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https://www.readbyqxmd.com/read/28433571/antitumor-and-chemosensitizing-action-of-3-bromopyruvate-implication-of-deregulated-metabolism
#1
Saveg Yadav, Shrish Kumar Pandey, Ajay Kumar, Praveen Kumar Kujur, Rana Pratap Singh, Sukh Mahendra Singh
3-Bromopyruvate (3-BP), brominated derivative of pyruvate, possesses strong antitumor potential, owing to its ability to inhibit multiple target molecules crucial for survival of neoplastic cells. Although, 3-BP displays cytotoxicity against a wide variety of tumors, there is no report with respect to malignancies of thymic origin. Therefore, we investigated its antineoplastic action in vitro against tumor cells of a murine transplantable lymphoma of thymoma origin, designated as Dalton's lymphoma (DL). 3-BP treatment of tumor cells inhibited metabolism and survival with augmented induction of apoptosis and necrosis...
April 19, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28413646/role-of-malate-dehydrogenase-in-facilitating-lactate-dehydrogenase-to-support-the-glycolysis-pathway-in-tumors
#2
Siavash Mansouri, Ali Shahriari, Hadi Kalantar, Taraneh Moini Zanjani, Mojtaba Haghi Karamallah
High aerobic glycolysis, as one of the hallmarks of cancer cells, requires nicotinamide adenine dinucleotide (NAD(+)) as a vital co-factor, to guarantee the flow of glycolysis. Malate dehydrogenase (MDH), as an important enzyme in cancer metabolism, is a source of NAD(+) additional to lactate dehydrogenase (LDH). The current study aimed to elucidate the kinetic parameters of MDH in human breast cancer and evaluate its supportive role in the glycolysis pathway. The Michaelis-Menten constant (Km) and maximum velocity (Vmax) of MDH were determined in the crude extracts of human breast tumors and healthy tissue samples, which were obtained directly from the operating theatre...
April 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28411102/zl006-protects-spinal-cord-neurons-against-ischemia-induced-oxidative-stress-through-ampk-pgc-1%C3%AE-sirt3-pathway
#3
Shu-Guang Liu, Yun-Mei Wang, Yan-Jun Zhang, Xi-Jing He, Tao Ma, Wei Song, Yu-Min Zhang
Spinal cord ischemia (SCI) induces a range of cellular and molecular cascades, including activation of glutamate receptors and downstream signaling. Post-synaptic density protein 95 (PSD-95) links neuronal nitric oxide synthase (nNOS) with the N-methyl-d-aspartic acid (NMDA) receptors to form a ternary complex in the CNS. This molecular complex-mediated cytotoxicity has been implicated in brain ischemia, but its role in SCI has not been determined. The goal of the study was to investigate the potential protective effects of ZL006, a small-molecule inhibitor of the PSD-95/nNOS interaction, in an in vitro SCI model induced by oxygen and glucose deprivation (OGD) in cultured spinal cord neurons...
April 12, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28398017/differential-effects-of-phosphodiesterase-5-inhibition-in-chronic-cardiac-decompensation-depending-on-the-type-whether-hfref-or-hfpef-of-heart-failure-a-meta-analysis
#4
Renato DE Vecchis, Arturo Cesaro, Carmelina Ariano
INTRODUCTION: According to 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension(PH), no specific drug is currently indicated for PH related to left heart disease( PH-LDH), i.e., the one secondary to left chronic heart failure (CHF), which coincides with the group 2 of the PH classification endorsed by the above-mentioned guidelines. In fact, adoption of therapies that specifically apply for so-called pulmonary arterial hypertension (group 1 of the PH classification) has been regarded as substantially contraindicated in patients with PH- LHD, according to current ESC/ERS guidelines...
