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https://www.readbyqxmd.com/read/28445730/ripk3-mediates-necroptosis-during-embryonic-development-and-postnatal-inflammation-in-fadd-deficient-mice
#1
Qun Zhao, XianJun Yu, HaiWei Zhang, YongBo Liu, XiXi Zhang, XiaoXia Wu, Qun Xie, Ming Li, Hao Ying, Haibing Zhang
RIPK3 mediates cell death and regulates inflammatory responses. Although genetic studies have suggested that RIPK3-MLKL-mediated necroptosis leads to embryonic lethality in Fadd or Caspase-8-deficient mice, the exact mechanisms are not fully understood. Here, we generated Ripk3 mutant mice by altering the RIPK3 kinase domain (Ripk3(Δ/Δ) mice), thus abolishing its kinase activity. Ripk3(Δ/Δ) cells were resistant to necroptosis stimulation in vitro, and Ripk3(Δ/Δ) mice were protected from necroptotic diseases...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445497/prostaglandin-e2-produced-following-infection-with-theiler-s-virus-promotes-the-pathogenesis-of-demyelinating-disease
#2
Seung Jae Kim, Young-Hee Jin, Byung S Kim
Infection of various cells with Theiler's murine encephalomyelitis virus (TMEV) activates the TLR- and melanoma differentiation-associated gene 5 (MDA5)-dependent pathways, resulting in the production of IL-1β via the activation of caspase-1 upon assembly of the node-like receptor protein 3 (NLRP3) inflammasome. The role of IL-1β in the pathogenesis of TMEV-induced demyelinating disease was previously investigated. However, the signaling effects of prostaglandin E2 (PGE2) downstream of the NLRP3 inflammasome on the immune responses to viral determinants and the pathogenesis of demyelinating disease are unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28444915/hydroquinone-induces-tk6-cell-growth-arrest-and-apoptosis-through-parp-1-p53-regulatory-pathway
#3
Hao Luo, Hairong Liang, Jiajia Chen, Yongchun Xu, Yuting Chen, Longmei Xu, Lin Yun, Jiaxian Liu, Hui Yang, Linhua Liu, Jianming Peng, Zhidong Liu, Lin Tang, Wen Chen, Huanwen Tang
Hydroquinone (HQ), one of the most important metabolites derived from benzene, induces cell cycle arrest and apoptosis. Poly(ADP-ribose) polymerase-1 (PARP-1) participates in various biological processes, including DNA repair and cell cycle regulation. To explore whether PARP-1 regulatory pathway mediated HQ-induced cell cycle arrest and apoptosis, we assessed the effect of PARP-1 suppression on induction of apoptosis analyzed by FACSCalibur flow cytometer in PARP-1 deficientTK6 cells (TK6-shPARP-1). We observed an increase in the fraction of cells in G1 phase by 7...
April 26, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28444898/an-isoquinolin-1-2h-imine-derivative-induces-cell-death-via-generation-of-reactive-oxygen-species-and-activation-of-jnk-in-human-a549-cancer-cells
#4
Jing Liu, Tongyang Liu, Hanchuan Mou, Shuting Jia, Chao Huang, Shengjiao Yan, Jun Lin, Ying Luo, Jihong Zhang
BACKGROUND: Compound11-benzoyl-10-chloro-7,9-difluoro-6-imino-2,3,4,6-tetrahydro-1H-pyrimido[1,2-b]isoquinoline-8-carbonitrile (HC6h) is a novel polyhalo 1,3-diazaheterocycle fused isoquinolin-1(2H)-imines derivative, which displays good anticancer activity and low toxicity in vivo. However, the underlying anticancer mechanisms have not previously been identified. METHODS: The proliferation of A549 was assessed by MTT assay. The reactive oxygen species (ROS) level was assessed in A549 with a H2 DCFDA probe...
