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https://www.readbyqxmd.com/read/28645007/activation-of-the-pi3k-akt-pathway-promotes-neuroprotection-of-the-%C3%AE-opioid-receptor-agonist-against-cerebral-ischemia-reperfusion-injury-in-rat-models
#1
Mei-Rong Lv, Bin Li, Ming-Guang Wang, Fan-Guo Meng, Jian-Jun Yu, Feng Guo, Ye Li
The central objective was to identify the role of the PI3K-Akt activation pathway on the neuroprotection of δ-opioid receptor agonist (DADLE) against cerebral ischemia-reperfusion (I/R) injury in a rat model. Fifty-five male Sprague-Dawley (SD) rats were included to establish a middle cerebral artery occlusion (MCAO) model which were then divided into the sham, MCAO, LY294002 (MCAO+DADLE+LY294002 [inhibitor of PI3K-Akt pathway]), DADLE (MCAO+DADLE) and DMSO (MCAO+DADLE+DMSO [dimethyl sulphoxide]) groups. The cerebral infarction (CI) volume and nerve cell apoptosis was determined using TTC and TUNEL staining...
June 20, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28645005/application-of-stem-cell-derived-neuronal-cells-to-evaluate-neurotoxic-chemotherapy
#2
Claudia Wing, Masaaki Komatsu, Shannon M Delaney, Matthew Krause, Heather E Wheeler, M Eileen Dolan
The generation of induced pluripotent stem cells (iPSCs) and differentiation to cells composing major organs has opened up the possibility for a new model system to study adverse toxicities associated with chemotherapy. Therefore, we used human iPSC-derived neurons to study peripheral neuropathy, one of the most common adverse effects of chemotherapy and cause for dose reduction. To determine the utility of these neurons in investigating the effects of neurotoxic chemotherapy, we measured morphological differences in neurite outgrowth, cell viability as determined by ATP levels and apoptosis through measures of caspase 3/7 activation following treatment with clinically relevant concentrations of platinating agents (cisplatin, oxaliplatin and carboplatin), taxanes (paclitaxel, docetaxel and nab-paclitaxel), a targeted proteasome inhibitor (bortezomib), an antiangiogenic compound (thalidomide), and 5-fluorouracil, a chemotherapeutic that does not cause neuropathy...
June 15, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28644464/a-synthetic-ion-transporter-that-disrupts-autophagy-and-induces-apoptosis-by-perturbing-cellular-chloride-concentrations
#3
Nathalie Busschaert, Seong-Hyun Park, Kyung-Hwa Baek, Yoon Pyo Choi, Jinhong Park, Ethan N W Howe, Jennifer R Hiscock, Louise E Karagiannidis, Igor Marques, Vítor Félix, Wan Namkung, Jonathan L Sessler, Philip A Gale, Injae Shin
Perturbations in cellular chloride concentrations can affect cellular pH and autophagy and lead to the onset of apoptosis. With this in mind, synthetic ion transporters have been used to disturb cellular ion homeostasis and thereby induce cell death; however, it is not clear whether synthetic ion transporters can also be used to disrupt autophagy. Here, we show that squaramide-based ion transporters enhance the transport of chloride anions in liposomal models and promote sodium chloride influx into the cytosol...
July 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28644437/more-alive-than-dead-non-apoptotic-roles-for-caspases-in-neuronal-development-plasticity-and-disease
#4
REVIEW
Amrita Mukherjee, Darren W Williams
Nervous systems are arguably the most fascinating and complex structures in the known universe. How they are built, changed by experience and then degenerate are some of the biggest questions in biology. Regressive phenomena, such as neuron pruning and programmed cell death, have a key role in the building and maintenance of the nervous systems. Both of these cellular mechanisms deploy the caspase family of protease enzymes. In this review, we highlight the non-apoptotic function of caspases during nervous system development, plasticity and disease, particularly focussing on their role in structural remodelling...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28644386/capsaicin-induces-autophagy-and-apoptosis-in-human-nasopharyngeal-carcinoma-cells-by-downregulating-the-pi3k-akt-mtor-pathway
#5
Yu-Tsai Lin, Hung-Chen Wang, Yi-Chiang Hsu, Chung-Lung Cho, Ming-Yu Yang, Chih-Yen Chien
Capsaicin is a potential chemotherapeutic agent for different human cancers. In Southeast China, nasopharyngeal carcinoma (NPC) has the highest incidence of all cancers, but final treatment outcomes are unsatisfactory. However, there is a lack of information regarding the anticancer activity of capsaicin in NPC cells, and its effects on the signaling transduction pathways related to apoptosis and autophagy remain unclear. In the present study, the precise mechanisms by which capsaicin exerts anti-proliferative effects, cell cycle arrest, autophagy and apoptosis were investigated in NPC-TW01 cells...
