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Y Jiang, H Y Chao, X W Zhang, M Zhou, X Z Lu, R Zhang, C He, Q Wang
Objective: To explore the effects and possible mechanisms of the novel pan-FGFR inhibitor BGJ398 on KG-1 cells in vitro. Methods: Effects of BGJ398 on cells proliferation were detected by CCK-8, the apoptosis was assessed by Annexin V-FITC. Reverse transcriptionquantitative polymerase chain reaction (q-PCR) analysis was used to detect the expression of apoptosis-related genes B cell lymphoma-2 (Bcl-2) and caspase-3. Western blotting analysis was performed to explore the proteins expression levels of Bcl-2, caspase-3 and the expression of p-AKT, p-S6K, p-ERK and FGFR1...
February 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Shuting Cao, Huan Wu, ChunChun Wang, Qianhui Zhang, Lefei Jiao, Fanghui Lin, Caihong Hu
In the present study, we investigated the influence of diquat-induced oxidative stress on intestinal barrier, mitochondrial function and the level of mitophagy in piglets. Twelve male Duroc×Landrace×Yorkshire 35-d-old pigs (weaned at 21d of age), with an average body of 9.6 kg, were allotted to two treatments of six piglets each including the challenged group and the control group. The challenged pigs were injected with 100 mg/kg bodyweight diquat and control pigs injected with 0.9% (w/v) NaCl solution. The results showed that diquat injection decreased average daily feed intake and average daily gain...
March 17, 2018: Journal of Animal Science
Emily G Kaye, Matthew Booker, Jesse V Kurland, Alexander E Conicella, Nicolas L Fawzi, Martha L Bulyk, Michael Y Tolstorukov, Erica Larschan
Little is known about how variation in sequence composition alters transcription factor occupancy to precisely recruit large transcription complexes. A key model for understanding how transcription complexes are targeted is the Drosophila dosage compensation system in which the male-specific lethal (MSL) transcription complex specifically identifies and regulates the male X chromosome. The chromatin-linked adaptor for MSL proteins (CLAMP) zinc-finger protein targets MSL to the X chromosome but also binds to GA-rich sequence elements throughout the genome...
March 20, 2018: Cell Reports
Marija Nišavić, Goran V Janjić, Amela Hozić, Marijana Petković, Miloš K Milčić, Zoran Vujčić, Mario Cindrić
Binding of three ruthenium(ii) compounds of general formula mer-[Ru(L3)(N-N)X][Y] (where L3 = 4'-chloro-2,2':6',2''-terpyridine (Cl-tpy); N-N = 1,2-diaminoethane (en), 1,2-diaminocyclohexane (dach) or 2,2'-bipyridine (bipy); X = Cl; Y = Cl) to human serum albumin (HSA) has been investigated by nano-LC/nano-ESI MS and docking studies. A bottom-up proteomics approach has been applied for the structural characterization of metallated proteins and the data were analyzed in both the positive and negative ion mode...
March 21, 2018: Metallomics: Integrated Biometal Science
Nicolette Kapp, Xiao X Stander, Barend A Stander
This project investigated the in-vitro effects of a glycolytic inhibitor, 3-bromopyruvate (3-BrP), in combination with and a new in silico-designed inhibitor of the bromodomain-4 (BRD-4) protein, ITH-47, on the U937 acute myeloid leukemia cell line. 3-BrP is an agent that targets the altered metabolism of cancer cells by interfering with glucose metabolism in the glycolytic pathway. ITH-47 is an acetyl-lysine inhibitor that displaces bromdomain 4 proteins from chromatin by competitively binding to the acetyl-lysine recognition pocket of this bromodomain and extraterminal (BET) BRD protein, thereby preventing transcription of cancer-associated genes and further cell growth...
