Mode Of Cell Death Research Articles

A Coordination Nanosystem Enables Endogenous Ferric Ion-Initiated Multi-Catalysis for Synergistic Tumor-Specific Ferroptosis and Gene Therapy.

Emerging evidence demonstrates that inducing ferroptosis, a nonapoptotic programmed cell death mode, holds significant potential for tumor treatment. However, current ferroptosis strategies utilizing exogenous Fenton-type heavy metal species or introducing glutathione (GSH)/glutathione peroxidase 4 (GPX4) suppressants are hampered by latent adverse effects toward organisms, while utilizing endogenous iron may cause undesirable tumor angiogenesis through specific signaling pathways. Here, aferric ion (Fe3+)-responsive and DNAzyme-delivered coordination nanosystem (ZDD) is developed to achieve a novel scheme of synergistic tumor-specific ferroptosis and gene therapy, which modulates and harnesses the endogenous iron in tumors for inducing ferroptosis while intercepting tumor angiogenesis to enhance therapeutic efficacy. Profiting from the characteristic coordination structure and components, ZDD can not only specifically capture tumor endogenous Fe3+ into the tumor cells to promote the catalytic generation of hydroxyl radicals (·OH) and superoxide anions (O2·-) under acidic environment and the catalytic GSH oxidation, arousing potent ferroptotic cell death, but also effectively deliver specific DNAzyme and release abundant zinc ion (Zn2+) as a powerful cofactor to activate the biocatalytic cleavage of vascular endothelial growth factor receptor 2 (VEGFR2) gene for angiogenesis suppression. Ultimately, the ZDD-enabled synergistic therapy prominently inhibited tumor growth and prevented metastasis, representing a promising nanotherapeutic formula for safe and efficient tumor therapy.

ZBP1-mediated PANoptosis is a crucial lethal form in diverse keratinocyte death modalities in UVB-induced skin injury

UVB irradiation induces diverse modalities of regulatory cell death in keratinocytes. Recently, the pattern of coexistence of pyroptosis, apoptosis, and necroptosis has been termed PANoptosis; however, whether PANoptosis occurs in keratinocytes in UVB-induced skin injury remains unclear. We observed that the key molecules of GSDMD-mediated pyroptosis, apoptosis, and necroptosis, which are N-terminal GSDMD, cleaved caspase-3/PARP, and phosphorylated MLKL, respectively, were elevated in keratinocytes of UVB-challenged mice and human skin tissue. Through keratinocyte-specific gene knockout or using corresponding inhibitors, we found that individual inhibition of GSDMD-mediated pyroptosis, caspase-3-mediated apoptosis, or MLKL-mediated necroptosis did not reduce the overall level of keratinocyte death after UVB exposure, and that the other two pathways maintained the activation. However, when the PANoptosome sensor ZBP1 was knocked out, keratinocyte death was reduced and epidermal thickening was alleviated in UVB-challenged mice. In conclusion, our study demonstrated that UVB irradiation induces ZBP1-mediated PANoptosis in keratinocytes, which is a crucial lethal form in diverse keratinocyte death modalities in UVB-induced skin injury. The above findings provide a new insight on the complexity of regulated cell death modalities in keratinocytes exposed to UV irradiation.

Cu-Mn Nanocomposite for Enhanced Tumor Cuproptosis achieved by Remodeling the Tumor Microenvironment and Activating the Antitumor Immunogenic Responses.

Cuproptosis is a newly discovered mode of cell death, which is caused by excess copper and results in cell death via the mitochondrial pathway. However, the complex tumor microenvironment (TME) is characterized by many factors, including high levels of glutathione and lack O2, limit the application of traditional cuproptosis agents in antitumor therapy. Herein, we report a hyaluronic acid modified copper-manganese composite nanomedicine (CMCNs@HA) to remodel the TME and facilitate efficient cuproptosis in tumor. The integration of CuO2 and MnO2 into CMCNs@HA endows this nanoplatform to generate O2 and deplete GSH in tumor site, ensuring the environment is beneficial to the cuproptosis of tumor. The glutathione (GSH) depletion process is accompanied by the release of Mn2+ ions. The released Mn2+ ions improve the cuproptosis through efficient chemodynamic therapy and initiate immune response via activating the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, which significantly suppresses tumor growth and inhibits tumor metastases. In addition, the Mn2+ ions release process enables this nanoplatform to work as activable T1 contrast agent to achieve accurate tumor diagnosis. This functionally complementary composite metal nanomaterial may provide effective ideas regarding the application of cuproptosis in designing tumor therapeutic regimens. STATEMENT OF SIGNIFICANCE: Cuproptosis in combination with cGAS-STING offers significant potential for tumor treatment. Here, we constructed TME responsive copper-manganese composite nanomaterials (CMCNs@HA) to augment tumor cuproptosis. GSH depletion, hypoxia relief, and effective chemodynamic therapy caused by CMCNs@HA facilitate the progression of cuproptosis. Besides, CMCNs@HA successfully initiate immune response via activating the cyclic GMP-AMP synthase-stimulator of interferon genes pathway and significantly inhibits tumor metastases. Simultaneously, released Mn2+ ions provide real-time magnetic resonance imaging (MRI) signal changes, enabling accurate tumor diagnosis and monitoring of the therapeutic process.