June 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28644062/4-nerolidylcatechol-apoptosis-by-mitochondrial-mechanisms-with-reduction-in-cyclin-d1-at-g0-g1-stage-of-the-chronic-myelogenous-k562-cell-line
#6
Polyana Lopes Benfica, Renato Ivan de Ávila, Bruna Dos Santos Rodrigues, Alane Pereira Cortez, Aline Carvalho Batista, Marilisa Pedroso Nogueira Gaeti, Eliana Martins Lima, Kênnia Rocha Rezende, Marize Campos Valadares
CONTEXT: 4-Nerolidylcatechol (4-NRC) has showed antitumor potential through apoptosis. However, its apoptotic mechanisms are still unclear, especially in leukemic cells. OBJECTIVES: To evaluate the cytotoxic potential of 4-NRC and its cell death pathways in p53-null K562 leukemic cells. MATERIALS AND METHODS: Cytotoxicity of 4-NRC (4.17-534.5 μM) over 24 h of exposure was evaluated by MTT assay. 4-NRC-induced apoptosis in K562 cells was investigated by phosphatidylserine (PS) externalization, cell cycle, sub-G1, mitochondrial evaluation, cytochrome c, cyclin D1 and intracellular reactive oxygen species (ROS) levels, and caspase activity analysis...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28643990/bcl-2-and-caspase-9-serum-levels-in-children-and-adolescents-with-idiopathic-epilepsy-and-active-seizures
#7
Angeliki Skardoutsou, Panagiotis Primikiris, Charalampos Tsentidis, Antonios Marmarinos, Dimitrios Gourgiotis
BACKROUND: In the present study we investigated the levels of proapoptotic Caspase-9 and antiapoptotic Bcl-2 proteins in the sera of children and adolescents with idiopathic epilepsy and tried to relate the findings to the patients clinical parameters. METHODS: This retrospective study consisted of 118 children and adolescents with idiopathic epilepsy, categorized according to type and number of seizures, duration of the disease and the control of seizures and 30 age and sex matched controls...
June 22, 2017: Minerva Pediatrica
https://www.readbyqxmd.com/read/28643870/type-iii-metacaspases-calcium-dependent-activity-proposes-new-function-for-the-p10-domain
#8
Marina Klemenčič, Christiane Funk
Metacaspases are a subgroup of caspase homologues represented in bacteria, algae and plants. Although type I and type II metacaspases are present in plants, recently discovered and uncharacterized type III metacaspases can only be found in algae which have undergone secondary endosymbiosis. We analysed the expression levels of all 13 caspase homologues in the cryptophyte Guillardia theta in vivo and biochemically characterized its only type III metacaspase, GtMC2, in vitro. Type III metacaspase GtMC2 was shown to be an endopeptidase with a preference for basic amino acids in the P1 position, which exhibited specific N-terminal proteolytic cleavage for full catalytic efficiency...
June 23, 2017: New Phytologist
https://www.readbyqxmd.com/read/28643758/effects-of-ef-24-rad001-and-paclitaxel-on-the-expression-profiles-of-apoptotic-and-anti-apoptotic-genes
#9
Ebru Alp, Akin Yilmaz, Hacer Ilke Onen, Emine Sevda Menevse
CONTEXT: Cancer cells exert differential responses to chemotherapeutics and inhibitors. To the best of our knowledge, a few or no research has been performed until now to determine the effect of EF-24 and RAD001 on MDA-MB-231 breast cancer cells with regard to mRNA expression of apoptotic and anti-apoptotic genes. AIMS: In this study, we aimed to investigate the mRNA expression levels of apoptotic (caspase 2 [CASP2], CASP8, and CASP9) and anti-apoptotic (B-cell lymphoma 2 [BCL2] and BCL2-like protein 1 [BCL2L1]) genes after exposure to paclitaxel, EF-24, and RAD001 in MDA-MB-231 cells...
April 2017: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28643236/multi-reservoir-phospholipid-shell-encapsulating-protamine-nanocapsules-for-co-delivery-of-letrozole-and-celecoxib-in-breast-cancer-therapy
#10
Ahmed O Elzoghby, Shaimaa K Mostafa, Maged W Helmy, Maha A ElDemellawy, Salah A Sheweita
PURPOSE: In the current work, we propose a combined delivery nanoplatform for letrozole (LTZ) and celecoxib (CXB). METHODS: Multi-reservoir nanocarriers were developed by enveloping protamine nanocapsules (PRM-NCs) within drug-phospholipid complex bilayer. RESULTS: Encapsulation of NCs within phospholipid bilayer was confirmed by both size increase from 109.7 to 179.8 nm and reduction of surface charge from +19.0 to +7.78 mV. The multi-compartmental core-shell structure enabled biphasic CXB release with initial fast release induced by complexation with phospholipid shell followed by prolonged release from oily core...
