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https://www.readbyqxmd.com/read/28445132/targeting-autophagic-cancer-stem-cells-to-reverse-chemoresistance-in-human-triple-negative-breast-cancer
#1
Guilhem Bousquet, Morad El Bouchtaoui, Tan Sophie, Christophe Leboeuf, Cédric de Bazelaire, Philippe Ratajczak, Sylvie Giacchetti, Anne de Roquancourt, Philippe Bertheau, Laurence Verneuil, Jean-Paul Feugeas, Marc Espié, Anne Janin
There is growing evidence for the role of cancer stem-cells in drug resistance, but with few in situ studies on human tumor samples to decipher the mechanisms by which they resist anticancer agents.Triple negative breast cancer (TNBC) is the most severe sub-type of breast cancer, occurring in younger women and associated with poor prognosis even when treated at a localized stage.We investigated here the relationship between complete pathological response after chemotherapy and breast cancer stem-cell characteristics in pre-treatment biopsies of 78 women with triple negative breast carcinoma (TNBC)...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28443679/emerging-roles-of-carbonyl-sulfide-cos-in-chemical-biology-sulfide-transporter-or-gasotransmitter
#2
Andrea K Steiger, Yu Zhao, Michael D Pluth
SIGNIFICANCE: Carbonyl sulfide (COS) is the most prevalent sulfur-containing gas in Earth's atmosphere and plays important roles in the global sulfur cycle. COS has been implicated in origin of life peptide ligation, is the primary energy source for certain bacteria, and has been detected in mammalian systems. Despite this long and intertwined history with terrestrial biology, limited attention has focused on potential roles of COS as a biological mediator. Recent Advances. Although bacterial COS production is well documented, definitive sources of mammalian COS production have not been confirmed...
April 26, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28441491/a-naturally-occurring-isoform-specific-probe-for-highly-selective-and-sensitive-detection-of-human-cytochrome-p450-3a5
#3
Jing-Jing Wu, Yun-Feng Cao, Liang Feng, Yu-Qi He, James Y Hong, Tong-Yi Dou, Ping Wang, Da-Cheng Hao, Guang-Bo Ge, Ling Yang
Cytochrome P450 (CYP) 3A5 characterized with polymorphic and extensive expression in multiple tissues is the most important P450 enzyme among the minor CYP3A isoforms. However, a selective and sensitive probe for CYP3A5 remains unavailable. In this study, we identified and characterized a naturally-occurring lignan 12 (Schisantherin E) as an isoform-specific probe for selective detection of CYP3A5 activity in complex biological samples. With thorough characterization including LC-MS and NMR, we found that 12 can be metabolized by CYP3A5 to generate a major metabolite 2-O-demethylated 12...
April 25, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28429225/design-of-chemical-conjugate-for-targeted-therapy-of-multiple-sclerosis-based-of-constant-fragment-of-human-antibody-heavy-chain-and-peptoid-analog-of-autoantigen-mog35-55
#4
Y A Lomakin, A V Stepanov, D S Balabashin, N A Ponomarenko, I V Smirnov, A A Belogurov
Elimination of B cells producing autoantibodies to neuroantigens is considered as beneficial in the treatment of multiple sclerosis. Myelin oligodendrocyte glycoprotein (MOG) is a significant autoantigen in multiple sclerosis. It was shown that MOG-like peptoid AMogP3 can bind autoantibodies produced by pathological lymphocytes. We propose a structure of an innovative drug for targeted elimination of the pool of autoreactive B cells responsible for multiple sclerosis pathogenesis; this compound is a complex of peptoid AMogP3 with Fc fragment of human immunoglobulin...
April 21, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28428217/microrna-33-regulates-macrophage-autophagy-in-atherosclerosis
#5
Mireille Ouimet, Hasini Ediriweera, Milessa Silva Afonso, Bhama Ramkhelawon, Ragunath Singaravelu, Xianghai Liao, Rachel C Bandler, Karishma Rahman, Edward A Fisher, Katey J Rayner, John P Pezacki, Ira Tabas, Kathryn J Moore
OBJECTIVE: Defective autophagy in macrophages leads to pathological processes that contribute to atherosclerosis, including impaired cholesterol metabolism and defective efferocytosis. Autophagy promotes the degradation of cytoplasmic components in lysosomes and plays a key role in the catabolism of stored lipids to maintain cellular homeostasis. microRNA-33 (miR-33) is a post-transcriptional regulator of genes involved in cholesterol homeostasis, yet the complete mechanisms by which miR-33 controls lipid metabolism are unknown...