P0190 Hypoglycemia induces SLC7A11-dependent disulfidptosis to regulate intestinal inflammation in IBD

Abstract Background IBD is an autoimmune disease related to intestinal mucosal immune dysregulation, and cellular metabolism is an important factor affecting intestinal immunity[1]. Previous studies have shown that the low-glucose environment inhibits the intestinal immune response to IBD, and the specific mechanism is unknown. Recently, a new mode of cell death has been discovered in the study of tumor cells, which is cytotoxic death caused by cysteine accumulation in cells with high expression of SLC7A11 in a low-glucose environment[2]. Therefore, we wanted to explore whether the phenomenon of disulfidptosis with low glucose environmental effects also exists in IBD and whether it has an impact on the regulation of intestinal inflammation in IBD. Methods We intend to explore the role and mechanism of SLC7A11-dependent disulfidptosis in low-glucose environment in regulating intestinal inflammation in IBD through mass spectrometry, multi-omics and cryo-electron microscopy, and further explore the molecular mechanism of regulating SLC7A11 at the protein structure level, so as to provide a solid theoretical basis for exploring new cell death modes in different glucose environments in IBD. Results We found that the expression of SLC7A11 in the colon of IBD patients and mice with DSS-induced colitis increased, the glucose content of the intestinal mucosa increased, and the genes related to disulfidptosis were down-regulated, suggesting that there may be inhibition of disulfide death in the high-glucose environment in IBD. We further showed that the low-glucose environment may induce disulfidptosis and inhibit inflammation in macrophages under inflammatory conditions, suggesting that the hypoglucose environment may inhibit IBD inflammation by promoting disulfidptosis. Conclusion The hypoglycemic environment in IBD may induce slc7a11-dependent disulfidptosis, thereby inhibiting intestinal inflammation.

Lidocaine could promote the cuproptosis through up-regulating the long noncoding RNA DNMBP-AS1 in Hep-2 cells

BackgroundLidocaine is a traditional local anesthetic, which has been reported to trigger apoptosis through the mitochondrial pathway, independent of death receptor signaling. Cuproptosis is a copper triggered mitochondrial cell death mode. In this study, we explored the biological effects of lidocaine on cuproptosis in Hep-2 cells and studied the relevant mechanisms.Methodsquantitative RT-PCR was used to measure the expression level of long noncoding RNA (IncRNA) DNMBP-AS1. DNMBP-AS1 siRNA (si-DNMBP-AS1) were transfected into Hep-2 cells to verify the roles of DNMBP-AS1 in cuproptosis. 24 h treatment with 20 nM elesclomol and 2 µM CuCl2 was performed to promote the occurrence of Cuproptosis. Cell proliferation, migration and apoptosis assays ware utilized to analyze biological effect of lidocaine and DNMBP-AS1 on Hep-2 cells. Active caspase-3 were also determined after treatment.ResultsDNMBP-AS1 was significantly upregulated during cuproptosis in Hep-2 cells. The si-DNMBP-AS1 significantly increased the cell viability with nonactivated caspase-3, promoted the cell migration and suppress the cuproptosis. Lidocaine was cytotoxic to the Hep-2 cells in a dose- and time-dependent manner. Exposure to 10 µM of lidocaine for 24 h did not reduce the viability or activated the caspase-3, but significantly increased the expression of DNMBP-AS1, and promote the cuproptosis. Anymore, si-DNMBP-AS1 reversed the pro-cuproptosis function of lidocaine.Conclusionslidocaine was cytotoxic to Hep-2 cells in a time- and dose-dependent manner, promoted the cuproptosis through up-regulating DNMBP-AS1. The results of this study offered initial optimism that lidocaine could be used in an adjuvant or neoadjuvant fashion in cancer treatment.

