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https://www.readbyqxmd.com/read/29150921/tgf-%C3%AE-and-hepatocellular-carcinoma-when-a-friend-becomes-an-enemy
#1
Marco Arrese, Daniel Cabrera, Alejandra Hernandez, Luis Astete, Lisbell Estrada, Claudio Cabello-Verrugio
Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide accounting for more than 700 thousand deaths per year. Most of the HCC develops in a cirrhotic liver, a microenvironment where fibrotic tissue replaces parenchymal cells. Thus, there is a close connection between fibrosis and HCC development. Understanding the cellular and molecular mechanisms involved in this process is a crucial step to advance in novel therapeutic or pharmacological strategies to prevent or improve the course of this malignancy...
November 16, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/29150865/enhanced-mu-opioid-receptor-dependent-opioidergic-modulation-of-striatal-cholinergic-transmission-in-dyt1-dystonia
#2
Giulia Ponterio, Annalisa Tassone, Giuseppe Sciamanna, Valentina Vanni, Maria Meringolo, Massimo Santoro, Nicola Biagio Mercuri, Paola Bonsi, Antonio Pisani
BACKGROUND: Mu opioid receptor activation modulates acetylcholine release in the dorsal striatum, an area deeply involved in motor function, habit formation, and reinforcement learning as well as in the pathophysiology of different movement disorders, such as dystonia. Although the role of opioids in drug reward and addiction is well established, their involvement in motor dysfunction remains largely unexplored. METHODS: We used a multidisciplinary approach to investigate the responses to mu activation in 2 mouse models of DYT1 dystonia (Tor1a(+/Δgag) mice, Tor1a(+/-) torsinA null mice, and their respective wild-types)...
November 18, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29150838/gi-530159-a-novel-selective-mechano-sensitive-k2p-channel-opener-reduces-rat-dorsal-root-ganglion-drg-neuron-excitability
#3
Alexandre J C Loucif, Pierre-Philippe Saintot, Jia Liu, Brett M Antonio, Shannon G Zellmer, Katrina Yoger, Emma L Veale, Anna Wilbrey, Kiyoyuki Omoto, Lishuang Cao, Alex Gutteridge, Neil A Castle, Edward B Stevens, Alistair Mathie
BACKGROUND AND PURPOSE: TREK two pore domain potassium channels play a critical role in regulating the excitability of somatosensory nociceptive neurons and are important mediators of pain perception. An understanding of the roles of TREK channels in pain perception and, indeed, in other pathophysiological conditions, has been severely hampered by the lack of potent and/or selective activators and inhibitors. In this study we describe a new, selective opener of TREK channels, GI-530159 (4,4'-(Hexafluoroisopropylidene)bis(p-phenyleneoxy)dianiline)...
November 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29150823/metabolic-dynamics-and-physiological-adaptation-of-panax-ginseng-during-development
#4
Yu-Jin Kim, Sung Chul Joo, Jianxin Shi, Chaoyang Hu, Sheng Quan, Jianping Hu, Johan Sukweenadhi, Padmanaban Mohanan, Deok-Chun Yang, Dabing Zhang
The dynamics of metabolites from leaves to roots of Panax ginseng during development has revealed the tissue-specific and year-specific metabolic networks. Being an essential Oriental medicinal plant, ginseng (Panax ginseng Meyer) is a slow-growing perennial herb-accumulating pharmaceutically active metabolites such as ginsenosides in roots during growth. However, little is known about how ginseng plants survive in the harsh environments such as winter cold and summer heat for a longer period and accumulates those active metabolites as the plant grows...
November 17, 2017: Plant Cell Reports
https://www.readbyqxmd.com/read/29150539/ros-and-glutathionylation-balance-cytoskeletal-dynamics-in-neutrophil-extracellular-trap-formation
#5
Darko Stojkov, Poorya Amini, Kevin Oberson, Christiane Sokollik, Andrea Duppenthaler, Hans-Uwe Simon, Shida Yousefi
The antimicrobial defense activity of neutrophils partly depends on their ability to form neutrophil extracellular traps (NETs), but the underlying mechanism controlling NET formation remains unclear. We demonstrate that inhibiting cytoskeletal dynamics with pharmacological agents or by genetic manipulation prevents the degranulation of neutrophils and mitochondrial DNA release required for NET formation. Wiskott-Aldrich syndrome protein-deficient neutrophils are unable to polymerize actin and exhibit a block in both degranulation and DNA release...
