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Background: The incidence of melanoma brain metastasis (MBM) is high and significantly compromises patient survival and quality of life. Effective treatment of MBM is made difficult by the blood-brain barrier (BBB), since it restricts the entry of drugs into the brain. Certain anti-psychotic drugs able to cross the BBB have demonstrated efficacy in suppressing brain metastasis in preclinical studies. However, the activity of zuclopenthixol against MBM is not yet clear., Methods: Cell viability assays were employed to investigate the potential of zuclopenthixol in the treatment of MBM. Subsequently, the mechanism of action was investigated by RNA-sequencing (RNAseq), flow cytometry-based cell cycle and apoptosis assays, protein expression analysis, and autophagy flux detection. Additionally, the efficacy of zuclopenthixol against tumor growth was investigated in vivo , including MBM models., Results: Zuclopenthixol inhibited the proliferation of various melanoma cell lines at minimal doses by causing cell cycle arrest in the G0/G1 phase and mitochondrial-mediated intrinsic apoptosis. Zuclopenthixol also induced cytoprotective autophagy, and inhibition of autophagy enhanced the anti-melanoma effects of zuclopenthixol. Furthermore, zuclopenthixol inhibited the growth of human melanoma tumors in nude mice, as well as the growth of intracranial metastases in a mouse model of MBM., Conclusions: These results demonstrate that zuclopenthixol has significant potential as an effective therapeutic agent for MBM., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Purpose: In this study, we sought to test the hypothesis that oxidative stress injury in ischemic brains and H 2 O 2 -treated mouse neuroblastoma Neuro-2a cells (N2a) was related to STAT3 activation. Materials and methods: Rat middle cerebral artery occlusion (MCAO) model and H 2 O 2 -treated mouse neuroblastoma Neuro-2a cells (N2a) were used to investigate the relationship between oxidative stress injury and STAT3 activation. Results: 8-Hydroxy-2'-deoxyguanosine (8-OHdG) content and STAT3 protein phosphorylation level were significantly increased after cerebral ischemia-reperfusion. H 2 O 2 treatment inhibited the cell viability, induced the apoptosis, and further raised pSTAT3 protein level in N2a cells. Moreover, the addition of AG490, the protein inhibitor of JAK2, significantly alleviated cerebral ischemic damage in vivo and H 2 O 2 -induced injury in vitro , and JAK2 siRNA also alleviated H 2 O 2 -induced injury in N2a cell. Conclusions: JAK2/STAT3 pathway may play a crucial role in mediating reactive oxidative species (ROS)-induced cell injury in rat middle cerebral artery occlusion (MCAO) model and N2a cells. ROS scavenging and down-regulation of STAT3 activation might be a candidate design of therapeutic strategies against oxidative stress-related neurological diseases.

Transcription factors are known to mediate the conversion of somatic cells to induced pluripotent stem cells (iPSCs). Transcription factor TFAP2C plays important roles in the regulation of embryonic development and carcinogenesis; however, the roles of Tfap2c in regulating somatic cell reprogramming are not well understood. Here we demonstrate Tfap2c is induced during the generation of iPSCs from mouse fibroblasts and acts as a facilitator for iPSCs formation. Mechanistically, the c-Myc-dependent apoptosis, which is a roadblock to reprogramming, can be significantly mitigated by Tfap2c overexpression. Meanwhile, Tfap2c can greatly promote mesenchymal-to-epithelial transition (MET) at initiation stage of OSKM-induced reprogramming. Further analysis of gene expression and targets of Tfap2c during reprogramming by RNA-sequencing (RNA-seq) and ChIP-qPCR indicates that TFAP2C can promote epithelial gene expression by binding to their promoters directly. Finally, knockdown of E-cadherin (Cdh1), an important downstream target of TFAP2C and a critical regulator of MET antagonizes Tfap2c-mediated reprogramming. Taken together, we conclude that Tfap2c serves as a strong activator for somatic cell reprogramming through promoting the MET and inhibiting c-Myc-dependent apoptosis.

