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Chemico-biological Interactions

Bong-Seon Lee, Changhun Lee, Sumin Yang, Eui Kyun Park, Sae-Kwang Ku, Jong-Sup Bae
Pelargonidin (PEL) is a well-known red pigment found in plants, and has been reported as having important biological activities that are potentially beneficial for human health. Here, we tested the possible use of PEL in the treatment of lipopolysaccharide (LPS)-mediated vascular inflammatory responses. The anti-inflammatory activities of PEL were determined by measuring permeability, neutrophils adhesion and migration, and activation of pro-inflammatory proteins in LPS-activated human umbilical vein endothelial cells (HUVECs) and mice...
February 9, 2019: Chemico-biological Interactions
Rebecca A Clewell, Chad M Thompson, Harvey J Clewell
Current regulatory practices for chemical carcinogens were established when scientific understanding of the molecular mechanisms of chemical carcinogenesis was in its infancy. Initial discovery that DNA mutation was the root of cancer led quickly to regulatory processes that assumed such a simple relationship could be described with a linear approach. This linear, no threshold approach has since become the default approach to risk assessment of chemicals with carcinogenic potential. Since then, a multitude of intrinsic processes have been identified at the molecular, cellular and organism level that work to prevent transient DNA damage from causing permanent mutations, and mutated cells from becoming cancer...
February 7, 2019: Chemico-biological Interactions
Jue Jiang, Xiaoyun Yang, Xin He, Wenqi Ma, Juan Wang, Qi Zhou, Miao Li, Shanshan Yu
Accumulating evidence has suggested that microRNA-449b-5p (miR-449b-5p) plays an important role in the development and progression of multiple cancers. However, little is known about the role of miR-449b-5p in breast cancer. In this study, we aimed to investigate the expression level, biological function and underlying mechanism of miR-449b-5p in breast cancer. Our results showed that miR-449b-5p expression was frequently down-regulated in breast cancer cell lines and tissues. The overexpression of miR-449b-5p significantly inhibited growth and invasion, and induced the cell cycle arrest of breast cancer cells...
February 7, 2019: Chemico-biological Interactions
Xiaohong Lv, Yazhen Li, Qingfei Xiao, Dan Li
NF-E2 p45-related factor 2 (Nrf2), which regulates the cellular antioxidant response, is a target for limiting tissue damage due to exposure to environmental toxicants, including arsenic. Daphnetin (Daph), a natural coumarin derivative, has been shown to induce remarkable antioxidant activity. The present study aimed to examine the protective effects and molecular mechanisms of Daph on arsenic-induced cytotoxicity in human lung epithelial cells. Our results demonstrate that Daph dramatically upregulated the antioxidant enzyme in a dose dependent manner, in association with induction of Nrf2 nuclear translocation and decreased Keap1 protein expression...
February 6, 2019: Chemico-biological Interactions
Marilyn Rocío Álvarez Santos, Yenny Bueno Duarte, Fausto M Güiza, Arnold R Romero Bohórquez, Stelia Carolina Mendez-Sanchez
New molecular hybrids were synthesized by combining tetrahydroquinoline (THQ) and isoxazole (ISX) scaffolds, in search for chemical structures with improved pharmacological properties. Our tetrahydroquinoline (THQ) and isoxazole (ISX) hybrids differ in the X and Y substituents: FM53 (X = H; Y= H), FM49 (X = CH3 ; Y= OCH3 ), FM50 (X = Cl; Y= H) and FM48 (X = Cl; Y= OCH3 ). Aiming at exploring their bioactivity in liver cancer cells, in this paper we report the effect of four THQ-ISX hybrids on viability, respiration and oxidative stress in Hep-G2 human hepatoma cells...
February 6, 2019: Chemico-biological Interactions
Kehuan Sun, Wenhui Mei, Shu Mo, Ling Xin, Xiaojun Lei, Mengtian Huang, Qiufang Chen, Li Han, Xiaofeng Zhu
Exposure to lead (Pb) poses a threat to human bone health, including changes in bone mineral composition and the inhibition of skeletal growth and bone maturation. However, little is known about how Pb directly affects osteoblasts. In this work, we found that sub-toxic Pb concentrations suppressed bone nodule formation and inhibited differentiation in MC3T3-E1 subclone 14 cells, as shown by decreased expression levels of the differentiation markers alkaline phosphatase (ALP), type 1 collagen (COL1), osteocalcin (OC), and runt-related transcription factor 2 (RUNX2)...
February 4, 2019: Chemico-biological Interactions
Lizhi Wu, Natalia Y Kedishvili, Olga V Belyaeva
Retinol dehydrogenase 11 (RDH11) is an NADPH-dependent retinaldehyde reductase that was previously reported to function in the visual cycle. Recently, we have shown that RDH11 contributes to the maintenance of retinol levels in extraocular tissues under conditions of vitamin A deficiency or reduced vitamin A availability. RDH11 is also expressed in the embryo. Rdh11 knockout animals do not display embryonic defects and appear to develop normally to the adult stage, but the exact function of RDH11 during development is not yet known...
