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https://www.readbyqxmd.com/read/28447514/neuroprotective-effects-of-ellagic-acid-on-cuprizone-induced-acute-demyelination-through-limitation-of-microgliosis-adjustment-of-cxcl12-il-17-il-11-axis-and-restriction-of-mature-oligodendrocytes-apoptosis
#1
Nima Sanadgol, Fereshteh Golab, Zakiyeh Tashakkor, Nooshin Taki, Samira Moradi Kouchi, Ali Mostafaie, Mehdi Mehdizadeh, Mohammad Abdollahi, Ghorban Taghizadeh, Mohammad Sharifzadeh
CONTEXT: Ellagic acid (EA) is a natural phenol antioxidant with various therapeutic activities. However, the efficacy of EA has not been examined in neuropathologic conditions. OBJECTIVE: In vivo neuroprotective effects of EA on cuprizone (cup)-induced demyelination were evaluated. MATERIAL AND METHODS: C57BL/6 J mice were fed with chow containing 0.2% cup for 4 weeks to induce oligodendrocytes (OLGs) depletion predominantly in the corpus callosum (CC)...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28446458/caspase-11-promotes-cisplatin-induced-renal-tubular-apoptosis-through-a-caspase-3-dependent-pathway
#2
Naijun Miao, Bao Wang, Dan Xu, Yanzhe Wang, Xinxin Gan, Li Zhou, Hong Xue, Wei Zhang, Xiaoxia Wang, Limin Lu
Renal tubular injury is the hallmark of cisplatin-induced nephrotoxicity. Caspase-11, a member of the caspase family, plays an important role in inflammation and cell death. However, its role in cisplatin-induced renal tubular injury remain unclear. We observed that caspase-11 expression was significantly elevated and the expression of caspase-11 mainly located in renal tubule in cisplatin-treated mice. Inhibition of caspase-11 by siRNA or wedelolactone (Wed) attenuated cisplatin-induced renal dysfunction and tubular injury...
April 26, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28429312/sox11-regulates-the-pro-apoptosis-signal-pathway-and-predicts-a-favorable-prognosis-of-mantle-cell-lymphoma
#3
Wenjuan Yang, Yanying Wang, Zhen Yu, Zengjun Li, Gang An, Wei Liu, Rui Lv, Liping Ma, Shuhua Yi, Lugui Qiu
Sex-determining region Y-box 11 (SOX11) is an important diagnostic marker in mantle cell lymphoma (MCL). However, the direct oncogenic mechanisms and downstream effector pathways implicated in SOX11-driven transformation remain poorly understood. In the present study, we analyzed SOX11 expression in B-NHL, and used lentivirus-mediated RNA interference targeting SOX11 to investigate the resulting changes in cellular processes and the underlying mechanisms in MCL cell lines. We found that patients with higher SOX11 expression have superior overall survival (OS) and progression-free survival (PFS) compared to those with lower SOX11 expression...
April 20, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28427227/high-dose-ascorbate-and-arsenic-trioxide-selectively-kill-acute-myeloid-leukemia-and-acute-promyelocytic-leukemia-blasts-in-vitro
#4
Nélida I Noguera, Elvira Pelosi, Daniela F Angelini, Maria Liliana Piredda, Gisella Guerrera, Eleonora Piras, Luca Battistini, Lauretta Massai, Anna Berardi, Gianfranco Catalano, Laura Cicconi, Germana Castelli, Agnese D'Angiò, Luca Pasquini, Grazia Graziani, Giuseppe Fioritoni, Maria Teresa Voso, Domenico Mastrangelo, Ugo Testa, Francesco Lo-Coco
The use of high-dose ascorbate (ASC) for the treatment of human cancer has been attempted several decades ago and has been recently revived by several in vitro and in vivo studies in solid tumors. We tested the cytotoxic effects of ASC, alone or in combination with arsenic trioxide (ATO) in acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL). Leukemic cell lines and primary blasts from AML and APL patients were treated with graded concentrations of ASC, alone or in association with standard concentration (1 μM) of ATO...
March 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427017/aromatase-inhibitors-and-apoptotic-inducers-design-synthesis-anticancer-activity-and-molecular-modeling-studies-of-novel-phenothiazine-derivatives-carrying-sulfonamide-moiety-as-hybrid-molecules
#5
Mostafa M Ghorab, Mansour S Alsaid, Nermin Samir, Ghada A Abdel-Latif, Aiten M Soliman, Fatma A Ragab, Dalal A Abou El Ella
Hybrid molecules are used as anticancer agents to improve effectiveness and diminish drug resistance. So, the current study aimed to introduce twenty novel phenothiazine sulfonamide hybrids 5-22, 24 and 25 of promising anticancer activity. Compounds 11 and 13 revealed more potent anticancer properties (IC50 8.1 and 8.8 μM) than that of the reference drug (doxorubicin, IC50 = 9.8 μM) against human breast cancer cell line (T47D). To determine the mechanism of their anticancer activity, compounds 5, 6, 7, 11, 13, 14, 16, 17, 19 and 22 that showed promising activity on T47D, were evaluated for their aromatase inhibitory effect...