Probing the effects of dextran-coated CeO2 nanoparticles on lung fibroblasts using multivariate single-cell Raman spectroscopy

In this study, we investigated the cytotoxic effect of highly soluble dextran-coated CeO2 nanoparticles on human fetal lung fibroblasts MRC-5. We examined individual nanoparticle-treated cells by Raman spectroscopy and analyzed Raman spectra using non-negative principal component analysis and k-means clustering. In this way, we determined dose-dependent differences between treated cells, which were reflected through the intensity change of lipid, phospholipid and RNA-related Raman modes. Performing standard biological tests for cell growth, viability and induction of apoptosis in parallel, these changes were correlated with nanoparticle-induced apoptotic processes. The cells with specific spectral characteristics, referring to non-apoptotic, but possibly autophagic cell death modality, were also detected. Additionally, Raman imaging combined with principal component and vertex component analysis was used to map the spatial distribution of biological molecules in treated and untreated cells. This work provided the description of different resulting states of the treated cells depending on the dextran-coated CeO2 nanoparticles dose, which can be later used in the design of the nanoparticles for industrial or medical applications. The wide content of information resulting from single-cell Raman spectroscopy has the potential to detect biochemical changes caused by nanoparticles that would otherwise require a series of expensive and time-consuming standard biological techniques.

Tilia species (linden) exert anti-cancer effects on MIA PaCa-2 cells through the modulation of oxidative stress and inflammation

This study investigated the anti-cancer effects of the chemically characterized Tilia species (linden) on MIA PaCa-2 cells by analyzing various cancer-triggering mechanisms, including oxidative stress and inflammation status. Extracts from the flowers, bracts, and inflorescences of T. cordata, T. platyphyllos, T. rubra, and T. tomentosa were evaluated for antioxidant activity; subsequently, their ability to mitigate inflammation was assessed through in vitro nitrite assays in LPS-induced RAW264.7 cells. The anticancer potentials of the extracts against MIA PaCa-2 pancreatic cancer cells were investigated in 2D (cytotoxic effect) and 3D (effect on spheroid growth) models in vitro. All investigated Tilia species displayed remarkable antioxidant activity and significantly inhibited LPS-induced nitrite, IL-6, and PGE2 production. Extract from T. rubra bracts showed the highest cytotoxic activity against MIA PaCa-2 cells with an IC50 value of 0.16 mg/mL, as well as the most significant delay on spheroid growth, which was further confirmed through the arrest in cell cycle. In the Annexin V cell death assays of T. rubra, cells treated with the flower extract exhibited the highest rate of necrotic population with 66.53%. Overall, our results highlight a potential use for Tilia extracts, particularly T. rubra, in pancreatic cancer treatment by modulating cell death.

Unusual Iron-Independent Ferroptosis-like Cell Death Induced by Photoactivation of a Typical Iridium Complex for Hypoxia Photodynamic Therapy.

Ferroptosis is a unique cell death mode that relies on iron and lipid peroxidation (LPO) and is extensively utilized to treat drug-resistant tumor. However, like the other antitumor model, requirement of oxygen limited its application in treating the malignant tumors in anaerobic environments, just as photodynamic therapy, a very promising anticancer therapy. Here, we show that an iridium(III) complex (Ir-dF), which was often used in proton-coupled electron transport (PCET) process, can induce efficient cell death upon photo irradiation, which can be effectively protected by the typical ferroptosis inhibitor Fer-1 but not by the classic iron chelating agents and ROS scavengers. Surprisingly, LPO was further demonstrated to be directly induced by Ir-dF/light activation via PCET, by utilizing a model polyunsaturated fatty acid. Ir-dF was found to be accumulated preferentially in mitochondria and the endoplasmic reticulum (ER), leading to mitochondrial swelling and ER stress accompanied by obvious LPO accumulation and downregulation of the characteristic ferroptosis protein GPX4. More interestingly, Ir-dF was also found to induce photocytotoxicity under hypoxia, and an in vivo experiment further confirmed that Ir-dF can effectively inhibit the growth of tumor under two-photon laser irradiation. Taken together, for the first time, this article introduces a new mechanism of inducing the LPO through a photoactivated PCET process, leading to a ferroptosis-like cell death which is independent of the iron and oxygen. This innovative mechanism holds great potential as a future treatment option for hypoxic malignant tumors and drug-resistant tumors.

