Blockade of hypoxia-caused nonmyocytes apoptosis helps improve survival and mitigate ventricular remodeling and dysfunction during the chronic stage of myocardial infarction. But tools affecting nonmyocyte apoptosis are very rare. Sphingosylphosphorylcholine (SPC), a naturally occurring bioactive sphingolipid in plasma, was proved to protect cardiomyocyte against apoptosis in an ischemic model in our

Small-molecule compound-based therapies have provided new insights into cancer treatment against mitochondrial impairment. N6-furfuryladenosine (kinetin riboside, KR) is a purine derivative and an anticancer agent that selectively affects the molecular pathways crucial for cell growth and apoptosis by interfering with mitochondrial functions and thus might be a potential mitotoxicant. Metabolism of

Ferroptosis is a newly defined form of regulated cell death (RCD) characterized by iron overload, lipid reactive oxygen species (ROS) accumulation, and lipid peroxidation, which is different from necrosis, apoptosis, autophagy and other forms of RCD in morphology, biochemistry, function and gene expression. Increasing evidence has shown that ferroptosis is intimately associated with cancer initiation

Breast cancer accounts for 1.4 million new cases every year. Triple-negative breast cancer (TNBC) is one the leading cause of mortality in developing countries and is associated with early age onset (under 40 years old). Chemotherapy has a poor success rate in patients with TNBC as compared to other types of breast cancers. It is due to the lack of expression of three validated molecular markers for

Ovarian cancer remains one of the most frequent causes of cancer-related death in women. Many patients with ovarian cancer suffer from de novo or acquired resistance to chemotherapy. Here, we report that RAB25 suppresses chemotherapy-induced mitochondrial apoptosis signaling in ovarian cancer cell lines and primary ovarian cancer cells. RAB25 blocks chemotherapy-induced apoptosis upstream of mitochondrial

The head and neck squamous cell carcinoma (HNSCC) constitute about 90% of all head and neck cancers. HNSCC falls in the top 10 cancers in men globally. Epoxyazadiradione (EPA) and Azadiradione (AZA) are the limonoids derived from the medicinal plant Azadirachta indica (popularly known as Neem). Whether or not the limonoids exhibit activities against HNSCC and the associated mechanism remains elusive

As a basic biological phenomenon of cells, regulated cell death (RCD) has irreplaceable influence on the occurrence and development of many processes of life and diseases. RCD plays an important role in the stability of the homeostasis, the development of multiple systems and the evolution of organisms. Thus comprehensively understanding of RCD is undoubtedly helpful in the innovation of disease treatment

Photodynamic therapy (PDT) is a light-catalyzed process that can initiate cellular death pathways from the formation of cytotoxic reactive oxygen species at sub-cellular sites. Apoptosis was the first such pathway to be identified. Autophagy can also occur and is often found to be cytoprotective. Another process termed paraptosis can also have lethal consequences, even in cells with an impaired apoptotic

Each year, 1 million children die due to perinatal asphyxia; however, there are no effective drugs to protect the neonatal brain against hypoxic/ischemic damage. In this study, we demonstrated for the first time the neuroprotective capacity of 3,3’-diindolylmethane (DIM) in an in vivo model of rat perinatal asphyxia, which has translational value and corresponds to hypoxic/ischemic episodes in human

Apoptosis plays a major role in development, tissue renewal and the progression of degenerative diseases. Studies on various types of mammalian cells reported a pro-apoptotic function of acetylcholinesterase (AChE), particularly in the formation of the apoptosome and the degradation of nuclear DNA. While three AChE splice variants are present in mammals, invertebrates typically express two ache genes

Ferroptosis is considered a distinctive form of cell death compared to other types of death such as apoptosis. It is known to result from iron-dependent accumulation of lipid peroxides rather than caspase activation. However, we reported recently that ferroptosis interplays with apoptosis. In this study, we investigated a possible mechanism of this interplay between ferroptosis and apoptosis. Results

Earlier we have reported that thymic regulatory T cells (Treg) are resistant to in vivo glucocorticoid hormone (GC)-induced apoptosis, while the most GC-sensitive DP thymocytes died through the activation of mitochondrial apoptotic pathway. Here we analyzed the apoptosis-inducing effect of high dose (10–6 M) in vitro dexamethasone (DX) treatment in mouse thymic- and splenic Tregs and CD4+ T cells.

