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Mostafa M Ghorab, Mansour S Alsaid, Ghada H Al-Ansary, Ghada A Abdel-Latif, Dalal A Abou El Ella
Twenty novel chromene derivatives carrying different sulfonamide moieties (3-22) were designed and synthesized. All the newly prepared compounds were evaluated for their in vitro anticancer activity against breast cancer cell line (T47D). Most of the synthesized compounds showed good to moderate activity (IC50 = 8.8-108.9 μM), where compound 16 (IC50 = 8.8 μM) exhibited higher activity compared to doxorubicin (IC50 = 9.8 μM). In order to determine the mechanism of the anticancer activity in T47D cells, the effect of the most potent compounds (5-8, 11-14, and 16-18) on the aromatase activity was tested...
October 13, 2016: European Journal of Medicinal Chemistry
Majid Zaki Dizaji, Seyed H Ghaffari, Elham Hosseini, Nasrin Alizadeh, Shahrbano Rostami, Majid Momeny, Kamran Alimoghaddam, Ardeshir Ghavamzadeh
AIM: Survivin, an inhibitor of apoptosis protein, is overexpressed in most cancers and is associated with chemotherapy resistance, increased tumor recurrence and shorter patient survival. Several survivin splice variants have been described, and none of their expressions have been defined in acute promyelocytic leukemia (APL). METHODS: Expression of the survivin gene isoforms (survivin, -2α, -2B, -ΔΕx3 and -3B) were analyzed in 50 peripheral blood and 19 bone marrow samples that were collected at different phases of the disease (diagnostic, remission and relapse) in APL patients treated with arsenic trioxide (ATO) as a front-line therapy...
October 22, 2016: Asia-Pacific Journal of Clinical Oncology
V Lakshma Nayak, Narayana Nagesh, A Ravikumar, Chandrakant Bagul, M V P S Vishnuvardhan, Vunnam Srinivasulu, Ahmed Kamal
Apoptosis is a representative form of programmed cell death, which has been assumed to be critical for cancer prevention. Thus, any agent that can induce apoptosis may be useful for cancer treatment and apoptosis induction is arguably the most potent defense against cancer promotion. In our previous studies, 2-aryl benzimidazole conjugates were synthesized and evaluated for their antiproliferative activity and one of the new molecule (2f) was considered as a potential lead. This lead molecule showed significant antiproliferative activity against human breast cancer cell line, MCF-7...
October 21, 2016: Apoptosis: An International Journal on Programmed Cell Death
Yoon Young Choi, Suji Kim, Jung-Hwa Han, Dae-Hwan Nam, Kwon Moo Park, Seong Yong Kim, Chang-Hoon Woo
Epidemiological studies suggested that diabetic patients are susceptible to develop cardiovascular complications along with having endothelial dysfunction. It has been suggested that methylglyoxal (MGO), a glycolytic metabolite, has more detrimental effects on endothelial dysfunction rather than glucose itself. Here, we investigated the molecular mechanism by which MGO induces endothelial dysfunction via the regulation of ER stress. Biochemical data showed that 4-PBA significantly inhibited MGO-induced protein cleavages of PARP-1 and caspase-3...
October 18, 2016: Biochemical and Biophysical Research Communications
Dongdong Chai, Hong Jiang, Qifang Li
OBJECTIVE: Previously, we found that the inhaled anesthetic isoflurane up-regulated the transcriptional factor hypoxia inducible factor (HIF)-1α protein levels during induction of neurodegeneration in the brain of neonatal rats. Here, we investigated the role of HIF-1α and the underlying signaling pathway in the neurodegenration induced by isoflurane in rodent developing brain. METHODS: Primary hippocampal neurons were exposed to isoflurane (0.4mM) for 12h. Neuron injury was analyzed by 3-(4,5-dimethyithiazol-2-yl)-2,5-diphenyl-tetra-zolium bromide (MTT) test and quantification of lactate dehydrogenaserelease...
October 18, 2016: Brain Research
Da-Shi Qi, Jin-Hao Tao, Lian-Qin Zhang, Mei Wang, Rui Qu, Lian-Qin Zhang, Pei Liu, Jian-Cheng Miu, Jing-Yi Ma, Xin-Yu Mei
Cilostazol(CTL) is a phosphodiesterase inhibitor, which has been widely used as anti-platelet agent. It also has preventive effects on various central nervous system (CNS) diseases, including ischemic stroke, Parkinson's disease and Alzheimer disease. However, the molecular mechanism underlying the protective effects of CTL is still unclear, and whether CTL can prevent I/R induced cognitive deficit has not been reported. Transient global brain ischemia was induced by 4-vessel occlusion in adult male Sprague-Dawley rats...
October 18, 2016: Brain Research
Yanyan Zheng, Li Zhu, Lulu Fan, Wenna Zhao, Jianlong Wang, Xianxiao Hao, Yunhui Zhu, Xiufang Hu, Yaofeng Yuan, Jingwei Shao, Wenfeng Wang
Emodin, a natural anthraquinone derivative isolated from Rheum palmatum L., has been demonstrated to exhibit good anti-cancer effect. In this study, a series of novel quaternary ammonium salts of emodin, anthraquinone and anthrone were synthesized and their anticancer activities were tested in vitro. The effects of emodin quaternary ammonium salts on cell viability, apoptosis, intracellular ROS, and mitochondrial membrane potential were investigated in A375, BGC-823, HepG2 and HELF cells. The results demonstrated that compound 4a induced morphological changes and decreased cell viability...
