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Biochemical Pharmacology

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https://read.qxmd.com/read/31415738/the-regulatory-roles-of-calcium-channels-in-tumors
#1
Tiecheng Zhong, Xiaohui Pan, Jian Wang, Bo Yang, Ling Ding
Calcium (Ca2+ ) and its relevant transmembrane and intracellular calcium channels were previously thought to be chiefly associated with the regulation of cardiovascular and neuronal systems. Nowadays, an increasing evidence shows those calcium channels are also responsible for tumorigenesis and progression. However, the general underlying mechanisms and the involving signaling transduction pathways still remain unclear. Therefore in this mini-review, we are mainly focusing on the linkage between calcium channels and major characteristics of tumors such as multi-drug resistance (MDR), metastasis, apoptosis, proliferation, evasion of immune surveillance, and the alterations of tumor microenvironment...
August 12, 2019: Biochemical Pharmacology
https://read.qxmd.com/read/31404530/parkin-is-transcriptionally-regulated-by-the-aryl-hydrocarbon-receptor-impact-on-%C3%AE-synuclein-protein-levels
#2
Emmanuel González-Barbosa, Rosario García-Aguilar, Libia Vega, María Asunción Cabañas-Cortés, Frank J Gonzalez, José Segovia, Sara L Morales-Lázaro, Bulmaro Cisneros, Guillermo Elizondo
Parkin (PRKN) is a ubiquitin E3 ligase that catalyzes the ubiquitination of several proteins. Mutations in the human Parkin gene, PRKN, leads to degeneration of dopaminergic (DA) neurons, resulting in autosomal recessive early-onset parkinsonism and the loss of PRKN function is linked to sporadic Parkinson's disease (PD). Additionally, several in vitro studies have shown that overexpression of exogenous PRKN protects against the neurotoxic effects induced by a wide range of cellular stressors, emphasizing the need to study the mechanism(s) governing PRKN expression and induction...
August 9, 2019: Biochemical Pharmacology
https://read.qxmd.com/read/31404529/developmental-nicotine-exposure-elicits-multigenerational-disequilibria-in-probdnf-proteolysis-and-glucocorticoid-signaling-in-the-frontal-cortices-striata-and-hippocampi-of-adolescent-mice
#3
Jordan M Buck, Heidi C O'Neill, Jerry A Stitzel
No abstract text is available yet for this article.
August 9, 2019: Biochemical Pharmacology
https://read.qxmd.com/read/31404528/withaferin-a-from-ayurvedic-folk-medicine-to-preclinical-anti-cancer-drug
#4
REVIEW
Behrouz Hassannia, Emilie Logie, Peter Vandenabeele, Tom Vanden Berghe, Wim Vanden Berghe
Despite the recent successes of targeted cancer immuno-therapies, drug resistance and disease relapse remain a huge burden in cancer patient treatment. This has fueled renewed interest in natural product discovery to identify new pharmacophores for innovative cancer drug development. Reverse pharmacology approaches of Withania somnifera leaves and roots (alternatively also called Ashwagandha or Indian ginseng in traditional Ayurvedic and Unani folk medicine) have identified Withaferin A (WA) as the most bioactive compound for treatment of inflammatory ailments, supporting traditional use of their corresponding extracts in indigenous medicine...
August 9, 2019: Biochemical Pharmacology
https://read.qxmd.com/read/31398312/commentary-hepatic-clearance-concepts-and-misconceptions-why-the-well-stirred-model-is-still-used-even-though-it-is-not-physiologic-reality
#5
REVIEW
K Sandy Pang, Yi Rang Han, Keumhan Noh, Ping I Lee, Malcolm Rowland
The liver is the most important drug metabolizing organ, endowed with a plethora of metabolizing enzymes and transporters to facilitate drug entry and removal via metabolism and/or biliary excretion. For this reason, much focus surrounds the development of clearance concepts, which are based on normalizing the rate of removal to the input or arterial concentration. By so doing, some authors have recently claimed that it implies one specific model of hepatic elimination, namely, the widely used well-stirred or venous equilibration model (WSM)...
