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https://www.readbyqxmd.com/read/29166726/-interaction-between-trpc1-and-stim1-in-calcium-sensing-receptor-mediated-calcium-influx-and-nitric-oxide-production-in-human-umbilical-vein-endothelial-cells
#1
L M Wang, H Zhong, N Tang, L J Pang, C J Zhang, F He
Objective: To investigate the interaction of Ca(2+) protein TRPC1 and STIM1 in extracellular Ca(2+) -sensing receptor (CaR)-induced extracellular Ca(2+) influx and the production of nitric oxide (NO). Methods: Human umbilical vein endothelial cells (HUVECs) were cultured and incubated with CaR agonist spermine (activating store-operates cation channels (SOC) and receptor-operated channels (ROC)), CaR negative allosteric modulator Calhex231 (blocking SOC, activating ROC) and ROC analogue TPA (activating ROC, blocking SOC), protein kinase C (PKC) inhibitor Ro31-8220, PKCs and PKCμ inhibitor Go6967(activate SOC, blocking ROC), respectively...
November 24, 2017: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/29166712/-effects-of-endostatin-pretreatment-on-fibrosis-of-human-skin-fibroblasts-and-the-mechanisms
#2
H T Ren, Y Li, S D Wang, C M Han
Objective: To explore the effects of endostatin pretreatment on fibrosis of human skin fibroblasts and the mechanisms. Methods: Human skin fibroblasts were routinely cultured in vitro, and then the cells of passage 3 to 5 were used in the following experiments. The cells were divided into blank control, endostatin, platelet-derived growth factor-BB (PDGF-BB), endostatin+ PDGF-BB, transforming growth factor-β(1) (TGF-β(1)), and endostatin+ TGF-β(1) groups according to the random number table, with 3 wells in each group...
November 20, 2017: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/29166708/-effects-of-astragalus-polysaccharide-on-cardiac-dysfunction-in-rabbits-with-severe-scald-injury
#3
L Zhong, J H Zhan, J H Luo, X Cheng
Objective: To investigate the effects of astragalus polysaccharide (AP) on cardiac dysfunction in rabbits with severe scald injury. Methods: Sixty-four New Zealand white rabbits were divided into pure scald group and AP group according to the random number table, with 32 rabbits in each group. Rabbits in the two groups were all inflicted with 30% total body surface area full-thickness scald on the back. Immediately after injury, rabbits in two groups were intraperitoneally injected with lactated Ringer's solution once for antishock...
November 20, 2017: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
https://www.readbyqxmd.com/read/29166608/s-nitrosylation-of-pink1-attenuates-pink1-parkin-dependent-mitophagy-in-hipsc-based-parkinson-s-disease-models
#4
Chang-Ki Oh, Abdullah Sultan, Joseph Platzer, Nima Dolatabadi, Frank Soldner, Daniel B McClatchy, Jolene K Diedrich, John R Yates, Rajesh Ambasudhan, Tomohiro Nakamura, Rudolf Jaenisch, Stuart A Lipton
Mutations in PARK6 (PINK1) and PARK2 (Parkin) are linked to rare familial cases of Parkinson's disease (PD). Mutations in these genes result in pathological dysregulation of mitophagy, contributing to neurodegeneration. Here, we report that environmental factors causing a specific posttranslational modification on PINK1 can mimic these genetic mutations. We describe a molecular mechanism for impairment of mitophagy via formation of S-nitrosylated PINK1 (SNO-PINK1). Mitochondrial insults simulating age- or environmental-related stress lead to increased SNO-PINK1, inhibiting its kinase activity...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29166606/sumoylation-promotes-nuclear-import-and-stabilization-of-polo-like-kinase-1-to-support-its-mitotic-function
#5
Donghua Wen, Jianguo Wu, Lei Wang, Zheng Fu
As a pivotal mitotic regulator, polo-like kinase 1 (PLK1) is under highly coordinated and multi-layered regulation. However, the pathways that control PLK1's activity and function have just begun to be elucidated. PLK1 has recently been shown to be functionally modulated by post-translational modifications (PTMs), including phosphorylation and ubiquitination. Herein, we report that SUMOylation plays an essential role in regulating PLK1's mitotic function. We found that Ubc9 was recruited to PLK1 upon initial phosphorylation and activation by CDK1/cyclin B...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29166598/biological-significance-of-the-suppression-of-oxidative-phosphorylation-in-induced-pluripotent-stem-cells
