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Apoptotic cells

Walderik W Zomerman, Sabine L A Plasschaert, Siobhan Conroy, Frank J Scherpen, Tiny G J Meeuwsen-de Boer, Harm J Lourens, Sergi Guerrero Llobet, Marlinde J Smit, Lorian Slagter-Menkema, Annika Seitz, Corrie E M Gidding, Esther Hulleman, Pieter Wesseling, Lisethe Meijer, Leon C van Kempen, Anke van den Berg, Daniël O Warmerdam, Frank A E Kruyt, Floris Foijer, Marcel A T M van Vugt, Wilfred F A den Dunnen, Eelco W Hoving, Victor Guryev, Eveline S J M de Bont, Sophia W M Bruggeman
The brain cancer medulloblastoma consists of different transcriptional subgroups. To characterize medulloblastoma at the phosphoprotein-signaling level, we performed high-throughput peptide phosphorylation profiling on a large cohort of SHH (Sonic Hedgehog), group 3, and group 4 medulloblastomas. We identified two major protein-signaling profiles. One profile was associated with rapid death post-recurrence and resembled MYC-like signaling for which MYC lesions are sufficient but not necessary. The second profile showed enrichment for DNA damage, as well as apoptotic and neuronal signaling...
March 20, 2018: Cell Reports
Qifan Zhu, Si Ming Man, Rajendra Karki, R K Subbarao Malireddi, Thirumala-Devi Kanneganti
Interferons (IFNs) and inflammasomes are essential mediators of anti-microbial immunity. Type I IFN signaling drives activation of the AIM2 inflammasome in macrophages; however, the relative contribution of IFNs and inflammasome responses in host defense is less understood. We report intact AIM2 inflammasome responses in mice lacking type I IFN signaling during infection with F. novicida. Lack of type I IFN signaling conferred protection to F. novicida infection in contrast to the increased susceptibility in AIM2-deficient mice...
March 20, 2018: Cell Reports
Jie Han, Leslie A Goldstein, Wen Hou, Suman Chatterjee, Timothy F Burns, Hannah Rabinowich
Macroautophagy/autophagy has emerged as a resistance mechanism to anticancer drug treatments that induce metabolic stress. Certain tumors, including a subset of KRAS-mutant NSCLCs have been shown to be addicted to autophagy, and potentially vulnerable to autophagy inhibition. Currently, autophagy inhibition is being tested in the clinic as a therapeutic component for tumors that utilize this degradation process as a drug resistance mechanism. The current study provides evidence that HSP90 (heat shock protein 90) inhibition diminishes the expression of ATG7, thereby impeding the cellular capability of mounting an effective autophagic response in NSCLC cells...
March 21, 2018: Autophagy
Nicolette Kapp, Xiao X Stander, Barend A Stander
This project investigated the in-vitro effects of a glycolytic inhibitor, 3-bromopyruvate (3-BrP), in combination with and a new in silico-designed inhibitor of the bromodomain-4 (BRD-4) protein, ITH-47, on the U937 acute myeloid leukemia cell line. 3-BrP is an agent that targets the altered metabolism of cancer cells by interfering with glucose metabolism in the glycolytic pathway. ITH-47 is an acetyl-lysine inhibitor that displaces bromdomain 4 proteins from chromatin by competitively binding to the acetyl-lysine recognition pocket of this bromodomain and extraterminal (BET) BRD protein, thereby preventing transcription of cancer-associated genes and further cell growth...
March 20, 2018: Anti-cancer Drugs
Fahmi Yakop, Siti Aisyah Abd Ghafar, Yoke Keong Yong, Latifah Saiful Yazan, Rohazila Mohamad Hanafiah, Vuanghao Lim, Zolkapli Eshak
PURPOSE: The purpose of this study was to investigate apoptotic activity of silver nanoparticle Clinacanthus nutans (AgNps-CN) towards HSC-4 cell lines (oral squamous cell carcinoma cell lines). METHODS: Methods involved were MTT assay (cytotoxic activity), morphological cells analysis, flow cytometry and cell cycle analysis and western blot. RESULTS: MTT assay revealed IC50 concentration was 1.61 µg/mL, 3T3-L1 cell lines were used to determine whether AgNps-CN is cytotoxic to normal cells...