April 15, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28421347/tu-100-exerts-a-protective-effect-against-bacterial-translocation-by-maintaining-the-tight-junction
#6
Chie Takasu, Wubetu Gizachew Yismaw, Nobuhiro Kurita, Kozo Yoshikawa, Hideya Kashihara, Toru Kono, Mitsuo Shimada
PURPOSE: We previously reported that TU-100 suppresses irinotecan hydrochloride (CPT-11)-induced inflammatory cytokines and apoptosis. However, the mechanism underlying this effect has not been fully elucidated. The aim of this study was to further clarify the mechanism of CPT-11-induced bacterial translocation (BT) and the effect of TU-100 on BT. METHODS: Cell cytotoxicity was assessed in vitro by a WST-8 assay. For the in vivo experiments, rats were randomly divided into 3 groups: the control group, the CPT-11 group (250 mg/kg i...
April 18, 2017: Surgery Today
https://www.readbyqxmd.com/read/28421122/potential-antitumor-activity-and-apoptosis-induction-of-glossostemon-bruguieri-root-extract-against-hepatocellular-carcinoma-cells
#7
Mona S Alwhibi, Mahmoud I M Khalil, Mohamed M Ibrahim, Gehan A El-Gaaly, Ahmed S Sultan
Glossostemon bruguieri (moghat) is used as a nutritive and demulcent drink. This study was performed to investigate the antiproliferative effects of moghat root extract (MRE) and its apoptotic mechanism in hepatocellular carcinoma (HCC) cells, HepG2 and Hep3B. MTT assay, morphological changes, apoptosis enzyme linked immunosorbent assay, caspase and apoptotic activation, flow cytometry, and immunoblot analysis were employed. The IC50 of MRE for HepG2 (910 ± 6 μg/ml) and for Hep3B (1510 ± 5 μg/ml) induced significant growth-inhibitory effects against HCC cells, with no cytotoxic effect on normal hepatocytes...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28416543/potential-toxicity-of-polymyxins-in-human-lung-epithelial-cells
#8
Maizbha U Ahmed, Tony Velkov, Yu-Wei Lin, Bo Yun, Cameron J Nowell, Fanfan Zhou, Qi Tony Zhou, Kim Chan, Mohammad A K Azad, Jian Li
Inhaled polymyxins are of considerable utility to achieve optimal exposure in the respiratory tract for the treatment of lung infections caused by multidrug-resistant Gram-negative pathogens. Current inhaled polymyxin therapy is empirical and often high doses are used which may lead to potential pulmonary adverse effects. This study aimed to investigate the effect of polymyxins on human lung epithelial cells (A549). Viability of A549 cells was examined after treatment with polymyxins using flow cytometry. Activation of caspase-3, -8, -9, expression of Fas ligand (FasL), loss of mitochondrial membrane potential and mitochondrial oxidative stress induced by polymyxin B was evaluated...
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28413509/effects-of-sirna-mediated-suppression-of-hpv-11-l1-expression-on-the-proliferation-and-apoptosis-of-vaginal-epithelial-cells
#9
Juan Zeng, Shumei Yang, Xiaorui Wang, Yan Gao, Mei Zhang
The aim of the present study was to investigate the effects of human papillomavirus (HPV) infection on the gynecological disease of vaginitis and to demonstrate how the small interfering RNA (siRNA) method may be used for HPV prevention in the clinic. Human vaginal epithelial cells were transfected with HPV-11 L1 expression vector and siRNA-HPV-11 L1 vectors and a control group was transfected with scrambled siRNA. Cell proliferation in each group was analyzed using the MTT assay and the expression of apoptosis-associated proteins was measured by western blot analysis...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28410843/left-ventricular-hypertrophy-does-not-prevent-heart-failure-in-experimental-hypertension
#10
H Hernán Gómez Llambí, G Cao, M Donato, D Suárez, G Ottaviano, A Müller, B Buchholz, R Gelpi, M Otero-Losada, J Milei
BACKGROUND: Left ventricular hypertrophy (LVH) secondary to hypertension has been accepted to prevent heart failure (HF) while paradoxically increasing cardiovascular morbi-mortality. OBJECTIVES: To evaluate whether antihypertensive treatment inhibits LVH, restores beta-adrenergic response and affects myocardial oxidative metabolism. METHODS: Ninety spontaneously hypertensive rats (SHR) were distributed into groups and treated (mg/kg, p.o...
