Near-infrared laser diode mitigates Aß1-42-induced neurodegeneration in cortical neurons.

Alzheimer's disease, a prevalent neurodegenerative condition primarily affecting older adults, remains incurable. Its principle pathological hallmark is the accelerated accumulation of amyloid ß (Aß) protein. This study investigates the potential of photobiomodulation using near infrared light to counteract Aß1-42-induced synaptic degeneration and neurotoxicity. We focused on the effect of 808 nm near-infrared laser diode (LD) on Aß1-42 cytotoxicity in primary cultured cortical neurons. We assessed cell survival using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, observing substantial benefits from LD irradiation with a power of 10 mW and a dose of 30 J. Cells exposed to Aß1-42 exhibited morphological changes indicative of synaptic damage and a significant decrease in the number of postsynaptic density protein-95 (PSD-95) contacts, which were significantly improved with near-infrared LD therapy. Furthermore, this therapy reduced Aß and phosphorylated tau (P-tau) protein accumulation. Additionally, near-infrared LD irradiation substantially lessened the Aß1-42-induced rise in glial fibrillary acid protein (GFAP) and ionized calcium-binding adaptor molecule 1 (IBA1) in astrocytes and microglia. Remarkably, near-infrared LD irradiation effectively inhibited phosphorylation of key proteins involved in Aß1-42-induced necroptosis, namely Receptor-interacting protein kinase-3 (RIP3) and Mixed Lineage Kinase domain-Like protein (MLKL). Our findings suggest that near-infrared LD treatment significantly reduces neurodegeneration by reducing glial overactivation and neuronal necroptosis triggered by Aß1-42. Thus, near-infrared LD treatment emerges as a promising approach for slowing or treating Alzheimer's disease, offering new avenues in its management.

Mechanisms of retinal photoreceptor loss in spontaneously hypertensive rats.

Retinal neurodegenerative diseases, including hypertensive retinopathy, involve progressive damage to retinal neurons, leading to visual impairment. In this study, we investigated the pathological mechanisms underlying retinal neurodegeneration in spontaneously hypertensive rats (SHR), using Wistar Kyoto (WKY) rats as normotensive controls. We observed that SHR exhibited significantly higher blood pressure and decreased retinal thickness, indicating retinal neurodegeneration. Molecular tests including quantitative real-time polymerase chain reaction, immunoblot, and immunofluorescent staining showed elevated levels of the pro-inflammatory cytokine tumor necrosis factor-α, apoptotic markers (Fas, FasL, caspase-8, active caspase-3, and cleaved poly (ADP-ribose) polymerase), and necroptotic markers (receptor-interacting protein kinase-1 and -3) in SHR retinas. Additionally, we found elevated transforming growth factor-ß (TGF-ß) levels in the retinal pigment epithelium (RPE) of SHR, with a decrease in lecithin retinol acyltransferase (LRAT), which regulates retinoid metabolism and photoreceptor health. In human RPE cells (ARPE-19), TGF-ß administration suppressed mRNA and protein levels of LRAT; and vactosertib, a selective inhibitor of TGF-ß receptor kinase type 1, reversed the effect of TGF-ß. These findings suggest that hypertension-induced retinal neurodegeneration involves inflammation, apoptosis, necroptosis, and disrupted retinoid metabolism, providing potential therapeutic targets for hypertensive retinopathy.

S-nitrosoglutathione (GSNO) induces necroptotic cell death in K562 cells: Involvement of p73, TSC2 and SIRT1.

BACKGROUND: Nitric oxide and Reactive Nitrogen Species are known to effect tumorigenicity. GSNO is one of the main NO carrying signalling moiety in cell. In the current study, we tried to delve into the effect of GSNO induced nitrosative stress in three different myelogenous leukemic K562, U937 and THP-1 cell lines. METHOD: WST-8 assay was performed to investigate cell viability. RT-PCR and western-blot analysis were done to investigate mRNA and protein expression. Spectrophotometric and fluorimetric assays were done to investigate enzyme activities. RESULT: We found that GSNO exposure led to reduced cell viability and the mode of cell death in K562 was non apoptotic in nature. GSNO promoted impaired autophagic flux and necroptosis. GSNO treatment heightened phosphorylation of AMPK and TSC2 and inhibited mTOR pathway. We observed increase in NAD+/ NADH ratio following GSNO treatment. Increase in both SIRT1 m-RNA and protein expression was observed. While total SIRT activity remained unaltered. GSNO increased tumor suppressor TAp73/ oncogenic ∆Np73 ratio in K562 cells which was correlated with cell mortality. Surprisingly, GSNO did not alter cellular redox status or redox associated protein expression. However, steep increase in total SNO and PSNO content was observed. Furthermore, inhibition of autophagy, AMPK phosphorylation or SIRT1 exacerbated the effect of GSNO. Altogether our work gives insights into GSNO mediated necroptotic event in K562 cells which can be excavated to develop NO based anticancer therapeutics. CONCLUSION: Our data suggests that GSNO could induce necroptotic cell death in K562 through mitochondrial dysfunctionality and PTM of different cellular proteins.