August 6, 2019: Biochemical Pharmacology
https://read.qxmd.com/read/31386827/telluric-acid-ameliorates-hepatic-ischemia-reperfusion-induced-injury-in-rats-involvement-of-tlr4-nrf2-and-pi3k-akt-signaling-pathways
#6
Mostafa A Rabie, Hala F Zaki, Helmy M Sayed
In past tellurium-based compounds had limited use, however, their therapeutic potential have been target of interest recently due to antioxidant and anti-inflammatory capabilities in experimental endotoxemia. Nevertheless, their potential hepatoprotective effect against ischemia reperfusion (IR) injury is still obscure. This study examined the possible hepatoprotective effect of telluric acid (TELL), one of tellurium-based compound, against the deteriorating effect hepatic IR injury in rats through directing toll like receptor-4 (TLR4) cascade, phosphoinositide 3-kinase(PI3K)/Akt axis, and nuclear erythroid-related factor-2 (Nrf-2) pathway as possible mechanisms contributed to TELL's effect...
August 3, 2019: Biochemical Pharmacology
https://read.qxmd.com/read/31381873/scavenger-receptor-a1-attenuates-aortic-dissection-via-promoting-efferocytosis-in-macrophages
#7
Zhi Zhang, Yunlong Jiang, Zhongqiu Zhou, Jianan Huang, Shichao Chen, Wenying Zhou, Qing Yang, Hui Bai, Hanwen Zhang, Jingjing Ben, Xudong Zhu, Xiaoyu Li, Qi Chen
Macrophage class A1 scavenger receptor (SR-A1) is a pattern recognition receptor with an anti-inflammatory feature in cardiovascular diseases. However, its role in acute aortic dissection (AD) is not known yet. Using an aortic dissection model in SR-A1-deficient mice and their wild type littermates, we found that SR-A1 deficiency aggravated beta-aminopropionitrile monofumarate induced thoracic aortic dilation, false lumen formation, extracellular matrix degradation, vascular inflammation and accumulation of apoptotic cells...
August 2, 2019: Biochemical Pharmacology
https://read.qxmd.com/read/31381872/protein-protein-interactions-of-drug-uptake-transporters-that-are-important-for-liver-and-kidney
#8
REVIEW
Yuchen Zhang, Bruno Hagenbuch
Drug uptake transporters are membrane proteins responsible for the trans-membrane transport of endo- and xenobiotics, including numerous drugs. They are important for the uptake of drugs into target tissues or into organs for metabolism and excretion. Many drug uptake transporters have a broad spectrum of structural-independent substrates, which make them vulnerable to drug-drug interactions. Recent studies have shown more and more complex pharmacokinetics involving transporters, and regulatory agencies now require studies to be performed to measure the involvement of transporters in drug development...
August 2, 2019: Biochemical Pharmacology
https://read.qxmd.com/read/31377420/corrigendum-to-effects-of-17%C3%AE-estradiol-on-colorectal-cancer-development-after-azoxymethane-dextran-sulfate-sodium-treatment-of-ovariectomized-mice-biochem-pharmacol-164-2019-139-151
#9
Chin-Hee Song, Nayoung Kim, Sun Min Lee, Ryoung Hee Nam, Soo In Choi, So Ra Kang, Eun Shin, Dong Ho Lee, Ha-Na Lee, Young-Joon Surh
No abstract text is available yet for this article.
August 1, 2019: Biochemical Pharmacology
https://read.qxmd.com/read/31377232/vitamin-d-and-evolution-pharmacologic-implications
#10
REVIEW
Andrea Hanel, Carsten Carlberg
VitaminD3 is produced non-enzymatically when the cholesterol precursor 7-dehydrocholesterol is exposed to UV-B, i.e., evolutionary the first function of the molecule was that of an UV-B radiation scavenging end product. VitaminD endocrinology started when some 550million years ago first species developed a vitaminD receptor (VDR) that binds with high affinity the vitaminD metabolite 1α,25-dihydroxyvitaminD3 . VDR evolved from a subfamily of nuclear receptors sensing the levels of cholesterol derivatives, such as bile acids, and controlling metabolic genes supporting cellular processes, such as innate and adaptive immunity...
August 1, 2019: Biochemical Pharmacology
https://read.qxmd.com/read/31374192/s-nitrosoglutathione-prevents-cognitive-impairment-through-epigenetic-reprogramming-in-ovariectomised-mice
#11
Aanchal Aggarwal, Nishtha Sharma, Rajat Sandhir, Vikas Rishi
The epigenetic signatures associated with cognitive decline driven by lack of estrogen in post-menopausal state, is not well-understood. The present study is an attempt to unravel the epigenetic mechanisms involved in cognitive impairment preceding ovariectomy in mice and evaluate the protective effects of S-nitrosoglutathione (GSNO). A significant decline in cognitive functions was observed in mice following ovariectomy as assessed by Morris water maze and Novel object recognition test. Administration of GSNO (100 µg/kg body weight, orally) daily for 4 weeks was found to ameliorate cognitive deficits observed in ovariectomised (OVX) mice...