March 21, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Arnab Bhattacharyya, Aida Jameei, Aditya Garai, Rupak Saha, Anjali A Karande, Akhil R Chakravarty
Copper(ii) acetylacetonates of N,N,N-donor dipicolylamine (dpa) ligands, viz. [Cu(L1)(acac)]ClO4 (1), [Cu(L2)(acac)]ClO4 (2) and [Cu(L3)(acac)]ClO4 (3), where L1 is benzyldipicolylamine (bzdpa), L2 and L3 are non-iodinated and diiodinated BODIPY (borondipyrromethene) ligands and Hacac is acetylacetone, were synthesized and characterized and their photocytotoxicity was studied. The BODIPY complex 2, structurally characterized by X-ray crystallography, has copper(ii) in a distorted square-pyramidal geometry (degree of trigonality, τ5 = 0...
March 21, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
Eva Ramos, Alejandro Romero, Javier Egea, José Marco-Contelles, Javier Del Pino, Cristóbal de Los Ríos
AIM: The 1,8-naphthyridine CR80 (ethyl 5-amino-2-methyl-6,7,8,9-tetrahydrobenzo[b] [1,8]naphthyridine-3-carboxylate) has shown interesting neuroprotective properties in in vitro and in vivo models of neurodegeneration. In spite of these promising outcomes, the molecular and cellular mechanisms underlying CR80 actions need to be further explored. MATERIALS & METHODS: We herein report the signal transduction pathways involved in developmental, neuroprotective and stress-activated processes, as well as the gene expression regulation by CR80 in SH-SY5Y neuroblastoma cells...
March 21, 2018: Future Medicinal Chemistry
Wagdy M Eldehna, Mahmoud F Abo-Ashour, Hany S Ibrahim, Ghada H Al-Ansary, Hazem A Ghabbour, Mahmoud M Elaasser, Hanaa Y A Ahmed, Nesreen A Safwat
On account of their significance as apoptosis inducing agents, merging indole and 3-hydrazinoindolin-2-one scaffolds is a logic tactic for designing pro-apoptotic agents. Consequently, 27 hybrids (6a-r, 9a-f and 11a-c) were synthesised and evaluated for their cytotoxicity against MCF-7, HepG-2 and HCT-116 cancer cell lines. SAR studies unravelled that N-propylindole derivatives were the most active compounds such as 6n (MCF-7; IC50 =1.04 µM), which displayed a significant decrease of cell population in the G2/M phase and significant increase in the early and late apoptosis by 19-folds in Annexin-V-FTIC assay...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
Jiantong Hou, Gaoliang Yan, Bo Liu, Boqian Zhu, Yong Qiao, Dong Wang, Ruifeng Li, Erfei Luo, Chengchun Tang
Background: Renal vasoconstriction, oxidative stress, endothelial dysfunction, and apoptosis are the major causes of contrast-induced nephropathy (CIN). The aim of this study was to evaluate the protective effects of enalapril maleate and folic acid tablets on CIN in diabetic rats. Methods: Thirty-two Sprague-Dawley rats were divided into four groups: CIN (C), CIN + enalapril maleate (CE), CIN + folic acid (CF), and CIN + enalapril maleate and folic acid tablets (CEF)...
2018: BioMed Research International
Safia Ladha, Xiaofan Qiu, Lorenzo Casal, Nicholas S Caron, Dagmar E Ehrnhoefer, Michael R Hayden
Traditionally, the family of caspases has been subcategorised according to their respective main roles in mediating apoptosis or inflammation. However, recent studies have revealed that caspases participate in diverse cellular functions beyond their canonical roles. Caspase-6 (C6) is one such protease known for its role as a pro-apoptotic executioner caspase and its aberrant activity in several neurodegenerative diseases. In addition to apoptosis, C6 has been shown to regulate B-cell activation and differentiation in plasma cells as well as macrophage activation...