Cell death pathways: molecular mechanisms and therapeutic targets for cancer.

Cell death regulation is essential for tissue homeostasis and its dysregulation often underlies cancer development. Understanding the different pathways of cell death can provide novel therapeutic strategies for battling cancer. This review explores several key cell death mechanisms of apoptosis, necroptosis, autophagic cell death, ferroptosis, and pyroptosis. The research gap addressed involves a thorough analysis of how these cell death pathways can be precisely targeted for cancer therapy, considering tumor heterogeneity and adaptation. It delves into genetic and epigenetic factors and signaling cascades like the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathways, which are critical for the regulation of cell death. Additionally, the interaction of the microenvironment with tumor cells, and particularly the influence of hypoxia, nutrient deprivation, and immune cellular interactions, are explored. Emphasizing therapeutic strategies, this review highlights emerging modulators and inducers such as B cell lymphoma 2 (BCL2) homology domain 3 (BH3) mimetics, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), chloroquine, and innovative approaches to induce ferroptosis and pyroptosis. This review provides insights into cancer therapy's future direction, focusing on multifaceted approaches to influence cell death pathways and circumvent drug resistance. This examination of evolving strategies underlines the considerable clinical potential and the continuous necessity for in-depth exploration within this scientific domain.

Parkin deficiency exacerbates particulate matter-induced injury by enhancing airway epithelial necroptosis.

Exposure to fine particulate matter (PM) disrupts the function of airway epithelial barriers causing cellular stress and damage. However, the precise mechanisms underlying PM-induced cellular injury and the associated molecular pathways remain incompletely understood. In this study, we used intratracheal instillation of PM in C57BL6 mice and PM treatment of the BEAS-2B cell line as in vivo and in vitro models, respectively, to simulate PM-induced cellular damage and inflammation. We collected lung tissues and bronchoalveolar lavage fluids to assess histopathological changes, necroptosis, and airway inflammation. Our findings reveal that PM exposure induces necroptosis in mouse airway epithelial cells. Importantly, concurrent administration of a receptor interacting protein kinases 3 (RIPK3) inhibitor or the deletion of the necroptosis effector mixed-lineage kinase domain-like protein (MLKL) effectively attenuated PM-induced airway inflammation. PM exposure dose-dependently induces the expression of Parkin, an E3 ligase we recently reported to play a pivotal role in necroptosis through regulating necrosome formation. Significantly, deletion of endogenous Parkin exacerbates inflammation by enhancing epithelial necroptosis. These results indicate that PM-induced Parkin expression plays a crucial role in suppressing epithelial necroptosis, thereby reducing airway inflammation. Overall, these findings offer valuable mechanistic insights into PM-induced airway injury and identify a potential target for clinical intervention.

Modulatory effects of necroptosis: A potential preventive approach to control diseases in fish.

Necroptosis is a caspase-independent programmed cell death process characterized by morphological similarities to necrosis and the potential to cause significant inflammatory reactions. The initiation, execution, and inhibition of necroptosis involve a complex interplay of various signaling proteins. When death receptors bind to ligands, necroptosis is triggered through the receptor-interacting serine/threonine-protein kinase 1 (RIPK1)/RIPK3/Mixed Lineage Kinase Domain-Like (MLKL) axis, leading to inflammatory reactions in the surrounding tissues. This process encompasses numerous physiological regulatory mechanisms and contributes to the development and progression of certain diseases. The mechanisms of necroptosis were not well conserved across terrestrial and aquatic organisms, with differences in some components and functions. Given the significant challenges that aquatic animal diseases pose to aquaculture, research interest in necroptosis has surged recently, particularly in studies focusing on fish. Understanding necroptosis in fish can lead to interventions that offer potential breakthroughs in disease inhibition and fish health improvement.