April 26, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28444885/hypoxia-induced-apoptosis-of-mouse-spermatocytes-is-mediated-by-hif-1%C3%AE-through-a-death-receptor-pathway-and-a-mitochondrial-pathway
#5
Jun Yin, Bing Ni, Wei-Gong Liao, Yu-Qi Gao
Hypoxia in vivo induces oligozoospermia, azoospermia and degeneration of the germinal epithelium, but the underlying molecular mechanism of this induction is not fully clarified. The aim of this study was to investigate the role of the death receptor pathway and the mitochondrial pathway in hypoxia-induced apoptosis of mouse GC-2spd (GC-2) cells and the relationship between HIF-1α and apoptosis of GC-2 cells induced by hypoxia. GC-2 cells were subjected to 1% oxygen for 48 h. Apoptosis was detected by flow cytometry, TUNEL staining, LDH, caspase-3/8/9 in the absence and presence of HIF-1α siRNA...
April 26, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28444790/aloe-emodin-induces-apoptosis-in-human-liver-hl-7702-cells-through-fas-death-pathway-and-the-mitochondrial-pathway-by-generating-reactive-oxygen-species
#6
Xiaoxv Dong, Jing Fu, Xingbin Yin, Chunjing Yang, Jian Ni
Aloe-emodin (1,8-dihydroxy-3-hydroxymethyl-anthraquinone) is one of the primary active compounds in total rhubarb anthraquinones isolated from some traditional medicinal plants such as Rheum palmatum L. and Cassia occidentalis, which induce hepatotoxicity in rats. Thus, the aim of this study was to determine the potential cytotoxic effects and the underlying mechanism of aloe-emodin on human normal liver HL-7702 cells. The CCK-8 assays demonstrated that aloe-emodin decreased the viability of HL-7702 cells in a dose-dependent and time-dependent manner...
April 26, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28443516/synergistic-effect-of-graphene-oxide-coated-nanotised-apigenin-with-paclitaxel-go-na-ptx-a-ros-dependent-mitochondrial-mediated-apoptosis-in-ovarian-cancer
#7
Manish Kumar Pal, Shyam Pyari Jaiswar, Ashish Dwivedi, Shruti Goyal, Vinay Nand Dwivedi, Anumesh Kumar Pathak, Vinod Kumar, Pushp Lata Sankhwar, Ratan Singh Ray
Ovarian cancer is most lethal among all gynecologic malignancies. Paclitaxel (PTX) is well used chemotherapeutic regimen for cancer control; however its undesired toxicity has been always a matter of concern for clinicians. Here we used the graphene oxide coated nanotised apigenin (GO-NA) as chemo sensitizing agent to enhance the efficacy of paclitaxel to overcome the limitations of chemotherapy. GO and GO-Apigenin was prepared by modified Hummers method and the nanoparticles were characterized by dynamic light scattering and transmission electron microscopy Human ovarian adenocarcinomas (SKOV-3) cells was treated by DMSO, Group I (Control)-McCoy's 5A Medium, Group II-Paclitaxel (5nM) alone, Group III- Nanotised Apigenin (GO-NA-10μM) Group IV- Paclitaxel (5nM) + GO-NA (10μM)...
April 24, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28442553/nlrp3-signaling-drives-macrophage-induced-adaptive-immune-suppression-in-pancreatic-carcinoma
#8
Donnele Daley, Vishnu R Mani, Navyatha Mohan, Neha Akkad, Gautam S D Balasubramania Pandian, Shivraj Savadkar, Ki Buom Lee, Alejandro Torres-Hernandez, Berk Aykut, Brian Diskin, Wei Wang, Mohammad S Farooq, Arif I Mahmud, Gregor Werba, Eduardo J Morales, Sarah Lall, Benjamin J Wadowski, Amanda G Rubin, Matthew E Berman, Rajkishen Narayanan, Mautin Hundeyin, George Miller
The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDA) is characterized by immune tolerance, which enables disease to progress unabated by adaptive immunity. However, the drivers of this tolerogenic program are incompletely defined. In this study, we found that NLRP3 promotes expansion of immune-suppressive macrophages in PDA. NLRP3 signaling in macrophages drives the differentiation of CD4(+) T cells into tumor-promoting T helper type 2 cell (Th2 cell), Th17 cell, and regulatory T cell populations while suppressing Th1 cell polarization and cytotoxic CD8(+) T cell activation...