Keloids are benign fibrous overgrowths that occur as a result of abnormal wound healing following cutaneous injury. MicroRNAs (miRNAs/miRs) are short non‑coding RNAs that serve critical roles in numerous important biological processes, such as cell proliferation, differentiation and apoptosis. However, their role in keloid development remains largely unknown. In the present study, the role of miR‑30a‑5p, a miRNA regulated by Trichostatin A (TSA), in apoptosis within cultured keloid fibroblasts was investigated. An MTT assay was used to detect the proliferation of cultured keloid fibroblasts treated with TSA. Cell apoptosis and cell cycle phases were analyzed using flow cytometry. In addition, an miRNA microarray was performed to compare expression profiles between cultured keloid fibroblasts treated with or without 1,000 nM TSA. Reverse transcription‑quantitative polymerase chain reaction analysis was conducted to estimate miRNA expression levels. The direct target of miR‑30a‑5p was identified using a dual‑luciferase reporter assay. Western blotting was employed to assess protein expression levels in keloid fibroblasts. The results demonstrated that TSA inhibited the proliferation of keloid fibroblasts in a time‑ and dose‑dependent manner. The miRNA microarray revealed alterations in the expression of numerous miRNA sequences in response to TSA when compared with controls. Notably, the expression of miR‑30a‑5p was downregulated in keloid tissues. In addition, overexpression of miR‑30a‑5p induced apoptosis by targeting B‑cell lymphoma 2, which was similar to that observed in response to TSA. These results provide important information regarding a novel miR‑30a‑5p‑mediated signaling pathway induced by TSA treatment, and suggest a potential use for TSA and miR‑30a‑5p as effective therapeutic strategies for keloids.

MicroRNAs are essential for the maintenance of podocyte homeostasis. Emerging evidence has demonstrated a protective role of microRNA-30a (miR-30a), a member of the miR-30 family, in podocyte injury. However, the roles of other miR-30 family members in podocyte injury are unclear. The present study was undertaken to investigate the contribution of miR-30e to the pathogenesis of podocyte injury induced by aldosterone (Aldo), as well as the underlying mechanism. After Aldo treatment, miR-30e was reduced in a dose-and time-dependent manner. Notably, overexpression of miR-30e markedly attenuated Aldo-induced apoptosis in podocytes. In agreement with this finding, miR-30e silencing led to significant podocyte apoptosis. Mitochondrial dysfunction (MtD) has been shown to be an early event in Aldo-induced podocyte injury. Here we found that overexpression of miR-30e improved Aldo-induced MtD while miR-30e silencing resulted in MtD. Next, we found that miR-30e could directly target the BCL2/adenovirus E1B-interacting protein 3-like (BNIP3L) gene. Aldo markedly enhanced BNIP3L expression in podocytes, and silencing of BNIP3L largely abolished Aldo-induced MtD and cell apoptosis. On the contrary, overexpression of BNIP3L induced MtD and apoptosis in podocytes. Together, these findings demonstrate that miR-30e protects mitochondria and podocytes from Aldo challenge by targeting BNIP3L., (Copyright © 2017 the American Physiological Society.)

Neuroprotection is defined as using a therapy that affects the brain tissue in the still-viable ischemic penumbra to salvage or delay the infarction. Catalpol, the main active principle of the root of Radix Rehmanniae, was reported to have pleiotropic neuroprotective effects in neurodegenerative diseases including ischemic stroke. Here, we evaluated the neuroprotective effects of catalpol in experimental acute ischemic stroke. Studies on catalpol in animal models of acute ischemic stroke were identified from 6 databases. Twenty-five studies involving 805 animals were included. Twelve comparisons showed significant effects of catalpol on decreasing infarct size according to 2,3,5-triphenyltetrazolium chloride staining compared with the control ( P < 0.05). One study reported significant effect of catalpol on reducing infarct size according to magnetic resonance imaging scan compared with the control ( P < 0.05). Meta-analysis of these studies indicated that catalpol significantly improved the neurological function score according to Zea Longa score, Bederson score, balance beam-walking test, adhesive removal test, bar-grasping score, and corner test compared with the control ( P < 0.05). In conclusion, catalpol exerted neuroprotective effects for experimental acute focal ischemic stroke, largely through reducing oxidative reactions, inhibiting apoptosis, and repressing inflammatory reactions and autophagy. However, these apparently positive findings should be interpreted with caution because of the methodological flaws.