April 10, 2017: Minerva Cardioangiologica
https://www.readbyqxmd.com/read/28396174/sirt3-confers-protection-against-neuronal-ischemia-by-inducing-autophagy-involvement-of-the-ampk-mtor-pathway
#5
Shu-Hui Dai, Tao Chen, Xia Li, Kang-Yi Yue, Peng Luo, Li-Kun Yang, Jie Zhu, Yu-Hai Wang, Zhou Fei, Xiao-Fan Jiang
Sirtuin3 (Sirt3) is a member of the silent information regulator 2 (Sir2) family of proteins located in mitochondria that influences almost every major aspect of mitochondrial biology, including ATP generation and reactive oxygen species (ROS) production. Our previous study showed that Sirt3 exerts protective effects against oxidative stress in neuronal cells. In this study, we investigated the role of Sirt3 in neuronal ischemia using an oxygen and glucose deprivation (OGD) model. Sirt3 was up-regulated by OGD and overexpression of Sirt3 through lentivirus transfection significantly reduced OGD-induced lactate dehydrogenase (LDH) release and neuronal apoptosis...
April 7, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28392989/sevoflurane-postconditioning-protects-the-myocardium-against-ischemia-reperfusion-injury-via-activation-of-the-jak2-stat3-pathway
#6
Jianjiang Wu, Jin Yu, Peng Xie, Yiliyaer Maimaitili, Jiang Wang, Long Yang, Haiping Ma, Xing Zhang, Yining Yang, Hong Zheng
BACKGROUND: Sevoflurane postconditioning (S-post) has similar cardioprotective effects as ischemic preconditioning. However, the underlying mechanism of S-post has not been fully elucidated. Janus kinase signaling transduction/transcription activator (JAK2-STAT3) plays an important role in cardioprotection. The purpose of this study was to determine whether the cardioprotective effects of S-post are associated with activation of the JAK2-STAT3 signal pathway. METHODS: An adult male Sprague-Dawley (SD) rat model of myocardial ischemia/reperfusion (I/R) injury was established using the Langendorff isolated heart perfusion apparatus...
2017: PeerJ
https://www.readbyqxmd.com/read/28386372/thioredoxin-2-protects-against-oxygen-glucose-deprivation-reperfusion-injury-by-inhibiting-autophagy-and-apoptosis-in-h9c2-cardiomyocytes
#7
Yan-Yan Li, Yin Xiang, Song Zhang, Yan Wang, Jie Yang, Wei Liu, Feng-Tai Xue
The aim of this study is to examine the role of thioredoxin-2 (Trx2) in autophagy and apoptosis during myocardial ischemia-reperfusion (I/R) injury in vitro. We employed the oxygen-glucose deprivation and reperfusion (OGD/R) model of H9c2 cells and used lentiviral infection to overexpress Trx2. H9c2 cell viability and injury assays were conducted using a Cell Counting Kit-8 (CCK-8) and alactate dehydrogenase (LDH) kit. The effects of Trx2 on autophagy and apoptosis were measured by transmission electron microscopy (TEM), western blot, and flow cytometry...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28370165/neuroprotective-effects-of-a-novel-poly-adp-ribose-polymerase-1-inhibitor-jpi-289-in-hypoxic-rat-cortical-neurons
#8
Youngchul Kim, Young Seo Kim, Min-Young Noh, Hanchang Lee, Boyoung Joe, Hyun Young Kim, Jeongmin Kim, Seung Hyun Kim, Jiseon Park
Excessive activation of Poly (ADP-ribose) polymerase-1 (PARP-1) is known to develop neuronal apoptosis, necrosis and inflammation after ischemic brain injury. Therefore, PARP-1 inhibition after ischemic stroke has been attemptedin successful animal studies. The purpose of present work was to develop a novel water soluble PARP-1 inhibitor (JPI-289) and explore its neuroprotective effect on ischemic injury in an in vitro model. The half-life of JPI-289 after Intravenous or oral administration in rats was relatively long (1...