April 25, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28442378/antihyperlipidemic-and-antiapoptotic-potential-of-zingerone-on-alcohol-induced-hepatotoxicity-in-experimental-rats
#9
Vijay Mani, Sivaranjani Arivalagan, Aktarul Islam Siddique, Nalini Namasivayam
The ultimate aim of this present study was to investigate the antihyperlipidemic and antiapoptotic potential of zingerone (ZO) on alcohol induced hepatotoxicity in experimental rats. Male albino wistar rats were divided in four groups. Groups 1 and 2 rats received isocaloric glucose and dimethyl sulphoxide (2% DMSO), liver toxicity was induced in groups 3 and 4 by supplementing 30% ethanol post orally for 60 days. In addition, groups 2 and 4 received zingerone (20 mg/kg body weight in 2% DMSO) daily during the final 30 days of the experimental period...
April 22, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28442376/copper-sulfate-pretreatment-prevents-mitochondrial-electron-transport-chain-damage-and-apoptosis-against-mpp-induced-neurotoxicity
#10
Moisés Rubio-Osornio, Marisol Orozco-Ibarra, Araceli Díaz-Ruiz, Eduardo Brambila, Marie-Catherine Boll, Antonio Monroy-Noyola, Jorge Guevara, Sergio Montes, Camilo Ríos
Intrastriatal injection of 1-methyl-4-phenylpyridinium (MPP(+)) is considered a model to reproduce some biochemical alterations observed in Parkinson's disease (PD) patients. Among those alterations, inhibition of mitochondrial complex I activity, increased free radical production and reduced antioxidant responses have been reported. Copper (Cu) plays an important role in the metabolism and antioxidative responses through its participation as a cofactor in the cytochrome c oxidase enzyme (COX), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), and metallothioneins...
April 22, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28442025/protective-effects-of-polydatin-on-experimental-testicular-torsion-and-detorsion-injury-in-rats
#11
Huilian Qiao, He Ma, Wanjun Cao, Hao Chen, Jinhua Wei, Zhen Li
Oxidative stress plays a critical role in the process of testicular torsion and detorsion (T/D). The purpose of the present study was to investigate the protective effect of polydatin (PD) on testicular T/D injury. Rats were randomly divided into three groups, a sham group, a group subjected to 2h torsion followed by 24h detorsion and a group subjected to T/D and injected i.p. with 20mgkg-1 PD 30min before detorsion. Unilateral orchiectomy was performed after 24h of reperfusion. Half the testes were prepared for histological examination by haematoxylin-eosin staining and the terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL) technique...
April 26, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28441582/synthesis-and-antiproteasomal-activity-of-novel-o-benzyl-salicylamide-based-inhibitors-built-from-leucine-and-phenylalanine
#12
Radek Jorda, Jan Dušek, Eva Řezníčková, Karel Pauk, Pratibha P Magar, Aleš Imramovský, Vladimír Kryštof
Inhibition of protein degradation is one of strategies for suppression of uncontrolled proliferation of cancer cells. Proteolytic degradation in cells is mainly ensured by proteasome and its inhibition by bortezomib showed benefit in clinical use for the treatment of multiple myeloma. We report here the library of antiproteasomal O-benzyl salicylamides built from leucine and phenylalanine. Prepared compounds displayed antiproliferative activity on K562, CEM and U266 cancer cell lines, ranging from high micromolar to submicromolar GI50 values...