June 22, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28643232/caffeine-protects-against-anticonvulsant-induced-neurotoxicity-in-the-developing-rat-brain
#11
Stefanie Endesfelder, Ulrike Weichelt, Cornelia Schiller, Marco Sifringer, Ivo Bendix, Christoph Bührer
Phenobarbital is the most commonly used drug for the treatment of neonatal seizures but may induce neurodegeneration in the developing brain. Methylxanthine caffeine is used for the treatment of apnea in newborn infants and appears to be neuroprotective, as shown by antiapoptotic and anti-inflammatory effects in oxidative stress models in newborn rodents and reduced rates of cerebral palsy in human infants treated with caffeine. We hypothesized that caffeine may counteract the proapoptotic effects of phenobarbital in newborn rats...
June 22, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28643149/surface-modification-minimizes-the-toxicity-of-silver-nanoparticles-an-in-vitro-and-in-vivo-study
#12
Balaram Das, Satyajit Tripathy, Jaydeep Adhikary, Sourav Chattopadhyay, Debasis Mandal, Sandeep Kumar Dash, Sabyasachi Das, Aditi Dey, Sankar Kumar Dey, Debasis Das, Somenath Roy
Currently toxicological research in Silver nanoparticle is a leading issue in medical science. The surface chemistry and physical dimensions of silver nanoparticles (Ag-NPs) play an important role in toxicity. The aim of this present study was to evaluate the in vitro and in vivo toxicity of Ag-NPs as well as the alteration of toxicity profile due to surface functionalization (PEG and BSA) and the intracellular signaling pathways involved in nanoparticles mediated oxidative stress and apoptosis in vitro and in vivo system...
June 22, 2017: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/28643087/antioxidant-and-antiapoptotic-actions-of-selegiline-protect-against-3-np-induced-neurotoxicity-in-rats
#13
Sara A Wahdan, Mariane G Tadros, Amani E Khalifa
The present study was designed to investigate the neuroprotective effect of selegiline on 3-nitropropionic acid (3-NP)-induced neurotoxicity. Selegiline was intraperitoneally injected at doses 2.5, 5, and 10 mg/kg, 3 days prior to and continued daily, 30 min before 3-NP administration. 3-NP (20 mg/kg, i.p.) was administered for four consecutive days. 3-NP-treated rats exhibited PPI deficits, locomotor hypoactivity, increased striatal and cortical lipid peroxidation, and reduced respective glutathione (GSH) levels as well as catalase and superoxide dismutase (SOD) activities...
June 23, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28642847/heat-labile-enterotoxin-induced-perk-chop-pathway-activation-causes-intestinal-epithelial-cell-apoptosis
#14
Xi Lu, Chunmeng Li, Congcong Li, Pengcheng Li, Enqing Fu, Yonghong Xie, Faguang Jin
Enterotoxigenic Escherichia coli (ETEC) is a leading cause of diarrhea among children and travelers in developing countries, and heat-labile enterotoxin (LT) is one of the most important virulence factors. The pathogenesis of and virulence factors associated with ETEC have been well-characterized; however, the extent to which ETEC damages host cells remains unclear. In this study, we found that LT could induce decreases in intestinal epithelial cell viability and induce apoptosis in a dose- and time- dependent manner in both HCT-8 and Caco-2 cells...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28642708/myricitrin-protects-cardiomyocytes-from-hypoxia-reoxygenation-injury-involvement-of-heat-shock-protein-90
#15
Min Wang, Gui-Bo Sun, Yu-Yang Du, Yu Tian, Ping Liao, Xue-Song Liu, Jing-Xue Ye, Xiao-Bo Sun
Modulation of oxidative stress is therapeutically effective in ischemia/reperfusion (I/R) injury. Myricitrin, a naturally occurring phenolic compound, is a potent antioxidant. However, little is known about its effect on I/R injury to cardiac myocytes. The present study was performed to investigate the potential protective effect of myricitrin against hypoxia/reoxygenation (H/R)-induced H9c2 cardiomyocyte injury and its underlying mechanisms. Myricitrin pretreatment improved cardiomyocyte viability, inhibited ROS generation, maintained the mitochondrial membrane potential, reduced apoptotic cardiomyocytes, decreased the caspase-3 activity, upregulated antiapoptotic proteins and downregulated proapoptotic proteins during H/R injury...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28642707/tetrandrine-an-activator-of-autophagy-induces-autophagic-cell-death-via-pkc-%C3%AE-inhibition-and-mtor-dependent-mechanisms