Background: Necroptosis is an important mode of cell death, which is due to oxidant stress accumulation. Our previous study indicated that oxidant stresses could be reduced by Timosaponin B-II (TBII), a kind of Chinese herb RhizomaAnemarrhenae monomer extraction. We wonder the possible effect of Timosaponin B-II, whether it can protect cells from necroptosis via reducing the oxidant stress, in RGC-5 following hydrogen peroxide (H2O2) insult., Methods: RGC-5 cells were grown in DMEM, the model group was exposed in H2O2 with the concentration of 300 μM, and the experimental group was pre-treated with Timosaponin B-II at different concentrations (1 μM, 10 μM, 100 μM and 1000 μM) for 24 hrs. MTT assay was carried out to measure the cytotoxicity of H2O2, MDA concentration assay was executed to evaluate the degree of oxidative stress, TNF-α ELISA Assay was used to measure the concentration of TNF-α, finally, the degree of necrosis were analyzed using flow cytometry., Results: We first constructed the cell injury model of necroptosis in RGC-5 upon H2O2 exposure. Morphological observation and MTT assay were used to evaluate the degree of RGC-5 death. MDA assay were carried out to describe the degree of oxidant stress. Annexin V/PI staining was used to detect necroptotic cells pre-treated with or without Timosaponin B-II following H2O2 injury. TNF-α ELISA was carried out to detect the TNF-α accumulation in RGC-5. Upon using Timosaponin B-II with concentration of 100 μM, the percentage of cell viability was increased from 50% to 75%, and the necrosis of cells was reduced from 35% to 20% comparing with H2O2 injury group. Oxidant stress and TNF-α was reduced upon injury which decreased the ratio of RGC-5 necroptosis., Conclusion: Our study found out that Timosaponin B-II might reduce necroptosis via inhibition of ROS and TNF-α accumulation in RGC-5 following H2O2 injury.

Bim contributes to resistance to various standard and novel agents. Here we demonstrate that Bim plays a functional role in bortezomib resistance in multiple myeloma (MM) cells and that targeting Bim by combining histone deacetylase inhibitors (HDACIs) with BH3 mimetics (eg, ABT-737) overcomes bortezomib resistance. BH3-only protein profiling revealed high Bim levels (Bim(hi)) in most MM cell lines and primary CD138(+) MM samples. Whereas short hairpin RNA Bim knockdown conferred bortezomib resistance in Bim(hi) cells, adaptive bortezomib-resistant cells displayed marked Bim downregulation. HDACI upregulated Bim and, when combined with ABT-737, which released Bim from Bcl-2/Bcl-xL, potently killed bortezomib-resistant cells. These events were correlated with Bim-associated autophagy attenuation, whereas Bim knockdown sharply increased autophagy in Bim(hi) cells. In Bim(low) cells, autophagy disruption by chloroquine (CQ) was required for HDACI/ABT-737 to induce Bim expression and lethality. CQ also further enhanced HDACI/ABT-737 lethality in bortezomib-resistant cells. Finally, HDACI failed to diminish autophagy or potentiate ABT-737-induced apoptosis in bim(-/-) mouse embryonic fibroblasts. Thus, Bim deficiency represents a novel mechanism of adaptive bortezomib resistance in MM cells, and Bim-targeting strategies combining HDACIs (which upregulate Bim) and BH3 mimetics (which unleash Bim from antiapoptotic proteins) overcomes such resistance, in part by disabling cytoprotective autophagy., (© 2014 by The American Society of Hematology.)

Temperature is a crucial environmental factor that affects embryonic development, particularly for marine organisms with long embryonic development periods. However, the sensitive period of embryonic development and the role of autophagy/apoptosis in temperature regulation in cephalopods remain unclear. In this study, we cultured embryos of Sepiella japonica, a typical species in the local area of the East China Sea, at different incubation temperatures (18 °C, 23 °C, and 28 °C) to investigate various developmental aspects, including morphological and histological characteristics, mortality rates, the duration of embryonic development, and expression patterns of autophagy-related genes (LC3, BECN1, Inx4) and apoptosis marker genes (Cas3, p53) at 25 developmental stages. Our findings indicate that embryos in the high-temperature (28 °C) group had significantly higher mortality and embryonic malformation rates than those in the low-temperature (18 °C) group. Furthermore, high temperature (28 °C) shortened the duration of embryonic development by 7 days compared to the optimal temperature (23 °C), while low temperature (18 °C) caused a delay of 9 days. Therefore, embryos of S. japonica were more intolerant to high temperatures (28 °C), emphasizing the critical importance of maintaining an appropriate incubation temperature (approximately 23 °C). Additionally, our study observed, for the first time, that the Early blastula, Blastopore closure, and Optic vesicle to Caudal end stages were the most sensitive stages. During these periods, abnormalities in the expression of autophagy-related and apoptosis-related genes were associated with higher rates of mortality and malformations, highlighting the strong correlation and potential interaction between autophagy and apoptosis in embryonic development under varying temperature conditions. [ABSTRACT FROM AUTHOR]