The antiepileptic and mood stabilizer agent valproic acid (VPA) has been shown to exert anti-tumour effects and to cause neuronal damage in the developing brain through mechanisms not completely understood. In the present study we show that prolonged exposure of SH-SY5Y and LAN-1 human neuroblastoma cells to clinically relevant concentrations of VPA caused a marked induction of the protein and transcript

The original version of this article unfortunately contains errors in methods and figures. In methods, animal experiments part: “2 ml/kg” and “after two days” were described incorrectly which were actually “4 ml/kg” and “after eight days” respectively.

Caloric restriction mimetics (CRMs) are promising molecules to prevent age-related diseases as they activate pathways driven by a true caloric restriction. Hydroxycitric acid (HCA) is considered a bona fide CRM since it depletes acetyl-CoA pools by acting as a competitive inhibitor of ATP citrate lyase (ACLY), ultimately repressing protein acetylation and promoting autophagy. Importantly, it can reduce

Costunolide, a natural sesquiterpene lactone, has multiple pharmacological activities such as neuroprotection or induction of apoptosis and eryptosis. However, the effects of costunolide on pro-survival factors and enzymes in human erythrocytes, e.g. glutathione and glucose-6-phosphate dehydrogenase (G6PDH) respectively, have not been studied yet. Our aim was to determine the mechanisms underlying

IL-22 is known to mediate inflammation in psoriasis, while IL-22 binding protein (IL-22BP) binds IL-22 to suppress IL-22 signaling. However, the function of IL-22 in regulating apoptosis in psoriasis remains poorly understood. In this study, we found that IL-22/IL-22R1 in lesional skin and IL-22 in serum from psoriatic patients were highly upregulated compared with healthy controls, while IL-22BP was

Vascular smooth muscle cells (VSMCs) are the main structural cell of blood vessels, and VSMC apoptosis occurs in vascular disease, after injury, and in vessel remodeling during development. Although VSMC apoptosis is viewed as silent, recent studies show that apoptotic cells can promote apoptosis-induced compensatory proliferation (AICP), apoptosis-induced apoptosis (AIA), and migration of both local

Apoptosis is a process in which cells are genetically regulated to cause a series of changes in morphology and metabolic activity, which ultimately lead to cell death. Apoptosis plays a vital role in the entire life cycle of an organism. Too much or too little apoptosis can cause a variety of diseases. Therefore, efficient and convenient methods for detecting apoptosis are necessary for clinical treatment

Cervix adenocarcinoma rendered by human papillomavirus (HPV) integration is an aggressive cancer that occurs by dysregulation of multiple pathways, including oncogenes, proto-oncogenes, and tumor suppressors. The PI3K/Akt/mTOR pathway, which cross-talks with the Ras–ERK pathway, has been associated with cervical cancers (CC), which includes signaling pathways related to carcinoma aggressiveness, metastasis

Chronic alcohol consumption induces myocardial damage and a type of non-ischemic cardiomyopathy termed alcoholic cardiomyopathy, where mitochondrial ultrastructural damages and suppressed fusion activity promote cardiomyocyte apoptosis. The aim of the present study is to determine the role of mitochondrial fission proteins and/or other proteins that localise on cardiac mitochondria for apoptosis upon

Apoptosis is increased in the hippocampus of infants who died of sudden infant death syndrome (SIDS), yet it is not known via which mechanism this has occurred. Following existing support for a role of the α7 and β2 nicotinic acetylcholine receptor (nAChR) subunits in apoptotic regulation, we aimed to determine whether these subunits are altered in the SIDS hippocampus and if they are correlated with

ARTS (Sept4_i2) is a pro-apoptotic protein and a product of the Sept4 gene. ARTS acts upstream of mitochondria to initiate caspase activation. ARTS induces apoptosis by specifically binding XIAP and allowing de-repression of active caspases required for Mitochondrial Outer Membrane Permeabilzation (MOMP). Moreover, ARTS promotes apoptosis by inducing ubiquitin-mediated degradation of both major anti-apoptotic

The release of DNA into the cytoplasm upon damage to the nucleus or during viral infection triggers an interferon-mediated defense response, inflammation and cell death. In human cells cytoplasmic DNA is sensed by cyclic GMP-AMP Synthase (cGAS) and Absent In Melanoma 2 (AIM2). Here, we report the identification of a “natural knockout” model of cGAS. Comparative genomics of phylogenetically diverse

