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https://www.readbyqxmd.com/read/28208047/targeted-therapy-for-chronic-respiratory-disease-a-new-paradigm
#1
Peter G Gibson, Matthew J Peters, Claire E Wainwright
Targeted therapy has emerged as a highly effective treatment approach for chronic respiratory diseases. Many of these conditions have dismal outcomes; however, targeted therapy shows great results for the subgroup who respond. This represents a new way to approach these conditions and offers great promise as a future treatment direction. In severe eosinophilic asthma, therapy that targets the interleukin-5 pathway with monoclonal antibodies leads to a 50% reduction in asthma exacerbations in previously refractory disease...
February 20, 2017: Medical Journal of Australia
https://www.readbyqxmd.com/read/28168001/the-neuroprotective-effects-of-tao-ren-cheng-qi-tang-against-embolic-stroke-in-rats
#2
Ling-Wei Hsu, Wei-Cheng Shiao, Nen-Chung Chang, Meng-Che Yu, Ting-Lin Yen, Philip Aloysius Thomas, Thanasekaran Jayakumar, Joen-Rong Sheu
BACKGROUND: Combinations of the traditional Chinese and Western medicines have been used to treat numerous diseases throughout the world, and there is a growing body of evidence showing that some of the herbs used in traditional Chinese medicine elicit significant pharmacological effects. The aim of this study was to demonstrate the neuroprotective effects of Tao-Ren-Cheng-Qi Tang (TRCQT) in combination with aspirin following middle cerebral artery occlusion (MCAO)-induced embolic stroke in rats...
2017: Chinese Medicine
https://www.readbyqxmd.com/read/28165470/sodium-chloride-promotes-tissue-inflammation-via-osmotic-stimuli-in-subtotal-nephrectomized-mice
#3
Fumiko Sakata, Yasuhiko Ito, Masashi Mizuno, Akiho Sawai, Yasuhiro Suzuki, Takako Tomita, Mitsuhiro Tawada, Akio Tanaka, Akiyoshi Hirayama, Akihiro Sagara, Takashi Wada, Shoichi Maruyama, Tomoyoshi Soga, Seiichi Matsuo, Enyu Imai, Yoshifumi Takei
Chronic inflammation, which is often associated with high all-cause and cardiovascular mortality, is prevalent in patients with renal failure; however, the precise mechanisms remain unclear. High-salt intake was reported to induce lymphangiogenesis and autoimmune diseases via osmotic stimuli with accumulation of sodium or chloride. In addition, sodium was recently reported to be stored in the extremities of dialysis patients. We studied the effects and mechanisms of high salt loading on tissue and systemic inflammation in subtotal-nephrectomized mice (5/6Nx) and in cultured cells...
February 6, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28164762/regulation-of-ion-channels-cellular-carriers-and-na-k-atpase-by-janus-kinase-3
#4
Mentor Sopjani, Shpëtim Thaçi, Berat Krasniqi, Miranda Selmonaj, Mark Rinnerthaler, Miribane Dërmaku-Sopjani
Janus kinase-3 (JAK3), a tyrosine kinase, is expressed in a variety of tissues, including the brain, and is involved in the signaling of cytokine receptors. JAK3 participates in numerous functions, among other the cell survival and proliferation, neuroprotection, apoptosis, as well as cellular response to hypoxia and ischemia-reperfusion. This kinase further contributes in the signaling of hematopoietic cell cytokine receptors, dendritic cells activation, maturation, and immune suppression as well as to cell volume regulation...