Integrative analysis of ferroptosis in the hypoxic microenvironment of gastric cancer unveils the immune landscape and personalized therapeutic strategies.

Ferroptosis is a cell death mode caused by excessive accumulation of lipid peroxides caused by disturbance of intracellular metabolic pathway, which is closely related to iron and cholesterol metabolism homeostasis. Its regulation within the hypoxic metabolic tumor microenvironment (TME) has the potential to improve the effectiveness of tumor immunotherapy. The predictive role of ferroptosis in gastric cancer (GC) hypoxia TME, particularly in relation to TME immune cell infiltration, has not been fully explained. By analyzing the mRNA expression data of ferroptosis and hypoxia-related genes, a prediction model was constructed to evaluate further the predictive value of immune cell infiltration, clinical characteristics, and immunotherapy efficacy of gastric cancer, and the essential genes were validated. Two distinct molecular states of ferroptosis-hypoxia were identified in GC. Notably, patients with high ferroptosis-hypoxia risk scores (FHRS) displayed significant levels of hypoxia and epithelial-mesenchymal transition (EMT), which were associated with unfavorable prognosis, increased chemoresistance, and heightened immunosuppression. This study demonstrates that ferroptosis under hypoxic conditions significantly affects the modulation of the tumor immune microenvironment. The FHRS can independently predict prognosis in gastric cancer. Assessing the molecular status of ferroptosis-hypoxia in individual patients will help in selecting more suitable immunotherapy regimens by providing a better understanding of TME characteristics and predicting immunotherapeutic outcomes.

RuIII-Morpholine-Derived Thiosemicarbazone-Based Metallodrugs: Lysosome-Targeted Anticancer Agents.

The idea of coordinating biologically active ligand systems to metal centers to exploit their synergistic effects has gained momentum. Therefore, in this report, three RuIII complexes 1-3 of morpholine-derived thiosemicarbazone ligands have been prepared and characterized by spectroscopy and HRMS along with the structure of 2 through a single-crystal X-ray diffraction study. The solution stability of 1-3 was tested using conventional techniques such as UV-vis and HRMS. Further, the anticancer activity of 1-3 was tested in HT-29 and HeLa cancer cell lines. To gain insight into their mechanism of action, the cytotoxicity, hydrophobicity, and the interaction of 1-3 with DNA and HSA were evaluated by different conventional methods such as absorption, fluorescence, and circular dichroism studies. Along with favorable biomolecule interaction, 1-3 revealed potent selectivity toward cancer cells, which is a prerequisite for the generation of an anticancer drug. According to cell viability results, 1 has the highest cytotoxicity among all in the group, against both cells, respectively. Additionally, the fluorescence-active ruthenium complexes selectively target lysosomes, which is evaluated by live-cell imaging. 1-3 disrupt the lysosome membrane potential by generating an excessive amount of reactive oxygen species, which results in an apoptotic mode of cell death.

Copper homeostasis and pregnancy complications: a comprehensive review.

Pregnancy complications pose challenges for both pregnant women and obstetricians globally, with the pathogenesis of many remaining poorly understood. Recently coined as a mode of cell death, cuproptosis has been proposed but remains largely unexplored. This process involves copper overload, resulting in the accumulation of fatty acylated proteins and subsequent loss of iron-sulfur cluster proteins. This cascade induces proteotoxic stress, leading to cell death. In recent years, studies have indicated a connection between abnormal copper metabolism and several pregnancy-related diseases, including maternal placental dysplasia, gestational diabetes mellitus (GDM), gestational hypertension (PIH), preterm birth or abortion, as well as conditions in offspring such as intrauterine growth restriction (IUGR), allergic disease, Menkes disease, and Wilson's disease. Investigating the mechanism of cuproptosis and abnormal copper metabolism in these pregnancy-related diseases emerges as a critical research area. This article provides a concise review of cuproptosis mechanisms and emphasizes the association between abnormal copper metabolism and pregnancy-related diseases. Nevertheless, the doubtful viewpoints were also discussed.

