535 results match your criteria Cell death discovery[Journal]


The role of MDM2-p53 axis dysfunction in the hepatocellular carcinoma transformation.

Cell Death Discov 2020 19;6:53. Epub 2020 Jun 19.

Department of Liver Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200030 China.

Liver cancer is the second most frequent cause of cancer-related death globally. The main histological subtype is hepatocellular carcinoma (HCC), which is derived from hepatocytes. According to the epidemiologic studies, the most important risk factors of HCC are chronic viral infections (HBV, HCV, and HIV) and metabolic disease (metabolic syndrome). Read More

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http://dx.doi.org/10.1038/s41420-020-0287-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305227PMC

Metformin effectively treats deletion-caused kidney pathology by upregulating AMPK phosphorylation.

Cell Death Discov 2020 15;6:52. Epub 2020 Jun 15.

Department of Pathology, School of Basic Medical Science, Fudan University, Shanghai, 200032 PR China.

Tuberous sclerosis complex (TSC) is characterized by hamartomatous lesions in multiple organs, with most patients developing polycystic kidney disease and leading to a decline of renal function. TSC is caused by loss-of-function mutations in either or gene, but currently, there is no effective treatment for aberrant kidney growth in TSC patients. By generating a renal proximal tubule-specific gene-knockout () mouse model, we observed that mice developed aberrantly enlarged kidneys primarily due to hypertrophy and proliferation of proximal tubule cells, along with some cystogenesis, interstitial inflammation, and fibrosis. Read More

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http://dx.doi.org/10.1038/s41420-020-0285-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295815PMC

Convergence of therapy-induced senescence (TIS) and EMT in multistep carcinogenesis: current opinions and emerging perspectives.

Cell Death Discov 2020 15;6:51. Epub 2020 Jun 15.

Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, 180001 India.

Drug induced resistance is a widespread problem in the clinical management of cancer. Cancer cells, when exposed to cytotoxic drugs, can reprogram their cellular machinery and resist cell death. Evasion of cell death mechanisms, such as apoptosis and necroptosis, are part of a transcriptional reprogramming that cancer cells utilize to mediate cytotoxic threats. Read More

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http://dx.doi.org/10.1038/s41420-020-0286-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295779PMC

Biochemical activity of RAGs is impeded by Dolutegravir, an HIV integrase inhibitor.

Cell Death Discov 2020 12;6:50. Epub 2020 Jun 12.

Department of Biochemistry, Indian Institute of Science, Bangalore, 560012 India.

HIV is a retrovirus that infects CD4 T lymphocytes in human beings and causes immunodeficiency. In the recent years, various therapies have been developed against HIV, including targeting the HIV specific protein, integrase, responsible for integration of HIV cDNA into host DNA. Although, integrase is specific to HIV, it has functional and structural similarity with RAG1, one of the partner proteins associated with V(D)J recombination, a process by which immune diversity is generated in humans. Read More

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http://dx.doi.org/10.1038/s41420-020-0281-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293277PMC

Zoledronic acid regulates the synthesis and secretion of IL-1β through Histone methylation in macrophages.

Cell Death Discov 2020 11;6:47. Epub 2020 Jun 11.

Department of Stomatology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Long-term administration of nitrogen-containing bisphosphonates increases the risk of detrimental side effects, such as bisphosphonate-related osteonecrosis of the jaw (BRONJ). BRONJ development is associated with inflammation, but its pathophysiology remains unknown. Here, we examined whether histone methylation is responsible for zoledronic acid (Zol)-induced inflammatory responses. Read More

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http://dx.doi.org/10.1038/s41420-020-0273-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289826PMC

Expression profiling of microRNAs and isomiRs in conventional central chondrosarcoma.

Cell Death Discov 2020 10;6:46. Epub 2020 Jun 10.

U.O.C. of Immunohaematology and Transfusion Medicine, Laboratory of Stem Cells, Spirito Santo Hospital, Pescara, Italy.

Conventional central chondrosarcoma (CCC) is a malignant bone tumor that is characterized by the production of chondroid tissue. Since radiation therapy and chemotherapy have limited effects on CCC, treatment of most patients depends on surgical resection. This study aimed to identify the expression profiles of microRNAs (miRNAs) and isomiRs in CCC tissues to highlight their possible participation to the regulation of pathways critical for the formation and growth of this type of tumor. Read More

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http://dx.doi.org/10.1038/s41420-020-0282-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287106PMC

Kinase inhibition of G2019S-LRRK2 enhances autolysosome formation and function to reduce endogenous alpha-synuclein intracellular inclusions.