Renalase alleviates salt-induced kidney necroptosis and inflammation.

Recent evidence suggests that necroptosis may contribute to the development of kidney injury. Renalase is a novel secretory protein that exerts potent prosurvival and anti-inflammatory effects. We hypothesized that renalase could protect the kidney from salt-induced injury by modulating necroptosis. High salt and renalase treatments were administered to Dahl salt-sensitive (SS) rats, renalase knockout (KO) mice, and HK-2 cells. Furthermore, a cohort of 514 eligible participants was utilized to investigate the association between single nucleotide polymorphisms (SNPs) in the genes RIPK1, RIPK3, and MLKL, and the risk of subclinical renal damage (SRD) over 14 years. A high-salt diet significantly increased the expression of key components of necroptosis, namely RIPK1, RIPK3, and MLKL, as well as the release of inflammatory factors in SS rats. Treatment with recombinant renalase reduced both necroptosis and inflammation. In renalase KO mice, salt-induced kidney injury was more severe than in wild-type mice, but supplementation with renalase attenuated the kidney injury. In vitro experiments with HK-2 cells revealed high salt increased necroptosis and inflammation. Renalase exhibited a dose-dependent decrease in salt-induced necroptosis, and this cytoprotective effect was negated by the knockdown of PMCA4b, which is the receptor of renalase. Furthermore, the cohort study showed that SNP rs3736724 in RIPK1 and rs11640974 in MLKL were significantly associated with the risk of SRD over 14 years. Our analysis shows that necroptosis plays a significant role in the development of salt-induced kidney injury and that renalase confers its cytoprotective effects by inhibiting necroptosis and inflammation.

Identification of PANoptosis-relevant subgroups and predicting signature to evaluate the prognosis and immune landscape of patients with biliary tract cancer.

BACKGROUND: This study conducted molecular subtyping of biliary tract cancer patients based on 19 PANoptosis-related gene signatures. METHODS: Through consensus clustering, patients were categorized into two subtypes, A and B. By integrating multi-omics data and clinical information from different cohorts, we elucidated the association between different subtypes of biliary tract cancer and patient prognosis, which correlated with the immune infiltration characteristics of patients. RESULTS: LASSO regression analysis was performed on the 19 gene signatures, and we constructed and validated a 9-gene risk score prognostic model that accurately predicts the overall survival rate of different biliary tract cancer patients. Additionally, we developed a predictive nomogram demonstrating the clinical utility and robustness of our model. Further analysis of the risk score-based immune landscape highlighted potential associations with immune cell infiltration, chemotherapy, and immune therapy response. CONCLUSION: Our study provides valuable insights into personalized treatment strategies for biliary tract cancer, which are crucial for improving patient prognosis and guiding treatment decisions in clinical practice.

Preliminary evidence for the presence of programmed cell death in pressure injuries.

Pressure injuries (PIs) are a common healthcare problem worldwide and are considered to be the most expensive chronic wounds after arterial ulcers. Although the gross factors including ischemia-reperfusion (I/R) have been identified in the etiology of PIs, the precise cellular and molecular mechanisms contributing to PIs development remain unclear. Various forms of programmed cell death including apoptosis, autophagy, pyroptosis, necroptosis and ferroptosis have been identified in PIs. In this paper, we present a detailed overview on various forms of cell death; discuss the recent advances in the roles of cell death in the occurrence and development of PIs and found much of the evidence is novel and based on animal experiments. Herein, we also state critical evaluation of the existing data and future perspective in the field. A better understanding of the programmed cell death mechanism in PIs may have important implications in driving the development of new preventive and therapeutic strategies.

Screening chondrocyte necroptosis-related genes in the diagnosis and treatment of osteoarthritis.

Background: Osteoarthritis (OA) is the most common form of joint diseases, with hallmark of cartilage degeneration. Recent studies have shown that the pathogenesis of OA is associated with chondrocyte necroptosis. Methods: In this study, we used single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing data to analyze necroptosis regulation in OA chondrocytes. We performed enrichment analysis, carried out experimental validation, constructed machine learning models, and docked drug molecules. Results: After least absolute shrinkage and selection operator (LASSO) algorithm screening, 4 hub genes (RIPK3, CYBB, HSP90AB1, and TRAF5) with diagnostic characteristics were obtained. Following the comparison of multiple models, the Bayesian model with an average area under curve (AUC) value of 0.944 was finally selected. We found that nimesulide exhibited strong binding affinity to CYBB and HSP90AB1, and experimentally verified that nimesulide reduced the expression of RIPK3 and CYBB, suggesting its potential as an inhibitor of chondrocyte necroptosis. Furthermore, scRNA-seq results showed that necroptosis in OA was significantly upregulated on regulatory chondrocytes (RegC) compared to other chondrocyte subtypes. Conclusions: The results indicate that nimesulide might be used to treat OA by inhibiting chondrocyte necroptosis through down-regulation of RIK3 and CYBB genes. This study reveals the role of chondrocyte necroptosis in OA, and suggests a potential therapeutic strategy by regulating necroptosis with nimesulide.

