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https://www.readbyqxmd.com/read/28829799/novel-histone-deacetylase-inhibitor-ar-42-exhibits-antitumor-activity-in-pancreatic-cancer-cells-by-affecting-multiple-biochemical-pathways
#1
Yi-Jin Chen, Wen-Hung Wang, Wan-Yu Wu, Chia-Chi Hsu, Ling-Rung Wei, Sheng-Fan Wang, Ya-Wen Hsu, Chih-Chuang Liaw, Wan-Chi Tsai
OBJECTIVE: Pancreatic cancer is one of the most lethal types of cancer with a 5-year survival rate of ~5%. Histone deacetylases (HDACs) participate in many cellular processes, including carcinogenesis, and pharmacological inhibition of HDACs has emerged as a potential therapeutic strategy. In this study, we explored antitumor activity of the novel HDAC inhibitor AR-42 in pancreatic cancer. METHODS: Human pancreatic cancer cell lines BxPC-3 and PANC-1 were used in this study...
2017: PloS One
https://www.readbyqxmd.com/read/28828727/concurrent-assessment-of-calpain-and-caspase3-activities-in-brains-of-mice-with-acetaminophen-induced-acute-hepatic-encephalopathy
#2
Bahareh Shabrang, Akram Jamshidzadeh, Mojtaba Farjam, Azin Ebrahimpour, Omid Koohi-Hosseinabadi
To develop pharmacological therapy for acute hepatic encephalopathy (AHE), understanding the molecular basis for cell injury is essential. Excitotoxic neural cell injury mediated by calpain as a post- receptor mechanism has been proposed as a player in neuronal injury in AHE. Concurrent assessment of Calpain and Caspase3 activities in the brain of AHE mice in acetaminophen- induced mourine model was performed. After induction of AHE by acetaminophen in mice, the model was confirmed by histopathological, biochemical and behavioural studies...
August 21, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28828705/glucotoxicity-promotes-aberrant-activation-and-mislocalization-of-ras-related-c3-botulinum-toxin-substrate-1-rac1-and-metabolic-dysfunction-in-pancreatic-islet-%C3%AE-cells-reversal-of-such-metabolic-defects-by-metformin
#3
Sartaj Baidwan, Anil Chekuri, DiAnna L Hynds, Anjaneyulu Kowluru
Emerging evidence suggests that long-term exposure of insulin-secreting pancreatic β-cells to hyperglycemic (HG; glucotoxic) conditions promotes oxidative stress, which, in turn, leads to stress kinase activation, mitochondrial dysfunction, loss of nuclear structure and integrity and cell apoptosis. Original observations from our laboratory have proposed that Rac1 plays a key regulatory role in the generation of oxidative stress and downstream signaling events culminating in the onset of dysfunction of pancreatic β-cells under the duress of metabolic stress...
August 21, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28828001/structure-activity-relationships-and-molecular-docking-studies-of-chromene-and-chromene-based-azo-chromophores-a-novel-series-of-potent-antimicrobial-and-anticancer-agents
#4
Tarek H Afifi, Rawda M Okasha, Hany E A Ahmed, Janez Ilaš, Tarek Saleh, Alaa S Abd-El-Aziz
The design of novel materials with significant biological properties is a main target in drug design research. Chromene compounds represent an interesting medicinal scaffold in drug replacement systems. This report illustrates a successful synthesis and characterization of two novel series of chromene compounds using multi-component reactions. The synthesis of the first example of azo chromophores containing chromene moieties has also been established using the same methodology. The antimicrobial activity of the new molecules has been tested against seven human pathogens including two Gm+ve, two Gm-ve bacteria, and four fungi, and the results of the inhibition zones with minimum inhibitory concentrations were reported as compared to reference drugs...
2017: EXCLI journal
https://www.readbyqxmd.com/read/28827961/uncaria-tomentosa-willd-ex-schult-dc-rubiaceae-sensitizes-thp-1-cells-to-radiation-induced-cell-death
#5
Lisa Allen, Alison Buckner, Carly A Buckner, Pablo Cano, Robert M Lafrenie
BACKGROUND: Uncaria tomentosa (Willd. ex Schult.) DC (Rubiaceae), known as Cat's Claw or Uña de gato, is a traditionally used medicinal plant native to Peru. Some studies have shown that U. tomentosa can act as an antiapoptotic agent and enhance DNA repair in chemotherapy-treated cells although others have shown that U. tomentosa enhanced apoptosis. OBJECTIVE: To determine if treatment with U. tomentosa can significantly enhance cell death in THP-1 cells exposed to ionizing radiation...