April 15, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28441581/design-combinatorial-synthesis-and-biological-evaluations-of-novel-3-amino-1-1-aryl-1h-1-2-3-triazol-5-yl-methyl-2-oxospiro-benzo-a-pyrano-2-3-c-phenazine-1-3-indoline-2-carbonitrile-antitumor-hybrid-molecules
#13
Yuanyuan Lu, Linlin Wang, Xiaobing Wang, Tao Xi, Jianmin Liao, Zhixiang Wang, Feng Jiang
A combinatorial chemical library of fifty-nine novel 3-amino-1'-((1-aryl-1H-1,2,3-triazol-5-yl)methyl)-2'-oxospiro[benzo[a]pyrano[2,3-c]phenazine-1,3'-indoline]-2-carbonitrile, designed as hybrid molecules of phenazine, pyran, indole and 1,2,3-triazole pharmacophores, were constructed in this study. Cytotoxic evaluation indicated that some compounds exhibited moderate cytotoxicity against HCT116, MCF7, HepG2 and A549 cancer cell lines in vitro, in which compound 36 was found to have best antiproliferative activity against the A549 cancer cell line with IC50 value of 5...
April 18, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28440486/synergistic-antitumor-effects-of-cdk-inhibitor-sns%C3%A2-032-and-an-oncolytic-adenovirus-co%C3%A2-expressing-trail-and-smac-in-pancreatic-cancer
#14
Yun Ge, Wen Lei, Yingyu Ma, Yigang Wang, Buyun Wei, Xiaoyi Chen, Guoqing Ru, Xianglei He, Xiaozhou Mou, Shibing Wang
Gene therapy using oncolytic adenoviruses is a novel approach for human cancer therapeutics. The current study aimed to investigate whether the combined use of an adenovirus expressing tumor necrosis factor‑related apoptosis‑inducing ligand (TRAIL) and second mitochondria‑derived activator of caspase (Smac) upon caspase activation (ZD55‑TRAIL‑IETD‑Smac) and cyclin‑dependent kinase (CDK) inhibitor SNS‑032 will synergistically reinforce their anti‑pancreatic cancer activities. The experiments in vitro demonstrated that SNS‑032 enhances ZD55‑TRAIL‑IETD‑Smac‑induced apoptosis and causes marked pancreatic cancer cell death...
April 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28440479/wip1-regulates-skov3-cell-apoptosis-through-the-p38-mapk-signaling-pathway
#15
Yanping Feng, Fang Liu, Zhixiang Du, Dongjie Zhao, Jianxin Cheng, Wei Guo
The aim of the present study was to explore the effect of silencing wild‑type p53‑induced phosphatase 1 (Wip1) on apoptosis of human ovarian cancer SKOV3 cells. SKOV3 cells cultured in vitro were divided into three groups: untreated cells, cells transfected with control small interfering RNA (siRNA) and cells transfected with siRNA targeting Wip1. Flow cytometry analysis was used to detect cell apoptosis. Western blot analysis was performed to determine expression of tumor protein 53 (p53), cleaved caspase‑3, caspase‑3, BCL2 associated X (Bax), BCL2 apoptosis regulator (Bcl‑2), p38 mitogen‑activated protein kinase (p38 MAPK) and phosphorylated (p)‑p38 MAPK...
April 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28440458/role-of-the-cystathionine-%C3%AE-synthase-h2s-system-in-liver-cancer-cells-and-the-inhibitory-effect-of-quinolone-indolone-conjugate-qic2-on-the-system
#16
Huina Jia, Juan Ye, Jing You, Xiaoyan Shi, Wenyi Kang, Tianxiao Wang
Hydrogen sulfide (H2S), the third gasotransmitter, plays important roles in cancer biological processes. As endogenous H2S exerts pro-cancer functions, inhibition of its production in cancer cells may provide a new cancer treatment strategy and be achieved via regulation of the function of cystathionine β-synthase (CBS), one of the main metabolic enzymes synthesizing H2S. This enzyme plays important roles in the development and progression of colon and ovarian cancer, primarily regulating mitochondrial bioenergetics and accelerating cell cycle progression...