April 2, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28363742/liraglutide-relieves-myocardial-damage-by-promoting-autophagy-via-ampk-mtor-signaling-pathway-in-zucker-diabetic-fatty-rat
#9
Ya Zhang, Yuanna Ling, Li Yang, Yanzhen Cheng, Pingzhen Yang, Xudong Song, Huixiong Tang, Yongkang Zhong, Lu Tang, Shangfei He, Shuangli Yang, Aihua Chen, Xianbao Wang
Liraglutide, a glucose-lowering agent used to treat type 2 diabetic mellitus is reported to exert cardioprotective effects in clinical trials and animal experiments. However, the cardioprotective mechanism of liraglutide on diabetic cardiomyopathy has not been fully illustrated. The present study was performed to investigate whether liraglutide alleviates diabetic myocardium injury by promoting autophagy and its underlying mechanisms. Our results show that liraglutide significantly reduced the levels of creatine kinase (CK) and lactate dehydrogenase (LDH), improved left ventricular functional status and alleviated myocardial fibrosis in the Zucker diabetic fatty (ZDF) rat model...
March 29, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28345875/reactive-oxygen-species-synergize-to-potently-and-selectively-induce-cancer-cell-death
#10
Hyang Yeon Lee, Elizabeth I Parkinson, Carlotta Granchi, Ilaria Paterni, Dipak Panigrahy, Pankaj Seth, Filippo Minutolo, Paul J Hergenrother
A distinctive feature of cancer cells is their elevated levels of reactive oxygen species (ROS), a trait that can cause cancer cells to be more sensitive to ROS-inducing agents than normal cells. ROS take several forms, each with different reactivity and downstream consequence. Here we show that simultaneous generation of superoxide and hydrogen peroxide within cancer cells results in significant synergy, potently and selectively causing cancer cell death. In these experiments superoxide is generated using the NAD(P)H quinone oxidoreductase 1 (NQO1) substrate deoxynyboquinone (DNQ), and hydrogen peroxide is generated using the lactate dehydrogenase A (LDH-A) inhibitor NHI-Glc-2...
April 7, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28327969/circulating-tumour-dna-predicts-response-to-anti-pd1-antibodies-in-metastatic-melanoma
#11
J H Lee, G V Long, S Boyd, S Lo, A M Menzies, V Tembe, A Guminski, V Jakrot, R A Scolyer, G J Mann, R F Kefford, M S Carlino, H Rizos
Background: Programmed death 1 (PD1) inhibitors are now a foundation of medical management of metastatic melanoma. This study sought to determine whether circulating tumour DNA (ctDNA) provides useful early response and prognostic information. Patients and methods: We evaluated the relationship between pre-treatment and early on treatment ctDNA and outcome in melanoma patients treated with PD1 inhibitors alone or in combination with ipilimumab. Results: ctDNA was detected in 40/76 patients (53%) at baseline, and correlated with stage, LDH levels, disease volume and ECOG performance...
January 24, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28323904/pyrrolidine-dithiocarbamate-administered-during-ex-vivo-lung-perfusion-promotes-rehabilitation-of-injured-donor-rat-lungs-obtained-after-prolonged-warm-ischemia
#12
Cyril Francioli, Xingyu Wang, Roumen Parapanov, Etienne Abdelnour, Jérôme Lugrin, Fabrizio Gronchi, Jean Perentes, Philippe Eckert, Hans-Beat Ris, Lise Piquilloud, Thorsten Krueger, Lucas Liaudet
Damaged lung grafts obtained after circulatory death (DCD lungs) and warm ischemia may be at high risk of reperfusion injury after transplantation. Such lungs could be pharmacologically reconditioned using ex-vivo lung perfusion (EVLP). Since acute inflammation related to the activation of nuclear factor kappaB (NF-κB) is instrumental in lung reperfusion injury, we hypothesized that DCD lungs might be treated during EVLP by pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB. Rat lungs exposed to 1h warm ischemia and 2 h cold ischemia were subjected to EVLP during 4h, in absence (CTRL group, N = 6) or in presence of PDTC (2...