#6
Cheng Zhang, Maria Skamagki, Zhong Liu, Aparna Ananthanarayanan, Rui Zhao, Hu Li, Kitai Kim
We discovered that induced pluripotent stem cell (iPSC) clones generated from aged tissue donors (A-iPSCs) fail to suppress oxidative phosphorylation. Compared to embryonic stem cells (ESCs) and iPSCs generated from young donors (Y-iPSCs), A-iPSCs show poor expression of the pluripotent stem cell-specific glucose transporter 3 (GLUT3) and impaired glucose uptake, making them unable to support the high glucose demands of glycolysis. Persistent oxidative phosphorylation in A-iPSCs generates higher levels of reactive oxygen species (ROS), which leads to excessive elevation of glutathione (a ROS-scavenging metabolite) and a blunted DNA damage response...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29166596/the-gcn2-atf4-signaling-pathway-induces-4e-bp-to-bias-translation-and-boost-antimicrobial-peptide-synthesis-in-response-to-bacterial-infection
#7
Deepika Vasudevan, Nicholas K Clark, Jessica Sam, Victoria C Cotham, Beatrix Ueberheide, Michael T Marr, Hyung Don Ryoo
Bacterial infection often leads to suppression of mRNA translation, but hosts are nonetheless able to express immune response genes through as yet unknown mechanisms. Here, we use a Drosophila model to demonstrate that antimicrobial peptide (AMP) production during infection is paradoxically stimulated by the inhibitor of cap-dependent translation, 4E-BP (eIF4E-binding protein; encoded by the Thor gene). We found that 4E-BP is induced upon infection with pathogenic bacteria by the stress-response transcription factor ATF4 and its upstream kinase, GCN2...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29166587/migrating-myeloid-cells-sense-temporal-dynamics-of-chemoattractant-concentrations
#8
Caren E Petrie Aronin, Yun M Zhao, Justine S Yoon, Nicole Y Morgan, Thorsten Prüstel, Ronald N Germain, Martin Meier-Schellersheim
Chemoattractant-mediated recruitment of hematopoietic cells to sites of pathogen growth or tissue damage is critical to host defense and organ homeostasis. Chemotaxis is typically considered to rely on spatial sensing, with cells following concentration gradients as long as these are present. Utilizing a microfluidic approach, we found that stable gradients of intermediate chemokines (CCL19 and CXCL12) failed to promote persistent directional migration of dendritic cells or neutrophils. Instead, rising chemokine concentrations were needed, implying that temporal sensing mechanisms controlled prolonged responses to these ligands...
November 21, 2017: Immunity
https://www.readbyqxmd.com/read/29166577/cell-cycle-related-kinase-regulates-mammalian-eye-development-through-positive-and-negative-regulation-of-the-hedgehog-pathway
#9
Floria I Lupu, Jacob B Burnett, Jonathan T Eggenschwiler
Cell cycle-related kinase (CCRK) is a conserved regulator of ciliogenesis whose loss in mice leads to a wide range of developmental defects, including exencephaly, preaxial polydactyly, skeletal abnormalities, and microphthalmia. Here, we investigate the role of CCRK in mouse eye development. Ccrk mutants show dramatic patterning defects, with an expansion of the optic stalk domain into the optic cup, as well as an expansion of the retinal pigment epithelium (RPE) into neural retina (NR) territory. In addition, Ccrk mutants display a shortened optic stalk...
November 19, 2017: Developmental Biology
https://www.readbyqxmd.com/read/29166574/altered-tnf-%C3%AE-response-by-aconibal-%C3%A2-and-methotrexate-in-a-lipopolysaccharide-induced-setting-of-inflammatory-conditions-potential-on-a-synergistic-combination
#10
Gunhyuk Park, Seoung Hoon Lee, Ji-Ye Han, Dal-Seok Oh
ETHNOPHARMACOLOGICAL RELEVANCE: Aconitum carmichaelii (AC) is a common herbal medicine used as anti-inflammatory and analgesic agent in Eastern Asia. In Korea, a commercial processed AC (Aconibal(®)) is traditionally used to treat the symptoms of spondylosis deformans and rheumatic pain. AIM OF STUDY: Rheumatoid arthritis (RA) is systemic and auto-immune disease characterized by chronic inflammation. Methotrexate (MTX) is often the first-line therapy for RA. If MTX monotherapy is ineffective or RA is initially severe, adding a tumor necrosis factor (TNF)-α inhibitor to the treatment can be beneficial...