July 2017: Pharmacognosy Research
https://www.readbyqxmd.com/read/28827819/the-effects-of-dexamethasone-administered-during-pregnancy-on-the-postpartum-spiny-mouse-ovary
#6
Monika Hułas-Stasiak, Piotr Dobrowolski, Bożena Pawlikowska-Pawlęga, Ewa Tomaszewska, Siemowit Muszyński
Excessive exposure to glucocorticoids can alter ovarian function by modulating oogenesis, folliculogenesis and steroidogenesis. The aim of the present study was to examine the effects of dexamethasone (DEX) administered during pregnancy on folliculogenesis and corpus luteum development in the postpartum spiny mouse ovary. DEX (125 μg kg-1 body weight per day) was applied to pregnant spiny mouse from day 20 of gestation to parturition. The obtained ovaries were fixed and used for immunohistochemistry and TEM analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28827731/microrna-7641-is-a-regulator-of-ribosomal-proteins-and-a-promising-targeting-factor-to-improve-the-efficacy-of-cancer-therapy
#7
Abu Musa Md Talimur Reza, Yun-Jung Choi, Yu-Guo Yuan, Joydeep Das, Hideyo Yasuda, Jin-Hoi Kim
Many diseases, including myocardial infarction, autoimmune disease, viral diseases, neurodegenerative diseases, and cancers, are frequently diagnosed with aberrant expression of microRNAs (miRNAs) and their allied pathways. This indicates the crucial role of miRNAs in maintaining biological and physiological processes. miR-7641 is a miRNA whose role in disease has not been fully investigated. In the present study, we investigated the expression pattern of miR-7641 and its target genes in different cancer cells, as well as in clinical cancer patients...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28827077/high-potential-defense-mechanisms-of-neocortex-in-a-rat-model-of-transient-asphyxia-induced-cardiac-arrest
#8
Gerburg Keilhoff, Torben Esser, Maximilian Titze, Uwe Ebmeyer, Lorenz Schild
Cardiac arrest (CA) is a common cause of disability and mortality and thus an important risk for human health. Circulatory failure has dramatic consequences for the brain as one of the most oxygen-consuming organs. Hippocampus, striatum and neocortex rate among the most vulnerable brain regions. The neocortex is less sensitive to hypoxia/reperfusion in comparison with the hippocampal CA1 region. That implicates the existence of efficient defense mechanisms in the neocortex against hypoxia/reperfusion injury, which we analyzed in a well-established CA rat model...
August 18, 2017: Brain Research
https://www.readbyqxmd.com/read/28827028/the-s1p1-receptor-selective-agonist-cym-5442-protects-retinal-ganglion-cells-in-endothelin-1-induced-retinal-ganglion-cell-loss
#9
Román Blanco, Gema Martínez-Navarrete, Francisco J Valiente-Soriano, Marcelino Avilés-Trigueros, Consuelo Pérez-Rico, Ana Serrano-Puebla, Patricia Boya, Eduardo Fernández, Manuel Vidal-Sanz, Pedro de la Villa
We investigated the feasibility and efficacy of using a specific sphingosine 1-phosphate (S1P1) receptor agonist, CYM-5442, to slow or block retinal ganglion cell (RGC) loss in endothelin-1 (ET-1) induced RGC loss. A single intravitreal injection of ET-1 (20pmol/ul), a potent vasoactive peptide that produces retinal vessels vasoconstriction, was used to induce and characterize RGC-specific cell death. CYM-5442 (1 mgr/kg) or vehicle was administered intraperitoneally for five consecutive days after ET-1-induced RGC loss...
August 4, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28826530/a-mechanistic-understanding-of-pyroptosis-the-fiery-death-triggered-by-invasive-infection
#10
Xing Liu, Judy Lieberman
Immune cells and skin and mucosal epithelial cells recognize invasive microbes and other signs of danger to sound alarms that recruit responder cells and initiate an immediate "innate" immune response. An especially powerful alarm is triggered by cytosolic sensors of invasive infection that assemble into multimolecular complexes, called inflammasomes, that activate the inflammatory caspases, leading to maturation and secretion of proinflammatory cytokines and pyroptosis, an inflammatory death of the infected cell...