2018: Cell Death Discovery
Hadas Pahima, Simona Reina, Noa Tadmor, Daniella Dadon-Klein, Anna Shteinfer-Kuzmine, Nathalie M Mazure, Vito De Pinto, Varda Shoshan-Barmatz
The voltage-dependent anion channel 1 (VDAC1), an outer mitochondria membrane (OMM) protein, serves as a mitochondrial gatekeeper, mediating the transport of nucleotides, Ca2+ and other metabolites across the OMM. VDAC1 also plays a central role in mitochondria-mediated apoptosis by facilitating the release of apoptotic proteins and by association with both pro- and anti-apoptotic proteins. Tumor cells, which are constantly exposed to hypoxic conditions, affect the cell via the transcription factor hypoxia-inducible factor (HIF) that induces transcriptional activity...
February 27, 2018: Oncotarget
Zunyue Zhang, Guohong Lin, Yujing Yan, Xiang Li, Yibing Hu, Jing Wang, Bingjiao Yin, Yaqun Wu, Zhuoya Li, Xiang-Ping Yang
Chemoresistance remains a major obstacle to successful treatment of breast cancer. Although soluble tumor necrosis factor-α (sTNF-α) has been implicated in mediating drug-resistance in human cancers, whether transmembrane tumor necrosis factor-α (tmTNF-α) plays a role in chemoresistance remains unclear. Here we found that over 50% of studied patients expressed tmTNF-α at high levels in breast cancer tissues and tmTNF-α expression positively correlated with resistance to anthracycline chemotherapy. Alteration of tmTNF-α expression changed the sensitivity of primary human breast cancer cells and breast cancer cell lines to doxorubicin (DOX)...
March 21, 2018: Oncogene
Petrus Linge, Paul R Fortin, Christian Lood, Anders A Bengtsson, Eric Boilard
Dysregulation of lymphocyte function, accumulation of autoantibodies and defective clearance of circulating immune complexes and apoptotic cells are hallmarks of systemic lupus erythematosus (SLE). Moreover, it is now evident that an intricate interplay between the adaptive and innate immune systems contributes to the pathogenesis of SLE, ultimately resulting in chronic inflammation and organ damage. Platelets circulate in the blood and are chiefly recognized for their role in the prevention of bleeding and promotion of haemostasis; however, accumulating evidence points to a role for platelets in both adaptive and innate immunity...
March 21, 2018: Nature Reviews. Rheumatology
Ruifang Li, Ruiling Zhang, Yanhui Yang, Xueqin Wang, Yanjie Yi, Pei Fan, Zhengwei Liu, Chen Chen, Junpeng Chang
CGA-N12 is an antifungal peptide derived from human chromogranin A. In our previous investigation, CGA-N12 was found to have specific anti-candidal activity, though the mechanism of action remained unclear. Herein, we investigated the effects of CGA-N12 on mitochondria. We found that CGA-N12 induced an over-generation of intracellular reactive oxygen species and dissipation in mitochondrial membrane potential, in which the former plays key roles in the initiation of apoptosis and the latter is a sign of the cell apoptosis...
March 20, 2018: Biochemical Journal
Mohamed Rahmani, Jewel Nkwocha, Elisa Hawkins, Xinyan Pei, Rebecca E Parker, Maciej Kmieciak, Joel D Leverson, Deepak Sampath, Andrea Ferreira-Gonzalez, Steven Grant
Inhibitors targeting BCL-2 apoptotic proteins have significant potential for the treatment of acute myeloid leukemia (AML); however, complete responses are observed in only 20% of patients suggesting targeting BCL-2 alone is insufficient to yield durable responses. Here we assessed the efficacy of co-administration of the PI3K/mTOR inhibitor GDC-0980 or the p110β-sparing PI3K inhibitor taselisib with the selective BCL-2 antagonist venetoclax in AML cells. Tetracycline-inducible downregulation of BCL-2 significantly sensitized MV4-11 and MOLM-13 AML cells to PI3K inhibition...