Deoxynivalenol (DON), a frequent food and feed contaminant, poses a severe threat to human and livestock health. Some studies have demonstrated that DON could induce liver damage and cell death. However, novel cell death styles and detailed mechanisms to explain DON-induced liver inflammatory injury are still lacking. Here, we found both chronic and subacute oral administration of DON (3 mg/kg for 4 weeks and 4 mg/kg for 8 days) induced mouse liver inflammatory injury and activated caspase-3, PARP and gasdermin E (GSDME), which were inhibited by caspase-3 inhibitor Z-DEVD and Ac-DEVD. In vitro, HepaRG cells showed typical pyroptotic characteristics after 32 and 64 μM DON exposure for 24 h, including balloon-like bubbling emerging, release of lactate dehydrogenase (LDH), secretion of IL-1β and IL-6 and activation of caspase-3 and GSDME. Furthermore, knocking down GSDME and inhibiting caspases activity by Z-VAD and Z-DEVD dramatically blocked DON-induced pyroptotic characteristics, while over-expressed GSDME prompted that. These data demonstrate that caspase-3/GSDME pathway plays a key factor in DON-induced pyroptosis and inflammation in liver. Interestingly, knocking down GSDME could inhibit DON-induced pyroptosis but prompt DON-induced apoptosis, while opposite results were obtained when over-expressed GSDME, indicating the critical role of GSDME in DON-induced crosstalk between apoptosis and pyroptosis. Taken together, our data determine DON-induced caspase-3/GSDME-dependent pyroptosis in liver and its role in DON-induced liver inflammatory injury, which provide a novel mechanistic view into DON-induced hepatotoxicity and may offer a new target to reduce latent harm of DON to both humans and animals. [ABSTRACT FROM AUTHOR]

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]

Thrombocytopenia is a critical complication after radiation therapy and exposure. Dysfunction of megakaryocyte development and platelet production are key pathophysiological stages in ionizing radiation (IR)-induced thrombocytopenia. Protein kinase C (PKC) plays an important role in regulating megakaryocyte development and platelet production. However, it remains unclear how PKC regulates IR-induced megakaryocyte apoptosis. In this study, we found that pretreatment of PKC pan-inhibitor Go6983 delayed IR-induced megakaryocyte apoptosis, and inhibited IR-induced mitochondrial membrane potential and ROS production in CMK cells. Moreover, suppressing PKC activation inhibited cleaved caspase3 expression and reduced p38 phosphorylation levels, and IR-induced PKC activation might be regulated by p53. In vivo experiments confirmed that Go6983 promoted platelet count recovery after 21 days of 3 Gy total body irradiation. Furthermore, Go6983 reduced megakaryocyte apoptosis, increased the number of megakaryocyte and polyploid formation in bone marrow, and improved the survival rate of 6 Gy total body irradiation. In conclusion, our results provided a potential therapeutic target for IR-induced thrombocytopenia. [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]

Macrophages are the master regulator of the dynamic fibrogenesis-fibrosis resolution paradigm. TNF-like ligand 1 aberrance (TL1A) was found to be able to induce intestinal inflammation and fibrosis. Furthermore, significantly increased TL1A had been detected in liver tissues and mononuclear cells of patients with primary biliary cirrhosis (PBC). This study was to investigate the effect of myeloid cells with constitutive TL1A expression on liver fibrogenesis. We found that TL1A expressions in liver tissues and macrophages were significantly increased in mice with liver fibrosis induced by injection of carbon tetrachloride (CCl4). TL1A overexpression in myeloid cells induced liver function injury, accelerated the necrosis and apoptosis of hepatocytes, recruited macrophages, and promoted activation of hepatic stellate cells (HSCs) and fibrosis. In vitro results of our study showed that TL1A overexpression in macrophages promoted secretion of platelet-derived growth factor-BB (PDGF-BB), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β). Culturing macrophages with TL1A overexpression could accelerate the activation and proliferation of primary HSCs. These results indicated that constitutive TL1A expression in myeloid cells exacerbated liver fibrosis, probably through macrophage recruitment and secretion of proinflammatory and profibrotic cytokines. [ABSTRACT FROM AUTHOR]

Many cellular processes are driven by spatially and temporally regulated microRNAs (miRNAs)-dependent signaling events. Substantial evidence collected over the years indicates that miRNAs are pivotal regulators that contribute to the initiation and development of EV71-related disorders. Importantly, so far, no clinical trial has been undertaken to address the effect of miRNAs on EV71-related diseases. In this study, we show that EV71 infection results in up-regulation of hsa-miR-494-3p levels, and that EV71-induced hsa-miR-494-3p impacts PI3K/Akt signaling pathway by targeting PTEN. However, very little is known about the relationship between hsa-miR-494-3p and EV71 infection. The overall goal of the study is to get a better insight into whether or not hsa-miR-494-3p is involved in the EV71 infection. We found that the EV71 infection induces cellular apoptosis, and that this process can be counteracted by the over-expression of hsa-miR-494-3p mimics. We also present evidence that cell lines deficient in hsa-miR-494-3p are more sensitive to EV71-induced cell death than the corresponding control cells. Collectively, these findings confirm and extend the pervious observation suggesting that disturbances in miRNAs expression can influence EV71 propagation. In addition, they lend strong support to the ideas that hsa-miR-494-3p-mediated signaling pathway plays an important role in the EV71 replication, and that this may have profound implications on our views on EV71-related diseases. [ABSTRACT FROM AUTHOR]