November 17, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29150487/dynamin-inhibitors-block-mtorc1-activation-by-amino-acids-independently-of-dynamin
#6
Persaud Avinash, Cormerais Yann, Pouyssegur Jacques, Rotin Daniela
mTORC1 plays a critical role in protein synthesis and cell proliferation and growth. It is activated by growth factors and amino acids, including essential amino acid (EAA), such as Leu; Leu enters cells via the Leu transporter LAT1-4F2hc and potentially via endocytosis. Here we investigated the contribution of the different routes of Leu entry into cells to mTORC1 activation using pharmacological inhibitors and cells that lack LAT1 or dynamin1/2/3. Our results show that LAT1 is the major route of Leu entry into cells and mTORC1 activation (∼70%), while dynamin-dependent endocytosis and macropinocytosis contribute minimally to both (5-15%)...
November 17, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29150333/design-synthesis-and-evaluation-of-novel-dihydrostilbene-derivatives-as-potential-anti-melanogenic-skin-protecting-agents
#7
Yu Zhu, Wen-Hui Pan, Chuen Fai Ku, Hong-Jie Zhang, Siu Wai Tsang
The stems of Dendrobium orchids (Orchidaceae), also known as Shi Hu, have been used for medicinal purposes for centuries in oriental countries. In fact, the health benefits of Shi Hu have been evidenced by its modern pharmacological actions on conquering oxidative stress in pathological conditions. From the extracts of two commonly used Dendrobium species, we obtained discernible amounts of stilbenoids, explicitly trans-resveratrol (1) and dihydro-resveratrol (2), which are prototypical antioxidants. When applied to cultured melanocytes, these stilbenoids, dihydro-resveratrol (2) in particular, significantly reduced melanin formation via inhibiting tyrosinase activity and expression of tyrosinase-related proteins...
October 10, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29150317/amp-activated-protein-kinase-regulation-of-the-nlrp3-inflammasome-during-aging
#8
REVIEW
Mario D Cordero, Matthew R Williams, Bernhard Ryffel
The NLRP3 inflammasome has recently emerged as an unexpected marker of stress and metabolic risk and has also been implicated in the development of major aging-related diseases such as gout, type 2 diabetes, obesity, cancer, and neurodegenerative and cardiovascular disorders. Several pathways regulating the NLRP3 inflammasome are currently being studied, but how the NLRP3 inflammasome is regulated remains unknown. AMP-activated protein kinase (AMPK), a central regulator of multiple metabolic pathways involved in the pathophysiology of aging and age-related diseases, has emerged as an important integrator of signals controlling inflammation including the inflammasome...
November 14, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/29150298/spontaneous-osteoclastogenesis-hypothesis-for-gender-unrelated-osteoporosis-screening-and-diagnosis
#9
F Salamanna, R Giardino, M Fini
Women are at greater risk of developing osteoporosis (OP). However, in the past few years it has become more widely recognized that OP is a significant problem also in men although OP is frequently under-diagnosed and, consequently, under treated in men. Most guidelines, screening and fracture risk evaluation methods as well as pharmacologic agents have been developed for women and then adapted to men. Bone Mineral Density (BMD) measurement by Dual X-ray Absorptiometry (DEXA) is reported as T score and the capability of DEXA to diagnose OP and predict fracture risk is still debated...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29150274/neuroprotective-potential-of-high-dose-biotin
#10
Mark F McCarty, James J DiNicolantonio
A recent controlled trial has established that high-dose biotin supplementation - 100 mg, three times daily - has a stabilizing effect on progression of multiple sclerosis (MS). Although this effect has been attributed to an optimization of biotin's essential cofactor role in the brain, a case can be made that direct stimulation of soluble guanylate cyclase (sGC) by pharmacological concentrations of biotin plays a key role in this regard. The utility of high-dose biotin in MS might reflect an anti-inflammatory effect of cGMP on the cerebral microvasculature, as well on oligodendrocyte differentiation and on Schwann cell production of neurotrophic factors thought to have potential for managing MS...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29150271/xenohormesis-in-early-life-new-avenues-of-research-to-explore-anti-aging-strategies-through-the-maternal-diet