Bioinformatics analysis of ferroptosis-related hub genes and immunoinfiltration in myocardial ischemia/reperfusion following heart transplantation

BackgroundIschemia/reperfusion (I/R) is an inevitable pathophysiological process during heart transplantation, and ferroptosis is an important pathogenic mechanism. Unlike other modes of cell death, ferroptosis depends on the accumulation of iron within the cell and the oxidative degradation of polyunsaturated fatty acids. Dysregulation of this pathway has been linked to the progression of multiple pathological conditions, making it an attractive target for therapeutic intervention. Therefore, this study aims to explore the effect of ferroptosis on I/R during heart transplantation.MethodsGEO2R was applied to identify differentially expressed genes (DEGs) obtained from GSE50884 data, which was involved in I/R and heart transplantation. And ferroptosis-related DEGs (FRDEGs) were screened by venn diagram with ferroptosis-related genes downloaded from FerDb database. FRDEGs was enriched and analyzed by GO and KEGG, and hub genes related to ferroptosis were screened by Cytoscape software and database STRING. Additionally, considering the relationship between ferroptosis and immunity, CIBERSORTx was to analyze the infiltration of 22 kinds of immune cells in I/R during heart transplantation, and the correlation between each immune cell and the expression of FRDEGs was also discussed. Finally, the mouse model of heart transplantation with I/R was constructed, and the hub genes was verified by RT-qPCR and western blot.Results12 FRDEGs were identified out of 327 DEGs in GSE50844, which were mainly involved in ferroptosis and other pathways. Three hub genes (SLC7A11, PSAT1, ASNS) were obtained by the degree algorithm of cytohubba plug-in. Immunoinfiltration analysis showed that 16 of 22 immune cells changed, and the immune score of heart transplantation with I/R was higher than that without I/R. In addition, hub genes exhibited significant correlation with Eosinophils, NK cells resting, Dendritic cells resting, NK cells activated and T cells CD4 memory activated. We verified the expression of SLC7A11, PSAT1 and ASNS was higher than that in normal tissues using RT-qPCR and western blot in mouse models of heart transplantation with I/R, companied by ferroptosis aggravated is involved.ConclusionsIn short, ferroptosis is involved in I/R injury during heart transplantation, which is related to immune cell infiltration. Three hub genes (SLC7A11, PSAT1 and ASNS) identified in this study provide therapeutic targets for ameliorating I/R injury in heart transplantation.

TRIM25: A Global Player of Cell Death Pathways and Promising Target of Tumor-Sensitizing Therapies.

Therapy resistance still constitutes a common hurdle in the treatment of many human cancers and is a major reason for treatment failure and patient relapse, concomitantly with a dismal prognosis. In addition to "intrinsic resistance", e.g., acquired by random mutations, cancer cells typically escape from certain treatments ("acquired resistance") by a large variety of means, including suppression of apoptosis and other cell death pathways via upregulation of anti-apoptotic factors or through inhibition of tumor-suppressive proteins. Therefore, ideally, the tumor-cell-restricted induction of apoptosis is still considered a promising avenue for the development of novel, tumor (re)sensitizing therapies. A growing body of evidence has highlighted the multifaceted role of tripartite motif 25 (TRIM25) in controlling different aspects of tumorigenesis, including chemotherapeutic drug resistance. Accordingly, overexpression of TRIM25 is observed in many tumors and frequently correlates with a poor patient survival. In addition to its originally described function in antiviral innate immune response, TRIM25 can play critical yet context-dependent roles in apoptotic- and non-apoptotic-regulated cell death pathways, including pyroposis, necroptosis, ferroptosis, and autophagy. The review summarizes current knowledge of molecular mechanisms by which TRIM25 can interfere with different cell death modalities and thereby affect the success of currently used chemotherapeutics. A better understanding of the complex repertoire of cell death modulatory effects by TRIM25 is an essential prerequisite for validating TRIM25 as a potential target for future anticancer therapy to surmount the high failure rate of currently used chemotherapies.

The COX-2 Inhibitor Celecoxib Sensitizes Nasopharyngeal Carcinoma Cells to Ferroptosis.