2017: Advances in Immunology
https://www.readbyqxmd.com/read/28826527/chromosome-17q21-genes-ormdl3-and-gsdmb-in-asthma-and-immune-diseases
#11
Sudipta Das, Marina Miller, David H Broide
Chromosome 17q21 contains a cluster of genes including ORMDL3 and GSDMB, which have been highly linked to asthma in genome-wide association studies. ORMDL3 is localized to the endoplasmic reticulum and regulates downstream pathways including sphingolipids, metalloproteases, remodeling genes, and chemokines. ORMDL3 inhibits serine palmitoyl-CoA transferase, the rate-limiting enzyme for sphingolipid biosynthesis. In addition, ORMDL3 activates the ATF6α branch of the unfolded protein response which regulates SERCA2b and IL-6, pathways of potential importance to asthma...
2017: Advances in Immunology
https://www.readbyqxmd.com/read/28826366/regeneration-of-the-fallopian-tube-mucosa-using-bone-marrow-mesenchymal-stem-cell-transplantation-after-induced-chemical-injury-in-a-rat-model
#12
Shaima M Almasry, Amr K Elfayomy, Mohamed H El-Sherbiny
In this study, we describe a novel insight about the use of bone marrow-derived mesenchymal stem cells (BM-MSCs) for fallopian tube (FT) regeneration. Seventy rats' tubes were involved in this study and divided into 4 groups: control (15), ethanol injured (20), mesenchymal stem cell (MSC)-recipient without injury (15), and MSC recipient after injury (20). The BM-MSCs were isolated from male rats, and their incorporation into the tissues was confirmed by the detection of Sry gene in MSC-recipient rats using RT-PCR...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28822990/%C3%AE-%C3%AE-mangostins-induces-autophagy-and-shows-synergistic-effectwith-gemcitabine-in-pancreatic-cancer-cell-lines
#13
Myoungjae Kim, Young-Won Chin, Eun Joo Lee
Pancreatic cancer is one of the most lethal and aggressive cancers in the world. However, no effective treatment is currently available for pancreatic cancer. The objective of this study was to determine the anti-pancreatic cancer effect of α-mangostin (αM) and γ-mangostin (γM) extracted from the pericarp of Garcinia mangostana L.. Both αM and γM reduced the viability of pancreatic cancer cells MIA PaCa-2 and PANC-1 in a dose-dependent manner. These compounds induced apoptosis by increasing c-PARP and c-Caspase 3 levels...
August 21, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28822989/cellular-prion-protein-enhances-drug-resistance-of-colorectal-cancer-cells-via-regulation-of-a-survival-signal-pathway
#14
Jun Hee Lee, Chul Won Yun, Sang Hun Lee
Anti-cancer drug resistance is a major problem in colorectal cancer (CRC) research. Although several studies have revealed the mechanism of cancer drug resistance, molecular targets for chemotherapeutic combinations remain elusive. To address this issue, we focused on the expression of cellular prion protein (PrP(C)) in 5-FU-resistant CRC cells. In 5-FU-resistant CRC cells, PrP(C) expression is significantly increased, compared with that in normal CRC cells. In the presence of 5-FU, PrP(C) increased CRC cell survival and proliferation by maintaining the activation of the PI3K-Akt signaling pathway and the expression of cell cycle-associated proteins, including cyclin E, CDK2, cyclin D1, and CDK4...
August 21, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28822855/tetrandrine-cardioprotection-in-ischemia-reperfusion-i-r-injury-via-jak3-stat3-hexokinase-ii
#15
Tie-Jun Zhang, Rui-Xia Guo, Xia Li, Yan-Wei Wang, Yong-Jun Li
Tetrandrine(TET), a bisbenzylisoquinoline alkaloid has been used for the treatment of cardiovascular diseases and hypertension. This study was to investigate whether tetrandrine exerts cardioprotection in ischemia-reperfusion (I/R) injury and the mechanisms involved. The cardioprotection effect and mechanisms of tetrandrine was evaluated by I/R injury cardiac cell model. Hexokinase II (HKII) is the critical regulators of mitochondrial dysfunction in cardiac I/R injury and it participate in the regulation of glycolysis and energy metabolism...
August 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28822757/quercetin-exerts-synergetic-anti-cancer-activity-with-10-hydroxy-camptothecin
#16
Qin Tang, Fangling Ji, Jingyun Wang, Lianying Guo, Yachen Li, Yongming Bao
Quercetin (Qu) is known as a dietary antioxidant with numerous bioactivities, but its function in anti-cancer has not been fully investigated. Here, we show that Qu at low doses (≤10μM) significantly enhances the inhibition of 10-hydroxy camptothecin (HCPT) on the proliferation of MCF7, BGC823 and HepG2 cells. A plasmid DNA relaxation assay indicates that the inhibition of HCPT on the catalytic activity of topoisomerase I (Topo I) is increased by Qu at 10μM. Compared to the treatment by Qu or HCPT alone, phosphorylation at Ser(139) of γH2A...
