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Globally, cancer is a serious health problem. It is unfortunate that current anti-cancer strategies are insufficiently specific and damage the normal tissues. There's urgent need for development of new anti-cancer strategies. More recently, increasing attention has been paid to the new application of ferroptosis and nano materials in cancer research. Ferroptosis, a condition characterized by excessive reactive oxygen species-induced lipid peroxidation, as a new programmed cell death mode, exists in the process of a number of diseases, including cancers, neurodegenerative disease, cerebral hemorrhage, liver disease, and renal failure. There is growing evidence that inducing ferroptosis has proven to be an effective strategy against a variety of chemo-resistant cancer cells. Nano-drug delivery system based on nanotechnology provides a highly promising platform with the benefits of precise control of drug release and reduced toxicity and side effects. This paper reviews the latest advances of combination therapy strategies based on biomedical nanotechnology induced ferroptosis for cancer therapeutics. Given the new chances and challenges in this emerging area, we need more attention to the combination of nanotechnology and ferroptosis in the treatment of cancer in the future. [Display omitted] • Current anti-cancer strategies are lack of specificity and damage normal tissues. • Ferroptosis is an effective strategy against chemo-resistant cancer cells. • Nanotechnology provides of precise control of drug release and reduced toxicity. • Combination therapy based on ferroptosis-induced nano-DDS brings enhanced antitumor effect and has satisfactory safety. [ABSTRACT FROM AUTHOR]

Coxsackievirus group B (CVB) is considered as one of the most common pathogens of human viral myocarditis. CVB-induced myocarditis is mainly characterized by the persistence of the virus infection and immune-mediated inflammatory injury. Costimulatory signals are crucial for the activation of adaptive immunity. Our data reveal that the CVB type 3 (CVB3) infection altered the expression profile of costimulatory molecules in host cells. CVB3 infection caused the decrease of PD-1 ligand expression, partially due to the cleavage of AU-rich element binding protein AUF1 by the viral protease 3Cpro, leading to the exacerbated inflammatory injury of the myocardium. Moreover, systemic PD-L1 treatment, which augmented the apoptosis of proliferating lymphocytes, alleviated myocardial inflammatory injury. Our findings suggest that PD1-pathway can be a potential immunologic therapeutic target for CVB-induced myocarditis. • Coxsackievirus B3 infection causes costimulatory molecules profile changes. • Coxsackievirus B3 induces decrease of programmed cell death 1 ligands. • Treatment with programmed cell death ligand recombinant Ig could relieve myocardial inflammatory injury. [ABSTRACT FROM AUTHOR]

Melatonin reversed arginine vasopressin-induced apoptosis on H9c2 cardiomyoblasts by increasing Mst1-Nrf2 activity, yielding anti-oxidative enzyme up-regulation and lowered apoptosis; thus, it could serve as a potential heart failure treatment. [Display omitted] Heart failure patients have elevated arginine vasopressin (AVP) levels, which are involved in inducing peripheral vasoconstriction and cardiac hypertrophy. This hypertrophy, along with cardiomyocyte apoptosis, results from oxidative stress. Therefore, the antioxidant drug, melatonin (Mel), is commonly used to treat cardiac hypertrophy and apoptosis; however, whether it could alleviate AVP-induced myocardial injury remains to be addressed. In this study, high AVP doses were found to induce H9c2 cardiomyoblast apoptosis, demonstrated by increased terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells, pro-apoptotic B-cell lymphoma-2 (Bcl-2)-associated X protein (Bax) up-regulation, and anti-apoptotic Bcl-2 downregulation. This AVP-induced apoptotic increase, along with lowered cell viability, was also associated with higher reactive oxygen species (ROS) levels and lowered mitochondrial membrane potentials (MMP), which were all reversed upon Mel administration. Further investigations found that apoptosis, ROS, and MMP outcomes under high AVP were associated with Mst1-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway suppression, yielding mitochondrial dysfunction, and Mel reversed them via promoting Mst1 phosphorylation, which then activated Nrf2 to increase anti-oxidative enzyme production. These findings were supported by siRNA gene suppression, where knocking down either Nrf2 or Mst1 abrogated the anti-apoptotic effects of Mel in cardiomyoblasts. Therefore, Mel could reduce cardiomyoblast apoptosis under high AVP levels, via Mst1-Nrf2 pathway re-activation, to enhance anti-oxidative responses. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to investigate the apoptotic effect of a proteasome inhibitor MG-132 on Tca-8113, a cell line of human tongue squamous cell carcinoma. Tca-8113 cells were treated with 10, 20, and 30μM of MG-132, or 5μM thapsigargin. Apoptosis rate was determined with annexin V/propidium iodide double staining. Expression of E3ubiquitin-protein ligase was determined by ELISA, and Grp78 and caspase-12 mRNA, and Grp78 and caspase-12 protein was assessed by RT-PCR and Western blot, respectively. Apoptosis was observed 18h after MG-132 treatment. The apoptotic rate in the 10, 20, and 30μM MG-132 group was 13.5, 19.6 and 34.7%, respectively, which was higher than in the thapsigargin (8.5%, P <0.01) or control group (0.5%, P <0.01). The expression of E3 ubiquitin-protein ligase in the 10, 20, and 30μM MG-132 group was 28.75±2.28, 18.16±0.65, 8.85±0.72, respectively, which was lower than in the thapsigargin (38.96±0.33, P <0.05 or 0.01) or control (40.88±4.52, P <0.05 or 0.01) group. The levels of Grp78 and capase-12 mRNA, Grp78 and caspase-12 protein in the MG-132 groups were higher than in the control group (P <0.01). In conclusion, MG-132 induces apoptosis in Tca-8113 cells in a concentration-dependent manner. The MG-132-induced apoptosis may involve downregulation of E3 ubiquitin ligase, and upregulation of Grp78 and caspase-12. [Copyright &y& Elsevier]