Shikonin induced necroptosis in Jurkat cells were identified flow cytometrically by the up-regulation of RIP3 in live cells and that a proportion of these cells underwent other forms of regulated cell death (RCD) which included parthanatos (< 10%), or cleaved PARP (< 10%) and DNA Damage (> 30%). Live necroptotic cells also possessed functioning mitochondria with hyper-polarized mitochondria membrane

A majority of mesothelioma had the wild-type p53 genotype but was defective of p53 functions primarily due to a genetic defect in INK4A/ARF region. We examined a growth suppressive activity of CP-31398 which was developed to restore the p53 functions irrespective of the genotype in mesothelioma with wild-type or mutated p53. CP-31398 up-regulated p53 levels in cells with wild-type p53 genotype but

The tissue factor/coagulation factor VIIa (TF/FVIIa) complex induces transactivation of the IGF-1 receptor (IGF-1R) in a number of different cell types. The mechanism is largely unknown. The transactivation leads to protection from apoptosis and nuclear translocation of the IGF-1R. The aim of this study was to clarify the signaling pathway between TF and IGF-1R after FVIIa treatment with PC3 and DU145

Smac mimetics, or IAP antagonists, are a class of drugs currently being evaluated as anti-cancer therapeutics. These agents antagonize IAP proteins, including cIAP1/2 and XIAP, to induce cell death via apoptotic or, upon caspase-8 deficiency, necroptotic cell death pathways. Many cancer cells are unresponsive to Smac mimetic treatment as a single agent but can be sensitized to killing in the presence

Type 2 diabetes has a strong association with the development of cardiovascular disease, which is grouped as diabetic heart disease (DHD). DHD is associated with the progressive loss of cardiovascular cells through the alteration of molecular signalling pathways associated with cell death. In this study, we sought to determine whether diabetes induces dysregulation of miR-532 and if this is associated

Smac/Diablo is a pro-apoptotic protein via interaction with inhibitors of apoptosis proteins (IAPs) to relieve their inhibition of caspases. Smac mimetic compounds (also known as antagonists of IAPs) mimic the function of Smac/Diablo and sensitize cancer cells to TNF-induced apoptosis. However, the majority of cancer cells are resistant to Smac mimetic alone. Doxorubicin is a widely used chemotherapeutic

Liver injury is the early stage of liver disease, which is caused by multiple factors. Baicalein has shown extensive bioactivity. But whether baicalein has a protective effect on liver injury has not been reported thus far. In this study, we aim to investigate the protective effects of baicalein on liver injury induced by oxidative stress. H2O2 and CCl4 were employed to establish liver injury models

Gedunin is a natural tetranorterpenoid secondary metabolite found in plants of the Meliaceae family, which has been reported for its antiparasitic, antifungal and anticancer activities. Here, we describe the molecular mechanisms underlying the in vitro anti proliferative activity of gedunin (isolated from the mangrove plant Xylocarpus granatum) in human ovarian cancer cells. We observed that gedunin

Increased amounts of amino acids are essential for cancer cells to support their sustained growth and survival. Therefore, inhibitors of amino acid transporters, such as L-type amino acid transporter 1 (LAT1) have been developed. In this study, a previously reported LAT1-inhibitor (KMH-233) was studied for its hemocompatibility and toxicity towards human umbilical vein endothelial cells (HUVEC) and

Histone deacetylase (HDAC) inhibitors represent an encouraging class of antitumor drugs. HDAC inhibitors induce a series of molecular and biological responses and minimal toxicity to normal cells. Citarinostat (Acy-241) is a second generation, orally administered, HDAC6-selective inhibitor. Momelotinib (CYT387) is an orally administered inhibitor of Janus kinase/signal transducer of transcription-3

RNase L is generally thought to play a key role in antiviral defenses. Although RNase L protein and mRNA are known to be highly expressed in myocardial tissue, there are few studies of the potential functions of RNase L in myocardial tissue. In this study, we tested the hypothesis that RNase L may be involved in the pathological process of cardiac ischemic injury. RNase L-overexpressing and RNase L

It is reported that baicalein can activate PI3K/AKT pathway, inhibit caspase activation and reduce cerebral infarct volume in middle cerebral artery occlusion (MCAO) rats. However, a caspase-independent mechanism initiated by poly (ADP-ribose) polymerase-1 (PARP-1) activation has been reported to make more contribution to cells death after ischemic stroke. In the present study, we established a cerebral

