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https://www.readbyqxmd.com/read/28634498/evaluation-of-in-vitro-cytotoxicity-biocompatibility-and-changes-in-the-expression-of-apoptosis-regulatory-proteins-induced-by-cerium-oxide-nanocrystals
#1
Shahanavaj Khan, Anees A Ansari, Christian Rolfo, Andreia Coelho, Maha Abdulla, Khayal Al-Khayal, Rehan Ahmad
Cerium oxide nanocrystals (CeO2-NCs) exhibit superoxide dismutase and catalase mimetic activities. Based on these catalytic activities, CeO2-NCs have been suggested to have the potential to treat various diseases. The crystalline size of these materials is an important factor that influences the performance of CeO2-NCs. Previous reports have shown that several metal-based nanocrystals, including CeO2-NCs, can induce cytotoxicity in cancer cells. However, the underlying mechanisms have remained unclear. To characterize the anticancer activities of CeO2-NCs, several assays related to the mechanism of cytotoxicity and induction of apoptosis has been performed...
2017: Science and Technology of Advanced Materials
https://www.readbyqxmd.com/read/28628639/small-molecule-inhibitors-uncover-synthetic-genetic-interactions-of-human-flap-endonuclease-1-fen1-with-dna-damage-response-genes
#2
Thomas A Ward, Peter J McHugh, Stephen T Durant
Flap endonuclease 1 (FEN1) is a structure selective endonuclease required for proficient DNA replication and the repair of DNA damage. Cellularly active inhibitors of this enzyme have previously been shown to induce a DNA damage response and, ultimately, cell death. High-throughput screens of human cancer cell-lines identify colorectal and gastric cell-lines with microsatellite instability (MSI) as enriched for cellular sensitivity to N-hydroxyurea series inhibitors of FEN1, but not the PARP inhibitor olaparib or other inhibitors of the DNA damage response...
2017: PloS One
https://www.readbyqxmd.com/read/28627168/mitochondria-associated-apoptosis-in-human-melanoma-cells-induced-by-cardanol-monoene-from-cashew-nut-shell-liquid
#3
Wei-Chao Su, Yu-Feng Lin, Xiang-Ping Yu, Yu-Xia Wang, Xiao-Dong Lin, Qiao-Zhen Su, Dong-Yan Shen, Qing-Xi Chen
Cardanol monoene (CM) is the major phenolic component extracted from cashew nut shell liquid (CNSL), which has been relevant to wide range of biological effects. In this study, we found that CM could inhibit the M14 human melanoma cells proliferation in a dose dependent and time dependent manner, and the IC50 values were determined to be 23.15 ± 2.42 μM and 12.30 ± 1.67 μM after 24 h and 48 h treatment, respectively. The flow cytometric analysis demonstrated that CM induced M14 cell cycle arrest at S phase, along with the collapse of mitochondrial membrane potential (ΔΨm) and the accumulation of reactive oxygen species (ROS) level in cells,but the apoptotic cells reduced when treated with Z-VAD-FMK (pan-caspase inhibitor)...
June 19, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28624812/extracorporeal-shock-wave-treatment-attenuated-left-ventricular-dysfunction-and-remodeling-in-mini-pig-with-cardiorenal-syndrome
#4
Jiunn-Jye Sheu, Hani E E Ali, Ben-Chung Cheng, Hsin-Ju Chiang, Pei-Hsun Sung, Kuan-Hung Chen, Chih-Chao Yang, Yen-Ta Chen, John Y Chiang, Pao-Yuan Lin, Sarah Chua, Han-Tan Chai, Sheng-Ying Chung, Cheuk-Kwan Sun, Hon-Kan Yip
This study tested the hypothesis that extracorporeal shock wave (ECSW) treatment can improve ischemia-induced left ventricular (LV) dysfunction in mini-pig with co-existing chronic kidney disease (CKD). LV ischemia in mini-pigs was induced by applying an ameroid constrictor over mid-left anterior descending artery (LAD), while model of CKD was established by right nephrectomy with partial ligation of left renal arterioles 2 weeks before LAD constriction. Thirty mini-pigs were randomly divided into group 1 (sham-control), group 2 (LV-ischemia), group 3 (LV-ischemia + CKD), Group 4 [LV-ischemia + ECSW (applied 1200 shots at 0...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28623292/structural-and-biochemical-characterization-of-poly-adp-ribose-polymerase-from-trypanosoma-brucei
#5
Teemu Haikarainen, Mariana Schlesinger, Ezeogo Obaji, Silvia H Fernández Villamil, Lari Lehtiö
Trypanosoma brucei is a unicellular parasite responsible for African trypanosomiasis or sleeping sickness. It contains a single PARP enzyme opposed to many higher eukaryotes, which have numerous PARPs. PARPs are responsible for a post-translational modification, ADP-ribosylation, regulating a multitude of cellular events. T. brucei PARP, like human PARPs-1-3, is activated by DNA binding and it potentially functions in DNA repair processes. Here we characterized activation requirements, structure and subcellular localization of T...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28622906/discovery-of-novel-quinazoline-2-4-1h-3h-dione-derivatives-as-potent-parp-2-selective-inhibitors
#6
Hailong Zhao, Ming Ji, Guonan Cui, Jie Zhou, Fangfang Lai, Xiaoguang Chen, Bailing Xu
The PARP-2 selective inhibitor is important for clarifying specific roles of PARP-2 in the pathophysiological process and developing desired drugs with reduced off-target side effects. In this work, a series of novel quinazoline-2,4(1H,3H)-dione derivatives was designed and synthesized to explore isoform selective PARP inhibitors. As a result, compound 11a (PARP-1 IC50=467nM, PARP-2 IC50=11.5nM, selectivity PARP-1/PARP-2=40.6) was disclosed as the most selective PARP-2 inhibitor with high potency to date. The binding features of compound 11a within PARP-1 and PARP-2 were investigated respectively to provide useful insights for the further construction of new isoform selective inhibitors of PARP-1 and PARP-2 by using CDOCKER program...