March 27, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28409545/high-affinity-caspase-4-binding-to-lps-presented-as-high-molecular-mass-aggregates-or-in-outer-membrane-vesicles
#11
Mark A Wacker, Athmane Teghanemt, Jerrold P Weiss, Jason H Barker
Caspases of the non-canonical inflammasome (caspases -4, -5, and -11) directly bind endotoxin (LOS/LPS) and can be activated in the absence of any co-factors. Models of LPS-induced caspase activation have postulated that 1:1 binding of endotoxin monomers to caspase trigger caspase oligomerization and activation, analogous to that established for endotoxin-induced activation of MD-2/TLR4. However, using metabolically radiolabeled LOS and LPS, we now show high affinity and selective binding of caspase-4 to high molecular mass aggregates of purified endotoxin and to endotoxin-rich outer membrane vesicles without formation of 1:1 endotoxin:caspase complexes...
May 2017: Innate Immunity
https://www.readbyqxmd.com/read/28405519/the-interleukin-il-1r1-pathway-is-a-critical-negative-regulator-of-pymt-mediated-mammary-tumorigenesis-and-pulmonary-metastasis
#12
Maryse Dagenais, Jeremy Dupaul-Chicoine, Todd Douglas, Claudia Champagne, Alexandre Morizot, Maya Saleh
Breast cancer is the most common cancer in women and the second leading cause of female cancer-related deaths worldwide. Inflammation is an established hallmark of tumorigenesis and an important determinant of tumor outcome and response to therapy. With advances in cancer immunotherapy, there is an urgent need to dissect the contribution of specific immune effectors in cancer development. Here, we genetically investigated the role of the Interleukin-1 (IL-1) receptor 1 (IL-1R1) pathway in breast cancer tumorigenesis and metastasis using the MMTV-PyMT mouse model...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28404595/nlr-members-nlrc4-and-nlrp3-mediate-sterile-inflammasome-activation-in-microglia-and-astrocytes
#13
Leslie Freeman, Haitao Guo, Clément N David, W June Brickey, Sushmita Jha, Jenny P-Y Ting
Inflammation in the brain accompanies several high-impact neurological diseases including multiple sclerosis (MS), stroke, and Alzheimer's disease. Neuroinflammation is sterile, as damage-associated molecular patterns rather than microbial pathogens elicit the response. The inflammasome, which leads to caspase-1 activation, is implicated in neuroinflammation. In this study, we reveal that lysophosphatidylcholine (LPC), a molecule associated with neurodegeneration and demyelination, elicits NLRP3 and NLRC4 inflammasome activation in microglia and astrocytes, which are central players in neuroinflammation...
April 12, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28403785/apoptotic-effects-of-some-tetrahydronaphthalene-derivatives-on-k562-human-chronic-myelogenous-leukemia-cell-line
#14
Aslı Koç, Tulin Ozkan, Arzu Zeynep Karabay, Yalda Hekmatshoar, Ayse Selen Gurkan-Alp, Fugen Aktan, Zeliha Buyukbingol, Asuman Sunguroglu, Erdem Buyukbingol
BACKGROUND: Retinoids are synthetic and naturally occurring derivatives of vitamin A (retinol) which have been suggested to mediate inhibition of cancer cell growth and apoptosis. It has been reported that all trans retinoic acid (ATRA) exhibited suppressive effects on different types of leukemia including chronic myelogenous leukemia. OBJECTIVE: In the present study, we aim to find out the effects of 6 synthetic N-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalene-2-yl)-carboxamide derivatives (compound 6-12) on cell viability and apoptotic pathways in K562 human chronic myelogenous leukemia cell line...
April 12, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28403776/eco-friendly-synthesis-of-pyrido-2-3-d-pyrimidine-analogs-and-their-anticancer-and-tyrosine-kinase-inhibition-activities
#15
Wael M El-Sayed, Abeer El-Naggar, Ali Khalil, Hala Zeidan
BACKGROUND: One of the promising scaffolds in drug discovery is the fused pyrimidine derivatives. OBJECTIVE AND METHOD: Efficient synthesis of a novel series of 18 new 1,8-naphthyridine-3-carbonitrile, 2-amino pyrido[2,3-d]pyrimidine derivatives via multi-component reactions of aromatic aldehydes, active methylene, and an aromatic amine under microwave irradiation and evaluation of their anticancer activity and possible mechanisms. RESULTS: Only compounds 5 (a-c) had a significant antiproliferative activity in hepatic HepG2 cells at submicromolar concentration (7...