Cell Death Discov 2020 8;6:45. Epub 2020 Jun 8.

Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of Lübeck - Via Galvani 31, 39100 Bolzano, Italy.

The Parkinson's disease (PD)-associated kinase Leucine-Rich Repeat Kinase 2 (LRRK2) is a crucial modulator of the autophagy-lysosome pathway, but unclarity exists on the precise mechanics of its role and the direction of this modulation. In particular, LRRK2 is involved in the degradation of pathological alpha-synuclein, with pathogenic mutations precipitating neuropathology in cellular and animal models of PD, and a significant proportion of LRRK2 patients presenting Lewy neuropathology. Defects in autophagic processing and lysosomal degradation of alpha-synuclein have been postulated to underlie its accumulation and onset of neuropathology. Read More

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http://dx.doi.org/10.1038/s41420-020-0279-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280235PMC

MicroRNA-674-5p induced by HIF-1α targets XBP-1 in intestinal epithelial cell injury during endotoxemia.

Cell Death Discov 2020 4;6:44. Epub 2020 Jun 4.

Division of Emergency Medicine, Department of General Internal Medicine, Department of Emergency Intensive Care Unit, The First Affiliated Hospital of Sun Yat-sen University, No.58, Zhongshan 2nd Road, 510080 Guangzhou, China.

Intestinal mucosal integrity dysfunction during endotoxemia can contribute to translocation of intestinal bacteria and a persistent systemic inflammatory response, which both fuel the pathophysiological development of sepsis or endotoxemia. The pathogenesis of intestinal damage induced by endotoxemia remains poorly understood. Here, we identified the microRNA (miR)-674-5p/X-box binding protein 1 (XBP-1) axis as a critical regulator and therapeutic target in preventing intestinal crypt cell proliferation during endotoxemia. Read More

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http://dx.doi.org/10.1038/s41420-020-0280-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272402PMC

Effect of microvesicles from containing miRNA on proliferation and apoptosis in tumor cell lines.

Cell Death Discov 2020 4;6:43. Epub 2020 Jun 4.

Department of Biology, University of Rome 'Tor Vergata', via della Ricerca Scientifica 1, 00133 Rome, Italy.

Human microvesicles are key mediators of cell-cell communication. Exosomes function as microRNA transporters, playing a crucial role in physiological and pathological processes. Plant microvesicles (MVs) display similar features to mammalian exosomes, and these MVs might enhance plant microRNA delivery in mammals. Read More

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http://dx.doi.org/10.1038/s41420-020-0271-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272625PMC

Off-label therapy targeting pathogenic inflammation in COVID-19.

Cell Death Discov 2020 12;6:49. Epub 2020 Jun 12.

University San Raffaele and IRCCS San Raffaele, 00166 Rome, Italy.

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http://dx.doi.org/10.1038/s41420-020-0283-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290072PMC

From threat to cure: understanding of virus-induced cell death leads to highly immunogenic oncolytic influenza viruses.

Cell Death Discov 2020 11;6:48. Epub 2020 Jun 11.

Division of General Surgery, Department of Surgery, Comprehensive Cancer Center Vienna, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.

Oncolytic viruses constitute an emerging strategy in immunomodulatory cancer treatment. The first oncolytic virus, Talimogene laherparepvec (T-VEC), based on herpes simplex virus 1 (HSV-1), was approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) in 2015. The field of oncolytic virotherapy is still in its beginnings, since many promising viruses remain only superficially explored. Read More

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http://dx.doi.org/10.1038/s41420-020-0284-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288254PMC

Interleukin-6 derived from cancer-associated fibroblasts attenuates the p53 response to doxorubicin in prostate cancer cells.

Cell Death Discov 2020 2;6:42. Epub 2020 Jun 2.

Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.

Cancer-associated fibroblasts (CAFs) promote tumor growth and progression, and increase drug resistance through several mechanisms. We have investigated the effect of CAFs on the p53 response to doxorubicin in prostate cancer cells. We show that CAFs produce interleukin-6 (IL-6), and that IL-6 attenuates p53 induction and upregulation of the pro-apoptotic p53 target Bax upon treatment with doxorubicin. Read More

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http://dx.doi.org/10.1038/s41420-020-0272-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265343PMC

SIRT1 directly activates autophagy in human chondrocytes.

Cell Death Discov 2020 29;6:41. Epub 2020 May 29.

The Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, L7 8TX UK.

