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https://www.readbyqxmd.com/read/28723569/xiap-loss-triggers-ripk3-and-caspase-8-driven-il-1%C3%AE-activation-and-cell-death-as-a-consequence-of-tlr-myd88-induced-ciap1-traf2-degradation
#1
Kate E Lawlor, Rebecca Feltham, Monica Yabal, Stephanie A Conos, Kaiwen W Chen, Stephanie Ziehe, Carina Graß, Yifan Zhan, Tan A Nguyen, Cathrine Hall, Angelina J Vince, Simon M Chatfield, Damian B D'Silva, Kenneth C Pang, Kate Schroder, John Silke, David L Vaux, Philipp J Jost, James E Vince
X-linked Inhibitor of Apoptosis (XIAP) deficiency predisposes people to pathogen-associated hyperinflammation. Upon XIAP loss, Toll-like receptor (TLR) ligation triggers RIPK3-caspase-8-mediated IL-1β activation and death in myeloid cells. How XIAP suppresses these events remains unclear. Here, we show that TLR-MyD88 causes the proteasomal degradation of the related IAP, cIAP1, and its adaptor, TRAF2, by inducing TNF and TNF Receptor 2 (TNFR2) signaling. Genetically, we define that myeloid-specific cIAP1 loss promotes TLR-induced RIPK3-caspase-8 and IL-1β activity in the absence of XIAP...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28719951/neuronal-apoptosis-pathological-basis-of-behavioral-dysfunctions-induced-by-angiostrongylus-cantonensis-in-rodents-model
#2
Shiqi Luo, Lisi OuYang, Jie Wei, Feng Wu, Zhongdao Wu, Wanlong Lei, Dongjuan Yuan
Angiostrongylus cantonensis invades the central nervous system (CNS) of humans to induce eosinophilic meningitis and meningoencephalitis and leads to persistent headache, cognitive dysfunction, and ataxic gait. Infected mice (nonpermissive host), admittedly, suffer more serious pathological injuries than rats (permissive host). However, the pathological basis of these manifestations is incompletely elucidated. In this study, the behavioral test, histological and immunohistochemical techniques, and analysis of apoptotic gene expression, especially caspase-3, were conducted...
June 2017: Korean Journal of Parasitology
https://www.readbyqxmd.com/read/28719803/elevated-sterol-regulatory-elementary-binding-protein-1-and-glua2-levels-in-the-hippocampal-nuclear-fraction-of-genetic-absence-epilepsy-rats-from-strasbourg
#3
Sathiya Sekar, Entesar Omran, Venkat Gopalakrishnan, John G Howland, Terrance P Snutch, Changiz Taghibiglou
Studies in animal models and human tissues show that nuclear translocation of sterol regulatory element binding protein 1 (SREBP1) and glutamate A2 subunit (GluA2) of cell-surface AMPA receptor (AMPAR) trigger neuronal excitotoxicity-induced apoptosis in stroke. However, it is not known whether a similar type of underlying pathophysiology occurs in absence epilepsy. To explore this issue, we examined the levels of mature SREBP1, GluA2, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), p53, and activated to total caspase 3 ratio in nuclear fractions (NF) of hippocampal homogenate from 8 to 10 week old male Genetic Absence Epilepsy Rats from Strasbourg (GAERS) and non-epileptic control (NEC) strains...
July 12, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28718726/effects-of-the-notch1-signaling-pathway-on-human-lung-cancer-a549-cells
#4
Yun Zeng, Bijian Yin, Xinwei Wang, Guohao Xia, Zhengjie Shen, Wenzhe Gu, Mianhua Wu
PURPOSE: To evaluate the effects of the Notch1 signaling pathway on human lung cancer A549 cells. MATERIALS AND METHODS: A549 cells were transfected with recombinant plasmids. Cell proliferation was detected by MTT assay. A tumor-bearing mouse model was established for intratumoral gene injection. Apoptosis-related factors were detected by immunohistochemical assay. Caspase-8, caspase-3, caspase-9, PI3K, pAkt and pSTAT3 expressions were detected by Western blotting...