#16
Vincent Kam Wai Wong, Wu Zeng, Juan Chen, Xiao Jun Yao, Elaine Lai Han Leung, Qian Qian Wang, Pauline Chiu, Ben C B Ko, Betty Yuen Kwan Law
Emerging evidence suggests the therapeutic role of autophagic modulators in cancer therapy. This study aims to identify novel traditional Chinese medicinal herbs as potential anti-tumor agents through autophagic induction, which finally lead to autophagy mediated-cell death in apoptosis-resistant cancer cells. Using bioactivity-guided purification, we identified tetrandrine (Tet) from herbal plant, Radix stephaniae tetrandrae, as an inducer of autophagy. Across a number of cancer cell lines, we found that breast cancer cells treated with tetrandrine show an increase autophagic flux and formation of autophagosomes...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28642633/proteases-revisited-roles-and-therapeutic-implications-in-fibrosis
#17
REVIEW
Jakub Kryczka, Joanna Boncela
Proteases target many substrates, triggering changes in distinct biological processes correlated with cell migration, EMT/EndMT and fibrosis. Extracellular protease activity, demonstrated by secreted and membrane-bound protease forms, leads to ECM degradation, activation of other proteases (i.e., proteolysis of nonactive zymogens), decomposition of cell-cell junctions, release of sequestered growth factors (TGF-β and VEGF), activation of signal proteins and receptors, degradation of inflammatory inhibitors or inflammation-related proteins, and changes in cell mechanosensing and motility...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28642243/anti-inflammatory-and-anti-osteoarthritis-effects-of-tectorigenin
#18
Cheng-Long Wang, De Li, Chuan-Dong Wang, Fei Xiao, Jun-Feng Zhu, Chao Shen, Bin Zuo, Yi-Min Cui, Hui Wang, Yuan Gao, Guo-Li Hu, Xiao-Ling Zhang, Xiao-Dong Chen
Osteoarthritis (OA) is a common and dynamic joint disease, including the articular cartilage, underlying bones, and synovium. In particular, OA is considered as the degeneration of the cartilage. Tectorigenin (Tec) can affect many biological processes. However, its effect on articular chondrocytes remains unclear. This study aimed to assess the role of Tec in articular cartilage. In vitro, Tec inhibited the expression levels of type X collagen, cyclooxigenase-2, matrix metalloproteinase (MMP)-3, and MMP-13 gene but enhanced those of Runx1, type II collagen, and aggrecan in the presence of IL-1β...
June 22, 2017: Biology Open
https://www.readbyqxmd.com/read/28642201/combination-of-coenzyme-q10-loaded-liposomes-with-ultrasound-targeted-microbubbles-destruction-utmd-for-early-theranostics-of-diabetic-nephropathy
#19
Ting Yue, He-Lin Xu, Pian-Pian Chen, Lei Zheng, Qun Huang, Wen-Shuang Sheng, Yuan-Di Zhuang, Li-Zhuo Jiao, Ting-Ting Chi, De-Li ZhuGe, Jin-Jin Liu, Ying-Zheng Zhao, Li Lan
Diabetic nephropathy (DN) is one of the most common and lethal microvascular complications of diabetes. This study aimed to explore whether coenzymeQ10 (CoQ10) as an antioxidant combined with ultrasound-targeted microbubble destruction (UTMD) could reverse the progress of early diabetic nephropathy (DN). CoQ10 has great potential to treat early DN. However, the clinical application of CoQ10 has been limited because of its low aqueous solubility and non-specific distribution. Therefore, CoQ10-loaded liposomes (CoQ10-lip) were prepared and combined with ultrasound microbubbles for the early theranostics of DN...
June 19, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28642133/s-allylmercaptocysteine-suppresses-the-growth-of-human-gastric-cancer-xenografts-through-induction-of-apoptosis-and-regulation-of-mapk-and-pi3k-akt-signaling-pathways
#20
Xiaosong Zhu, Xiaoyan Jiang, Ang Li, Yueyue Sun, Yan Liu, Xiao Sun, Xiuli Feng, Siying Li, Zhongxi Zhao
Gastric cancer remains as a common lethal malignancy worldwide. Developing novel anti-gastric cancer drugs with minimal side effects is necessary to address this public health issue. S-allylmercaptocysteine (SAMC), one of the water-soluble organosulfur garlic derivatives, has been demonstrated as a suppressive agent against tumors. In this study, we examined the effect of SAMC on human gastric carcinoma growth in vivo and explored the underlying mechanism. Human gastric cancer SGC-7901 cells were inoculated subcutaneously in BALB/c nude mice...
June 19, 2017: Biochemical and Biophysical Research Communications
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