Osteoarthritis (OA) is the most common form of arthritis worldwide with no effective treatment. Ageing is the primary risk factor for OA. We sought to investigate if there is a distinct and functional convergence of ageing-related mechanisms SIRT1 and autophagy in chondrocytes. Read More

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http://dx.doi.org/10.1038/s41420-020-0277-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260231PMC

Loss of Rictor in tubular cells exaggerates lipopolysaccharide induced renal inflammation and acute kidney injury via Yap/Taz-NF-κB axis.

Cell Death Discov 2020 29;6:40. Epub 2020 May 29.

Department of Nephrology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006 China.

Our previous study demonstrated that the mammalian target of rapamycin complex 2 (mTORC2) signaling alleviates renal inflammation and protects against cisplatin-induced AKI. However, the underlying mechanisms for mTORC2 in regulating renal inflammation in AKI remain to be determined. In this study, we found that lipopolysaccharide (LPS) could activate mTORC2 signaling in NRK-52E cells, and blockage of mTORC2 signaling led to Yap/Taz degradation, which in turn activated NF-κB signaling and induced inflammatory cytokines secretion. Read More

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http://dx.doi.org/10.1038/s41420-020-0274-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260239PMC

SARS-CoV-2 infection serology: a useful tool to overcome lockdown?

Cell Death Discov 2020 26;6:38. Epub 2020 May 26.

Department of Experimental Medicine, University of Tor Vergata, Rome, Italy.

The outbreak of 2019 novel coronavirus disease (Covid-19) caused by SARS-CoV-2 has spread rapidly, inducing a progressive growth in infected patients number. Social isolation (lockdown) has been assessed to prevent and control virus diffusion, leading to a worldwide financial and political crisis. Currently, SARS-CoV-2 RNA detection in nasopharyngeal swab takes place by real-time PCR (RT-qPCR). Read More

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http://dx.doi.org/10.1038/s41420-020-0275-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249039PMC

ACE2 expression and sex disparity in COVID-19.

Cell Death Discov 2020 26;6:37. Epub 2020 May 26.

Center for Gender Specific Medicine, Istituto Superiore di Sanità, Rome, Italy.

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http://dx.doi.org/10.1038/s41420-020-0276-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248455PMC

Inhibition of IKKβ/NF-κB signaling pathway to improve Dasatinib efficacy in suppression of cisplatin-resistant head and neck squamous cell carcinoma.

Cell Death Discov 2020 15;6:36. Epub 2020 May 15.

1Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD USA.

Proto-oncogene tyrosine-protein kinase Src plays an important role in Head and Neck Squamous Cell Carcinoma (HNSCC). However, the FDA-approved SRC inhibitor Dasatinib shows very limited efficacy in HNSCC clinical trials, even though Dasatinib can completely inhibit SRC in the laboratory setting. These results suggest that SRC inhibition can cause compensatory up-regulation and/or activation of other survival pathways, which suggests that co-targeting of SRC and the potential signaling pathways may improve the Dasatinib efficacy. Read More

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http://dx.doi.org/10.1038/s41420-020-0270-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229171PMC

Elevated microRNA-125b inhibits cytotrophoblast invasion and impairs endothelial cell function in preeclampsia.

Cell Death Discov 2020 13;6:35. Epub 2020 May 13.

2School of Biosciences, Weifang Medical University, Weifang, 261053 Shandong China.

Preeclampsia (PE) is a life-threatening disorder of human pregnancy affecting 5-8% of all pregnancies. Currently, PE remains an elusive complicated and heterogenous medical condition with no early marker or symptoms is recognized for this serious pregnancy complications. Here, we profiled the plasma miRNA expression patterns associated with preeclampsia and found 16 miRNAs were deregulated ( < 0. Read More

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http://dx.doi.org/10.1038/s41420-020-0269-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220944PMC

Deubiquitinase USP47-stabilized splicing factor IK regulates the splicing of pre-mRNA.

Cell Death Discov 2020 4;6:34. Epub 2020 May 4.

1Department of Biological Sciences, Sookmyung Women's University, Seoul, 04310 Korea.

IK depletion leads to an aberrant mitotic entry because of chromosomal misalignment through the enhancement of Aurora B activity at the interphase. Here, we demonstrate that IK, a spliceosomal component, plays a crucial role in the proper splicing of the pre-mRNA among other genes related with the DNA Damage Response (DDR). Intron 1 in the pre-mRNA, having lengths <200 bp, was not spliced in the IK-depleted cells and led to a deficiency of the ATM protein. Read More

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http://dx.doi.org/10.1038/s41420-020-0268-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198525PMC

IL-33-induced neutrophil extracellular traps degrade fibronectin in a murine model of bronchopulmonary dysplasia.