February 3, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28161653/low-level-laser-therapy-lllt-accelerates-the-sternomastoid-muscle-regeneration-process-after-myonecrosis-due-to-bupivacaine
#5
Cristiane Neves Alessi Pissulin, Ana Angélica Henrique Fernandes, Alejandro Manuel Sanchez Orellana, Renata Calciolari Rossi E Silva, Selma Maria Michelin Matheus
BACKGROUND: Because of its long-lasting analgesic action, bupivacaine is an anesthetic used for peripheral nerve block and relief of postoperative pain. Muscle degeneration and neurotoxicity are its main limitations. There is strong evidence that low-level laser therapy (LLLT) assists in muscle and nerve repair. The authors evaluated the effects of a Gallium Arsenide laser (GaAs), on the regeneration of muscle fibers of the sternomastoid muscle and accessory nerve after injection of bupivacaine...
January 26, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28160636/daily-sesame-oil-supplementation-attenuates-local-renin-angiotensin-system-via-inhibiting-mapk-activation-and-oxidative-stress-in-cardiac-hypertrophy
#6
Chuan-Teng Liu, Ming-Yie Liu
The renin-angiotensin system (RAS) is involved in the development of left ventricular hypertrophy (LVH) by which increases cardiac morbidity and mortality. Activation of mitogen-activated protein kinases (MAPKs) and oxidative stress are important in RAS-mediated cardiac hypertrophy. Sesame oil, a potent antioxidant, attenuates hypertension-dependent LVH. We examined the protective role of sesame oil on RAS-mediated MAPK activation and oxidative stress in rats. We induced LVH using a hypertensive model by subcutaneously injecting deoxycorticosterone acetate (DOCA; 15 mg/ml/kg in mineral oil; twice weekly for 5 weeks) and supplementing with 1% sodium chloride drinking water (DOCA/salt) to uninephrectomized rats...
May 28, 2016: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28126833/ghrelin-induces-clock-gene-expression-in-the-liver-of-goldfish-in-vitro-via-protein-kinase-c-and-protein-kinase-a-pathways
#7
Aída Sánchez-Bretaño, Ayelén M Blanco, Ángel L Alonso-Gómez, María J Delgado, Olivier Kah, Esther Isorna
The liver is the most important link between the circadian system and metabolism. As a food entrainable oscillator, the hepatic clock needs to be entrained by food-related signals. The objective of the present study was to investigate the possible role of ghrelin (an orexigenic peptide mainly synthesized in the gastrointestinal tract) as an endogenous synchronizer of the liver oscillator in teleosts. To achieve this aim, we first examined the presence of ghrelin receptors in the liver of goldfish. Then, the ghrelin regulation of clock gene expression in the goldfish liver was studied...
January 26, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28125813/signal-transduction-underlying-the-inhibitory-mechanism-of-fluoxetine-on-electrical-field-stimulation-response-in-rat-ileal-smooth-muscle
#8
Phyu Phyu Khin, Tin Sandar Zaw, Uy Dong Sohn
Fluoxetine (FLX), a well-known antidepressant drug under the class of selective serotonin reuptake inhibitor, exerts its action by inhibiting the reuptake of serotonin selectively. In some studies, it has been demonstrated that FLX relaxes the intestinal smooth muscle. In this study, we aimed at studying the signal transduction pathway underlying the muscle relaxation effect of FLX on electrically stimulated rat ileal muscle contraction. To investigate the possible mechanism involved, various antagonists were used...
January 27, 2017: Pharmacology
https://www.readbyqxmd.com/read/28115189/rosmarinic-acid-counteracts-activation-of-hepatic-stellate-cells-via-inhibiting-the-ros-dependent-mmp-2-activity-involvement-of-nrf2-antioxidant-system
#9
Changfang Lu, Yu Zou, Yuzhang Liu, Yingcai Niu
Recently, oxidative stress is involved in hepatofibrogenesis. Matrix metalloproteinase-2 (MMP-2) is required for activation of hepatic stellate cells (HSCs) in response to reactive oxygen species (ROS). This study was designed to explore the hypothesis that the inhibitory effect of rosmarinic acid (RA) on HSCs activation might mainly result from its antioxidant capability by increasing the synthesis of glutathione (GSH) involved in nuclear factor kappa B (NF-κB)-dependent inhibition of MMP-2 activity. Here, we demonstrate that RA reverses activated HSCs to quiescent cells...