#11
Philippe de Medina
Aging is a progressive internal physiological deterioration of the organism, leading to the occurrence of age-related lethal diseases. It has become a major societal challenge to understand the processes that drive aging and to develop rational pharmacological agents and dietary approaches to fight against age-related deterioration and diseases. Interestingly, several lines of evidence highlight an influence of the developmental period on the risk of age-related diseases later in life. This field is known as the developmental origins of health and disease...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29150198/comparative-effectiveness-of-extended-release-naltrexone-versus-buprenorphine-naloxone-for-opioid-relapse-prevention-x-bot-a-multicentre-open-label-randomised-controlled-trial
#12
Joshua D Lee, Edward V Nunes, Patricia Novo, Ken Bachrach, Genie L Bailey, Snehal Bhatt, Sarah Farkas, Marc Fishman, Phoebe Gauthier, Candace C Hodgkins, Jacquie King, Robert Lindblad, David Liu, Abigail G Matthews, Jeanine May, K Michelle Peavy, Stephen Ross, Dagmar Salazar, Paul Schkolnik, Dikla Shmueli-Blumberg, Don Stablein, Geetha Subramaniam, John Rotrosen
BACKGROUND: Extended-release naltrexone (XR-NTX), an opioid antagonist, and sublingual buprenorphine-naloxone (BUP-NX), a partial opioid agonist, are pharmacologically and conceptually distinct interventions to prevent opioid relapse. We aimed to estimate the difference in opioid relapse-free survival between XR-NTX and BUP-NX. METHODS: We initiated this 24 week, open-label, randomised controlled, comparative effectiveness trial at eight US community-based inpatient services and followed up participants as outpatients...
November 14, 2017: Lancet
https://www.readbyqxmd.com/read/29150182/mature-hippocampal-neurons-require-lis1-for-synaptic-integrity-implications-for-cognition
#13
Anamaria Sudarov, Xin-Jun Zhang, Leighton Braunstein, Eve LoCastro, Shawn Singh, Yu Taniguchi, Ashish Raj, Song-Hai Shi, Holly Moore, M Elizabeth Ross
BACKGROUND: Platelet-activating factor acetylhydrolase 1B1 (LIS1), a critical mediator of neuronal migration in developing brain, is expressed throughout life. However, relatively little is known about LIS1 function in the mature brain. We previously demonstrated that LIS1 involvement in the formation and turnover of synaptic protrusions and synapses of young brain after neuronal migration is complete. Here we examine the requirement for LIS1 to maintain hippocampal circuit function in adulthood...
September 23, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29150145/neuroimaging-biomarkers-as-predictors-of-treatment-outcome-in-major-depressive-disorder
#14
REVIEW
Trehani M Fonseka, Glenda M MacQueen, Sidney H Kennedy
BACKGROUND: Current practice for selecting pharmacological and non-pharmacological antidepressant treatments has yielded low response and remission rates in Major Depressive Disorder (MDD). Neuroimaging biomarkers of brain structure and function may be useful in guiding treatment selection by predicting response vs. non-response outcomes. METHODS: In this review, we summarize data from studies examining predictors of treatment response using structural and functional neuroimaging modalities, as they pertain to pharmacotherapy, psychotherapy, and stimulation treatment strategies...
October 31, 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/29149817/high-density-lipoprotein-hdl-dysfunction-and-future-of-hdl
#15
Sibel Ertek
Although high density lipoprotein cholesterol (HDL-C) levels are inversely proportional to cardiovascular risk in many studies, recent pharmacological interventional studies with HDL-C raising strategies did not show a benefit in terms of vascular events. The HDL particle is heterogenous with anti-atherogenic functions and non-vascular effects. Many factors affect HDL components and may either cause compositional changes, post-translational modifications of proteins, or alter lipids and other cargo molecules; generally these factors cause more than one of these changes, resulting in functional differences...