May 26, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28620309/inhibition-of-the-trpm2-and-trpv1-channels-through-hypericum-perforatum-in-sciatic-nerve-injury-induced-rats-demonstrates-their-key-role-in-apoptosis-and-mitochondrial-oxidative-stress-of-sciatic-nerve-and-dorsal-root-ganglion
#7
Fuat Uslusoy, Mustafa Nazıroğlu, Bilal Çiğ
Sciatic nerve injury (SNI) results in neuropathic pain, which is characterized by the excessive Ca(2+) entry, reactive oxygen species (ROS) and apoptosis processes although involvement of antioxidant Hypericum perforatum (HP) through TRPM2 and TRPV1 activation has not been clarified on the processes in SNI-induced rat, yet. We investigated the protective property of HP on the processes in the sciatic nerve and dorsal root ganglion neuron (DRGN) of SNI-induced rats. The rats were divided into five groups as control, sham, sham+HP, SNI, and SNI+HP...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28618413/induction-of-apoptosis-in-heparg-cell-line-by-aloe-emodin-through-generation-of-reactive-oxygen-species-and-the-mitochondrial-pathway
#8
Xiaoxv Dong, Jing Fu, Xingbin Yin, Changhai Qu, Chunjing Yang, Huyiligeqi He, Jian Ni
BACKGROUND/AIMS: Aloe-emodin (1,8-dihydroxy-3-hydroxymethyl-anthraquinone), an anthraquinone active compounds, is isolated from some traditional medicinal plants such as Rheum palmatum L. and Cassia occidentalis, which induce hepatotoxicity in rats. The aim of this study was to determine potential cytotoxic effects of aloe-emodin on HepaRG cells and to define the underlying mechanism. METHODS: MTT was used to evaluate cell viability. Apoptotic cell death was analyzed via Annexin V-FITC/PI double staining...
June 15, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28616020/minocycline-targets-multiple-secondary-injury-mechanisms-in-traumatic-spinal-cord-injury
#9
REVIEW
Robert B Shultz, Yinghui Zhong
Minocycline hydrochloride (MH), a semi-synthetic tetracycline derivative, is a clinically available antibiotic and anti-inflammatory drug that also exhibits potent neuroprotective activities. It has been shown to target multiple secondary injury mechanisms in spinal cord injury, via its anti-inflammatory, anti-oxidant, and anti-apoptotic properties. The secondary injury mechanisms that MH can potentially target include inflammation, free radicals and oxidative stress, glutamate excitotoxicity, calcium influx, mitochondrial dysfunction, ischemia, hemorrhage, and edema...