March 20, 2018: Anti-cancer Drugs
R Ravikanth Reddy, Ganesh Shanmugam, Balaraman Madhan, B V N Phani Kumar
The interaction of ionic liquid (IL) with protein is now becoming important as it stabilizes the protein due to the selective cation-anion combination of the IL. The binding and dynamics of the green solvents such as imidazole alkyl sulfate based ILs, viz., 1-butyl-3-methylimidazolium alkyl [where alkyl = hydrogen, methyl, octyl and dodecyl] sulfate, with two distinct model proteins, namely human serum albumin (HSA) and collagen in aqueous solution, have been investigated with the aid of solution nuclear magnetic resonance (NMR)...
March 21, 2018: Physical Chemistry Chemical Physics: PCCP
G V Ponomarev, T V Lalayan, S A Dambinova, A A Skoromets
The study aimed at assessing the level of glutamate receptors antibodies (Abs) in blood serum and cerebrospinal fluid (CSF) of patients with spinal cord ischemia along with traditional diagnostic approaches. MATERIAL AND METHODS: Forty patients with spinal cord ischemia (10 with spinal stroke and 30 with subacute and chronic course of the disease) were enrolled. After exclusion of some participants, 27 patients continued the study. Comparison groups included 30 patients with ischemic stroke and 30 patients with radiculopathy...
2018: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
Feng Liu, Priyatanu Roy, Qi Shao, Chunlan Jiang, Jeunghwan Choi, Connie Chung, Dushyant Mehra, Dr John Bischof
Atrial fibrillation affects millions of people in the US. Focal therapy is an attractive treatment for atrial fibrillation that avoids the debilitating effects of drugs for disease control. Perhaps the most widely used focal therapy for atrial fibrillation (AF) is heat-based radiofrequency (heating), although cryotherapy (cryo) is rapidly replacing it due to a reduction in side effects and positive clinical outcomes. A third focal therapy, irreversible electroporation (IRE), is also being considered. This study was designed to help guide treatment thresholds and compare mechanism of action across heating, cryo, and IRE...
February 17, 2018: Journal of Biomechanical Engineering
Alla M Zaydman, Elena L Strokova, Elena V Kiseleva, Lubov A Suldina, Anton A Strunov, Alexander I Shevchenko, Pavel P Laktionov, Vladimir M Subbotin
Idiopathic scoliosis is one of the most common disabling pathologies of children and adolescents. Etiology and pathogenesis of idiopathic scoliosis remain unknown. To study the etiology of this disease we identified the cells' phenotypes in the vertebral body growth plates in patients with idiopathic scoliosis. Materials and methods: The cells were isolated from vertebral body growth plates of the convex and concave sides of the deformity harvested intraoperatively in 50 patients with scoliosis. Cells were cultured and identified by methods of common morphology, neuromorphology, electron microscopy, immunohistochemistry and PCR analysis...
2018: International Journal of Medical Sciences
Elizabeth S Silagi, Philip Batista, Irving M Shapiro, Makarand V Risbud
The integrity of the avascular nucleus pulposus (NP) phenotype plays a crucial role in the maintenance of intervertebral disc health. While advances have been made to define the molecular phenotype of healthy NP cells, the functional relevance of several of these markers remains unknown. In this study, we test the hypothesis that expression of Carbonic Anhydrase III (CAIII), a marker of the notochordal NP, is hypoxia-responsive and functions as a potent antioxidant without a significant contribution to pH homeostasis...
March 20, 2018: Scientific Reports
Yuen K Ip, Kum C Hiong, Leon J Y Lim, Celine Y L Choo, Mel V Boo, Wai P Wong, Mei L Neo, Shit F Chew
The giant clam, Tridacna squamosa, represents a clam-zooxanthellae association. In light, the host clam and the symbiotic zooxanthellae conduct light-enhanced calcification and photosynthesis, respectively. We had cloned the cDNA coding sequence of a Vacuolar-type Proton ATPase (VHA) subunit A, ATP6V1A, from T. squamosa, whereby the VHA is an electrogenic transporter that actively 'pumps' H+ out of the cell. The ATP6V1A of T. squamosa comprised 1866 bp, encoding a protein of 622 amino acids and 69.9 kDa, and has a host-origin...