Intervertebral disc degeneration (IVDD) constitutes a crucial pathological foundation for spinal degenerative diseases (SDD) and stands as a primary contributor to both low back pain (LBP) and disability. The progression of IVDD is linked to structural and functional alterations in tissues, where an imbalance in the inflammatory microenvironment can induce extracellular matrix (ECM) degradation, senescence, and apoptosis. This imbalance is a key pathomechanism in the disease's development, gaining considerable attention in recent years. This study aims to conduct a bibliometric analysis of publications pertaining to the inflammatory mechanisms of IVDD to quantitatively assess current research hotspots and directions. In this study, we queried the Web of Science Core Collection (WOSCC) database covering the period from January 1, 2001, to November 7, 2023. Content in this area was analyzed and visualized using software such as Citespace, Vosviewer, and the bibliometrix package. Findings indicate a consistent annual increase in the number of publications, highlighting the widespread attention garnered by research on the inflammatory mechanisms of IVDD. In terms of journal research, Spine emerged with the highest number of publications, along with significantly elevated total citations and average citations compared to other journals. Regarding country analysis, China led in the number of publications, while the USA claimed the highest number of citations and total link strength. Institutional analysis revealed Sun Yat-sen University as having the highest number of publications and total link strength, with Thomas Jefferson University securing the highest total citations. Author analysis identified Ohtori, S. with the highest number of publications, Risbud, M.V. with the highest number of citations, and Inoue, G. with the highest total link strength, all of whom have made significant contributions to the field's development. Citation and co-citation analyses indicated that highly cited documents primarily focused on classical studies exploring inflammatory mechanisms in IVDD pathogenesis. Keyword analysis showcased the ongoing research hotspot as the further investigation of mechanisms and treatment studies. Recent years have seen a shift towards exploring pyroptosis, necrotic apoptosis, autophagy, ferroptosis, oxidative stress, and bacterial infection, among other mechanisms. In terms of treatment, alongside traditional monomer, drug, and compound therapies for IVDD, research is increasingly concentrating on stem cell therapy, exosomes, hydrogels, and scaffolds. This bibliometric analysis of research on inflammatory mechanisms in IVDD provides insights into the current status, hotspots, and potential future trends. These findings can serve as a valuable reference and guide for researchers in the field. • This study is the first to explore the hotspots and future trends in the study of inflammatory mechanisms in IVDD through bibliometric methods. • The ongoing research hotspot as the further investigation of mechanisms and treatment studies. [ABSTRACT FROM AUTHOR]

Abstract: This study was designed to investigate the function of 17β-estradiol (17β-E2) against oxidative stress on the cell death of mice bone marrow mesenchymal stem cells (BMSCs) induced by hydrogen peroxide (H2O2). BMSCs were treated with 17β-E2 for 24h and then treated with 100μM H2O2 for 1h. Cell viability, apoptosis, caspase-9 mRNA, JNKs (Jun N-terminal kinases) and c-Jun protein expression in BMSCs were evaluated. Cell apoptosis of BMSCs were increased in a dose-dependent manner after treated with H2O2 compared to control group. But pretreatment with 17β-E2 can inhibit apoptosis of BMSCs, preserve the mitochondrial transmembrane potential, decrease caspase-9 mRNA, JNK1/2 and c-Jun protein expression. In conclusion, 17β-E2 exerts antiapoptotic effects in BMSCs which related to the mitochondria death pathway and JNKs pathway. The study revealed that 17β-E2 can reduce the donor stem cells damage. [Copyright &y& Elsevier]