May 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28615517/mtor-signaling-mediates-resistance-to-tankyrase-inhibitors-in-wnt-driven-colorectal-cancer
#10
Tetsuo Mashima, Yoko Taneda, Myung-Kyu Jang, Anna Mizutani, Yukiko Muramatsu, Haruka Yoshida, Ayana Sato, Noritaka Tanaka, Yoshikazu Sugimoto, Hiroyuki Seimiya
Activation of Wnt/β-catenin signaling is essential for colorectal carcinogenesis. Tankyrase, a member of the poly(ADP-ribose) polymerase (PARP) family, is a positive regulator of the Wnt/β-catenin signaling. Accordingly, tankyrase inhibitors are under preclinical development for colorectal cancer (CRC) therapy. However, Wnt-driven colorectal cancer cells are not equally sensitive to tankyrase inhibitors, and cellular factors that affect tankyrase inhibitor sensitivity remain elusive. Here, we established a tankyrase inhibitor-resistant cell line, 320-IWR, from Wnt/β-catenin-dependent CRC COLO-320DM cells...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28615297/disruption-of-aneuploidy-and-senescence-induced-by-aurora-inhibition-promotes-intrinsic-apoptosis-in-double-hit-or-double-expressor-diffuse-large-b-cell-lymphomas
#11
Daruka Mahadevan, Shariful Islam, Wenqing Qi, Carla Morales, Laurence Cooke, Catherine Spier, Eric Weterings
Double Hit (DH) or Double Expressor (DE) diffuse large B-cell lymphoma (DLBCL) are aggressive Non-Hodgkin's Lymphomas (NHLs) with translocations and/or over-expressions of MYC and BCL-2, that are difficult to treat. Aurora kinase (AK) inhibition with alisertib in DH/DE-DLBCL induces cell death in ~30%, while ~70% are aneuploid and senescent cells (AASCs), a mitotic escape mechanism contributing to drug resistance. These AASCs elaborated a high metabolic rate by increased AKT/mTOR and ERK/MAPK activity via BTK signaling through the chronic active B-cell receptor (BCR) pathway...
June 14, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28614779/the-effect-of-the-nitroxide-pirolin-on-oxidative-stress-induced-by-doxorubicin-and-taxanes-in-the-rat-brain
#12
S Tabaczar, J Czepas, A Koceva-Chyla, E Kilanczyk, J Piasecka-Zelga, K Gwozdzinski
The anticancer drugs doxorubicin (DOX), paclitaxel (PTX) and docetaxel (DTX) have been proven to induce oxidative stress (OS)-dependent side-effects in non-targeted tissues. In normal conditions, the blood-brain barrier (BBB) prevents these drugs from penetrating into the brain. However, some studies have demonstrated that small amounts of DOX can penetrate the brain via an oxidatively impaired BBB and cause damage, which suggests that including antioxidants in chemotherapy could possibly protect the brain against the toxicity of anticancer drugs...
April 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28613245/population-characteristics-in-a-tertiary-pain-service-cohort-experiencing-chronic-non-cancer-pain-weight-status-comorbidities-and-patient-goals
#13
Katherine Brain, Tracy Burrows, Megan E Rollo, Chris Hayes, Fiona J Hodson, Clare E Collins
We describe the characteristics of patients attending an Australian tertiary multidisciplinary pain service and identify areas for nutrition interventions. This cross-sectional study targets patients experiencing chronic pain who attended the service between June-December 2014. Self-reported data was captured from: (1) an Electronic Persistent Pain Outcomes Collaboration (ePPOC) referral questionnaire, incorporating demographics, pain status, and mental health; (2) a Pain Assessment and Recovery Plan (PARP), which documents patients' perceived problems associated with pain and personal treatment goals...
June 14, 2017: Healthcare (Basel, Switzerland)
https://www.readbyqxmd.com/read/28610746/a-universal-genetic-testing-initiative-for-patients-with-high-grade-non-mucinous-epithelial-ovarian-cancer-and-the-implications-for-cancer-treatment
#14
Erica M Bednar, Holly D Oakley, Charlotte C Sun, Catherine C Burke, Mark F Munsell, Shannon N Westin, Karen H Lu
OBJECTIVE: Genetic counseling (GC) and germline genetic testing (GT) for BRCA1 and BRCA2 are considered standard of care for patients with high-grade, non-mucinous epithelial ovarian, fallopian tube, and primary peritoneal cancers (HGOC). We describe a universal genetic testing initiative to increase the rates of recommendation and acceptance of GC and GT to >80% for patients with HGOC at our institution. METHODS: Data from a consecutive cohort of patients seen in our gynecologic oncology clinics between 9/1/2012 and 8/31/2015 for evaluation of HGOC were retrospectively analyzed...
June 10, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28608237/exogenous-adipokine-peptide-resistin-protects-against-focal-cerebral-ischemia-reperfusion-injury-in-mice
#15
Jiangtao Zhu, Di Wu, Chenyu Zhao, Man Luo, Ronald C Hamdy, Balvin H L Chua, Xingshun Xu, Zhigang Miao
Previous studies have demonstrated that plasma resistin levels were increased in patients with acute ischemic stroke. However, the role of resistin after ischemic brain injury is still unclear. In this study, we investigated the protective effects of resistin on cerebral ischemia/reperfusion injury in a middle cerebral artery occlusion mouse model. We found that resistin (i.c.v.) significantly reduced infarct volume and improved neurological deficits after 45 min of ischemia and 24 h of reperfusion. Furthermore, our data demonstrate that intraperitoneal administration of resistin (10 µg/kg body weight) also had protective effects on infarct volume, indicating the crossing of resistin through the impaired BBB after ischemia injury...