Cell Death Discov 2020 4;6:33. Epub 2020 May 4.

1Department of Neonatal Medical Center, Children's Hospital of Nanjing Medical University, 210008 Nanjing, China.

Bronchopulmonary dysplasia (BPD) is the leading cause of chronic lung disease in preterm neonates. Extracellular matrix (ECM) abnormalities reshape lung development, contributing to BPD progression. In the present study, we first discovered that the ECM component fibronectin was reduced in the pulmonary tissues of model mice with BPD induced by lipopolysaccharide (LPS) and hyper-oxygen. Read More

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http://dx.doi.org/10.1038/s41420-020-0267-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198621PMC

Regulation of TFEB activity and its potential as a therapeutic target against kidney diseases.

Cell Death Discov 2020 1;6:32. Epub 2020 May 1.

Institute of Nephrology, and Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Affiliated Hospital of Guangdong Medical University, 524001 Zhanjiang, Guangdong China.

The transcription factor EB (TFEB) regulates the expression of target genes bearing the Coordinated Lysosomal Expression and Regulation (CLEAR) motif, thereby modulating autophagy and lysosomal biogenesis. Furthermore, TFEB can bind to the promoter of autophagy-associated genes and induce the formation of autophagosomes, autophagosome-lysosome fusion, and lysosomal cargo degradation. An increasing number of studies have shown that TFEB stimulates the intracellular clearance of pathogenic factors by enhancing autophagy and lysosomal function in multiple kidney diseases, such as cystinosis, acute kidney injury, and diabetic nephropathy. Read More

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http://dx.doi.org/10.1038/s41420-020-0265-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195473PMC

Dysfunction of ATG7-dependent autophagy dysregulates the antioxidant response and contributes to oxidative stress-induced biological impairments in human epidermal melanocytes.

Cell Death Discov 2020 1;6:31. Epub 2020 May 1.

Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.

Autophagy is a process involving the self-digestion of components that participates in anti-oxidative stress responses and protects cells against oxidative damage. However, the role of autophagy in the anti-oxidative stress responses of melanocytes remains unclear. To investigate the role of autophagy in human epidermal melanocytes, we knocked down and overexpressed ATG7, the critical gene of autophagy, in normal human epidermal melanocytes. Read More

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http://dx.doi.org/10.1038/s41420-020-0266-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195468PMC

Tet2-mediated epigenetic drive for astrocyte differentiation from embryonic neural stem cells.

Cell Death Discov 2020 29;6:30. Epub 2020 Apr 29.

1Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200092 China.

DNA methylation and demethylation at CpG di-nucleotide sites plays important roles in cell fate specification of neural stem cells (NSCs). We have previously reported that DNA methyltransferases, Dnmt1and Dnmt3a, serve to suppress precocious astrocyte differentiation from NSCs via methylation of astroglial lineage genes. However, whether active DNA demethylase also participates in astrogliogenesis remains undetermined. Read More

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http://dx.doi.org/10.1038/s41420-020-0264-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190615PMC

The nuclear envelope: target and mediator of the apoptotic process.

Cell Death Discov 2020 27;6:29. Epub 2020 Apr 27.

1Department of Neurobiology, School of Neurobiology, Biochemistry and Biophysics, George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978 Ramat Aviv, Israel.

Apoptosis is characterized by the destruction of essential cell organelles, including the cell nucleus. The nuclear envelope (NE) separates the nuclear interior from the cytosol. During apoptosis, the apoptotic machinery, in particular caspases, increases NE permeability by cleaving its proteins, such as those of the nuclear pore complex (NPC) and the nuclear lamina. Read More

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http://dx.doi.org/10.1038/s41420-020-0256-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184752PMC

Temporal transcriptome analysis of neuronal commitment reveals the preeminent role of the divergent lncRNA biotype and a critical candidate gene during differentiation.

Cell Death Discov 2020 24;6:28. Epub 2020 Apr 24.

National Brain Research Centre, Manesar, Gurgaon, Haryana India.

lncRNA genes can be genic or "intergenic". "Genic" RNAs can be further divided into six biotypes. Through genome-wide analysis of a publicly available data set on corticogenesis, we found that the divergent lncRNA (XH) biotype, comprising the lncRNA and the coding gene being in opposite directions in a head-to-head manner, was most prominent during neural commitment. Read More

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http://dx.doi.org/10.1038/s41420-020-0263-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181654PMC

How does mTOR sense glucose starvation? AMPK is the usual suspect.

Cell Death Discov 2020 22;6:27. Epub 2020 Apr 22.

2Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva, 84105 Israel.

Glucose is a major requirement for biological life. Its concentration is constantly sensed at the cellular level, allowing for adequate responses to any changes of glucose availability. Such responses are mediated by key sensors and signaling pathway components that adapt cellular metabolism to glucose levels. Read More

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http://dx.doi.org/10.1038/s41420-020-0260-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176732PMC

The role of neutrophil death in chronic inflammation and cancer.

Cell Death Discov 2020 22;6:26. Epub 2020 Apr 22.

Department of Surgery, Medical University of Vienna, Vienna, Austria.

The lifespan of a neutrophil is short and limited by programmed cell death, followed by efferocytosis. When activated or exposed to insult, neutrophil death may be delayed to support neutrophil effector functions such as phagocytosis, cytokine release, and pathogen destruction by degranulation. However, neutrophils may also alter the type of cell death and thereby affect inflammatory responses and tissue remodeling. Read More

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http://dx.doi.org/10.1038/s41420-020-0255-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176663PMC

Kinesin-7 CENP-E regulates chromosome alignment and genome stability of spermatogenic cells.

Cell Death Discov 2020 20;6:25. Epub 2020 Apr 20.

Department of Cell Biology and Genetics, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, 350122 China.

Kinesin-7 CENP-E is an essential kinetochore motor required for chromosome alignment and congression. However, the specific functions of CENP-E in the spermatogenic cells during spermatogenesis remain unknown. In this study, we find that CENP-E proteins are expressed in the spermatogonia, spermatocytes, and the elongating spermatids. Read More

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http://dx.doi.org/10.1038/s41420-020-0261-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171076PMC

Endoplasmic reticulum stress mediates resistance to BCL-2 inhibitor in uveal melanoma cells.

Cell Death Discov 2020 17;6:22. Epub 2020 Apr 17.

1Université Nice Côte d'Azur, Inserm, C3M Nice, France.

To address unmet clinical need for uveal melanomas, we assessed the effects of BH3-mimetic molecules, the ABT family, known to exert pro-apoptotic activities in cancer cells. Our results uncovered that ABT-263 (Navitoclax), a potent and orally bioavailable BCL-2 family inhibitor, induced antiproliferative effects in metastatic human uveal melanoma cells through cell cycle arrest at the G0/G1 phase, loss of mitochondrial membrane potential, and subsequently apoptotic cell death monitored by caspase activation and poly-ADP ribose polymerase cleavage. ABT-263-mediated reduction in tumor growth was also observed in vivo. Read More

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http://dx.doi.org/10.1038/s41420-020-0259-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165182PMC

Age related retinal Ganglion cell susceptibility in context of autophagy deficiency.

Cell Death Discov 2020 17;6:21. Epub 2020 Apr 17.

1Department of Cellular and Molecular Biology, Centro de Investigaciones Biológicas Margarita Salas, CSIC, Madrid, Spain.

Glaucoma is a common age-related disease leading to progressive retinal ganglion cell (RGC) death, visual field defects and vision loss and is the second leading cause of blindness in the elderly worldwide. Mitochondrial dysfunction and impaired autophagy have been linked to glaucoma and induction of autophagy shows neuroprotective effects in glaucoma animal models. We have shown that autophagy decreases with aging in the retina and that autophagy can be neuroprotective for RGCs, but it is currently unknown how aging and autophagy deficiency impact RGCs susceptibility and survival. Read More

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http://dx.doi.org/10.1038/s41420-020-0257-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165178PMC

A comparative pharmaco-metabolomic study of glutaminase inhibitors in glioma stem-like cells confirms biological effectiveness but reveals differences in target-specificity.

Cell Death Discov 2020 16;6:20. Epub 2020 Apr 16.

1Neurosurgery Department, University Hospital Duesseldorf, 40225 Duesseldorf, Germany.

Cancer cells upregulate anabolic processes to maintain high rates of cellular turnover. Limiting the supply of macromolecular precursors by targeting enzymes involved in biosynthesis is a promising strategy in cancer therapy. Several tumors excessively metabolize glutamine to generate precursors for nonessential amino acids, nucleotides, and lipids, in a process called glutaminolysis. Read More

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http://dx.doi.org/10.1038/s41420-020-0258-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7162917PMC

HSD11B1 is upregulated synergistically by IFNγ and TNFα and mediates TSG-6 expression in human UC-MSCs.

Cell Death Discov 2020 20;6:24. Epub 2020 Apr 20.