Nasopharyngeal cancer (NPC) is prevalent in Southeast Asia and North Africa, which is generally associated with limited treatment options and poor patient prognosis. Ferroptosis is a recently observed cell death modality and has been shown to link to the efficacy of different anti-cancer treatments, thus offering opportunities to the development of novel therapies. This study aims to investigate the potentiating effects of COX-2 inhibitors on ferroptosis in nasopharyngeal cancer. The inhibitory effects of COX-2 inhibitors celecoxib and rofecoxib on nasopharyngeal cancer cells were assessed with MTT, colony formation, sphere formation, Transwell, wound healing assays. The status of COX-2 with celecoxib and rofecoxib treatment was investigated by Western blotting and immunofluorescence experiments. Ferroptosis was induced with the GPX4 inhibitor RSL3 with or without COX-2 inhibition and was monitored by fluorescence microscopy. Transcriptomic profiling was conducted with 5-8F cells treated with DMSO as control or celecoxib, and ferroptosis-related candidates were validated by RT- PCR analysis. Celecoxib and rofecoxib effectively inhibited the growth and migration of nasopharyngeal cancer cells. Both inhibitors evidently sensitized nasopharyngeal cancer cells to ferroptosis induction by RSL3, with celecoxib outperforming rofecoxib. Celecoxib treatment resulted in significantly differentially expressed genes in 5-8F cells, among which CHAC1 was validated as a ferroptosis-related target. The COX-2 inhibitor celecoxib effectively sensitized nasopharyngeal cancer cells to ferroptosis induction.

Regulation and therapy: the role of ferroptosis in DLBCL.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of B-cell non-Hodgkin's lymphoma (NHL), up to 30%-40% of patients will relapse and 10%-15% of patients have primary refractory disease, so exploring new treatment options is necessary. Ferroptosis is a non-apoptotic cell death mode discovered in recent years. Its occurrence pathway plays an essential impact on the therapeutic effect of tumors. Numerous studies have shown that modulating critical factors in the ferroptosis pathway can influence the growth of tumor cells in hematological malignancies including DLBCL. This review highlights recent advances in ferroptosis-related genes (FRGs), including STAT3, Nrf2, and ZEB1, and focuses on the clinical potential of ferroptosis inducers such as IKE, α-KG, DMF, and APR-246, which are currently being explored in clinical studies for their therapeutic effects in DLBCL. Correlational studies provide a novel idea for the research and treatment of ferroptosis in DLBCL and other hematological malignancies and lay a solid foundation for future studies.

A Structural Effect of the Antioxidant Curcuminoids on the Aβ(1-42) Amyloid Peptide.

Investigating amyloid-β (Aβ) peptides in solution is essential during the initial stages of developing lead compounds that can influence Aβ fibrillation while the peptide is still in a soluble state. The tendency of the Aβ(1-42) peptide to misfold in solution, correlated to the aetiology of Alzheimer's disease (AD), is one of the main hindrances to characterising its aggregation kinetics in a cell-mimetic environment. Moreover, the Aβ(1-42) aggregation triggers the unfolded protein response (UPR) in the endoplasmic reticulum (ER), leading to cellular dysfunction and multiple cell death modalities, exacerbated by reactive oxygen species (ROS), which damage cellular components and trigger inflammation. Antioxidants like curcumin, a derivative of Curcuma longa, help mitigate ER stress by scavenging ROS and enhancing antioxidant enzymes. Furthermore, evidence in the literature highlights the effect of curcumin on the secondary structure of Aβ(1-42). This explorative study investigates the Aβ(1-42) peptide conformational behaviour in the presence of curcumin and six derivatives using circular dichroism (CD) to explore their interactions with lipid bilayers, potentially preventing aggregate formation. The results suggest that the synthetic tetrahydrocurcumin (THC) derivative interacts with the amyloid peptide in all the systems presented, while cyclocurcumin (CYC) and bisdemethoxycurcumin (BMDC) only interact when the peptide is in a less stable conformation. Molecular dynamics simulations helped visualise the curcuminoids' effect in an aqueous system and hypothesise the importance of the peptide surface exposition to the solvent, differently modulated by the curcumin derivatives.

The Dual Role of ADAMTS9-AS1 in Various Human Cancers: Molecular Pathogenesis and Clinical Implications.