November 19, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29166570/splenectomy-after-partial-hepatectomy-accelerates-liver-regeneration-in-mice-by-promoting-tight-junction-formation-via-polarity-protein-par-3-apkc
#11
Guoxing Liu, Chengzhi Xie, Yu Fang, Ke Qian, Qiang Liu, Gao Liu, Zhenyu Cao, Huihui Du, Jie Fu, Xundi Xu
AIMS: Several experimental studies have demonstrated that removal of the spleen accelerates liver regeneration after partial hepatectomy. While the mechanism of splenectomy promotes liver regeneration by the improvement of the formation of tight junction and the establishment of hepatocyte polarity is still unknown. MAIN METHODS: We analyzed the cytokines, genes and proteins expression between 70% partial hepatectomy mice (PHx) and simultaneous 70% partial hepatectomy and splenectomy mice (PHs) at predetermined timed points...
November 19, 2017: Life Sciences
https://www.readbyqxmd.com/read/29166513/primary-cutaneous-amelanotic-melanoma-and-gastrointestinal-stromal-tumor-in-synchronous-evolution
#12
Fernanda Teixeira Ortega, Rogério Nabor Kondo, Francine Milenkovich Belinetti, Mariana Onuki Okamura, Bruna Tuma
Gastrointestinal stromal tumor is rare digestive tract mesenchymal tumor, most often in the wall of the stomach. It is a benign neoplasm, but it can become malignant if not treated. We report a case of gastrointestinal stromal tumor that was discovered after abdominal ultrasonography during staging of a patient with primary cutaneous amelanotic melanoma. Mutation in the tyrosine kinase receptor could explain the development of two types of tumors in the same patient.
September 2017: Anais Brasileiros de Dermatologia
https://www.readbyqxmd.com/read/29166283/cardiac-disorders-in-dogs-infected-with-babesia-canis
#13
M Bartnicki, P Łyp, P Dębiak, M Staniec, S Winiarczyk, K Buczek, Ł Adaszek
The aim of this study was to assess cardiac disorders in dogs infected with B. canis. The study included 50 dogs with babesiosis and 20 healthy control animals. All the animals had haematological tests, ECG, echocardiography and serum troponin I and CK-MB levels checked. The haematology in the group of dogs with babesiosis confirmed thrombocytopaenia in 100% of dogs, decreased haematocrit in 52% and anaemia in 46%. The most common abnormalities in ECG and echocardiography in dogs infected with protozoa included: change in appearance and/or amplitude of the T-wave (34%), increased fractional shortening (24%), an increased sinus rhythm (14%) and heart axis deviation (10%)...
September 26, 2017: Polish Journal of Veterinary Sciences
https://www.readbyqxmd.com/read/29165897/lithospermum-erythrorhizon-root-and-its-naphthoquinones-repress-srebp1c-and-activate-pgc1%C3%AE-through-ampk%C3%AE
#14
Rodney A Velliquette, Arun Rajgopal, John Rebhun, Kelly Glynn
OBJECTIVE: To examine specific molecular mechanisms involved in modulating hepatic lipogenesis and mitochondria biogenesis signals by Lithospermum erythrorhizon (gromwell) root extract. METHODS: Stable cell lines with luciferase reporter constructs were generated to examine sterol regulatory element binding protein 1c (SREBP1c) and peroxisome proliferator-activated receptor gamma, coactivator 1 (PGC1) α promoter activity and estrogen-related receptor (ERR) α response element activity...
November 22, 2017: Obesity
https://www.readbyqxmd.com/read/29165873/andrographolide-inhibits-hypoxia-induced-hypoxia-inducible-factor-1%C3%AE-and-endothelin-1-expression-through-the-heme-oxygenase-1-co-cgmp-mkp-5-pathways-in-ea-hy926-cells
#15
Hung-Chih Lin, Shih-Li Su, Wan-Chun Lin, Ai-Hsuan Lin, Ya-Chen Yang, Chong-Kuei Lii, Haw-Wen Chen
Andrographolide is a potent anti-inflammatory agent found in Andrographis paniculata. Endothelin 1 (ET-1) is an endothelium-derived vasoconstrictor with pro-inflammatory properties secreted in response to hypoxia. Mitogen-activated protein kinase phosphatase 5 (MKP-5) is a dual-specificity phosphatase that dephosphorylates threonine and tyrosine residues of MAPKs. We showed previously that hypoxia-induced HIF-1α expression and ET-1 secretion are dependent on p38 MAPK in EA.hy926 cells. Here, we investigate what role MKP-5 plays in andrographolide's inhibition of hypoxia-induced expression of HIF-1α and ET-1...
November 22, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/29165856/saccharomyces-cerevisiae-hog1-map-kinase-pathway-is-activated-in-response-to-honokiol-exposure
#16
Lingmei Sun, Kai Liao
AIM: The goal of the study was to investigate the cellular tolerance mechanism in response to honokiol exposure. METHODS AND RESULTS: The broth microdilution method was employed to test the sensitivity of different Saccharomyces cerevisiae strains to honokiol. Intracellular levels of reactive oxygen species (ROS) were determined by DCFH-DA staining. The phosphorylation of Hog1 was evaluated by western blot analysis. The mRNA expressions of genes involved in the Ras-cyclic AMP (cAMP) pathway were analyzed by real-time reverse transcription polymerase chain reaction...