March 17, 2018: Gene
Yuwen Zhang, Jiaqing Hao, Jun Zeng, Qiang Li, Enyu Rao, Yanwen Sun, Lianliang Liu, Anita Mandal, V Douglas Landers, Rebecca J Morris, Margot P Cleary, Jill Suttles, Bing Li
Skin lipids (e.g. fatty acids) are essential for normal skin functions. Epidermal fatty acid-binding protein (E-FABP) is the predominant FABP expressed in skin epidermis. However, the role of E-FABP in skin homeostasis and pathology remains largely unknown. Herein, we utilized the 7,12-dimethylbenz(a)anthracene (DMBA) and 12-O-tetradecanolyphorbol-13-acetate (TPA)-induced skin tumorigenesis model to assess the role of E-FABP in chemical-induced skin tumorigenesis. Compared to their wild type (WT) littermates, mice deficient in E-FABP, but not adipose FABP (A-FABP), developed more skin tumors with higher incidence...
March 17, 2018: Journal of Investigative Dermatology
Xiujuan Zhou, Jing Xing, Xiaoqian Tang, Wenbin Zhan
Outer membrane protein (Omp) K, OmpR and VAA have been identified with good immunogenicity from Vibrio anguillarum, and their recombinant proteins showed variable relative percent survival (RPS) in previous study. In order to develop effective bivalent vaccine candidates, recombinant (r) VAA + rOmpK (AK), rVAA + rOmpR (AR), rOmpK + rOmpR (KR) among VAA, OmpK and OmpR, or formalin-killed cells (FKC) of V. anguillarum were immunized in flounder, respectively. Results revealed that AK, AR, KR and FKC could induce the proliferation of surface membrane immunoglobulin-positive B lymphocytes or CD3+ T lymphocytes in peripheral blood lymphocytes, and significantly enhance the total antibodies, specific antibodies and immune-related gene than those of control group...
March 17, 2018: Developmental and Comparative Immunology
Eun Ju Shin, Hyo-Kyoung Choi, Mi Jeong Sung, Jae Ho Park, Min-Yu Chung, Sangwon Chung, Jin-Taek Hwang
We investigated the anti-cancer effects of beta-sitosterol (BS), a plant-derived sterol in AGS human gastric adenocarcinoma cells and xenograft mouse models. BS significantly reduced cell viability by inducing apoptosis in AGS adenocarcinoma cells. This was accompanied by the formation of apoptotic bodies, as detected by Annexin V, caspase 3/7 activity, and MitoPotential assay. BS stimulated phosphatase and tensin homolog (PTEN) and phospho-AMP-activated protein kinase (p-AMPK) expression. Pharmacological inhibitors or siRNA were used to further analyse the relationship between the two proteins...
March 17, 2018: Biochemical Pharmacology
Asmah Hamid, Farah Wahida Ibrahim, Teoh Hooi Ming, Mohd Nazir Nasrom, Norelina Eusoff, Khairana Husain, Mazlyzam Abdul Latif
BACKGROUND: Zingiber zerumbet (L.) Smith belongs to the Zingiberaceae family that is widely distributed throughout the tropics, particularly in Southeast Asia. It is locally known as 'Lempoyang' and traditionally used to treat fever, constipation and to relieve pain. It is also known to possess antioxidant and anti-inflammatory activities. Based on these antioxidant and anti-inflammatory activities, this study was conducted to investigate the effects of ethyl-acetate extract of Z. zerumbet rhizomes against ethanol-induced brain damage in male Wistar rats...