1State Key Laboratory of Radiation Medicine and Protection, Institute for Translational Medicine, Key Laboratory of Stem Cells and Medical Biomaterials of Jiangsu Province, Medical College of Soochow University, Suzhou, China.

Inflammatory factors such as IFNγ and TNFα could endow mesenchymal stem cells (MSCs) a potent immunomodulatory property, a process called licensing, but the mechanisms are not fully understood. We here found that glucocorticoid-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1), which converts inactive cortisone to the active cortisol and thereby regulates tissue glucocorticoid (GC) levels, was greatly upregulated by IFNγ and TNFα in human umbilical cord-derived MSCs (UC-MSCs) in a synergistic manner. While IFNγ alone was not able to induce HSD11B1, it could increase the activity of NF-kB and thus augment the upregulation of HSD11B1 by TNFα. Read More

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http://dx.doi.org/10.1038/s41420-020-0262-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168568PMC

LncRNA GAS5 promotes apoptosis as a competing endogenous RNA for miR-21 via thrombospondin 1 in ischemic AKI.

Cell Death Discov 2020 2;6:19. Epub 2020 Apr 2.

1Department of Nephrology, Zhongshan Hospital, Fudan University; Shanghai Institute of Kidney and Dialysis; Shanghai Key Laboratory of Kidney and Blood Purification; Shanghai Medical Center of Kidney Disease, Shanghai, China.

Mounting evidence has indicated that long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) played important roles in renal ischemia/reperfusion (I/R) injury. However, the involvement of lncRNA growth arrest specific 5 (GAS5) in acute kidney injury (AKI) remained largely unexplored. This study aimed to determine possible mechanisms of GAS5 in the renal I/R process. Read More

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http://dx.doi.org/10.1038/s41420-020-0253-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118150PMC

Proteomic and functional analyses in disease models reveal CLN5 protein involvement in mitochondrial dysfunction.

Cell Death Discov 2020 30;6:18. Epub 2020 Mar 30.

Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Stella Maris Foundation, Pisa, Italy.

CLN5 disease is a rare form of late-infantile neuronal ceroid lipofuscinosis (NCL) caused by mutations in the gene that encodes a protein whose primary function and physiological roles remains unresolved. Emerging lines of evidence point to mitochondrial dysfunction in the onset and progression of several forms of NCL, offering new insights into putative biomarkers and shared biological processes. In this work, we employed cellular and murine models of the disease, in an effort to clarify disease pathways associated with CLN5 depletion. Read More

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http://dx.doi.org/10.1038/s41420-020-0250-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105465PMC

Atorvastatin-induced senescence of hepatocellular carcinoma is mediated by downregulation of hTERT through the suppression of the IL-6/STAT3 pathway.

Cell Death Discov 2020 30;6:17. Epub 2020 Mar 30.

1Division of Translational Research and Center of Excellence for Cancer Research, Taipei Veterans General Hospital, Taipei, Taiwan.

Hepatocellular carcinoma (HCC), a hepatic malignancy, has a poor prognosis and contributes to cancer-related death worldwide. Cellular senescence is an anticancer therapeutic strategy that causes irreversible cell cycle arrest and enables immune-mediated clearance of cancer cells. Atorvastatin, an HMG-CoA reductase inhibitor, has been shown to inhibit tumor growth and induce apoptosis or autophagy in malignant tumors. Read More

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http://dx.doi.org/10.1038/s41420-020-0252-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105491PMC

Context is everything: extrinsic signalling and gain-of-function p53 mutants.

Cell Death Discov 2020 23;6:16. Epub 2020 Mar 23.

1Department of Experimental Medicine, TOR, University of Rome ''Tor Vergata", 00133 Rome, Italy.

The genomic locus is a target of mutational events in at least half of cancers. Despite several decades of study, a full consensus on the relevance of the acquisition of p53 gain-of-function missense mutants has not been reached. Depending on cancer type, type of mutations and other unidentified factors, the relevance for tumour development and progression of the oncogenic signalling directed by p53 mutants might significantly vary, leading to inconsistent observations that have fuelled a long and fierce debate in the field. Read More

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http://dx.doi.org/10.1038/s41420-020-0251-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7090043PMC

An unexpected turn of fortune: targeting TRAIL-Rs in KRAS-driven cancer.

Cell Death Discov 2020 17;6:14. Epub 2020 Mar 17.

2CECAD Cluster of Excellence, University of Cologne, Cologne, Germany.

