Cell Death Pathways Research Articles

Role of interleukin-16 in human diseases: a novel potential therapeutic target

Interleukin (IL)-16 is expressed mostly by the cells of the human immune system. Upon cell activation IL-16 is cleaved, forming two functional proteins, one regulating cell cycle and the other acting as chemoattractant for the cells carrying CD4 or CD9. Increased levels of IL-16 are found in the circulation and at the sites of inflammation, infection and cancer. Polymorphisms in the IL-16 gene have been coupled to several of these conditions and high IL-16 has been suggested as a disease biomarker. Using unbiased proteomic approach we and others independently identified IL-16 as a biomarker of severe lupus nephritis, and top-expressed cytokine in skin lesions of lupus erythematosus. Recently, an unbiased investigation identified IL-16 as a top candidate for novel drug target. Blockade of IL-16 showed positive therapeutic effects in several animal models of human disease with low rate of side effects. Importantly, it has been recently demonstrated that IL-16 can be released during pyroptosis, a proinflammatory cell death pathway. This finding disclosed a novel role of IL-16 as a mediator of response to the proinflammatory cell death and may explain why IL-16 is detected at the sites of inflammation, infection or cancer. In this review we cover the knowledge on the biology of IL-16 and its importance in human diseases. We aim that this manuscript will be informative and prove benefits of possible therapeutic blockade of IL-16.

Molecular mechanism of PANoptosis and programmed cell death in neurological diseases.

Molecular mechanism of PANoptosis and programmed cell death in neurological diseases.

Mutations in Necroptosis-Related Genes Reported in Breast Cancer: A Cosmic and Uniport Database-Based Study.

Mutations in Necroptosis-Related Genes Reported in Breast Cancer: A Cosmic and Uniport Database-Based Study.

Genetic analysis of mixed lineage kinase domain-like pseudokinase (MLKL) in oral squamous cell carcinoma: A comparative evaluation between young and old patients.

Genetic analysis of mixed lineage kinase domain-like pseudokinase (MLKL) in oral squamous cell carcinoma: A comparative evaluation between young and old patients.

Copper-quercetin complexes: methods of study, relevance to cell death pathways, therapeutic applications.

Copper-quercetin complexes: methods of study, relevance to cell death pathways, therapeutic applications.

Vitamin K2 prevents postoperative cognitive impairments, anxiety-like behavior, and motor dysfunction induced by nanoplastics in young adult mice.

Vitamin K2 prevents postoperative cognitive impairments, anxiety-like behavior, and motor dysfunction induced by nanoplastics in young adult mice.

Research Progress on the Regulatory Role of Different Cell Death Pathways in Metabolic-dysfunction-associated Steatotic Liver Disease.

Research Progress on the Regulatory Role of Different Cell Death Pathways in Metabolic-dysfunction-associated Steatotic Liver Disease.

Cell-death pathways and tau-associated neuronal vulnerability in Alzheimer’s disease

Cell-death pathways and tau-associated neuronal vulnerability in Alzheimer’s disease

4, 9-dihydroxy-α-lapachone as a potent antiproliferation agent for triple-negative breast cancer via ferroptosis.

4, 9-dihydroxy-α-lapachone as a potent antiproliferation agent for triple-negative breast cancer via ferroptosis.

Predictive analysis of the impact of probiotic administration during pregnancy on the functional pathways of the gut microbiome in healthy infants based on 16S rRNA gene sequencing.

Predictive analysis of the impact of probiotic administration during pregnancy on the functional pathways of the gut microbiome in healthy infants based on 16S rRNA gene sequencing.

α-ketoglutarate ameliorates colitis through modulation of inflammation, ER stress, and apoptosis.

α-ketoglutarate ameliorates colitis through modulation of inflammation, ER stress, and apoptosis.

Identification of Potential Targets Associated With Programmed Cell Death for Acute Kidney Injury Based on WGCNA.

Programmed cell death (PCD) pathways play a crucial role in maintaining normal cell turnover and tissue homeostasis, encompassing apoptosis and regulated necrosis. However, the involvement of PCD in the pathogenesis of acute kidney disease remains unexplored. In this study, we utilized gene expression profiling datasets (GSE139061) obtained from the Gene Expression Omnibus (GEO) database. Through differential gene expression analysis and weighted gene co-expression network analysis (WGCNA), we identified five key genes associated with PCD, namely DPP4, ATF3, KIT, MSX1, and SNAI2 in acute kidney injury (AKI). Subsequently, single sample gene set enrichment analysis (ssGSEA) was employed to demonstrate the correlation between these five hub genes and immune cell infiltration as well as activation of immune pathways. Furthermore, we validated our findings by analyzing gene expression patterns using a mouse model of ischemia-reperfusion injury. In conclusion, our study is the first to propose the concept of PCD in the pathogenesis of AKI. This finding has significant implications for future investigations into pro-inflammatory immune mechanisms mediated by damage-associated molecular patterns (DAMPs) during the stages of AKI. Our findings underscore the necessity for further investigation into these molecules, which may offer new avenues for therapeutic intervention in AKI. These identified genes may serve as promising targets for intervention in cases of acute kidney diseases.