April 20, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28427557/oxidative-stress-love-and-hate-history-in-central-nervous-system
#6
Genaro Gabriel Ortiz, Fermín P Pacheco Moisés, Mario Mireles-Ramírez, Luis J Flores-Alvarado, Héctor González-Usigli, Víctor J Sánchez-González, Angélica L Sánchez-López, Lorenzo Sánchez-Romero, Eduardo I Díaz-Barba, J Francisco Santoscoy-Gutiérrez, Paloma Rivero-Moragrega
Molecular oxygen is essential for aerobic organisms in order to synthesize large amounts of energy during the process of oxidative phosphorylation and it is harnessed in the form of adenosine triphosphate, the chemical energy of the cell. Oxygen is toxic for anaerobic organisms but it is also less obvious that oxygen is poisonous to aerobic organisms at higher concentrations of oxygen. For instance, oxygen toxicity is a condition resulting from the harmful effects of breathing molecular oxygen at increased partial pressures...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28426875/bisphenol-a-activates-egfr-and-erk-promoting-proliferation-tumor-spheroid-formation-and-resistance-to-egfr-pathway-inhibition-in-estrogen-receptor-negative-inflammatory-breast-cancer-cells
#7
Scott J Sauer, Michael Tarpley, Imran Shah, Akshay V Save, H Kim Lyerly, Steven R Patierno, Kevin P Williams, Gayathri R Devi
Emerging evidence from epidemiological studies suggests a link between environmental chemical exposure and progression of aggressive breast cancer subtypes. Of all clinically distinct types of breast cancers, the most lethal phenotypic variant is inflammatory breast cancer (IBC). Overexpression of epidermal growth factor receptors (EGFR/HER2) along with estrogen receptor (ER) negativity is common in IBC tumor cells, which instead of a solid mass present as rapidly proliferating diffuse tumor cell clusters. Our previous studies have demonstrated a role of an adaptive response of increased antioxidants in acquired resistance to EGFR-targeting drugs in IBC...
March 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28426781/tauroursodeoxycholic-acid-tudca-attenuates-pressure-overload-induced-cardiac-remodeling-by-reducing-endoplasmic-reticulum-stress
#8
Shilpa Rani, Pradeep Kumar Sreenivasaiah, Jin Ock Kim, Mi Young Lee, Wan Seok Kang, Yong Sook Kim, Youngkeun Ahn, Woo Jin Park, Chunghee Cho, Do Han Kim
Pressure overload in the heart induces pathological hypertrophy and is associated with cardiac dysfunction. Apoptosis and fibrosis signaling initiated by the endoplasmic reticulum stress (ERS) is known to contribute to these maladaptive effects. The aim of this study was to investigate whether reduction of ERS by a known chemical chaperone, tauroursodeoxycholic acid (TUDCA) can attenuate pressure overload-induced cardiac remodeling in a mouse model of transverse aortic constriction (TAC). Oral administration of TUDCA at a dose of 300 mg/kg body weight (BW) in the TUDCA-TAC group reduced ERS markers (GRP78, p-PERK, and p-eIf2α), compared to the Vehicle (Veh)-TAC group...
2017: PloS One
https://www.readbyqxmd.com/read/28422543/newer-insights-into-the-antidiarrheal-effects-of-acacia-catechu-willd-extract-in-guinea-pig
#9
Matteo Micucci, Roberto Gotti, Ivan Corazza, Gabriella Tocci, Alberto Chiarini, Marta De Giorgio, Luca Camarda, Maria Frosini, Carla Marzetti, Monica Cevenini, Roberta Budriesi
Acacia catechu Willd. is a plant diffused in India and other Asian countries, where it is used as a traditional medicine for the treatment of several ailments including diarrhea, one of the most common pathologies worldwide. In this study, we determined the chemical composition of Acacia catechu Willd. extract (AC) and evaluated its effect on spontaneous and induced contractility in isolated guinea pig ileum and proximal colon. Preliminary data about its antimicrobial effect against some pathogen agents versus some microbiota intestinal strain have been also reported...
April 19, 2017: Journal of Medicinal Food
https://www.readbyqxmd.com/read/28415050/free-radicals-and-polyphenols-the-redox-chemistry-of-neurodegenerative-diseases
#10
REVIEW
Sonia Losada-Barreiro, Carlos Bravo-Díaz
The oxidation of bioorganic materials by air and, particularly, the oxidative stress involved in the cell loss and other pathologies associated with neurodegenerative diseases (NDs) are of enormous social and economic importance. NDs generally involve free radical reactions, beginning with the formation of an initiating radical by some redox, thermal or photochemical process, causing nucleic acid, protein and lipid oxidations and the production of harmful oxidative products. Physically, persons afflicted by NDs suffer progressive loss of memory and thinking ability, mood swings, personality changes, and loss of independence...