November 16, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/29149782/frequency-of-circulatory-regulatory-immune-cells-in-iranian-patients-with-type-1-diabetes
#16
Tahereh Khamehchian, Eqlim Nemati, Marziyeh Jazayeri, Shirin Azimi, Hassan Nikoueinejad, Hossein Akbari, Behnaz Irandoust
Type 1 diabetes (T1D) is the result of the autoimmune destruction of insulin-producing beta cells. Regulatory T cells (Tregs) and plasmacytoid dendritic cells (PDCs) act as mediators of peripheral tolerance. We investigated the possible alterations of such cells in peripheral blood of patients with T1D compared to normal individuals. This comparison may lead to a better understanding of the immunopathogenesis processes involved in T1D. 92 participants, including 49 patients with T1D and 43 healthy controls were studied...
October 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/29149530/proteases-and-protease-inhibitors-in-infectious-diseases
#17
REVIEW
Ayodeji A Agbowuro, Wilhelmina M Huston, Allan B Gamble, Joel D A Tyndall
There are numerous proteases of pathogenic organisms that are currently targeted for therapeutic intervention along with many that are seen as potential drug targets. This review discusses the chemical and biological makeup of some key druggable proteases expressed by the five major classes of disease causing agents, namely bacteria, viruses, fungi, eukaryotes, and prions. While a few of these enzymes including HIV protease and HCV NS3-4A protease have been targeted to a clinically useful level, a number are yet to yield any clinical outcomes in terms of antimicrobial therapy...
November 17, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29149494/inhibiting-mt2-tfe3-dependent-autophagy-enhances-melatonin-induced-apoptosis-in-tongue-squamous-cell-carcinoma
#18
Tengfei Fan, Huifeng Pi, Min Li, Zhenhu Ren, Zhijing He, Feiya Zhu, Li Tian, Manyu Tu, Jia Xie, Mengyu Liu, Yuming Li, Miduo Tan, Gaoming Li, Weijia Qing, Russel J Reiter, Zhengping Yu, Hanjiang Wu, Zhou Zhou
Autophagy modulation is a potential therapeutic strategy for tongue squamous cell carcinoma (TSCC). Melatonin possesses significant anti-carcinogenic activity. However, whether melatonin induces autophagy and its roles in cell death in TSCC are unclear. Herein, we show that melatonin induced significant apoptosis in the TSCC cell line Cal27. Apart from the induction of apoptosis, we demonstrated that melatonin-induced autophagic flux in Cal27 cells as evidenced by the formation of GFP-LC3 puncta, and the upregulation of LC3-II and downregulation of SQSTM1/P62...
November 17, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/29149457/hmgb1-controls-liver-cancer-initiation-through-yap-dependent-aerobic-glycolysis
#19
Ruochan Chen, Shan Zhu, Xue-Gong Fan, Haichao Wang, Michael T Lotze, Herbert J Zeh, Timothy R Billiar, Rui Kang, Daolin Tang
Emerging studies have suggested that the Hippo pathway is involved in the tumorigenesis of hepatocellular carcinoma (HCC). However, the key regulator of the Hippo pathway in liver tumor metabolic reprogramming remains elusive. Here, we provide evidence to support that high mobility group box 1 (HMGB1), a chromosomal protein, plays a role in the regulation of the Hippo pathway during liver tumorigenesis. Cre/loxP recombination-mediated HMGB1 depletion in hepatocytes blocks diethylnitrosamine-induced liver cancer initiation in mice, whereas shRNA-mediated gene silencing of HMGB1 inhibits HCC cell proliferation...
November 17, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29149415/targeting-tctp-with-sertraline-and-thioridazine-in-cancer-treatment
#20
Robert Amson, Christian Auclair, Fabrice André, Judith Karp, Adam Telerman
We have initially demonstrated in knocking down experiments that decreasing TCTP in cancer cells leads in some tissues to cell death while in others to a complete reorganization of the tumor into architectural structures reminiscent of normal ones. Based on these experiments and a series of other findings confirming the key role of TCTP in cancer, it became important to find pharmacological compounds to inhibit its function, and this became for us a priority. In the present text, we explain in detail the experiments that were performed and the perspectives of sertraline in cancer treatment, as this became today a reality with a clinical study that started in collaboration with Columbia University and Johns Hopkins University...
2017: Results and Problems in Cell Differentiation
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