October 7, 2016: European Journal of Medicinal Chemistry
Jing Qiu, Min Wang, Jun Zhang, Qing Cai, Dan Lu, Yansong Li, Yushu Dong, Tianzhi Zhao, Huisheng Chen
Neuroinflammation remains the primary cause of morbidity and mortality in stroke-induced secondary brain injury. The NOD-like receptor pyrin 3 (NLRP3) inflammasome is involved in diverse inflammatory diseases, including cerebral ischemia, and is thus considered an effective therapeutic target. In the present study, we investigated the neuroprotection of Sinomenine (SINO), a potent natural anti-apoptotic and anti-inflammatory molecule, against cerebral ischemia in a mouse model of middle cerebral artery occlusion (MCAO) in vivo and in an oxygen glucose deprivation (OGD)-treated astrocytes/microglia model in vitro...
October 18, 2016: International Immunopharmacology
Ning Jia, Qinru Sun, Qian Su, Shaokang Dang, Guomin Chen
Substantial evidence has shown that the oxidative damage to hippocampal neurons is associated with the cognitive impairment induced by adverse stimuli during gestation named prenatal stress (PS). Taurine, a conditionally essential amino acid, possesses multiple roles in the brain as a neuromodulator or antioxidant. In this study, to explore the roles of taurine in PS-induced learning and memory impairment, prenatal restraint stress was set up and Morris water maze (MWM) was employed for testing the cognitive function in the one-month-old rat offspring...
October 13, 2016: Redox Biology
Sarah Fernandes Teixeira, Ricardo Alexandre de Azevedo, Arthur Carvalho Silva, Rodolpho Campos Braga, Salomão Dória Jorge, José Alexandre Marzagão Barbuto, Carolina Horta Andrade, Adilson Kleber Ferreira
Even with all improvements in both diagnostic and therapeutic techniques, lung cancer remains as the most lethal and prevalent cancer in the world. Therefore, new therapeutic drugs and new strategies of drug combination are necessary to provide treatments that are more efficient. Currently, standard therapy regimen for lung cancer includes platinum drugs, such as cisplatin, oxaliplatin, and carboplatin. Besides of the better toxicity profile of oxaliplatin when compared with cisplatin, peripheral neuropathy remains as a limitation of oxaliplatin dose...
October 18, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Sinéad Kinsella, Jochen H M Prehn
In this issue of Molecular Cell, Fu et al. (2016) present a detailed structural analysis of death-inducing signaling complex (DISC) assembly and regulation through flexible caspase-8 interactions with cFLIPL, cFLIPS, and the viral inhibitor MC159, thereby identifying novel apoptosis control mechanisms.
October 20, 2016: Molecular Cell
Yanna Si, Yuan Zhang, Liu Han, Lihai Chen, Yajie Xu, Fan Sun, Muhuo Ji, Jianjun Yang, Hongguang Bao
BACKGROUND: Previous studies showed that isoflurane-induced cognitive deficits could be alleviated by dexmedetomidine in young animal subjects. In the current study, we examine whether dexmedetomidine could also alleviate isoflurane-induced cognitive deficits in senile animals. METHODS: Senile male C57BL/6 mice (20 months) received dexmedetomidine (50 μg/kg, i.p.) or vehicle 30 minutes prior to isoflurane exposure (1.3% for 4 h). Cognitive function was assessed 19 days later using a 5-day testing regimen with Morris water maze...
2016: PloS One
Katharina Meier, Stefan K Drexler, Franziska C Eberle, Karine Lefort, Amir S Yazdi
Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is an important adaptor protein for inflammasome activation, mediating the secretion of protumorigenic innate cytokines. However, ASC is also known to trigger apoptosis in tumor cells, acting as a tumor-suppressor gene, which is lost in several human cancers. The aim of this study was to evaluate the clinical significance of ASC in human cutaneous squamous cell carcinoma (SCC). Initially, ASC expression was immunohistochemically evaluated in non-metastic and metastatic SCC...
2016: PloS One
Qian Lu, Jihong Wang, Junshu Jiang, Shengnan Wang, Qilan Jia, Yue Wang, Weiping Li, Qin Zhou, Li Lv, Qingwei Li
BACKGROUND: The RGD-toxin protein Lj-RGD3 is a naturally occurring 118 amino acid peptide that can be obtained from the salivary gland of the Lampetra japonica fish. This unique peptide contains 3 RGD (Arg-Gly-Asp) motifs in its primary structure. Lj-RGD3 is available in recombinant form (rLj-RGD3) and can be produced in large quantities using DNA recombination techniques. The pharmacology of the three RGD motif-containing peptides has not been studied. This study investigated the protective effects of rLj-RGD3, a novel polypeptide, against ischemia/reperfusion-induced damage to the brain caused by middle cerebral artery occlusion (MCAO) in a rat stroke model...