March 29, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28413962/neurochemical-markers-in-the-mammalian-brain-structure-roles-in-synaptic-communication-and-pharmacological-relevance
#11
Christopher L Rees, Charise M White, Giorgio A Ascoli
BACKGROUND: Knowledge of molecular marker (typically protein or mRNA) expression in neural systems can provide insight to the chemical blueprint of signal processing and transmission, assist in tracking developmental or pathological progressions, and yield key information regarding potential medicinal targets. These markers are particularly relevant in the mammalian brain in light of its unsurpassed cellular diversity. Accordingly, molecular expression profiling is rapidly becoming a major approach to classify neuron types...
April 14, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28413899/changes-in-the-oxidative-stress-anti-oxidant-system-after-exposure-to-sulfur-mustard-and-antioxidant-strategies-in-the-therapy-a-review
#12
Miroslav Pohanka, Pavla Martinkova, Martin Brtnicky, Jindrich Kynicky
Sulfur mustard, in a chemical name bis(2-chloroethyl) sulfide, is a chemical warfare agent. It is cytotoxic and blister forming once spread over the skin. Though exact molecular mechanism of sulfur mustard toxic action remains unknown, inflammation and oxidative stress development are considered as the most relevant pathological consequences. Applications of either low molecular weight antioxidants or cofactors for enzymatic antioxidants are considered as suitable ways how to ameliorate the poisoning. In the presented paper, survey of literature on countermeasures against sulfur mustard poisoning are given and evidence of oxidative stress role during sulfur mustard poisoning and availability of antioxidants for the therapy are discussed...
April 16, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28408356/possible-antifibrotic-effect-of-gdc-0449-vismodegib-a-hedgehog-pathway-inhibitor-in-mice-model-of-schistosoma-induced-liver-fibrosis
#13
Abeer A Elhenawy, Rehab H Ashour, Nairmen Nabih, Naglaa M Shalaby, Nirmeen Megahed
Liver fibrosis is a pathological process complicating schistosomiasis. It is an active process of continuous extracellular matrix accumulation. In Egypt, schistosomiasis re-infection is a continuing problem especially in rural areas. In this study we examined the antifibrotic effect of GDC-0449 (Vismodegib), a hedgehog-pathway inhibitor as a new molecular target for Schistosoma-induced liver fibrosis, in addition to exploring its effect as antischistosomal drug. The effect of GDC-0449 alone or combined with Praziquantel was tried experimentally in infected mice with Schistosoma mansoni...
April 10, 2017: Parasitology International
https://www.readbyqxmd.com/read/28405790/csh-guidelines-for-the-diagnosis-and-treatment-of-drug-induced-liver-injury
#14
EDITORIAL
Yue-Cheng Yu, Yi-Min Mao, Cheng-Wei Chen, Jin-Jun Chen, Jun Chen, Wen-Ming Cong, Yang Ding, Zhong-Ping Duan, Qing-Chun Fu, Xiao-Yan Guo, Peng Hu, Xi-Qi Hu, Ji-Dong Jia, Rong-Tao Lai, Dong-Liang Li, Ying-Xia Liu, Lun-Gen Lu, Shi-Wu Ma, Xiong Ma, Yue-Min Nan, Hong Ren, Tao Shen, Hao Wang, Ji-Yao Wang, Tai-Ling Wang, Xiao-Jin Wang, Lai Wei, Qing Xie, Wen Xie, Chang-Qing Yang, Dong-Liang Yang, Yan-Yan Yu, Min-de Zeng, Li Zhang, Xin-Yan Zhao, Hui Zhuang
Drug-induced liver injury (DILI) is an important clinical problem, which has received more attention in recent decades. It can be induced by small chemical molecules, biological agents, traditional Chinese medicines (TCM), natural medicines (NM), health products (HP), and dietary supplements (DS). Idiosyncratic DILI is far more common than intrinsic DILI clinically and can be classified into hepatocellular injury, cholestatic injury, hepatocellular-cholestatic mixed injury, and vascular injury based on the types of injured target cells...