The insidious clinical symptoms of pancreatic cancer (PACA), extensive tolerance to radiotherapy and chemotherapy, and insensitivity to immunotherapy result in an inferior prognosis. Redox dyshomeostasis could trigger programmed cell death and contribute to functional changes in immune cells, which is strongly associated with tumorigenesis and tumor development. Therefore, it is warranted to decipher the crosstalk between regulated cell death and immunity in the context of redox dyshomeostasis for PACA. Herein, four redox-related subtypes of PACA were identified: C1 and C2 displayed malignant phenotypes with dismal clinical outcomes, conspicuous enrichment in cell death pathways, high redox score, low immune activation, and "immune-desert" tumor immune microenvironment (TIME); C3, an immune-rejection/excluded subtype, with abundant immune cells, high co-stimulatory, co-inhibitory, and MHC molecules, and potential response to immunotherapy; C4, with the best prognosis, low redox pattern, high level of autophagy, low enrichment of most cell death-related pathways, and "immune-hot" TIME. Overall, this study found an attractive platform from the perspective of redox-related pathways, which would propose insights into the intricate and elaborate molecular mechanisms of PACA and offer more effective and tailored intervention protocols. • The higher basal oxidative state in PACA was related to higher programmed cell death signals, conducting an "immune-cold" TIME. • Relatively low levels of redox state portended favorable clinical outcomes in PACA patients. • ROS manipulation treatment may be a novel potential therapeutic approach for C1 and C2 patients. [ABSTRACT FROM AUTHOR]

Exposure of Tca-8113 cells to proteasome inhibitor carbobenzoxy-Leu-Leu-leucinal (MG-132) causing apoptosis is associated with endoplasmic reticulum (ER) stress. X-box-binding protein-1 (XBP1) is an important regulator of a subset of genes active during ER stress, which is related to cell survival and is required for tumor growth. The present study is to evaluate the effect of MG-132 on ROS production, XBP1 gene expression, tumor necrosis factor receptor-associated factor 2 (TRAF2), ASK1 and c -jun protein expression in tongue squamous cell carcinoma cell line Tca-8113 cells. ROS production was measured by reactive oxygen species assay. X-box binding protein-1 (XBP1) mRNA was analyzed by real-time–PCR, TRAF2, ASK1 and c -jun protein were investigated by western blot and immunocytochemistry respectively. The result indicated that ROS production, TRAF2, ASK1 and c -jun were elevated in MG-132 treated cells. Giving ROS scavenger N -acetyl- L -cysteine (NAC) largely prevented the effects of MG-132. Furthermore, treating with MG-132 lead to decreased XBP1 mRNA expression but could not completely block the expression of XBP1. Taken together, these findings provide the evidence that MG-132 induced ER stress lead to Tca-8113 cells apoptosis through ROS generation and TRAF2-ASK1-JNK signal pathway activation. [ABSTRACT FROM AUTHOR]

Chemoresistance is one of the main obstacles in the therapy of human cancers, including colorectal cancer (CRC). Long non-coding RNA heart and neural crest derivatives expressed 2-antisense RNA 1 (lncRNA HAND2-AS1) has been demonstrated to be associated with CRC. However, the function of HAND2-AS1 in 5-Fluorouracil (5-FU) resistance of CRC remains unclear. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression of HAND2-AS1, miR-20a and programmed cell death factor 4 (PDCD4) mRNA. 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay was conducted to evaluate IC50 of 5-FU and cell proliferation. Flow cytometry analysis was used to determine cell apoptosis. Transwell assay was carried out to measure cell migration and invasion. Western blot assay was conducted to examine the protein levels of B-cell lymphoma-2 (Bcl-2), BCL2-Associated X (Bax), matrix metalloprotein 2 (MMP2), MMP9 and PDCD4. Dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull down assay were utilized to verify the combination between miR-20a and HAND2-AS1. Dual-luciferase reporter assay was used to analyze the association between miR-20a and PDCD4. Murine xenograft assay was used to confirm the function of HAND2-AS1 in vivo. HAND2-AS1 and PDCD4 were downregulated and miR-20a was upregulated in 5-FU-resistant CRC tissues and cells. HAND2-AS1 suppressed 5-FU resistance, cell proliferation, migration and invasion and promoted cell apoptosis in 5-FU-resistant CRC cells. HAND2-AS1 acted as a sponge of miR-20a to regulate PDCD4 expression. Moreover, HAND2-AS1 suppressed cell progression and 5-FU resistance by upregulating PDCD4 via sponging miR-20a in 5-FU-resistant CRC cells. Besides, HAND2-AS1 inhibited tumor growth in vivo. HAND2-AS1/miR-20a/PDCD4 axis inhibited cell progression and 5-FU resistance in 5-FU-resistant CRC cells. • HAND2-AS1, miR-20a and PDCD4 are dysregulated in 5-FU-resistant colorectal cancer tissues and cells. • HAND2-AS1 inhibits 5-FU resistance in 5-FU-resistant colorectal cancer cells. • HAND2-AS1 is a sponge of miR-20a and PDCD4 is a target of miR-20a in 5-FU-resistant colorectal cancer cells. • HAND2-AS1 suppresses 5-FU resistance by regulating miR-20a/PDCD4 axis in colorectal cancer cells. • HAND2-AS1 represses tumor growth in vivo. [ABSTRACT FROM AUTHOR]