April 12, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28395218/synthesis-and-in%C3%A2-vitro-and-in%C3%A2-vivo-antitumour-activity-study-of-11-hydroxyl-esterified-bergenin-cinnamic-acid-hybrids
#16
Chengyuan Liang, Shaomeng Pei, Weihui Ju, Minyi Jia, Danni Tian, Yonghong Tang, Gennian Mao
Fourteen bergenin/cinnamic acid hybrids were synthesized, characterized and evaluated for their antitumour activity both in vitro and in vivo. The most potent compound, 5c, arrested HepG2 cells (IC50 = 4.23 ± 0.79 μM) in the G2/M phase and induced cellular apoptosis. Moreover, compound 5c was also found to suppress the tumour growth in Heps xenograft-bearing mice with low toxicity. In the mechanistic study, 5c administration ignited a mitochondria-mediated apoptosis pathway of HepG2 cell death. Furthermore, 5c activated Akt-dependent pathways and further decreased the expression of the Bcl-2 family of proteins...
April 3, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28394604/neuroprotective-activity-of-cerebrosides-from-typhonium-giganteum-by-regulating-caspase-3-and-bax-bcl-2-signaling-pathways-in-pc12-cells
#17
Yang Jin, Jun-Ting Fan, Xiao-Ling Gu, Li-Ying Zhang, Jing Han, Shu-Hu Du, Ai-Xia Zhang
An investigation of the potential neuroprotective natural product constituents of the rhizomes of Typhonium giganteum led to the isolation of two new cerebrosides, typhonosides B (1) and C (2), along with 11 known analogues (3-13). The structures of compounds 1 and 2 were elucidated by spectroscopic data interpretation. The activity of these compounds against glutamate-induced cell apoptosis was investigated in PC12 cells. All compounds exhibited such activity, which was related to the length of the fatty acyl chain...
April 10, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28378450/asperflavipine%C3%A2-a-a-cytochalasan-heterotetramer-uniquely-defined-by-a-highly-complex-tetradecacyclic-ring-system-from-aspergillus-flavipes-qcs12
#18
Hucheng Zhu, Chunmei Chen, Qingyi Tong, Jing Yang, Guangzheng Wei, Yongbo Xue, Jianping Wang, Zengwei Luo, Yonghui Zhang
Asperflavipines A (1) and B (2), two structurally complex merocytochalasans, were isolated from Aspergillus flavipes. Asperflavipine A (1), which contains two cytochalasan moieties and two epicoccine moieties, is the first cytochalasan heterotetramer to be discovered. It is uniquely defined by 5/6/11/5/6/5/6/5/6/5/5/11/6/5 fused tetradecacyclic rings with three continuous bridged ring systems. Asperflavipine B (2) is a cytochalasan heterotrimer containing a cytochalasan and two epicoccine moieties with a 5/6/11/5/5/6/5/6/5 nonacyclic ring system...
May 2, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28377486/p2x7-deficiency-blocks-lesional-inflammasome-activity-and-ameliorates-atherosclerosis-in-mice
#19
Peter Stachon, Adrian Heidenreich, Julian Merz, Ingo Hilgendorf, Dennis Wolf, Florian Willecke, Sunaina von Garlen, Philipp Albrecht, Carmen Härdtner, Nicolas Ehrat, Natalie Hoppe, Jochen Reinöhl, Constantin von Zur Mühlen, Christoph Bode, Marco Idzko, Andreas Zirlik
Background -Extracellular ATP binds as a danger signal to purinergic receptor P2X7, promotes inflammasome assembly, and IL-1β expression. We hypothesized a functional role of the signal axis ATP - P2X7 in inflammasome activation and the chronic inflammation driving atherosclerosis. Methods -P2X7-competent and -deficient macrophages were isolated and stimulated with LPS, ATP, or both. To assess whether P2X7 may have a role in atherosclerosis, P2X7 expression was analyzed in aortic arches from LDLR(-/-) mice consuming high cholesterol diet (HCD) or chow diet...
April 4, 2017: Circulation
https://www.readbyqxmd.com/read/28375091/regulatory-effect-of-caspase-11-on-interleukin-1%C3%AE-in-the-fungal-keratitis
#20
Keke Zhu, Hongmei Mu, Baimu Pi
Caused by fungus, fungal keratitis is a kind of infections corneal disease with high rate of blindness, which patients are mainly farmers in developing countries. Interleukin, as important proinflammatory cytokines, involve in immune defense process against fungal infection of cornea. The expression of interleukin in the pathogenesis of fungal keratitis, especially the main source of its cells, is not clear and the cell signaling pathways which regulate the synthesis and modification of interleukin is still unknown...
November 2016: Pakistan Journal of Pharmaceutical Sciences
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