Twenty-one percent of all human cancers bear constitutively activating mutations in the proto-oncogene . This incidence is substantially higher in some of the most inherently therapy-resistant cancers including 30% of non-small cell lung cancers (NSCLC), 50% of colorectal cancers, and 95% of pancreatic ductal adenocarcinomas (PDAC). Importantly, survival of patients with KRAS-mutated PDAC and NSCLC has not significantly improved since the 1970s highlighting an urgent need to re-examine how oncogenic KRAS influences cell death signaling outputs. Read More

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http://dx.doi.org/10.1038/s41420-020-0249-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078304PMC

The role of noncoding RNAs in epithelial cancer.

Cell Death Discov 2020 12;6:13. Epub 2020 Mar 12.

1Department of Experimental Medicine, TOR, University of Rome "Tor Vergata", 00133 Rome, Italy.

Regulatory noncoding RNAs (ncRNAs) are a class of RNAs transcribed by regions of the human genome that do not encode for proteins. The three main members of this class, named microRNA, long noncoding RNA, and circular RNA play a key role in the regulation of gene expression, eventually shaping critical cellular processes. Compelling experimental evidence shows that ncRNAs function either as tumor suppressors or oncogenes by participating in the regulation of one or several cancer hallmarks, including evading cell death, and their expression is frequently deregulated during cancer onset, progression, and dissemination. Read More

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http://dx.doi.org/10.1038/s41420-020-0247-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067833PMC

TFEB-mediated lysosomal biogenesis and lysosomal drug sequestration confer resistance to MEK inhibition in pancreatic cancer.

Cell Death Discov 2020 11;6:12. Epub 2020 Mar 11.

Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK, partner site Essen) and German Cancer Research Center, DKFZ, Heidelberg, Germany, Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK, partner site Essen) and German Cancer Research Center, DKFZ, Heidelberg, Germany, Essen, Germany.

Oncogenic mutations are encountered in more than 90% of pancreatic ductal adenocarcinomas. MEK inhibition has failed to procure any clinical benefits in mutant RAS-driven cancers including pancreatic ductal adenocarcinoma (PDAC). To identify potential resistance mechanisms underlying MEK inhibitor (MEKi) resistance in PDAC, we investigated lysosomal drug accumulation in PDAC models both in vitro and in vivo. Read More

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http://dx.doi.org/10.1038/s41420-020-0246-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066197PMC

Metformin inhibits IL-1β secretion via impairment of NLRP3 inflammasome in keratinocytes: implications for preventing the development of psoriasis.

Cell Death Discov 2020 4;6:11. Epub 2020 Mar 4.

2Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashiku, Fukuoka, 812-8582 Japan.

Psoriasis is a systemic inflammatory disease significantly associated with comorbidities including type 2 diabetes mellitus (T2DM). Metformin is utilized as a first-line agent for treating T2DM. Although metformin reportedly inhibits mature IL-1β secretion via NLRP3 inflammasome in macrophages of T2DM patients, it remains unclear whether it affects skin inflammation in psoriasis. Read More

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http://dx.doi.org/10.1038/s41420-020-0245-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055596PMC

2-Aminoethoxydiphenylborate (2-APB) inhibits release of phosphatidylserine-exposing extracellular vesicles from platelets.

Cell Death Discov 2020 2;6:10. Epub 2020 Mar 2.

Department of Pharmacology, University of Cambridge, Cambridge, UK.

Activated, procoagulant platelets shed phosphatidylserine (PS)-exposing extracellular vesicles (EVs) from their surface in a Ca- and calpain-dependent manner. These PS-exposing EVs are prothrombotic and proinflammatory and are found at elevated levels in many cardiovascular and metabolic diseases. How PS-exposing EVs are shed is not fully understood. Read More

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http://dx.doi.org/10.1038/s41420-020-0244-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7051957PMC

Inhibition of IκBα phosphorylation potentiates regulated cell death induced by azidothymidine in HTLV-1 infected cells.

Cell Death Discov 2020 18;6. Epub 2020 Feb 18.

1Department of Experimental Medicine, University of Rome "Tor Vergata", Rome, Italy.

Adult T cell leukemia/lymphoma (ATL) can be susceptible, at least transiently, to treatments with azidothymidine (AZT) plus IFNα and/or arsenic trioxide. However, the real role of AZT in this effect is still unclear. In fact, while reverse transcriptase (RT) inhibition could explain reduction of clonal expansion and of renewal of HTLV-1 infected cells during ATL progression, this effect alone seems insufficient to justify the evident and prompt decrease of the pro-viral load in treated patients. Read More

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http://dx.doi.org/10.1038/s41420-020-0243-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7028944PMC
February 2020

Delivery of phosphatidylethanolamine blunts stress in hepatoma cells exposed to elevated palmitate by targeting the endoplasmic reticulum.