Background: G protein-coupled receptors (GPR) are involved in a wide range of physiological processes, some of which, however, can be hijacked by tumor cells. Over-expression of G protein-coupled receptors 137 (GPR137) are associated with the growth of tumor cells, but under-expression of GPR137 has shown to inhibit cell proliferation in several different types of cancers. Currently, the role of GPR137 in leukemia is still unclear. In this study, the effect of under-expression of GPR137 on inhibiting the proliferation of leukemia cells is explored, to identify a novel target for leukemia treatment. Materials and methods: In this study, lentivirus-mediated RNA interference (RNAi) was employed to investigate the role of GPR137 in two leukemia cell lines K562 and HL60. The gene expression of GPR137 was analyzed by RT-PCR and its protein expression was determined by Western blot. Flow cytometry and Annexin V/7-AAD Apoptosis Detection Kit was used respectively in cell cycle and apoptosis analysis. The protein expression of CyclinD1, CDK4, BCL-2 and caspase-3 were also determined. Results: There was high level of constitutive expression of GPR137 in leukemia cancer cell lines K562 and HL60. Lentivirus-mediated RNAi could significantly down-regulate gene and protein expression of GPR137 in both cell lines. Down regulation of GPR137 was associated with the reduction in proliferation rate and colony forming capacity. In addition, down regulation of GPR137 arrested cells in the G0/G1 phase of cell cycle and induced apoptosis in both leukemia cell lines K562 and HL60. Conclusions: The expression of GPR137 is associated with the proliferation of leukemia cell lines. Down regulation of GPR137 could inhibit proliferation and promote apoptosis in leukemia cells, which makes it a promising bio-marker and therapeutic target to treat patients with leukemia. [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]

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]

Glioma is a brain tumor that originates from brain or spine glial cells. Despite alternative treatments, the overall survival rate remains low. Oridonin (ORI) is purified from the Chinese herb Rabdosia rubescens, which has exhibited positive effects on tumors. This study aimed to investigate the effect of ORI on U87MG glioblastoma cells and whether the Hippo/YAP-related signaling pathway was involved. Malignant glioblastoma U87MG cells and male athymic nude mice (BALB/cnu/nu) were used as the experimental models. The YAP inhibitor Verteporfin (VP) and the overexpression of YAP were used to investigate its potential relation with glioma. Here, we found that ORI inhibited cell proliferation and promoted cell apoptosis in a dose-dependent manner in U87MG cells. Moreover, ORI inhibited Bcl-2, YAP, and c-Myc protein expression but increased Bax, caspase-3, and p-YAP protein expression. Furthermore, the effect of ORI was also confirmed in a mouse model bearing glioma. ORI reversed the effect of overexpression of YAP. Collectively, oridonin suppressed glioblastoma oncogenesis via the Hippo/YAP signaling pathway and could be a potential therapeutic target in the treatment of glioblastoma. [Display omitted] • Oridonin suppressed glioblastoma oncogenesis in U87MG glioblastoma cells. • Oridonin suppressed glioblastoma oncogenesis growth in mouse model bearing glioma. • Oridonin suppressed glioblastoma oncogenesis via the Hippo/YAP signaling pathway. [ABSTRACT FROM AUTHOR]

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]

Previous evidences suggested that atorvastatin not only reduced blood lipids but also reduced myocardial hypertrophy and remodeling. And it was reported that C/EBPβ (CCAAT/enhancer-binding protein β) played a pivotal role both in the physiologic and pathological cardiac hypertrophy. However, it has not been reported before whether this signaling pathway of C/EBPβ participates in protective effect of atorvastatin for hypertrophy cardiomyocytes. In present study, We found that overexpression of C/EBPβ significantly abrogated the effect of atorvastatin on increasing Bcl-2/Bax and PGC-1α while the early and late apoptosis rate increased and mitochondrial membrane potential (MMP) was reduced. In conclusion, we further identified the protective effect of atorvastatin on hypertrophic cardiomyocytes induced by Angiotensin II by rescuing the MMP and inhibiting apoptosis, which might be at least partly attributed to down-regulation of C/EBPβ. And C/EBPβ might be a new target to rescue mitochondrion function and apoptosis in pathological cardiac hypertrophy. [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]