July 30, 2019: Biochemical Pharmacology
https://read.qxmd.com/read/31351871/aromatic-hydrocarbon-receptor-regulates-chicken-cytochrome-p450-1a5-transcription-a-novel-insight-into-t-2-toxin-induced-gene-expression-and-cytotoxicity-in-lmh-cells
#12
Qian Liu, Jikai Wen, Jiahui Zhu, Tingting Zhang, Yiqun Deng, Jun Jiang
T-2 toxin is a secondary metabolite produced by the Fusarium genus and is highly toxic to both farmed animals and humans. In our previous study, we found that chicken cytochrome P450 1A5 (CYP1A5) can be significantly induced by T-2 toxin in chicken primary hepatocytes and catalyze T-2 toxin into a more toxic product, 3'-OH-T-2. Here, we showed that T-2 toxin also induced the expression of CYP1A5 in LMH cells at both the mRNA and protein levels, and this can be strongly inhibited by both resveratrol and siRNA targeting the aryl hydrocarbon receptor (AhR), indicating the involvement of AhR in T-2 toxin-induced transcriptional activation of CYP1A5...
July 25, 2019: Biochemical Pharmacology
https://read.qxmd.com/read/31351870/a-flibercept-regulates-retinal-inflammation-elicited-by-high-glucose-via-the-plgf-erk-pathway
#13
Francesca Lazzara, Annamaria Fidilio, Chiara Bianca Maria Platania, Giovanni Giurdanella, Salvatore Salomone, Gian Marco Leggio, Valeria Tarallo, Valeria Cicatiello, Sandro De Falco, Chiara Maria Eandi, Filippo Drago, Claudio Bucolo
Diabetic retinopathy (DR) is a secondary complication of diabetes. DR can cause irreversible blindness, and its pathogenesis has been considered multifactorial. DR can progress from non-proliferative DR to proliferative DR, characterized by retinal neovascularization. The main cause of vision loss in diabetic patients is diabetic macular edema, caused by vessel leakage and blood retinal barrier breakdown. Currently, aflibercept is an anti-VEGF approved for diabetic macular edema. Aflibercept can bind several members of vascular permeability factors, namely VEGF-A, B, and PlGF...
July 25, 2019: Biochemical Pharmacology
https://read.qxmd.com/read/31351052/the-strigolactone-analog-gr-24-inhibits-angiogenesis-in-vivo-and-in-vitro-by-a-mechanism-involving-cytoskeletal-reorganization-and-vegfr2-signalling
#14
Paloma Carrillo, Beatriz Martínez-Poveda, Miguel Ángel Medina, Ana R Quesada
Phytohormones have shown great potential as natural anticancer compounds, being interesting in cancer prevention and therapy. Strigolactones are a class of plant hormones involved in the inhibition of root branching and sprouting. The antiproliferative capacity of the synthetic strigolactone analog GR-24 has been described against breast cancer cell lines in vitro. In this study, we show for the fist time that GR-24 is a potent antiangiogenic compound in vivo and in vitro. In the in vivo tests, GR-24 shows a great inhibitory effect on vasculature formation in the chicken chorioallantoic membrane and in two different zebrafish models...
July 24, 2019: Biochemical Pharmacology
https://read.qxmd.com/read/31348898/interplay-between-intracellular-loop-1-and-helix-viii-of-the-angiotensin-ii-type-2-receptor-controls-its-activation
#15
Alexandre Connolly, Brian Holleran, Élie Simard, Jean-Patrice Baillargeon, Pierre Lavigne, Richard Leduc
The signaling mechanisms of the angiotensin II type 2 receptor (AT2 R), a heptahelical receptor, have not yet been clearly and completely defined. In the present contribution, we set out to identify the molecular determinants involved in AT2 R activation. Although AT2 R has not been shown to engage Gq/11 , G12 , Gi2 , and β-arrestin (βarr) pathways as does the AT1 R upon angiotensin II (AngII) stimulation, the atypical positioning of helix VIII in the recently published AT2 R structure may play a role in the receptor's capacity to couple to downstream effectors...