April 12, 2017: Hepatology International
https://www.readbyqxmd.com/read/28404519/proteasome-inhibitors-to-alleviate-aberrant-ikbkap-mrna-splicing-and-low-ikap-help1-synthesis-in-familial-dysautonomia
#15
Mylène Hervé, El Chérif Ibrahim
FD is a rare neurodegenerative disorder caused by a mutation of the IKBKAP gene, which induces low expression levels of the Elongator subunit IKAP/hELP1 protein. A rational strategy for FD treatment could be to identify drugs increasing IKAP/hELP1 expression levels by blocking protein degradation pathways such as the 26S proteasome. Proteasome inhibitors are promising molecules emerging in cancer treatment and could thus constitute an enticing pharmaceutical strategy for FD treatment. Therefore, we tested three proteasome inhibitors on FD human olfactory ecto-mesenchymal stem cells (hOE-MSCs): two approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA), bortezomib and carfilzomib, as well as epoxomicin...
April 9, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28401379/kidney-lung-pathophysiological-crosstalk-its-characteristics-and-importance
#16
REVIEW
Pilar Domenech, Tomas Perez, Agustina Saldarini, Pedro Uad, Carlos G Musso
Crosstalk between the lung and the kidney is based on the similarities that these organs share. This is why different diseases that affect one organ can have repercussions on the other. Patients with acute kidney injury can present complications such as pulmonary edema and require mechanical ventilation in respiratory failure. This interaction occurs due to the increase in systemic immune mediators that cause inflammatory reactions, oxidative stress, and an increase in vascular permeability in the lung. With regard to lung-induced renal damage, the kidney can also be affected by chemical mediators, which are translocated into the bloodstream...
April 11, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28398592/tributyltin-alters-the-bone-marrow-microenvironment-and-suppresses-b-cell-development
#17
Amelia H Baker, Ting Hua Wu, Alicia M Bolt, Louis C Gerstenfeld, Koren K Mann, Jennifer J Schlezinger
Organotins are industrial chemicals and agricultural pesticides, and they contaminate both outdoor and indoor environments. Organotins are detectable in human sera at biologically active concentrations and are immuno-and neuro-toxicants. Triphenyltin, tributyltin (TBT) and dibutyltin activate peroxisome proliferator-activated receptor γ (PPARγ) in bone marrow multipotent mesenchymal stromal cells (BM-MSC) and promote adipogenesis. TBT also has been shown to suppress osteogenesis; osteoblasts not only support bone homeostasis but also support B lymphopoiesis...
April 7, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28397086/structure-activity-relationship-of-piperine-and-its-synthetic-amide-analogs-for-therapeutic-potential-to-prevent-experimentally-induced-er-stress-in-vitro
#18
Ayat S Hammad, Sreenithya Ravindran, Ashraf Khalil, Shankar Munusamy
Endoplasmic reticulum (ER) is the key organelle involved in protein folding and maturation. Emerging studies implicate the role of ER stress in the development of chronic kidney disease. Thus, there is an urgent need for compounds that could ameliorate ER stress and prevent CKD. Piperine and its analogs have been reported to exhibit multiple pharmacological activities; however, their efficacy against ER stress in kidney cells has not been studied yet. Hence, the goal of this study was to synthesize amide-substituted piperine analogs and screen them for pharmacological activity to relieve ER stress using an in vitro model of tunicamycin-induced ER stress using normal rat kidney (NRK-52E) cells...
April 10, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28392102/creatine-phosphate-administration-in-cell-energy-impairment-conditions-a-summary-of-past-and-present-research
#19
REVIEW
A V Gaddi, P Galuppo, J Yang
BACKGROUND: Creatine phosphate (CrP) plays a fundamental physiological role by providing chemical energy for cell viability and activity, especially in muscle tissue. Numerous pathological conditions, caused by acute or chronic ischaemic situations, are related to its deficiency. For these reasons, it has been used as a cardioprotective agent in heart surgery and medical cardiology for many years. OBJECTIVE: This article gives a brief overview of the main characteristics of exogenous CrP...
March 14, 2017: Heart, Lung & Circulation
https://www.readbyqxmd.com/read/28391791/molecular-and-metabolic-imaging-in-multiple-sclerosis
#20
REVIEW
Marcello Moccia, Olga Ciccarelli
Multiple sclerosis is a multifactorial disease with heterogeneous pathogenetic mechanisms, which deserve to be studied to evaluate new possible targets for treatments and improve patient management. MR spectroscopy and PET allow assessing in vivo the molecular and metabolic mechanisms underlying the pathogenesis of multiple sclerosis. This article focuses on the relationship between these imaging techniques and the biologic and chemical pathways leading to multiple sclerosis pathology and its clinical features...
May 2017: Neuroimaging Clinics of North America
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