Long non-coding RNA (lncRNA) is a type of non-coding RNA distinguished by a length exceeding 200 nucleotides. Recent studies indicated that lncRNAs participate in various biological processes, such as chromatin remodeling, transcriptional and post-transcriptional regulation, and the modulation of cell proliferation, death, and differentiation, hence influencing gene expression and cellular function. ADAMTS9-AS1, an antisense long non-coding RNA situated on human chromosome 3p14.1, has garnered significant interest due to its pivotal involvement in the advancement and spread of diverse malignant tumors. ADAMTS9-AS1 functions as a competitive endogenous RNA (ceRNA) that interacts with multiple microRNAs (miRNAs) and plays a crucial role in regulating gene expression and cellular functions by modulating essential signaling pathways, including PI3K/AKT/mTOR, Wnt/β-catenin, and Ras/MAPK pathways. Dysregulation of this factor has been linked to tumor development, migration, invasion, and resistance to apoptotic mechanisms, including as iron-induced apoptosis, underscoring its intricate function in cancer pathology. While current research has clarified certain pathways involved in cancer formation, additional clinical and in vivo investigations are necessary to enhance comprehension of its specific involvement across various cancer types. This review encapsulates the recent discoveries on the correlation of ADAMTS9-AS1 with numerous malignancies, clarifying its molecular mechanisms and its prospective role as a therapeutic target in oncology. Furthermore, it identifies ADAMTS9-AS1 as a potential early diagnostic biomarker and therapeutic target, offering novel opportunities for targeted intervention in oncology.

The crosstalk between exosomal miRNA and ferroptosis: A narrative review.

Ferroptosis is a type of cell death that multiple mechanisms and pathways contribute to the positive and negative regulation of it. For example, increased levels of reactive oxygen species (ROS) induce ferroptosis. ferroptosis unlike apoptosis, it is not dependent on caspases, but is dependent on iron. Exosomes are membrane-bound vesicles with a size of about 30 to 150nm, contain various cellular components, including DNA, RNA, microRNAs (miRNAs), lipids, and proteins, which are genetically similar to their cells of origin. Exosomes are found in all bodily fluids, including blood, saliva, and urine. Cells often release exosomes after their fusion with the cell membrane. They play an important role in immune regulation and cell-cell communication. miRNAs, which are noncoding RNAs with a length of about 18 to 24 nucleotides, are involved in regulating gene expression after transcription. Emerging data suggests that exosomal miRNAs are implicated in various pathophysiological mechanisms of cells, including metastasis, drug resistance, and cell death. In addition, functional studies have indicated that exosomal miRNAs can play a key role in the modulation of cell death by regulating ferroptosis. Therefore, in this review, given the importance of exosomal miRNAs in ferroptosis, we decided to elucidate the relationship between exosomal miRNAs and ferroptosis in various diseases.

Programmed cell death in nasopharyngeal carcinoma: Mechanisms and therapeutic targets.

Programmed cell death is a type of autonomic and orderly cell death mode controlled by genes that maintain homeostasis and growth. Tumor is a typical manifestation of an imbalance in environmental homeostasis in the human body. Currently, several tumor treatments are designed to trigger the death of tumor cells. Nasopharyngeal carcinoma is one of the most common malignant tumors in China. It displays obvious regional and ethnic differences in its incidence, being typically high in the south and low in the north of China. Nasopharyngeal carcinoma is currently considered to be a polygenic inherited disease and is often mediated by the interaction between multiple genes or between genes and the environment. Apoptosis has long been considered the key to tumor treatment, while other cell death pathways have often been overlooked. The current study provides an overview of the relationship among apoptosis, autophagy, pyroptosis, necroptosis, ferroptosis, and nasopharyngeal carcinoma, and the regulatory pathways of nasopharyngeal carcinoma based on five cell death modes were synthesized from the view of molecule. We hope this review will help explore additional, novel programmed cell death targets for the treatment of nasopharyngeal carcinoma and thus promote in-depth research.

Nrf2 and Ferroptosis: Exploring Translational Avenues for Therapeutic Approaches to Neurological Diseases.

Nrf2, a crucial protein involved in defense mechanisms, particularly oxidative stress, plays a significant role in neurological diseases (NDs) by reducing oxidative stress and inflammation. NDs, including Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, stroke, epilepsy, schizophrenia, depression, and autism, exhibit ferroptosis, iron-dependent regulated cell death resulting from lipid and iron-dependent reactive oxygen species (ROS) accumulation. Nrf2 has been shown to play a critical role in regulating ferroptosis in NDs. Age-related decline in Nrf2 expression and its target genes (HO-1, Nqo-1, and Trx) coincides with increased iron-mediated cell death, leading to ND onset. The modulation of iron-dependent cell death and ferroptosis by Nrf2 through various cellular and molecular mechanisms offers a potential therapeutic pathway for understanding the pathological processes underlying these NDs. This review emphasizes the mechanistic role of Nrf2 and ferroptosis in multiple NDs, providing valuable insights for future research and therapeutic approaches.