February 4, 2019: Chemico-biological Interactions
Jinming Peng, Kaikai Li, Wei Zhu, Rongzu Nie, Ruifeng Wang, Chunmei Li
Penta-O-galloyl-β-D-glucose (PGG) was purified and identified from Radix Paeoniae Alba by HSCCC and HPLC/ESI-MS, and its inhibitory effects on adipogenesis and TNF-α-induced inflammation were assessed in 3T3-L1 cell line. The results showed that PGG dose-dependently reduced intracellular lipids accumulation, and this involved decrease the expression levels of major adipogenic markers, PPARγ, C/EBP α, through MAPKs inhibition. This was accompanied by a reduction of lipogenic genes, ACC, FAS, and SCD-1, involved in fatty acid synthesis...
February 2, 2019: Chemico-biological Interactions
Akiko Matsumoto, Shosuke Ito, Kazumasa Wakamatsu, Masayoshi Ichiba, Vasilis Vasiliou, Chiho Akao, Byoung-Joon Song, Mayumi Fujita
Alcohol induces various cutaneous changes, such as palmar erythema and jaundice. However, alcohol-induced skin hyperpigmentation due to melanin deposition has not been reported. Aldehyde dehydrogenase 2 (ALDH2), one of 19 human ALDH isozymes, metabolizes endogenous and exogenous aldehydes to their respective carboxylic acids. Reduced ALDH2 greatly affects acetaldehyde metabolism, leading to its accumulation in the body after the consumption of alcohol and the consequent development of a wide range of phenotypes...
February 2, 2019: Chemico-biological Interactions
Keehyuk Kim, Bryce V Plapp
The catalytic zincs in complexes of horse liver and yeast alcohol dehydrogenases (ADH) with NAD+ and the substrate analogue, 2,2,2-trifluoroethanol, are ligated to two cysteine residues and one histidine residue from the protein and the oxygen from the alcohol. The zinc facilitates deprotonation of the alcohol and is essential for catalysis. In the yeast apoenzyme, the zinc is coordinated to a nearby glutamic acid, which is displaced by the alcohol in the complex with NAD+ . Some homologous medium chain dehydrogenases have a cysteine replaced by aspartic or glutamic acid residues...
February 2, 2019: Chemico-biological Interactions
Richard A Williams
No abstract text is available yet for this article.
January 31, 2019: Chemico-biological Interactions
Xiaoying Liu, Lu Gan, Jing Zhang
Dysregulation of miR-543 has been implicated to play crucial roles in various human cancers. However, the function of miR-543 involved in cervical cancer (CC) progress remains largely unknown. Thus, this study aimed to explore the potential role of miR-543 and the underlying mechanisms in human CC. In this study, we found that miR-543 was significantly downregulated in 69 CC tissue samples and cell lines when compared to adjacent normal tissues and cell line. Decreased miR-543 was closely correlated with poor clinicopathological parameters including larger tumor size, late FIGO stage and lymph node metastasis...
January 30, 2019: Chemico-biological Interactions
Toru Nishinaka, Kahori Shimizu, Takeshi Miura, Chihiro Yabe-Nishimura, Tomoyuki Terada
Aldose reductase (AR), a member of aldo-keto reductase family, is the rate-limiting enzyme in the polyol pathway, and is known to play a key role in the pathogenesis of diabetic complications. AR also catalyzes the reduction of reactive aldehydes, thereby detoxifying endogenous as well as xenobiotic aldehydes in various tissues. The transcription of the AR gene was previously shown to be augmented by various stimuli including osmotic and oxidative stresses. A highly conserved region composed of an antioxidant response element (ARE), AP-1 site, and tonicity responsive enhancer (TonE) has been identified within the 5'-flanking region of the AR genes of humans, rats, and mice, which we designated as the multiple stress response region (MSRR)...
January 29, 2019: Chemico-biological Interactions
Navid Koleini, Barbara E Nickel, Andrea L Edel, Robert R Fandrich, Amir Ravandi, Elissavet Kardami
Doxorubicin (Dox), a widely used chemotherapy drug, can also cause cardiotoxic effects leading to heart failure. The excessive oxidative stress caused by Dox results in the modification of a variety of cellular molecules, including phospholipids. In cardiomyocytes, Dox increases oxidation of a species of phospholipids, phosphatidylcholine, which has been associated with increased cell death. Oxidized phospholipids (Ox-PL) are involved in development and progression of various pathologies, including atherosclerosis, thrombosis, and tissue inflammation...