PANoptosis opens new treatment options for allergic bronchopulmonary aspergillosis.

Background: Allergic bronchopulmonary aspergillosis (ABPA) is a rare airway disorder primarily affecting patients with asthma and cystic fibrosis. Persistent airway inflammation brought on by Aspergillus fumigatus exacerbates the underlying condition and can cause significant respiratory damage. Treatments center on reducing inflammation with the use of corticosteroids and antifungals. PANoptosis is a new concept in the field of cell death and inflammation that posits the existence of cross talk and a master control system for the 3 programmed cell death (PCD) pathways, namely, apoptosis, pyroptosis, and necroptosis. This concept has revolutionized the understanding of PCD and opened new avenues for its exploration. Studies show that Aspergillus is one of the pathogens that is capable of activating PANoptosis via the Z-DNA binding protein 1 (ZBP1) pathway and plays an active role in the inflammation caused by this organism. Objective: This article explores the nature of inflammation in ABPA and ways in which PCD could lead to novel treatment options. Method: PubMed was used to review the literature surrounding Aspergillus infection-related inflammation and PANoptosis. Results: There is evidence that apoptosis and pyroptosis protect against Aspergillus-induced inflammation, whereas necroptosis promotes inflammation. Conclusion: Experimental medications, in particular, necroptosis inhibitors such as necrosulfonamide and necrostatin-1, should be studied for use in the treatment of ABPA.

S100A8/A9-activated IFNγ+ NK cells trigger ß-cell necroptosis in hepatitis B virus-associated liver cirrhosis.

BACKGROUND AND AIMS: Hepatitis B virus (HBV)-associated liver cirrhosis (LC), a common condition with high incidence and mortality rates, is often associated with diabetes mellitus (DM). However, the molecular mechanisms underlying impaired glucose regulation during HBV-associated LC remain unclear. METHODS: Data from 63 patients with LC and 62 patients with LC-associated DM were analysed. Co-culture of NK cells and islet ß cell lines were used to study the glucose regulation mechanism. A mouse model of LC was used to verify the effect of S100A8/A9 on the glucose regulation. RESULTS: Higher levels of interferon (IFN)-γ derived from natural killer (NK) cells and lower levels of insulin emerged in the peripheral blood of patients with both LC and DM compared with those from patients with LC only. IFN-γ derived from NK cells facilitated ß cell necroptosis and impaired insulin production. Furthermore, S100A8/A9 elevation in patients with both LC and DM was found to upregulate IFN-γ production in NK cells. Consistently, in the mouse model for LC, mice treated with carbon tetrachloride (CCL4) and S100A8/A9 exhibited increased blood glucose, impaired insulin production, increased IFN-γ, and increased ß cells necroptosis compared with those treated with CCL4. Mechanistically, S100A8/A9 activated the p38 MAPK pathway to increase IFN-γ production in NK cells. These effects were diminished after blocking RAGE. CONCLUSION: Together, the data indicate that IFN-γ produced by NK cells induces ß cell necroptosis via the S100A8/A9-RAGE-p38 MAPK axis in patients with LC and DM. Reduced levels of S100A8/A9, NK cells, and IFN-γ could be valuable for the treatment of LC with DM. Accumulation of S100A8/A9 in patients with LC may indicate the emergence of DM.

Necroptosis in alveolar epithelial cells drives lung inflammation and injury caused by SARS-CoV-2 infection.