2016: PloS One
Boris Redko, Helena Tuchinsky, Tamar Segal, Dror Tobi, Galia Luboshits, Osnat Ashur-Fabian, Albert Pinhasov, Gabi Gerlitz, Gary Gellerman
The newly discovered short (9 amino acid) non-RGD S-S bridged cyclic peptide ALOS-4 (H-cycl(Cys-Ser-Ser-Ala-Gly-Ser-Leu-Phe-Cys)-OH), which binds to integrin αvβ3 is investigated as peptide carrier for targeted drug delivery against human metastatic melanoma. ALOS4 binds specifically the αvβ3 overexpressing human metastatic melanoma WM-266-4 cell line both in vitro and in ex vivo assays. Coupling ALOS4 to the topoisomerase I inhibitor Camptothecin (ALOS4-CPT) increases the cytotoxicity of CPT against human metastatic melanoma cells while reduces dramatically the cytotoxicity against non-cancerous cells as measured by the levels of γH2A...
October 19, 2016: Oncotarget
Hitesh Soni, Adebowale Adebiyi
Apoptosis of renal tubular and glomerular cells during kidney disease involves activation of Fas ligand (FasL)-dependent death pathway. The significance of FasL in neonates with septic acute kidney injury (AKI) is unresolved, but an increase in renal FasL production, and/or infiltration of circulating FasL into the kidneys may occur following initial septic insult. Here, we examined whether soluble Fas ligand (sFasL) levels are altered during early phase of septic AKI in neonates. Six hours of polymicrobial sepsis elicited by cecal ligation and puncture (CLP) elevated serum C-reactive protein (CRP) (a bacteremia and sepsis marker) concentration in anesthetized and mechanically ventilated neonatal pigs...
October 21, 2016: Renal Failure
Ramón Martínez-Mármol, Bruna Barneda-Zahonero, David Soto, Rosa Maria Andrés, Elena Coccia, Xavier Gasull, Laura Planells-Ferrer, Rana S Moubarak, Eduardo Soriano, Joan X Comella
Caspases have recently emerged as key regulators of axonal pruning and degeneration and of long-term depression (LTD), a long-lasting form of synaptic plasticity. However, the mechanism underlying these functions remains unclear. In this context, XIAP has been shown to modulate these processes. The neuron-specific form of FAIM protein (FAIM-L) is a death receptor antagonist that stabilizes XIAP protein levels, thus preventing death receptor-induced neuronal apoptosis. Here we show that FAIM-L modulates synaptic transmission, prevents chemical-LTD induction in hippocampal neurons, and thwarts axon degeneration after nerve growth factor (NGF) withdrawal...
October 21, 2016: Scientific Reports
Yun-Wen Yang, Chun-Mei Zhang, Xian-Jie Huang, Xiao-Xin Zhang, Lin-Kai Zhang, Jia-Huang Li, Zi-Chun Hua
Fas-associated protein with death domain (FADD), a pivotal adaptor protein transmitting apoptotic signals, is indispensable for the induction of extrinsic apoptosis. However, overexpression of FADD can form large, filamentous aggregates, termed death effector filaments (DEFs) by self-association and initiate apoptosis independent of receptor cross-linking. A mutant of FADD, which is truncated of the C-terminal tail (m-FADD, 182-205 aa) named N-FADD (m-FADD, 1-181 aa), can dramatically up-regulate the strength of FADD self-association and increase apoptosis...
October 21, 2016: Scientific Reports
Jinxin Xie, Huancheng Guo, Wenjie Gong, Daliang Jiang, Li Zhang, Junjie Jia, Changchun Tu
NS5A is a multifunctional non-structural protein of classical swine fever virus (CSFV) that plays an important role in viral replication, but how it exerts its functions is unknown. Here, we report the cleavage of NS5A of the vaccine C-strain, resulting in two truncated forms (b and c). Further experiments using calpain- and caspase-family-specific inhibitors, followed by a caspase-6-specific shRNAs and inhibitor, showed that the cleavage of C-strain NS5A to produce truncated form c is mediated by caspase-6, mapping to (272)DTTD(275), while the cleavage producing truncated form b is probably mediated by another unknown protease...
October 20, 2016: Archives of Virology
Na Han, You Jeong Kim, Su Min Park, Seung Man Kim, Ji Suk Lee, Hye Sook Jung, Eun Ju Lee, Tae Kyoon Kim, Tae Nyun Kim, Min Jeong Kwon, Soon Hee Lee, Mi-Kyung Kim, Byoung Doo Rhee, Jeong Hyun Park
BACKGROUND: Cognitive impairment and brain damage in diabetes is suggested to be associated with hypoglycemia. The mechanisms of hypoglycemia-induced neural death and apoptosis are not clear and reperfusion injury may be involved. Recent studies show that glucose deprivation/reperfusion induced more neuronal cell death than glucose deprivation itself. The forkhead box O (FOXO) transcription factors are implicated in the regulation of cell apoptosis and survival, but their role in neuronal cells remains unclear...
October 2016: Diabetes & Metabolism Journal
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