January 29, 2019: Chemico-biological Interactions
Oluyomi Stephen Adeyemi, Rhoda Ananu Uloko, Oluwakemi Josephine Awakan, Anne Adebukola Adeyanju, David Adeiza Otohinoyi
In this work, we determined whether oxidative stress contributed to the activation of the kynurenine pathway by AgNPs. Male Wistar rats weighing between 130 and 146 g were randomly assigned into six groups. Animals in the negative control group were orally administered distilled water while, the other treatment groups were respectively given AgNPs (25 and 50 mg/kg bw) alone or in combination with Trolox (100 mg/kg bw). Results showed that treatments with AgNPs significantly raised protein carbonyl level in rat liver, but the co-treatment with Trolox attenuated the elevation...
January 29, 2019: Chemico-biological Interactions
Fengjiao Zhang, Frances Munoz, Lanlan Sun, Shuya Zhang, Serrine S Lau, Terrence J Monks
2,3,5-tris(Glutathion-S-yl)hydroquinone (TGHQ), a potent nephrotoxic and nephroncarcinogenic metabolite of benzene and hydroquinone, retains the ability to redox cycle and create oxidative stress. We have previously detected that TGHQ induces ROS-dependent necrotic or apoptotic cell death in renal epithelial HK-2 and human leukemic HL-60 cells respectively. Herein, we sought to determine the nature of the Nrf2 regulation in HK-2 and HL-60 cells undergoing TGHQ-mediated ROS-dependent cell death, due to the key role of Nrf2 in oxidative stress...
January 28, 2019: Chemico-biological Interactions
Neslihan Bukum, Eva Novotna, Anselm Morell, Jakub Hofman, Vladimir Wsol
Buparlisib is a pan-class I phosphoinositide 3-kinase (PI3K) inhibitor and is currently under clinical evaluation for the treatment of different cancers. Because PI3K signalling is related to cell proliferation and resistance to chemotherapy, new therapeutic approaches are focused on combining PI3K inhibitors with other anti-cancer therapeutics. Carbonyl-reducing enzymes catalyse metabolic detoxification of anthracyclines and reduce their cytotoxicity. In the present work, the effects of buparlisib were tested on six human recombinant carbonyl-reducing enzymes: AKR1A1, AKR1B1, AKR1B10, AKR1C3, and AKR7A2 from the aldo-keto reductase superfamily and CBR1 from the short-chain dehydrogenase/reductase superfamily, all of which participate in the metabolism of daunorubicin...
January 28, 2019: Chemico-biological Interactions
Mohamed E Mostafa, Ahmed A Shaaban, Hatem A Salem
The current study was designed to assess the antifibrotic effect of dimethylfumarate (DMF) on CCl4 -induced hepatic injury in rats. Hepatic injury was induced by intraperitoneal twice weekly injection of CCl4 for 2 and 3 months. DMF was administered orally during the last 4 weeks in each model. Liver injury was estimated using biochemical parameters such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), total serum bilirubin (TSB), total protein, alkaline phosphatase (ALP) and lactate dehydrogenase (LDH)...
January 28, 2019: Chemico-biological Interactions
Rui-Rui Chen, Xue-Hui Fan, Gang Chen, Guang-Wei Zeng, Yu-Gang Xue, Xiong-Tao Liu, Chi-Yao Wang
Angiotensin II-related cardiac fibrosis is one of the key pathological changes of the hypertrophied left ventricle in various heart disease. Irisin was recently reported to confer cardio-protective and anti-oxidative effects, while whether it can reverse the renin-angiotensin-aldosterone system(RAAS) activation related(angiotensin II-induced) cardiac fibrosis is unknown. In this study, we found that angiotensin II-induced cardiac dysfunction and fibrotic responses were dampened by irisin treatment in mice. Mechanistically, angiotensin II induced robust ROS generation, which in turn triggered activation of pro-fibrotic TGFβ1-Smad2/3 signaling and subsequent collagen synthesis and fibroblast-myofibroblast transformation in cardiac fibroblasts...
January 28, 2019: Chemico-biological Interactions
Chang-En Yang, Wen-Ying Lee, Hung-Wei Cheng, Chu-Hung Chung, Fu-Lowng Mi, Cheng-Wei Lin
The major obstacle in current cancer therapy is the existence of cancer stem cells (CSCs), which are responsible for therapeutic resistance and contribute to metastasis and recurrence. Identification of reliable biomarkers for diagnostic and therapeutic targets is necessary for drug development and cancer treatment. In this study, we identified that the antipsychotic chlorpromazine (CPZ) exhibited potent anti-breast cancer and anti-CSC capabilities. Treatment with CPZ suppressed stemness properties including mammosphere formation, aldehyde dehydrogenase (ALDH) activity, and stemness-related gene expressions in breast cancer cells and CSCs...
January 28, 2019: Chemico-biological Interactions
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