July 18, 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/28717410/fish-scale-collagen-peptides-protect-against-cocl2-tnf-%C3%AE-induced-cytotoxicity-and-inflammation-via-inhibition-of-ros-mapk-and-nf-%C3%AE%C2%BAb-pathways-in-hacat-cells
#5
Fazli Subhan, Hae Yeong Kang, Yeseon Lim, Muhammad Ikram, Sun-Yong Baek, Songwan Jin, Young Hun Jeong, Jong Young Kwak, Sik Yoon
Skin diseases associated with inflammation or oxidative stress represent the most common problem in dermatology. The present study demonstrates that fish scale collagen peptides (FSCP) protect against CoCl2-induced cytotoxicity and TNF-α-induced inflammatory responses in human HaCaT keratinocyte cells. Our study is the first to report that FSCP increase cell viability and ameliorate oxidative injury in HaCaT cells through mechanisms mediated by the downregulation of key proinflammatory cytokines, namely, TNF-α, IL-1β, IL-8, and iNOS...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28716710/microrna-143-acts-as-a-suppressor-of-hemangioma-growth-by-targeting-bcl-2
#6
Chongqing Huang, JingYong Huang, Pengyan Ma, Guanfeng Yu
Infantile hemangioma is the most common vascular tumor affecting infants, which is associated with clonal expansion of endothelial cells. The aim of this study is to determine the role of microRNA (miR)-143 in the growth and survival of hemangioma-derived endothelial cells (HemECs). We examined the expression of miR-143 in patients with proliferating-phase (n=10) and involuting-phase (n=8) hemangiomas. The effects of ectopic expression of miR-143 on the viability, proliferation, cell cycle distribution, and apoptosis of HemECs were explored...
July 14, 2017: Gene
https://www.readbyqxmd.com/read/28716577/apoptosis-related-genes-induced-in-response-to-ketamine-during-early-life-stages-of-zebrafish
#7
Luís M Félix, Cindy Serafim, Ana M Valentim, Luís M Antunes, Manuela Matos, Ana M Coimbra
Increasing evidence supports that ketamine, a widely used anaesthetic, potentiates apoptosis during development through the mitochondrial pathway of apoptosis. Defects in the apoptotic machinery can cause or contribute to the developmental abnormalities previously described in ketamine-exposed zebrafish. The involvement of the apoptotic machinery in ketamine-induced teratogenicity was addressed by assessing the apoptotic signals at 8 and 24 hpf following 20min exposure to ketamine at three stages of early zebrafish embryo development (256 cell, 50% epiboly and 1-4 somites stages)...
July 14, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28716523/sensitivity-towards-the-grp78-inhibitor-kp1339-it-139-is-characterized-by-apoptosis-induction-via-caspase-8-upon-disruption-of-er-homeostasis
#8
Beatrix Schoenhacker-Alte, Thomas Mohr, Christine Pirker, Kushtrim Kryeziu, Paul-Steffen Kuhn, Alicia Buck, Thilo Hofmann, Christopher Gerner, Gerrit Hermann, Gunda Koellensperger, Bernhard K Keppler, Walter Berger, Petra Heffeter
The ruthenium drug and GRP78 inhibitor KP1339/IT-139 has already demonstrated promising anticancer activity in a phase I clinical trial. This study aimed to identify mechanisms underlying increased sensitivity to KP1339 treatment. Based on a screen utilizing 23 cell lines, a small panel was selected to compare KP1339-sensitive and low-responsive models. KP1339 sensitivity was neither based on differences in ruthenium accumulation, nor sensitivity to oxidative stress or constituents of KP1339 (ruthenium chloride and indazole)...
July 14, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28716455/the-vitamin-b6-paradox-supplementation-with-high-concentrations-of-pyridoxine-leads-to-decreased-vitamin-b6-function
#9
Misha F Vrolijk, Antoon Opperhuizen, Eugène H J M Jansen, Geja J Hageman, Aalt Bast, Guido R M M Haenen
Vitamin B6 is a water-soluble vitamin that functions as a coenzyme in many reactions involved in amino acid, carbohydrates and lipid metabolism. Since 2014, >50 cases of sensory neuronal pain due to vitamin B6 supplementation were reported. Up to now, the mechanism of this toxicity is enigmatic and the contribution of the various B6 vitamers to this toxicity is largely unknown. In the present study, the neurotoxicity of the different forms of vitamin B6 is tested on SHSY5Y and CaCo-2 cells. Cells were exposed to pyridoxine, pyridoxamine, pyridoxal, pyridoxal-5-phosphate or pyridoxamine-5-phosphate for 24h, after which cell viability was measured using the MTT assay...
July 14, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28715002/cationic-folate-mediated-liposomal-delivery-of-bis-arylidene-oxindole-induces-efficient-melanoma-tumor-regression
#10
Chandra Kumar Elechalawar, Kathyayani Sridharan, Abhishek Pal, Mohammed Tanveer Ahmed, Mohammed Yousuf, Susanta Sekhar Adhikari, Rajkumar Banerjee
The folate receptor (FR) is a well-validated and common target for cancer due to its high over-expression in many different cancer cells. Herein, we developed a new FR-targeting ligand (FA8) by conjugating folic acid and a cationic lipid. Owing to its favorable structural property FA8 as a ligand could be accommodated at an unusually higher molar ratio for a ligand-targeted liposome. We then encapsulated a drug-like molecule, bis-arylidene oxindole (NME2), in the targeted liposome. The resulting formulation induced potent caspase-8 up-regulation even in FR-moderately expressing melanoma cells...