May 2017: Oncology Reports
https://www.readbyqxmd.com/read/28440451/ppar%C3%AE-activation-protects-h9c2-cardiomyoblasts-from-lps%C3%A2-induced-apoptosis-through-the-heme-oxygenase%C3%A2-1%C3%A2-mediated-suppression-of-nf%C3%A2-%C3%AE%C2%BAb-activation
#17
Yao Shi, Hong Jiang, Xiaobo Yang
The aim of the present study was to investigate the protective effect of the selective peroxisome proliferator-activated receptor δ (PPARδ) agonist GW501516 (GW) on lipopolysaccharide (LPS)‑induced apoptosis in the rat cardiomyoblast cell line H9c2, and to investigate the possible underlying mechanisms. Cell viability was estimated using the MTT assay. Apoptosis was estimated by flow cytometry using Annexin V‑fluorescein isothiocyanate/propidium iodide staining and caspase‑3 activity assay. The protein level of heme oxygenase‑1 (HO‑1), cleaved caspase‑3 (CC3), apoptosis regulator Bcl‑2 (bcl‑2), apoptosis regulator BAX (bax) and nuclear factor‑κB (NF‑κB) p65 was measured by western blot analysis...
April 19, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28440433/effective-cytotoxic-activity-of-osw-1-on-colon-cancer-by-inducing-apoptosis-in%C3%A2-vitro-and-in%C3%A2-vivo
#18
Yanhong Zhang, Fengqi Fang, Kai Fan, Yanli Zhang, Jie Zhang, Huishu Guo, Peiyao Yu, Jianmei Ma
As a natural compound, Ornithogalum caudatum Ait is primarily used as an anti-inflammatory and antitumor agent in Chinese folk medicine. In 1992, OSW-1 was isolated from this compound, which is a new member of cholestane saponin family. In numerous recent studies, OSW-1 has been shown to have powerful cytotoxic anticancer effects against various malignant cells. However, the therapeutic efficacy of OSW-1 on colon cancer and the underlying mechanism are not understood. To explore the mechanism underlying OSW-1 in antitumor therapy, a therapeutic function analysis of OSW-1 on colon cancer was performed in vitro and in vivo...
April 19, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28439402/upregulation-of-heme-oxygenase-1-expression-by-curcumin-conferring-protection-from-hydrogen-peroxide-induced-apoptosis-in-h9c2-cardiomyoblasts
#19
Xiaobo Yang, Hong Jiang, Yao Shi
BACKGROUND: Curcumin is a major constituent of rhizomes of Curcuma longa that elicits beneficial effects for oxidative damage. The aim of this study was to investigate whether curcumin could attenuate hydrogen peroxide (H2O2)-induced apoptosis in H9c2 cardiomyoblasts and the underlying mechanisms. RESULTS: The present study showed that exposure of H9c2 cells to H2O2 caused a significant increase in apoptosis as evaluated by flow cytometry analysis and the pretreatment of curcumin protected against H2O2-induced apoptosis...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28438610/hyperglycemia-increases-interstitial-cells-of-cajal-via-mapk1-and-mapk3-signaling-to-etv1-and-kit-leading-to-rapid-gastric-emptying
#20
Yujiro Hayashi, Yoshitaka Toyomasu, Siva Arumugam Saravanaperumal, Michael R Bardsley, John A Smestad, Andrea Lorincz, Seth T Eisenman, Gianluca Cipriani, Molly H Nelson Holte, Fatimah J Al Khazal, Sabriya A Syed, Gabriella B Gajdos, Kyoung Moo Choi, Gary J Stoltz, Katie E Miller, Michael L Kendrick, Brian P Rubin, Simon J Gibbons, Adil E Bharucha, David R Linden, Louis James Maher, Gianrico Farrugia, Tamas Ordog
BACKGROUND & AIMS: Depletion of interstitial cells of Cajal (ICCs) is common in diabetic gastroparesis. However, in approximately 20% of patients with diabetes, gastric emptying (GE) is accelerated. GE is also faster in obese individuals, and is associated with increased blood levels of glucose in patients with type 2 diabetes. To understand the fate of ICCs in hyperinsulinemic, hyperglycemic states characterized by rapid GE, we studied mice with mutation of the leptin receptor (Lepr(db/db)), which in our colony had accelerated GE...
April 21, 2017: Gastroenterology
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