COVID-19, caused by SARS-CoV-2 infection, results in irreversible or fatal lung injury. We assumed that necroptosis of virus-infected alveolar epithelial cells (AEC) could promote local inflammation and further lung injury in COVID-19. Since CD8+ lymphocytes induced AEC cell death via cytotoxic molecules such as FAS ligands, we examined the involvement of FAS-mediated cell death in COVID-19 patients and murine COVID-19 model. We identified the occurrence of necroptosis and subsequent release of HMGB1 in the admitted patients with COVID-19. In the mouse model of COVID-19, lung inflammation and injury were attenuated in Fas-deficient mice compared to Fas-intact mice. The infection enhanced Type I interferon-inducible genes in both groups, while inflammasome-associated genes were specifically upregulated in Fas-intact mice. The treatment with necroptosis inhibitor, Nec1s, improved survival rate, lung injury, and systemic inflammation. SARS-CoV-2 induced necroptosis causes cytokine induction and lung damage, and its inhibition could be a novel therapeutic strategy for COVID-19.

Licochalcone A attenuates NMDA-induced neurotoxicity.

This study investigates the effect of Licochalcone A (Lico-A), a flavonoid from licorice roots known for its anti-inflammatory, anti-cancer, and antioxidant properties, on NMDA-induced neurotoxicity in primary cultured rat hippocampal neurons. The study measured cell survival following NMDA and Lico-A exposure, revealing that Lico-A at a 2.5 µg/ml significantly improved cell viability, countering the detrimental effects of NMDA. The study also analyzed synaptic changes by examining both postsynaptic density 95 (PSD95) and synaptophysin-targeted imaging, showing that Lico-A treatment resulted in a significant increase in synaptic puncta, contrasting with the reduction observed under NMDA exposure. Furthermore, levels of phosphorylated mixed lineage kinase domain-like pseudokinase (P-MLKL) and phosphorylated receptor-interacting serine/threonine-protein kinase 3 (P-RIP3), key necroptosis regulators, were measured using Western blotting. The results showed an increase in P-MLKL and P-RIP3 in neurons exposed to NMDA, which was reduced following Lico-A treatment. The response of astrocyte and microglia was also evaluated by immunostaining for glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule 1 (IBA-1) and tumor necrosis factor alpha (TNF-α). These markers exhibited heightened expression in the NMDA group, which was substantially reduced by Lico-A treatment. These findings suggest that Lico-A has neuroprotective effects against NMDA-induced neurotoxicity, potentially contributing to synaptic preservation, inhibition of neuronal necroptosis, and modulation of glial activation. Therefore, Lico-A shows promise as a neuroprotective agent for conditions associated with NMDA-related neurotoxicity.

The role of hydrogen sulfide in the regulation of necroptosis across various pathological processes.

Necroptosis is a programmed cell death form executed by receptor-interacting protein kinase (RIPK) 1, RIPK3 and mixed lineage kinase domain-like protein (MLKL), which assemble into an oligomer called necrosome. Accumulating evidence reveals that necroptosis participates in many types of pathological processes. Hence, clarifying the mechanism of necroptosis in pathological processes is particularly important for the prevention and treatment of various diseases. For over 300 years, hydrogen sulfide (H2S) has been widely known in the scientific community as a toxic and foul-smelling gas. However, after discovering the important physiological and pathological functions of H2S, human understanding of this small molecule changed, believing that H2S is the third gas signaling molecule after carbon monoxide (CO) and nitric oxide (NO). H2S plays an important role in various diseases, but the related mechanisms are not yet fully understood. In recent years, more and more studies have shown that H2S regulation of necroptosis is involved in various pathological processes. Herein, we focus on the recent progress on the role of H2S regulation of necroptosis in different pathological processes and profoundly analyze the related mechanisms.

Classical apoptotic stimulus, staurosporine, induces lytic inflammatory cell death, PANoptosis.

Innate immunity is the body's first line of defense against disease, and regulated cell death is a central component of this response that balances pathogen clearance and inflammation. Cell death pathways are generally categorized as non-lytic and lytic. While non-lytic apoptosis has been extensively studied in health and disease, lytic cell death pathways are increasingly implicated in infectious and inflammatory diseases and cancers. Staurosporine (STS) is a well-known inducer of non-lytic apoptosis. However, in this study, we observed that STS also induces lytic cell death at later timepoints. Using biochemical assessments with genetic knockouts, pharmacological inhibitors, and gene silencing, we identified that STS triggered PANoptosis via the caspase-8/RIPK3 axis, which was mediated by RIPK1. PANoptosis is a unique, lytic, innate immune cell death pathway initiated by innate immune sensors and driven by caspases and RIPKs through PANoptosome complexes. Deletion of caspase-8 and RIPK3, core components of the PANoptosome complex, protected against STS-induced lytic cell death. Overall, our study identifies STS as a time-dependent inducer of lytic inflammatory cell death, PANoptosis. These findings emphasize the importance of understanding trigger- and time-specific activation of distinct cell death pathways to advance our understanding of the molecular mechanisms of innate immunity and cell death for clinical translation.