July 17, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28714025/effect-of-ccl2-sirna-on-proliferation-and-apoptosis-in-the-u251-human-glioma-cell-line
#11
Bin Lu, Yue Zhou, Zhongzhou Su, Ai Yan, Peng Ding
Glioma is one of the most common types of tumor of the central nervous system. Increased expression of C‑C motif chemokine 2 (CCL2) has previously been observed in various types of cancer. The effect of CCL2 small interfering (si)RNA on the proliferation, angiogenesis and apoptosis of the glioma cell line U251 was investigated in the present study. Data on CCL2 expression in glioma and normal tissues were obtained from The Cancer Genome Atlas. A total of 30 patients with glioma were enrolled in the present study...
July 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713944/truncated-apolipoprotein-c-i-induces-apoptosis-in-neuroblastoma-by-activating-caspases-in-the-extrinsic-and-intrinsic-pathways
#12
Fei Guo, Wei Zhao, Lin Yang, Yang Yang, Saiqi Wang, Yingjun Wang, Zhaoming Li, Jiaxiang Wang
Truncated apolipoprotein C-I is a post-translationally modified protein characterized by the loss of threonine and proline residues from the N-terminus of the mature peptide. The truncated peptide is involved in many physiological and pathological processes in vivo and is related to malignant diseases. The aim of the present study was to assess the effects of the truncated peptide on tumorigenesis in neuroblastoma. The truncated peptide was chemically synthesized, and a signal peptide was used as the negative control...
July 14, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28713935/curcumin-pretreatment-protects-against-pm2-5%C3%A2-induced-oxidized-low%C3%A2-density-lipoprotein%C3%A2-mediated-oxidative-stress-and-inflammation-in-human-microvascular-endothelial-cells
#13
Jun Shi, Huiping Deng, Min Zhang
A previous study demonstrated that particulate matter (≤2.5 µm in diameter; PM2.5) may promote atherosclerosis. However, the underlying mechanisms of PM2.5 in human microvascular endothelial cells (HMEC‑1) remain to be elucidated. It has been reported that inflammation and oxidative stress can be reduced by curcumin, and in the present study, the aim was to investigate the protective effects of curcumin on PM2.5‑induced oxidative stress and inflammatory response in HMEC‑1. HMEC‑1 were stimulated with curcumin and PM2...
July 6, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713919/ganetespib-induces-g2-m-cell-cycle-arrest-and-apoptosis-in-gastric-cancer-cells-through-targeting-of-receptor-tyrosine-kinase-signaling
#14
Harry Lee, Nipun Saini, Amanda B Parris, Ming Zhao, Xiaohe Yang
Heat shock protein 90 (HSP90) regulates several important cellular processes via its repertoire of 'client proteins'. These client proteins have been found to play fundamental roles in signal transduction, cell proliferation, cell cycle progression and survival, as well as other features of malignant cells, such as invasion, tumor angiogenesis and metastasis. Thus, HSP90 is an emerging target for cancer therapy. To this end, we evaluated ganetespib (STA-9090), a novel and potent HSP90 inhibitor, for its activity in gastric cancer cell lines...
July 13, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28713913/upregulation-of-long-non-coding-rna-malat-1-confers-poor-prognosis-and-influences-cell-proliferation-and-apoptosis-in-acute-monocytic-leukemia
#15
Jin-Long Huang, Wei Liu, Li-Hong Tian, Ting-Ting Chai, Yang Liu, Feng Zhang, Hai-Ying Fu, Hua-Rong Zhou, Jian-Zhen Shen
Metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1), a long non-coding RNA, has been documented to be a new prognostic marker and gene regulator in several types of cancer, but its potential involvement in acute myeloid leukemia (AML) remains unclear. This study investigated the expression and functional role of MALAT-1 in AML. MALAT-1 expression was assessed by real-time quantitative PCR. After lentiviral-mediated MALAT-1 knockdown, the proliferation of AML cells was determined by CCK-8 and colony formation assays...