July 23, 2019: Biochemical Pharmacology
https://read.qxmd.com/read/31326434/development-of-renal-failure-in-pargparp-1-null-and-timm23-hypomorphic-mice
#16
Lichao Chen, Akemi Gunji, Akiko Uemura, Hisako Fujihara, Kentaro Nakamoto, Takae Onodera, Yuka Sasaki, Shoji Imamichi, Mayu Isumi, Tadashige Nozaki, Nobuo Kamada, Kou-Ichi Jishage, Mitsuko Masutani
Poly(ADP-ribose) glycohydrolase (Parg) is a central enzyme for poly(ADP-ribose) degradation. We established a Parg+/- mice strain by deletion of a part of exon 1 and around 0.4-kb upstream of sequences of the Parg gene. Parg-/- embryos obtained by intercrossing the Parg+/- mice died in utero between 4.5 and 9.5 days postcoitum. We examined whether poly(ADP-ribose) polymerase-1 (Parp-1) deficiency could rescue embryonic lethality of Parg-/- mice. Parg-/- Parp-1-/- mice were born viable at a reduced frequency from the expected mendelian ratio in the intercross progeny of Parg+/- Parp-1-/- mice...
July 18, 2019: Biochemical Pharmacology
https://read.qxmd.com/read/31325449/endocannabinoids-and-endocannabinoid-like-compounds-modulate-hypoxia-induced-permeability-in-caco-2-cells-via-cb-1-trpv1-and-ppar%C3%AE
#17
M A Karwad, D G Couch, K L Wright, C Tufarelli, M Larvin, J Lund, S E O'Sullivan
BACKGROUND AND PURPOSE: We have previously reported that endocannabinoids modulate permeability in Caco-2 cells under inflammatory conditions and hypothesised in the present study that endocannabinoids could also modulate permeability in ischemia/reperfusion. EXPERIMENTAL APPROACH: Caco-2 cells were grown on cell culture inserts to confluence. Trans-epithelial electrical resistance (TEER) was used to measure permeability. To generate hypoxia (0% O2 ), a GasPak™ EZ anaerobe pouch system was used...
July 17, 2019: Biochemical Pharmacology
https://read.qxmd.com/read/31325448/the-mtor-inhibitor-everolimus-overcomes-cxcr4-mediated-resistance-to-histone-deacetylase-inhibitor-panobinostat-through-inhibition-of-p21-and-mitotic-regulators
#18
Katia Beider, Hanna Bitner, Valeria Voevoda-Dimenshtein, Evgenia Rosenberg, Yaarit Sirovsky, Hila Magen, Jonathan Canaani, Olga Ostrovsky, Noya Shilo, Avichai Shimoni, Michal Abraham, Lola Weiss, Michael Milyavsky, Amnon Peled, Arnon Nagler
Although having promising anti-myeloma properties, the pan-histone deacetylase inhibitor (HDACi) panobinostat lacks therapeutic activity as a single agent. The aim of the current study was to elucidate the mechanisms underlying multiple myeloma (MM) resistance to panobinostat monotherapy and to define strategies to overcome it. Sensitivity of MM cell lines and primary CD138+ cells from MM patients to panobinostat correlated with reduced expression of the chemokine receptor CXCR4, whereas overexpression of CXCR4 in MM cell lines increased their resistance to panobinostat...
July 17, 2019: Biochemical Pharmacology
https://read.qxmd.com/read/31323186/intracellular-targets-as-source-for-cleaner-targets-for-the-treatment-of-solid-tumors
#19
REVIEW
Hans-Peter Gerber, Leah Sibener, Luke Lee, Marvin Gee
High-potency oncology compounds such as antibody- drug conjugates, T cell redirecting, and CAR-T cell therapies have provided transformational responses in patients with liquid tumors. However, they delivered only limited benefit to solid tumor patients due to the frequent onset of dose limiting toxicities in normal tissues. Such on-target, off-tumor toxicities are caused by recognition of targets present at low-levels on normal tissues. The apparent imbalance between the rapid development of high-potency therapeutic modalities and the slow progress in identification of cleaner targets is illustrated by the fact that most high-potency compounds currently developed in the clinic target cell surface antigens identified over 20 years ago...
July 16, 2019: Biochemical Pharmacology
https://read.qxmd.com/read/31310736/breast-cancer-occluded-role-of-mitochondria-n-acetylserotonin-melatonin-ratio-in-co-ordinating-pathophysiology
#20
REVIEW
George Anderson
A plethora of factors contribute to the biochemical underpinnings of breast cancer, in the absence of any clear, integrative framework. This article proposes that melatonergic pathway regulation within mitochondria provides an integrative framework for the wide array of data driving breast cancer pathophysiology. As melatonin is toxic to breast cancer cells, its production within mitochondria poses a significant challenge to breast cancer cell survival. Consequently, the diverse plasticity in breast cancer cells may arise from a requirement to decrease mitochondria melatonin synthesis...
July 13, 2019: Biochemical Pharmacology
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