Cell Death Discov 2020 18;6. Epub 2020 Feb 18.

1Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR USA.

Genetic obesity increases in liver phosphatidylcholine (PC)/phosphatidylethanolamine (PE) ratio, inducing endoplasmic reticulum (ER) stress without concomitant increase of ER chaperones. Here, it is found that exposing mice to a palm oil-based high fat (HF) diet induced obesity, loss of liver PE, and loss of the ER chaperone Grp78/BiP in pericentral hepatocytes. In Hepa1-6 cells treated with elevated concentration of palmitate to model lipid stress, Grp78/BiP mRNA was increased, indicating onset of stress-induced Unfolded Protein Response (UPR), but Grp78/BiP protein abundance was nevertheless decreased. Read More

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http://dx.doi.org/10.1038/s41420-020-0241-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7028721PMC
February 2020

Nucleolar localization of the Notch4 intracellular domain underpins its regulation of the cellular response to genotoxic stressors.

Cell Death Discov 2020 18;6. Epub 2020 Feb 18.

Institute for Stem Cell Science & Regenerative Medicine (inStem), Bellary Road, Bengaluru, Karnataka India.

Cell survival is one of the many cellular processes regulated by Notch family of proteins. A comparison of human breast cancer cell lines, which differ in the levels of endogenous Notch4, implicated the protein in regulating susceptibility to apoptosis triggered by genomic damage. In agreement with this observation, increased susceptibility to genotoxic damage was observed following siRNA ablations of Notch4 in two breast cancer cell lines. Read More

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http://dx.doi.org/10.1038/s41420-020-0242-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029026PMC
February 2020

Phenotypic high-throughput screening platform identifies novel chemotypes for necroptosis inhibition.

Cell Death Discov 2020 11;6. Epub 2020 Feb 11.

1Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal.

Regulated necrosis or necroptosis, mediated by receptor-interacting kinase 1 (RIPK1), RIPK3 and pseudokinase mixed lineage kinase domain-like protein (MLKL), contributes to the pathogenesis of inflammatory, infectious and degenerative diseases. Recently identified necroptosis inhibitors display moderate specificity, suboptimal pharmacokinetics, off-target effects and toxicity, preventing these molecules from reaching the clinic. Here, we developed a cell-based high-throughput screening (HTS) cascade for the identification of small-molecule inhibitors of necroptosis. Read More

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http://dx.doi.org/10.1038/s41420-020-0240-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026080PMC
February 2020

Genetic manipulation of SPG7 or NipSnap2 does not affect mitochondrial permeability transition.

Cell Death Discov 2020 29;6. Epub 2020 Jan 29.

1Dalton Cardiovascular Research Center, University of Missouri, Columbia, MO 65211 USA.

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http://dx.doi.org/10.1038/s41420-020-0239-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026053PMC
January 2020

Rho-ROCK signaling mediates entotic cell death in tumor.

Cell Death Discov 2020 23;6. Epub 2020 Jan 23.

1Institute of Tissue Transplantation and Immunology, Department of Immunobiology, Jinan University, Guangzhou, China.

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http://dx.doi.org/10.1038/s41420-020-0238-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026421PMC
January 2020

NF90 stabilizes cyclin E1 mRNA through phosphorylation of NF90-Ser382 by CDK2.

Cell Death Discov 2020 22;6. Epub 2020 Jan 22.

1Key Laboratory of Metabolism and Molecular Medicine, the Ministry of Education, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.

Nuclear factor 90 (NF90), an RNA-binding protein, has been implicated in regulating interleukin-2 (IL-2) and the immune response. It was recently reported that NF90 is upregulated in hepatocellular carcinoma (HCC) tissues and promotes HCC proliferation through upregulating cyclin E1 at the posttranscription level. However, the regulation of NF90 in HCC remains unclear. Read More

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http://dx.doi.org/10.1038/s41420-020-0236-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026180PMC
January 2020

Preclinical studies reveal MLN4924 is a promising new retinoblastoma therapy.

Cell Death Discov 2020 20;6. Epub 2020 Jan 20.

1Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health System, 600 University Avenue, Toronto, ON M5G 1X5 Canada.

loss ( or amplification ( ) in fetal human retina causes retinoblastoma. SKP2 loss kills cells, but small molecule SKP2 inhibitors remain unexplored therapeutically. Whether SKP2 is synthetic lethal in retinoblastoma is unclear. Read More

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http://dx.doi.org/10.1038/s41420-020-0237-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026052PMC
January 2020