March 20, 2018: BMC Complementary and Alternative Medicine
Teppei Okamoto, Shingo Hatakeyama, Hirotake Kodama, Hirotaka Horiguchi, Yuka Kubota, Koichi Kido, Masaki Momota, Shogo Hosogoe, Yoshimi Tanaka, Tooru Takashima, Fumitada Saitoh, Tadashi Suzuki, Chikara Ohyama
BACKGROUND: Although aortic calcification has a significant negative impact on prognosis in patients on hemodialysis (HD), risk factors for aortic calcification progression remain unclear. The aim of this study was to investigate the relationship between malnutrition and aortic calcification progression in patients on HD. METHODS: Between April 2015 and October 2016, we treated 232 patients on HD. Of those, we retrospectively evaluated data from 184 patients who had had regular blood tests and computed tomography (CT) scans...
March 20, 2018: BMC Nephrology
Ying Huang, Fang Liu, Fang Zhang, Pingsheng Liu, Tao Xu, Wenjun Ding
Numerous studies have demonstrated that vanadium compounds are able to improve lipemia and triglyceridemia in both humans and animals. However, the molecular mechanism remains elusive. The present study was conducted to investigate the anti-hyperlipidemic effect of vanadium(IV) complex with 4-chlorodipicolinic acid (VOdipic-Cl)-induced autophagy on hepatic lipid accumulation. To explore the possible underlying mechanisms, primary rat hepatocytes, human hepatoma cell line HepG2, and liver tissue from C57BL/6 mice fed a high-fat diet (HFD) were used...
March 14, 2018: Journal of Inorganic Biochemistry
Sowmya Mekala, Subbarao V Tullimilli, Ramasatyaveni Geesala, Kanakaraju Manupati, Neha R Dhoke, Amitava Das
Apoptotic hepatocytes release factors that activate Hepatic Stellate Cells (HSCs) thereby inducing hepatic fibrosis. In the present study, in vivo and in vitro injury models were established using acetaminophen, ethanol, carbon tetrachloride or thioacetamide. Hepatotoxicant-induced diseased hepatic tissue histology correlated with a differential expression of fibrosis-related genes. Marked increase in co-staining of TGFRIIβ-Desmin or α-SMA-PDGFRβ, markers of activated HSCs, in liver sections of these hepatotoxicant-treated mice also depicted an increase in Annexin V-Cytokeratin expressing hepatocytes...
March 20, 2018: Canadian Journal of Physiology and Pharmacology
Junghyun L Suh, Brian Watts, Jacob I Stuckey, Jacqueline L Norris-Drouin, Stephanie H Cholensky, Bradley M Dickson, Yi An, Sebastian Mathea, Eidarus Salah, Stefan Knapp, Abid Khan, Alexander T Adams, Brian D Strahl, Cari A Sagum, Mark T Bedford, Lindsey I James, Dmitri B Kireev, Stephen V Frye
Multivalent binding is an efficient means to enhance the affinity and specificity of chemical probes targeting multi-domain proteins in order to study their function and role in disease. While the theory of multivalent binding is straightforward, physical and structural characterization of bivalent binding encounters multiple technical difficulties. We present a case study where a combination of experimental techniques and computational simulations was used to comprehensively characterize the binding and structure-affinity relationships for a series of Bromosporine-based bivalent bromodomain ligands with a bivalent protein, Transcription Initiation Factor TFIID subunit 1 (TAF1)...
March 20, 2018: Biochemistry
George R Wendt, Julie Nr Collins, Jimin Pei, Mark S Pearson, Hayley M Bennett, Alex Loukas, Matthew Berriman, Nick V Grishin, James J Collins
Schistosomes infect more than 200 million people. These parasitic flatworms rely on a syncytial outer-coat called the tegument to survive within the vasculature of their host. Although the tegument is pivotal for their survival, little is known about maintenance of this tissue during the decades schistosomes survive in the bloodstream. Here, we demonstrate that the tegument relies on stem cells (neoblasts) to specify fusogenic progenitors that replace tegumental cells lost to turnover. Molecular characterization of neoblasts and tegumental progenitors led to the discovery of two flatworm-specific zinc finger proteins that are essential for tegumental cell specification...
March 20, 2018: ELife
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