November 22, 2017: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/29165716/targeting-bcr-abl-independent-tki-resistance-in-chronic-myeloid-leukemia-by-mtor-and-autophagy-inhibition
#17
Rebecca Mitchell, Lisa E M Hopcroft, Pablo Baquero, Elaine K Allan, Kay Hewit, Daniel James, Graham Hamilton, Arunima Mukhopadhyay, Jim O'Prey, Alan Hair, Junia V Melo, Edmond Chan, Kevin M Ryan, Véronique Maguer-Satta, Brian J Druker, Richard E Clark, Subir Mitra, Pawel Herzyk, Franck E Nicolini, Paolo Salomoni, G Vignir Helgason
Background: Imatinib and second-generation tyrosine kinase inhibitors (TKIs) nilotinib and dasatinib have statistically significantly improved the life expectancy of chronic myeloid leukemia (CML) patients; however, resistance to TKIs remains a major clinical challenge. Although ponatinib, a third-generation TKI, improves outcomes for patients with BCR-ABL-dependent mechanisms of resistance, including the T315I mutation, a proportion of patients may have or develop BCR-ABL-independent resistance and fail ponatinib treatment...
November 20, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29165709/structural-basis-for-the-gtp-specificity-of-the-rna-kinase-domain-of-fungal-trna-ligase
#18
Barbara S Remus, Yehuda Goldgur, Stewart Shuman
Fungal tRNA ligase (Trl1) is an essential enzyme that repairs RNA breaks with 2',3'-cyclic-PO4 and 5'-OH ends inflicted during tRNA splicing and non-canonical mRNA splicing in the fungal unfolded protein response. Trl1 is composed of C-terminal cyclic phosphodiesterase and central polynucleotide kinase domains that heal the broken ends to generate the 3'-OH,2'-PO4 and 5'-PO4 termini required for sealing by an N-terminal ligase domain. Trl1 enzymes are found in all human fungal pathogens and are promising targets for antifungal drug discovery because their domain compositions and biochemical mechanisms are unique compared to the mammalian RtcB-type tRNA splicing enzyme...
November 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29165691/estradiol-protects-proopiomelanocortin-neurons-against-insulin-resistance
#19
Jian Qiu, Martha A Bosch, Cecilia Meza, Uyen-Vy Navarro, Casey C Nestor, Edward J Wagner, Oline K Rønnekleiv, Martin J Kelly
Insulin resistance is at the core of the metabolic syndrome, and men exhibit a higher incidence of metabolic syndrome than women in early adult life, but this sex advantage diminishes sharply when women reach the postmenopausal state. Since 17β-estradiol (E2) augments the excitability of the anorexigenic POMC neurons, we investigated the neuroprotective effects of E2 against insulin resistance in POMC neurons from diet-induced obese (DIO) female and male mice. The efficacy of insulin to activate canonical transient receptor potential 5 (TRPC5) channels and depolarize POMC neurons was significantly reduced in DIO male but not in DIO female mice...
November 20, 2017: Endocrinology
https://www.readbyqxmd.com/read/29165638/feasibility-of-real-time-molecular-profiling-for-patients-with-newly-diagnosed-glioblastoma-without-mgmt-promoter-hypermethylation-the-nct-neuro-master-match-n2m2-pilot-study
#20
Elke Pfaff, Tobias Kessler, Gnana Prakash Balasubramanian, Anne Berberich, Daniel Schrimpf, Antje Wick, Jürgen Debus, Andreas Unterberg, Martin Bendszus, Christel Herold-Mende, David Capper, Irini Schenkel, Andreas Eisenmenger, Susan Dettmer, Benedikt Brors, Michael Platten, Stefan M Pfister, Andreas von Deimling, David T W Jones, Wolfgang Wick, Felix Sahm
Introduction: O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status is a predictive biomarker in glioblastoma patients. Glioblastoma without hypermethylated MGMT promoter are largely resistant to treatment with temozolomide. These patients are in particular need of new treatment approaches, which are offered by biomarker-driven clinical trials with targeted drugs based on molecular characterization of individual tumors. Methods: In preparation for an upcoming clinical study, a comprehensive molecular profiling approach was undertaken on tissues from 43 glioblastoma patients harboring an unmethylated MGMT promoter at diagnosis...
November 18, 2017: Neuro-oncology
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