March 20, 2018: Cancer Research
Eun Ju Shin, Hyo-Kyoung Choi, Mi Jeong Sung, Jae Ho Park, Min-Yu Chung, Sangwon Chung, Jin-Taek Hwang
We investigated the anti-cancer effects of beta-sitosterol (BS), a plant-derived sterol in AGS human gastric adenocarcinoma cells and xenograft mouse models. BS significantly reduced cell viability by inducing apoptosis in AGS adenocarcinoma cells. This was accompanied by the formation of apoptotic bodies, as detected by Annexin V, caspase 3/7 activity, and MitoPotential assay. BS stimulated phosphatase and tensin homolog (PTEN) and phospho-AMP-activated protein kinase (p-AMPK) expression. Pharmacological inhibitors or siRNA were used to further analyse the relationship between the two proteins...
March 17, 2018: Biochemical Pharmacology
Eric Wei Chiang Chan, Siu Kuin Wong, Hung Tuck Chan
This short review provides an update of the anticancer and anti-inflammatory properties of casticin from Vitex species. Casticin is a polymethylflavone with three rings, an orthocatechol moiety, a double bond, two hydroxyl groups and four methoxyl groups. Casticin has been isolated from various tissues of plants in the Vitex genus: fruits and leaves of V. trifolia; aerial parts and seeds of V. agnus-castus and leaves of V. negundo. Studies have reported the antiproliferative and apoptotic activities of casticin from Vitex species...
March 6, 2018: Journal of Integrative Medicine
Fazeela Mahaboob Begum S M, Kalai Chitra, Benin Joseph, Raji Sundararajan, Hemalatha S
BACKGROUND: Lung adenocarcinoma is the most common subtype of Non small cell lung cancer in which the PI3K/Akt cascade is frequently deregulated. The ubiquitous expression of the PI3K and the frequent inactivation of PTEN accounts for the prolonged survival, evasion of apoptosis and metastasis in cancer. This has led to the development of PI3K inhibitors in the treatment of cancer. Synthetic PI3K inhibitors undergoing clinical and preclinical studies are toxic in animals. Hence, there is a critical need to identify PI3K inhibitor(s) of natural origin...
March 20, 2018: BMC Complementary and Alternative Medicine
Hai-Cheng Dou, Jun-Yu Chen, Tang-Fei Ran, Wei-Min Jiang
The treatment goal in spinal cord injury (SCI) is to repair neurites and suppress cell apoptosis. Panax quinquefolius saponin (PQS) is the major active ingredient of American ginseng and has been demonstrated to have anti-inflammatory and anti-apoptotic roles in various diseases. However, the potential effect of PQS on the pathological process of acute SCI remains unknown. This work tested the effects of PQS on acute SCI and clarified its potential mechanisms. PQS treatment ameliorated the damage to spinal tissue and improved the functional recovery after SCI...
March 17, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Sowmya Mekala, Subbarao V Tullimilli, Ramasatyaveni Geesala, Kanakaraju Manupati, Neha R Dhoke, Amitava Das
Apoptotic hepatocytes release factors that activate Hepatic Stellate Cells (HSCs) thereby inducing hepatic fibrosis. In the present study, in vivo and in vitro injury models were established using acetaminophen, ethanol, carbon tetrachloride or thioacetamide. Hepatotoxicant-induced diseased hepatic tissue histology correlated with a differential expression of fibrosis-related genes. Marked increase in co-staining of TGFRIIβ-Desmin or α-SMA-PDGFRβ, markers of activated HSCs, in liver sections of these hepatotoxicant-treated mice also depicted an increase in Annexin V-Cytokeratin expressing hepatocytes...
March 20, 2018: Canadian Journal of Physiology and Pharmacology
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