Apoptosis is a form of programmed cell death that is essential for tissue homeostasis. De-regulation of the balance between proliferation and apoptosis contributes to tumor initiation. Particularly in the colon where apoptosis is a crucial process in intestinal turnover, inhibition of apoptosis facilitates transformation and tumor progression. The BCL-2 family of proteins are key regulators of apoptosis

Soluble receptor for advanced glycation end-products (sRAGE), which exerts cardioprotective effect through inhibiting cardiomyocyte apoptosis and autophagy during ischemia/reperfusion (I/R) injury, is also known to enhance angiogenesis in post-ischemic reperfusion injury-critical limb ischemia (PIRI-CLI) mice. However, whether sRAGE protects the heart from myocardial I/R injury via promoting angiogenesis

Artemisinin (ART) and dihydroartemisinin (DHA) are first-line antimalarial drugs and have been reported to have anti-obesity effects. Hyperlipidemia is associated with β-cell damage in obese subjects, which could contribute to the pathogenesis of type 2 diabetes. In addition to their anti-obesity effects, ART and DHA also have protective roles in some diseases. Thus, we investigated the effects of

Emerging evidence has indicated that microRNAs are involved in multiple processes of cancer development. Previous studies have demonstrated that microRNA-499a (miR-499a) plays both oncogenic and tumor suppressive roles in several types of malignancies, and genetic variants in miR-499a are associated with the risk of cervical cancer. However, the biological roles of miR-499a in cervical cancer have

BIM is the master BH3-only BCL-2 family regulator of lymphocyte survival. To understand how long-term loss of BIM affects apoptotic resistance in T cells we studied animals with T cell-specific deletion of Bim. Unlike CD19CREBimfl/fl animals, LCKCREBimfl/fl mice have pronounced early lymphocytosis followed by normalization of lymphocyte counts over time. This normalization occurred in mature T cells

Necroptosis is a noncaspase-dependent and precisely regulated mechanism of cell death. Necroptosis is mainly initiated by members of the tumor necrosis factor receptor (TNFR) and Toll-like receptor (TLR) families, interferon, intracellular RNA and DNA sensors and other mediators. Subsequently, the protein kinase RIPK1 (receptor-interacting protein kinase 1) and RIPK3 interact with the receptor protein

Platinum based drugs alone or in combination with 5FU and docetaxel are common regimen chemotherapeutics for the treatment of advanced OSCC. Chemoresistance is one of the major factors of treatment failure in OSCC. Human RNA helicase DDX3 plays an important role in cell proliferation, invasion, and metastasis in several neoplasms. The potential role of DDX3 in chemoresistance is yet to be explored

Hypoxic-ischemic brain damage (HIBD) represents one of the leading causes of neonatal mortality and permanent neurological disability worldwide. Compelling studies have identified implication of microRNAs (miRNAs) in HIBD. However, the molecular mechanism of miR-21 underlying the disease pathogenesis is unknown. The present study aims to explore the role of miR-21 in neonatal rats with HIBD. HIBD rat

Glucocorticoids are widely prescribed to treat various allergic and autoimmune diseases; however, long-term use results in glucocorticoid-induced osteoporosis, characterized by consistent changes in bone remodeling with decreased bone formation as well as increased bone resorption. Not only bone mass but also bone quality decrease, resulting in an increased incidence of fractures. The primary role

Our previous studies have shown that abdominal paracentesis drainage (APD) is a safe and effective strategy for patients with severe acute pancreatitis (SAP). However, the underlying mechanisms behind APD treatment remain poorly understood. Given that apoptosis is a critical pathological response of SAP, we here aim to investigate the effect of APD on cell apoptosis in pancreatic tissues during SAP

Treatment of advanced BRAFV600-mutant melanoma using BRAF inhibitors (BRAFi) eventually leads to drug resistance and selects for highly metastatic tumor cells. We compared the most differentially dysregulated miRNA expression profiles of vemurafenib-resistant and highly-metastatic melanoma cell lines obtained from GEO DataSets. We discovered miR-152-5p was a potential regulator mediating melanoma drug

Glioblastoma remains the most malignant of all primary adult brain tumours with poor patient survival and limited treatment options. This study adopts a drug repurposing approach by investigating the anti-cancer activity of a derivative of the antipsychotic drug phenothiazine (DS00329) in malignant U251 and U87 glioblastoma cells. Results from MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium

The original version of this article unfortunately contains an error in the acknowledgement section. The text "Brain Korea 21 PLUS Project for Medical Science, Chungnam National University" was omitted by mistake. The correct and complete acknowledgment is given below: Acknowledgments This work was supported by the research fund of Chungnam National University and the Brain Korea 21 PLUS Project for

Abstract Cardiovascular disease (CVD) serves as the major cause of mortality in chronic kidney disease (CKD) patients. The injury of endothelium associated with the long-term challenge of uremic toxins including the toxic indoxyl sulfate (IS) is one of key pathological factors leading to CVD. However, the mechanisms of uremic toxins, especially the IS, resulting in endothelial injury, remain unclear

Tumor suppressor p53 is not only affects immune responses but also contributes to antibacterial activity. However, its bactericidal function during mycobacterial infection remains unclear. In this study, we found that the p53-deficient macrophages failed to control Mycobacterium tuberculosis (Mtb), manifested as a lower apoptotic cell death rate and enhanced intracellular survival. The expression levels

Abstract Lysophosphatidic acid (LPA) is a bioactive lipid, which plays an indispensable role in various physiological and pathological processes. Moreover, an elevated level of LPA has been observed in malignancies of different origins and implicated in their progression via modulation of proliferation, apoptosis, invasion and metastasis. Interestingly, few recent reports suggest a pivotal role of

Weightlessness-induced cardiovascular dysfunction can lead to physiological and pathological consequences. It has been shown that spaceflight or simulated microgravity can alter expression profiles of some microRNAs (miRNAs). Here, we attempt to identify the role of miRNAs in human umbilical vein endothelial cells (HUVECs) apoptosis under simulated microgravity. RNA-sequencing and quantitative real-time

Accumulation of tissue factor (TF) within cells leads to cellular apoptosis mediated through p38 and p53 pathways. In this study, the involvement of Src1 in the induction of TF-mediated cell apoptosis, and the mechanisms of Src1 activation were investigated. Human coronary artery endothelial cell (HCAEC) were transfected with plasmids to express the wild-type TF (TFWt-tGFP), or a mutant (Ser253 → Ala)

Abstract Liver fibrosis usually progresses to liver cirrhosis and even hepatocellular carcinoma. Since activated hepatic stellate cells (aHSCs) are responsible for liver fibrosis, reducing the quantity of aHSCs was considered the essential strategy for clinical antihepatofibrotic therapy. Due to the overexpression of TRAIL receptor 2 (DR5) in aHSCs, human TNF-related apoptosis-inducing ligand (hTRAIL)

In the previous paper of our group, we have demonstrated that one of the crucial factors involved in the crosstalk between autophagy and apoptosis is klotho protein. We have shown that klotho silencing in normal human fibroblasts intensifies lipopolysaccharide (LPS)-induced p-eIF2a-mediated stress of endoplasmic reticulum and thus leads to retardation of prosurvival autophagy and induction of apoptotic

HSP90 (heat shock protein 90) is an ATP-dependent molecular chaperone involved in a proper folding and maturation of hundreds of proteins. HSP90 is abundantly expressed in cancer, including melanoma. HSP90 client proteins are the key oncoproteins of several signaling pathways controlling melanoma development, progression and response to therapy. A number of natural and synthetic compounds of different

Abstract Macrophages play a crucial role in several diseases’ development and progression, such as in cancer and arthritis through ROS generation and inflammation. This makes macrophages a therapeutic target in these diseases. While silver nanoparticles (AgNP) have been widely used as an antibacterial and investigated as anticancer, its potential against macrophages may be limited due to its inherent

Influenza A viruses (IAVs) are respiratory pathogens that cause severe morbidity and mortality worldwide. They affect cellular processes such as proliferation, protein synthesis, autophagy, and apoptosis. Although apoptosis is considered an innate cellular response to invading infectious pathogens, IAVs have evolved to encode viral proteins that modulate host cellular apoptosis in ways that support

Glioblastoma is the most malignant and prevalent brain tumor in adults. It can grow and spread quickly causing harm to the brain health. One of the major challenges in treatment of glioblastoma is drug resistance. Use of synergistic combination of two drugs with different anti-tumor effects is nowadays highly considered in the development of effective therapeutic strategies for many malignancies. In