Acetylshikonin induces cell necroptosis via mediating mitochondrial function and oxidative stress-regulated signaling in human Oral Cancer cells.

Acetylshikonin induces cell necroptosis via mediating mitochondrial function and oxidative stress-regulated signaling in human Oral Cancer cells.

Utilizing targeted intra-tumoral hyperthermia as an immunotherapy in immunogenically ‘cold’ tumor models.

2581 Background: Hyperthermia is an established adjunct in multimodal cancer treatments, with mechanisms including cell death, immune modulation, and vascular changes. Traditional hyperthermia applications are resource-intensive and often associated with patient morbidity, limiting their clinical accessibility. Gold nanorods (GNRs) offer a precise, minimally invasive alternative by leveraging near-infrared (NIR) light to deliver targeted hyperthermia therapy (THT). THT induces controlled tumor heating, promoting immunogenic cell death (ICD) and modulating the tumor microenvironment (TME) to enhance immune engagement. This study explores the synergistic potential of GNR-mediated THT with immunotherapies in immunogenically ‘cold’ tumors to achieve durable anti-tumor immunity. Methods: GNRs from Sona Nanotech Inc.™ were intratumorally injected and activated using NIR light to induce mild hyperthermia (42–48°C) for 5 minutes. Tumor responses were analyzed for cell death pathways and immune modulation. The immunogenic effects of THT were assessed alone and in combination with intratumoral interleukin-2 (i.t. IL-2) or systemic PD-1 immune checkpoint blockade. Immune cell infiltration, gene expression changes, and tumor growth kinetics were evaluated. Results: THT reduced tumor burden through cell death mechanisms, including upregulated ICD marked by calreticulin exposure within 48 hours. By 48 hours, CD45+ immune cell levels were increased, including increased levels of immunosuppressive M2 macrophages. While THT led to innate immune cell stimulations highlighted by gene expression upregulation in the STING cGAS pathway and enhanced M1 and dendritic cell levels, tumor regrowth was observed within six days post-treatment. To enhance THT's immunogenic effects, the therapy was combined with intratumoral interleukin-2 (i.t. IL-2) or systemic PD-1 immune checkpoint blockade. Sequential administration of i.t. IL-2 post-THT induced robust CD8+ T-cell infiltration and led to sustained tumor regression in both treated and distant tumors, accompanied by the emergence of memory T cells. However, IL-2-induced immunosuppressive T-reg populations were also sustained to tumor endpoint suggesting that therapy could be further enhanced. Additionally, PD-1 expression, which was upregulated in CD8+ T cells by THT, was targeted with systemic PD-1 inhibition, further augmenting immune engagement within the TME. Conclusions: These combinatory treatments demonstrated synergistic effects, promoting durable anti-tumor responses and immune memory. Collectively, GNR-mediated THT effectively reduces tumor burden and remodels the TME, potentiating systemic immunity and enhancing the impact of complementary immunotherapies.

Recent advances in the delivery of microRNAs via exosomes derived from MSCs, and their role in regulation of ferroptosis.

Recent advances in the delivery of microRNAs via exosomes derived from MSCs, and their role in regulation of ferroptosis.

Discovery of nuclear cavities in Epstein-Barr virus-infected cells.

Discovery of nuclear cavities in Epstein-Barr virus-infected cells.

Endothelial but not systemic ferroptosis inhibition protects from antineutrophil cytoplasmic antibody-induced crescentic glomerulonephritis.

Endothelial but not systemic ferroptosis inhibition protects from antineutrophil cytoplasmic antibody-induced crescentic glomerulonephritis.

The role of necroptosis in pathological pregnancies: Mechanisms and therapeutic opportunities.

The role of necroptosis in pathological pregnancies: Mechanisms and therapeutic opportunities.

Unraveling the molecular mechanism underlying the anticancer activity of CISD2/NAF-144-67.

Unraveling the molecular mechanism underlying the anticancer activity of CISD2/NAF-144-67.

Epigenetic mechanism of iPSC-MSC-EVs in colonic epithelial cell pyroptosis in ulcerative colitis cell models via modulation of ELF3/miR-342-3p/KDM6B axis and histone methylation.

Epigenetic mechanism of iPSC-MSC-EVs in colonic epithelial cell pyroptosis in ulcerative colitis cell models via modulation of ELF3/miR-342-3p/KDM6B axis and histone methylation.