Inhibitors identify an auxiliary role for mTOR signalling in necroptosis execution downstream of MLKL activation.

Necroptosis is a lytic and pro-inflammatory form of programmed cell death executed by the terminal effector, the MLKL (mixed lineage kinase domain-like) pseudokinase. Downstream of death and Toll-like receptor stimulation, MLKL is trafficked to the plasma membrane via the Golgi-, actin- and microtubule-machinery, where activated MLKL accumulates until a critical lytic threshold is exceeded and cell death ensues. Mechanistically, MLKL's lytic function relies on disengagement of the N-terminal membrane-permeabilising four-helix bundle domain from the central autoinhibitory brace helix: a process that can be experimentally mimicked by introducing the R30E MLKL mutation to induce stimulus-independent cell death. Here, we screened a library of 429 kinase inhibitors for their capacity to block R30E MLKL-mediated cell death, to identify co-effectors in the terminal steps of necroptotic signalling. We identified 13 compounds - ABT-578, AR-A014418, AZD1480, AZD5363, Idelalisib, Ipatasertib, LJI308, PHA-793887, Rapamycin, Ridaforolimus, SMI-4a, Temsirolimus and Tideglusib - each of which inhibits mammalian target of rapamycin (mTOR) signalling or regulators thereof, and blocked constitutive cell death executed by R30E MLKL. Our study implicates mTOR signalling as an auxiliary factor in promoting the transport of activated MLKL oligomers to the plasma membrane, where they accumulate into hotspots that permeabilise the lipid bilayer to cause cell death.

Epigenetic regulation of diverse regulated cell death modalities in cardiovascular disease: Insights into necroptosis, pyroptosis, ferroptosis, and cuproptosis.

Cell death constitutes a critical component of the pathophysiology of cardiovascular diseases. A growing array of non-apoptotic forms of regulated cell death (RCD)-such as necroptosis, ferroptosis, pyroptosis, and cuproptosis-has been identified and is intimately linked to various cardiovascular conditions. These forms of RCD are governed by genetically programmed mechanisms within the cell, with epigenetic modifications being a common and crucial regulatory method. Such modifications include DNA methylation, RNA methylation, histone methylation, histone acetylation, and non-coding RNAs. This review recaps the roles of DNA methylation, RNA methylation, histone modifications, and non-coding RNAs in cardiovascular diseases, as well as the mechanisms by which epigenetic modifications regulate key proteins involved in cell death. Furthermore, we systematically catalog the existing epigenetic pharmacological agents targeting novel forms of RCD and their mechanisms of action in cardiovascular diseases. This article aims to underscore the pivotal role of epigenetic modifications in precisely regulating specific pathways of novel RCD in cardiovascular diseases, thus offering potential new therapeutic avenues that may prove more effective and safer than traditional treatments.

Wogonin Inhibits Apoptosis and Necroptosis Induced by Nephropathogenic Infectious Bronchitis Virus in Chicken Renal Tubular Epithelial Cells.

NIBV is an acute and highly contagious virus that has a major impact on the poultry industry. Wogonin, as a flavonoid drug, has antiviral effects, but there have been no reports indicating its role in renal injury caused by NIBV infection. The aim of this study is to investigate the antiviral effect of wogonin against NIBV. Renal tubular epithelial cells were isolated and cultured, and divided into four groups: Con, Con+Wog, NIBV and NIBV+Wog. We found that wogonin significantly inhibited the copy number of NIBV and significantly alleviated NIBV-induced cell apoptosis and necrosis. Moreover, wogonin inhibited the reduction in mitochondrial membrane potential and the aberrant opening of mPTP caused by NIBV. In conclusion, wogonin can protect renal tubular epithelial cells from damage by inhibiting the replication of NIBV and preventing mitochondrial apoptosis and necroptosis induced by NIBV.

Acute liver failure: A clinically severe syndrome characterized by intricate mechanisms.

Acute liver failure presents as a clinical syndrome characterized by swift deterioration and significant mortality rates. Its underlying mechanisms are intricate, involving intricate interplays between various cells. Given the current scarcity of treatment options, there's a pressing need to diligently uncover the disease's core mechanisms and administer targeted therapies accordingly.