2017: PloS One
https://www.readbyqxmd.com/read/28322131/soluble-flt-1-has-cytotoxic-effects-on-bewo-choriocarcinoma-cells
#13
Michiko Yamashita, Keiichi Kumasawa, Tatsuya Miyake, Hitomi Nakamura, Tadashi Kimura
BACKGROUND: Vascular endothelial growth factor (VEGF) plays a pivotal role in angiogenesis and is overexpressed in many kinds of malignant tumors. Soluble VEGF receptor 1 (sVEGFR-1/ soluble fms-like tyrosine kinase 1 [sFlt-1]) plays a role as an inhibitor of VEGF, and an antitumor effect has been shown in several studies using sFlt-1. Recently, in addition to its antiangiogenic effect, it was reported that sFlt-1 has direct cytotoxicity. MATERIALS AND METHODS: Transfection of sFlt-1 plasmid DNA was performed in the BeWo choriocarcinoma cell line...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28296232/inhibitors-of-soluble-epoxide-hydrolase-minimize-ischemia-reperfusion-induced-cardiac-damage-in-normal-hypertensive-and-diabetic-rats
#14
Oliul Islam, Prashanth Patil, Sumanta K Goswami, Rema Razdan, Mohammed N Inamdar, Mohammed Rizwan, Jubin Mathew, Bora Inceoglu, Kin S Stephen Lee, Sung H Hwang, Bruce D Hammock
AIM: We designed a study to evaluate the cardioprotective effect of two soluble epoxide hydrolase (sEH) inhibitors, 1-(1-propanoylpiperidin-4-yl)-3-(4-trifluoromethoxy)phenyl)urea (TPPU) and trans-4-{4-[3-(4-trifluoromethoxyphenyl)-ureido]cyclohexyloxy}benzoic acid (t-TUCB), in ischemia-reperfusion (IR) model. METHODS: Cardioprotective effects of the sEH inhibitors were evaluated against IR-induced myocardial damage in hearts from normal, hypertensive and diabetic rats using Langendorff's apparatus...
March 15, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28292981/vaginal-heparan-sulfate-linked-to-neutrophil-dysfunction-in-the-acute-inflammatory-response-associated-with-experimental-vulvovaginal-candidiasis
#15
Junko Yano, Mairi C Noverr, Paul L Fidel
Despite acute inflammation by polymorphonuclear neutrophils (PMNs) during vulvovaginal candidiasis (VVC), clearance of Candida fails to occur. The purpose of this study was to uncover the mechanism of vaginal PMN dysfunction. Designs included assessing PMN migration, proinflammatory mediators, and tissue damage (by analysis of the activity of lactate dehydrogenase [LDH]) in mice susceptible (C3H/HeN-C57BL/6) or resistant (CD-1) to chronic VVC (CVVC-S or CVVC-R) and testing morphology-specific Candida albicans strains under conditions of preinduced PMN migration (CVVC-S mice) or PMN depletion (CVVC-R mice)...
March 14, 2017: MBio
https://www.readbyqxmd.com/read/28281186/calcium-sensing-receptor-mediated-mitogen-activated-protein-kinase-pathway-improves-the-status-of-transplanted-mouse-embryonic-stem-cells-in-rats-with-acute-myocardial-infarction
#16
Jian Sun, Tao Wei, Shuzhi Bai, Hongtao Zhao, Xiaoqin Liu, Jinfeng Yu, Li Li, Gaochen Song, Hairong Luan, Changqing Xu
Several studies have identified the critical role of calcium-sensing receptors (CaSRs) in cardiac ischaemia/reperfusion injury and cardiac hypertrophy and have demonstrated that CaSRs induce myocardial apoptosis by activating MAPKs. Using acute myocardial infarction rat models, we found that a combination therapy of CaSR inhibition and embryonic stem cell (ESC) transplantation after acute myocardial infarction (AMI) leads to a dramatic reduction in the infarct size; a significant increase in the maximum rising and falling rate (+dp/dtmax and -dp/dtmax, respectively) of left ventricular pressure; a significant decrease in left ventricular end-diastolic pressure; a significant decrease in the mRNA expression level of CaSR, Bax, Bcl-2, cleaved caspase-3, cleaved caspase-9, p-ERK, p-JNK and p-P38 protein together with apoptosis indexes in the C and E groups; and a significant decrease in cTnT levels as well as LDH and CK activity...