June 12, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28608226/blocking-rhoa-rock-inhibits-the-pathogenesis-of-pemphigus-vulgaris-by-suppressing-oxidative-stress-and-apoptosis-through-tak1-nod2-mediated-nf-%C3%AE%C2%BAb-pathway
#16
Junqin Liang, Xuewen Zeng, Yilinuer Halifu, Wenjing Chen, Fengxia Hu, Peng Wang, Huan Zhang, Xiaojing Kang
Oxidative stress and apoptosis play critical roles in pemphigus vulgaris (PV). The main aim of the present study was to investigate the effects of RhoA/ROCK signaling on UVB-induced oxidative damage, and to delineate the molecular mechanisms involved in the UVB-mediated inflammatory and apoptotic response. In HaCaT cells, we observed that blockage of RhoA/ROCK signaling with the inhibitor CT04 or Y27632 greatly inhibited the UVB-mediated increase in intracellular reactive oxygen species (ROS). Additionally, inhibition of RhoA/ROCK signaling reduced UVB-induced apoptosis, as exemplified by a reduction in DNA fragmentation, and also elevated anti-apoptotic Bcl-2 protein, concomitant with reduced levels of pro-apoptotic protein Bax, caspase-3 cleavage and decreased PARP-1 protein...
June 12, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28608001/anti-zn-2-toxicity-of-4-hydroxybenzyl-alcohol-in-astrocytes-and-neurons-contribute-to-a-robust-neuroprotective-effects-in-the-postischemic-brain
#17
Lidan Luo, Seung-Woo Kim, Hye-Kyung Lee, Il-Doo Kim, Hahnbie Lee, Ja-Kyeong Lee
4-Hydroxybenzyl alcohol (4-HBA) is an important phenolic constituent of Gastrodia elata (GE) Blume, which is used as a traditional herbal medicine in East Asia. Many activities have been reported to underlie the beneficial effects of 4-HBA in brain, such as, anti-oxidative, anti-inflammatory, anti-excitotoxic, and anti-apoptotic effects in neurons and microglia. Here, the authors demonstrate the robust neuroprotective effects of 4-HBA in rat middle cerebral artery occlusion (MCAO) model of stroke, and showed anti-Zn(2+) toxicity in neurons and astrocytes as a molecular mechanism contributing to these effects...
June 12, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28605880/js-k-a-nitric-oxide-prodrug-induces-dna-damage-and-apoptosis-in-hbv-positive-hepatocellular-carcinoma-hepg2-2-15-cell
#18
Zhengyun Liu, Guangmin Li, Ying Gou, Dongyan Xiao, Guo Luo, Joseph E Saavedra, Jie Liu, Huan Wang
Hepatocellular carcinoma (HCC) is the most important cause of cancer-related death, and 85% of HCC is caused by chronic HBV infection, the prognosis of patients and the reduction of HBV DNA levels remain unsatisfactory. JS-K, a nitric oxide-releasing diazeniumdiolates, is effective against various tumors, but little is known on its effects on HBV positive HCC. We found that JS-K reduced the expression of HBsAg and HBeAg in HBV-positive HepG2.2.15 cells. This study aimed to further examine anti-tumor effects of JS-K on HepG2...
June 8, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28604593/melatonin-modulates-neuronal-cell-death-induced-by-endoplasmic-reticulum-stress-under-insulin-resistance-condition
#19
Juhyun Song, Oh Yoen Kim
Insulin resistance (IR) is an important stress factor in the central nervous system, thereby aggravating neuropathogenesis and triggering cognitive decline. Melatonin, which is an antioxidant phytochemical and synthesized by the pineal gland, has multiple functions in cellular responses such as apoptosis and survival against stress. This study investigated whether melatonin modulates the signaling of neuronal cell death induced by endoplasmic reticulum (ER) stress under IR condition using SH-SY5Y neuroblastoma cells...
June 10, 2017: Nutrients
https://www.readbyqxmd.com/read/28601509/olaparib-hydroxamic-acid-derivatives-as-dual-parp-and-hdac-inhibitors-for-cancer-therapy
#20
Zigao Yuan, Shaopeng Chen, Qinsheng Sun, Ning Wang, Dan Li, Shuangshuang Miao, Chunmei Gao, Yuzong Chen, Chunyan Tan, Yuyang Jiang
Olaparib was the first PARP inhibitor approved by the FDA for patients with BRCA-mutated ovarian cancer. Recent studies have demonstrated enhanced anticancer effects of combination therapy consisting of olaparib and HDAC inhibitors. Herein, based on rational drug design strategy, hydroxamic acid derivatives of olaparib were constructed as dual PARP and HDAC inhibitors. These hybrid compounds showed potent inhibitory activities against PARP1/2 and HDAC1/6 with IC50 values in the nanomolar range. Furthermore, compound P1 exhibited broad-spectrum antiproliferative activities in selected human cancer cell lines...
May 31, 2017: Bioorganic & Medicinal Chemistry
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