August 16, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28822194/-effect-of-oridonin-on-apoptosis-and-intracellular-reactive-oxygen-species-level-in-triple-negative-breast-cancer-mda-mb-231-cells
#17
Qi Qi, Pei Zhang, Qi-Xiang Li, Qiong Pan, Hai-Lun Zheng, Su-Rong Zhao
Oridonin, which is an ent-kaurene diterpenoid isolated from traditional Chinese medicine Rabdosia rubescens, displays various bioactivities, including anti-inflammation, anti-bacteria and anti-tumor. This study aimed to investigate the effect of oridonin on apoptosis of triple-negative breast cancer MDA-MB-231 cells and its underlying mechanisms. The inhibitory effect of oridonin on proliferation of MDA-MB-231 cells was measured by MTT assay; Apoptosis was analyzed by flow cytometry with PI staining and Annexin V-FITC/PI staining; Intracellular reactive oxygen species (ROS) level was determined by ROS detection kit, and expressions of PARP, Bcl-2, caspase-3 were analyzed by Western blot...
June 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28822080/soluble-epoxide-hydrolase-inhibition-attenuates-mptp-induced-neurotoxicity-in-the-nigrostriatal-dopaminergic-system-involvement-of-%C3%AE-synuclein-aggregation-and-er-stress
#18
Hui-Ju Huang, Yi-Ting Wang, Hui-Ching Lin, Yi-Hsuan Lee, Anya Maan-Yuh Lin
Soluble epoxide hydrolase (sEH) is widely expressed in the mammalian brain and possesses dual enzymatic activities, including C-terminal epoxide hydrolase (C-EH) which degrades epoxyeicosatrienoic acid (EET), a beneficial arachidonic acid metabolite. In the present study, the neuroprotective effect of sEH inhibition on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurodegeneration of nigrostriatal dopaminergic system was investigated using genetic and pharmacological approaches. MPTP (15 mg/kg) was intraperitoneally injected in sEH knockout (KO) mice and C57BL/6J mice as wild-type (WT) mice...
August 18, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28822073/isorhynchophylline-attenuates-mpp-induced-apoptosis-through-endoplasmic-reticulum-stress-and-mitochondria-dependent-pathways-in-pc12-cells-involvement-of-antioxidant-activity
#19
Xiao-Ming Li, Xiao-Jie Zhang, Miao-Xian Dong
Endoplasmic reticulum stress (ERS) and mitochondrial dysfunctions are thought to be involved in the dopaminergic neuronal death in Parkinson's disease (PD). In this study, we found that isorhynchophylline (IRN) significantly attenuated 1-methyl-4-phenylpyridinium (MPP(+))-induced apoptotic cell death and oxidative stress in PC12 cells. IRN markedly reduced MPP(+)-induced-ERS responses, indicative of inositol-requiring enzyme 1 (IRE1) phosphorylation and caspase-12 activation. Furthermore, IRN inhibits MPP(+)-triggered apoptosis signal-regulating kinase 1 (ASK1)/c-Jun N-terminal Kinase (JNK) signaling-mediated mitochondria-dependent apoptosis pathway...
August 18, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28821999/developmental-neurotoxicity-of-the-hippocampus-following-in-utero-exposure-to-methylmercury-impairment-in-cell-signaling
#20
Luana Heimfarth, Jeferson Delgado, Moara Rodrigues Mignori, Daniel Pens Gelain, José Cláudio Fonseca Moreira, Regina Pessoa-Pureur
In this study, we assessed some hippocampal signaling cascades and behavioral impairments in 30-day-old rat pups prenatally exposed to methylmercury (MeHg). Pregnant rats were exposed to 1.0 or 2.0 mg/kg MeHg by gavage in alternated days from gestational day 5 until parturition. We found increased anxiety-like and decreased exploration behavior evaluated by open field test and deficit of both short- and long-term memories by novel object recognition task, respectively, in MeHg-treated pups. Downregulated PI3K/Akt/mTOR pathway and activated/hypophosphorylated (Ser9) GSK3β in MeHg-treated pups could be upstream of hyperphosphorylated Tau (Ser396) destabilizing microtubules and contributing to neural dysfunction in the hippocampus of these rats...
August 18, 2017: Archives of Toxicology
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