March 9, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28274156/folic-acid-ameliorates-celecoxib-cardiotoxicity-in-a-doxorubicin-heart-failure-rat-model
#17
Shafique Ahmad, Bibhu Prasad Panda, Kanchan Kohli, Mohammad Fahim, Kiran Dubey
CONTEXT: The cardiotoxic effect of selective cyclo-oxygenase-2 inhibitors is well known. While rofecoxib and valdecoxib have been withdrawn, celecoxib remains on the market. Folic acid, a naturally occurring vitamin, has been shown to reduce myocardial ischemia and post-reperfusion injury in rats. OBJECTIVE: This study examined the cardiac effects of celecoxib and folic acid on doxorubicin-induced cardiomyopathy in rats. MATERIALS AND METHODS: Cardiomyopathy was induced in male Wistar rats with six intraperitoneal injections of 2...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28250059/netrin-1-restores-cell-injury-and-impaired-angiogenesis-in-vascular-endothelial-cells
#18
Ying Xing, Jingbo Lai, Xiangyang Liu, Nana Zhang, Jie Ming, Hengxin Liu, Xi Zhang
Diabetic foot ulceration (DFU) represents a common vascular complication of diabetes mellitus (DM) with high morbidity and disability resulting from amputation. Netrin-1 level was decreased in type 2 DM patients and has been identified as a protective regulator against diabetes-triggered myocardial infarction and nephropathy. Unfortunately, its role and molecular mechanism in DFU remain poorly elucidated. Here, netrin-1 levels were reduced in DM and DFU patients relative to healthy controls, with netrin-1 levels being lowest in DFU patients...
March 1, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28243322/targeting-metabolic-remodeling-in-triple-negative-breast-cancer-in-a-murine-model
#19
Verónica García-Castillo, Eduardo López-Urrutia, Octavio Villanueva-Sánchez, Miguel Á Ávila-Rodríguez, Alejandro Zentella-Dehesa, Carlo Cortés-González, César López-Camarillo, Nadia J Jacobo-Herrera, Carlos Pérez-Plasencia
Background: Chemotherapy is the backbone of systemic treatment for triple negative breast cancer (TNBC), which is one of the most relevant breast cancers molecular types due to the ability of tumor cells to develop drug resistance, highlighting the urgent need to design newer and safer drug combinations for treatment. In this context, to overcome tumor cell drug resistance, we employed a novel combinatorial treatment including Doxorubicin, Metformin, and Sodium Oxamate (DoxMetOx). Such pharmacological combination targets indispensable hallmarks of cancer-related to aerobic glycolysis and DNA synthesis...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28243141/bay11-7082-attenuates-neuropathic-pain-via-inhibition-of-nuclear-factor-kappa-b-and-nucleotide-binding-domain-like-receptor-protein-3-inflammasome-activation-in-dorsal-root-ganglions-in-a-rat-model-of-lumbar-disc-herniation
#20
Ailiang Zhang, Kun Wang, Lianghua Ding, Xinnan Bao, Xuan Wang, Xubin Qiu, Jinbo Liu
Lumbar disc herniation (LDH) is an important cause of radiculopathy, but the underlying mechanisms are incompletely understood. Many studies suggested that local inflammation, rather than mechanical compression, results in radiculopathy induced by LDH. On the molecular and cellular level, nuclear factor-kappa B (NF-κB) and nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome have been implicated in the regulation of neuroinflammation formation and progression. In this study, the autologous nucleus pulposus (NP) was implanted in the left L5 dorsal root ganglion (DRG) to mimic LDH in rats...
2017: Journal of Pain Research
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