July 10, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28713162/abt-263-induces-g1-g0-phase-arrest-apoptosis-and-autophagy-in-human-esophageal-cancer-cells-in-vitro
#16
Qing-Huan Lin, Fu-Chang Que, Chun-Ping Gu, De-Sheng Zhong, Dan Zhou, Yi Kong, Le Yu, Shu-Wen Liu
Both the anti- and pro-apoptotic members of the Bcl-2 family are regulated by a conserved Bcl-2 homology (BH3) domain. ABT-263 (Navitoclax), a novel BH3 mimetic and orally bioavailable Bcl-2 family inhibitor with high affinity for Bcl-xL, Bcl-2 and Bcl-w has entered clinical trials for cancer treatment. But the anticancer mechanisms of ABT-263 have not been fully elucidated. In this study we investigated the effects of ABT-263 on human esophageal cancer cells in vitro and to explore its anticancer mechanisms...
July 17, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28713009/aeromonas-hydrophila-induced-alterations-in-cytosolic-calcium-activate-pro-apoptotic-cpkc-mek1-2-tnf%C3%AE-axis-in-infected-headkidney-macrophages-of-clarias-gariepinus
#17
Asha Shelly, Chaitali Banerjee, Gunjan Kumar Saurav, Atish Ray, Vipin Singh Rana, Rajagopal Raman, Shibnath Mazumder
Alterations in intracellular-calcium (Ca(2+))i homeostasis is critical to Aeromonas hydrophila-induced headkidney macrophages (HKM) apoptosis of Clarias gariepinus, though the implications are poorly understood. Here, we describe the role of intermediate molecules of Ca(2+-)signaling pathway that are involved in HKM apoptosis. We observed phosphoinositide-3-kinase/phospholipase C is critical for (Ca(2+))i release in infected HKM. Heightened protein kinase-C (PKC) activity and phosphorylation of MEK1/2-ERK1/2 was noted which declined in presence of 2-APB, Go6976 and PD98059, inhibitors to IP3-receptor, conventional PKC isoforms (cPKC) and MEK1/2 respectively implicating Ca(2+)/cPKC/MEK-ERK1/2 axis imperative in A...
July 13, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28712913/acute-ochratoxin-a-exposure-induces-inflammation-and-apoptosis-in-human-embryonic-kidney-hek293-cells
#18
Shanel Raghubeer, Savania Nagiah, Anil A Chuturgoon
Ochratoxin A (OTA), a common contaminant of grain and fruit and known carcinogen, has been linked to impaired antioxidant response and cellular repair. The effect of OTA on inflammation in cells has not been explored. This study investigated OTA's influence on inflammatory mediators using a range of OTA concentrations (0.5 μM (sub-IC50), 1.2 μm (IC50) and 2 μm (supra-IC50)) on human embryonic kidney (HEK293) cells over 24hr. The markers of inflammation in HEK293 cells were evaluated using the following techniques: western blotting (phosphorylated (p-)NFκB (Ser536), p-IKK (Ser176/180) and p-p53 (Ser392), total NFκB, IKK, IκBα and p53), luminometry (caspases 1, 3/7, 8, 9, ATP) and ELISA to determine IL-1β levels...
July 13, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28712880/the-role-of-oxidative-stress-in-antipsychotics-induced-ovarian-toxicity
#19
Ekramy Elmorsy, Ayat Al-Ghafari, Amal Misbah Aggour, Raheela Khan, Saad Amer
This study tested the hypothesis that oxidative stress could be an underlying mechanism for APs-induced ovarian cytotoxicity and reproductive dysfunction. Rat ovarian theca interstitial cells (TICs) were isolated and treated with four APs [chlorpromazine (CPZ), haloperidol (HAL), risperidone (RIS) and clozapine (CLZ)]. MTT assay was used to test the effects of these antipsychotics on TICs viability and to estimate their 50% inhibitory concentrations (IC50s). The effects of APs (IC50s and 1μM concentrations) on the activities of caspases-3, -8 and -9, reactive oxygen species (ROS) production, total intracellular glutathione and lipid peroxidation (LPO) in TICs were assessed...
July 13, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28712878/antidepressants-are-cytotoxic-to-rat-primary-blood-brain-barrier-endothelial-cells-at-high-therapeutic-concentrations
#20
Ekramy Elmorsy, Ayat Al-Ghafari, Fahd M Almutairi, Amal Misbah Aggour, Wayne G Carter
Antidepressants are commonly employed for the treatment of major depressive disorders and other psychiatric conditions. We investigated the relatively acute cytotoxic effects of three commonly prescribed antidepressants: fluoxetine, sertraline, and clomipramine on rat primary blood brain barrier endothelial cells over a concentration range of 0.1-100μM. At therapeutic concentrations (0.1μM) no significant cytotoxicity was observed after 4, 24, or 48h. At high therapeutic to overdose concentrations (1-100μM), antidepressants reduced cell viability in proportion to their concentration and exposure duration...
July 13, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
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