and NETs formation in vivo. In vitro investigations demonstrated that HMGB1 release from macrophage PMR and NETs formation in neutrophils mediated by NINJ1 oligomerization, which consequently coordinated to enhance renal tubular epithelial cell death. Our findings elucidate the pivotal role of NINJ1-dependent macrophage PMR and NETs formation in the progression of acute oxalate nephropathy, providing novel insights for its prevention and therapeutic targets.

Unveiling the Self-assembly and Therapeutic Efficacy of Antimicrobial Peptides SA4 Against Multidrug-Resistant A. baumannii.

Infections linked to Acinetobacter baumannii are one of the main risks of modern medicine. Biofilms formed by A. baumannii due to a protective extracellular polysaccharide matrix make them highly tolerant to conventional antibiotics and raise the possibility of antibiotic resistance. Antimicrobial peptides (AMPs) are gaining popularity due to their broad-spectrum actions and key properties of peptide self-assembly, making them a promising alternative to antibiotics. Here, we demonstrate that 12-residue synthetic self-assembled peptide SA4 nanostructures have enough antibacterial action to prevent the growth of mature bacterial biofilms. The SA4 peptide was successfully synthesized by using the solid-phase peptide synthesis method, and its self-assembly was prepared in water. The self-assembled peptide hydrogel formed nanotube structure was observed under a scanning electron microscope and further characterized to confirm their physical and molecular properties. The resulting hydrogel exhibits significant antibacterial activity against MDR A. baumannii strains (MDR-1 and MDR-2), responsible for many nosocomial infections. In addition, at various gel concentrations, this hydrogel has the potential to inhibit about 30-80% of biofilms formed by MDR strains. Furthermore, under a microscope, it has been observed that the rupture of the bacterial cell membrane and cell wall of A. baumannii cells is caused by peptide nanotubes generated by self-assemblies. Thus, peptide-based nanotubes present intriguing avenues for various biomedical applications. This is the first report of bacterial biofilm removal with SA4 peptide nanotubes, and offering a unique treatment for infections linked to biofilms.