March 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28077321/camkii%C3%AE-subtypes-differentially-regulate-infarct-formation-following-ex-vivo-myocardial-ischemia-reperfusion-through-nf-%C3%AE%C2%BAb-and-tnf-%C3%AE
#10
Charles B B Gray, Takeshi Suetomi, Sunny Xiang, Erik A Blackwood, Christopher C Glembotski, Shigeki Miyamoto, B Daan Westenbrink, Shikha Mishra, Joan Heller Brown
Deletion of Ca(2+)/calmodulin-dependent protein kinase II delta (CaMKIIδ) has been shown to protect against in vivo ischemia/reperfusion (I/R) injury. It remains unclear which CaMKIIδ isoforms and downstream mechanisms are responsible for the salutary effects of CaMKIIδ gene deletion. In this study we sought to compare the roles of the CaMKIIδB and CaMKIIδC subtypes and the mechanisms by which they contribute to ex vivo I/R damage. WT, CaMKIIδKO, and mice expressing only CaMKIIδB or δC were subjected to ex vivo global ischemia for 25min followed by reperfusion...
January 7, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28067240/cd8-t-cells-stimulate-na-cl-co-transporter-ncc-in-distal-convoluted-tubules-leading-to-salt-sensitive-hypertension
#11
Yunmeng Liu, Tonya M Rafferty, Sung W Rhee, Jessica S Webber, Li Song, Benjamin Ko, Robert S Hoover, Beixiang He, Shengyu Mu
Recent studies suggest a role for T lymphocytes in hypertension. However, whether T cells contribute to renal sodium retention and salt-sensitive hypertension is unknown. Here we demonstrate that T cells infiltrate into the kidney of salt-sensitive hypertensive animals. In particular, CD8(+) T cells directly contact the distal convoluted tubule (DCT) in the kidneys of DOCA-salt mice and CD8(+) T cell-injected mice, leading to up-regulation of the Na-Cl co-transporter NCC, p-NCC and the development of salt-sensitive hypertension...
January 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28060847/enhanced-chondrogenic-differentiation-of-human-umbilical-cord-wharton-s-jelly-derived-mesenchymal-stem-cells-by-gsk-3-inhibitors
#12
Prapot Tanthaisong, Sumeth Imsoonthornruksa, Apichart Ngernsoungnern, Piyada Ngernsoungnern, Mariena Ketudat-Cairns, Rangsun Parnpai
Articular cartilage is an avascular, alymphatic, and aneural system with very low regeneration potential because of its limited capacity for self-repair. Mesenchymal stem cells (MSCs) are the preferred choice for cell-based therapies. Glycogen synthase kinase 3 (GSK-3) inhibitors are compounds that can induce the Wnt signaling pathway, which is involved in chondrogenesis and cartilage development. Here, we investigated the influence of lithium chloride (LiCl) and SB216763 synergistically with TGF-β3 on chondrogenic differentiation in human mesenchymal stem cells derived from Wharton's jelly tissue (hWJ-MSCs)...
2017: PloS One
https://www.readbyqxmd.com/read/28056927/kudiezi-injection-mitigates-myocardial-injury-induced-by-acute-cerebral-ischemia-in-rats
#13
Xuemei Liu, Ye Tao, Fengli Wang, Ting Yao, Chen Fu, Hong Zheng, Yan Yan, Xiao Liang, Xiangning Jiang, Yunling Zhang
BACKGROUND: Kudiezi (KDZ) injection is commonly used in traditional Chinese medicine as treatment for cerebral infarction and angina pectoris. The present study investigated the therapeutic effects of KDZ injection on myocardial injury induced by acute cerebral ischemia and the possibly protective mechanisms. METHODS: Rats were divided into three groups: sham, 6h-ischemia, and KDZ treatment (KDZ). The neurological deficits were determined by the Garcia score. The cerebral infarct volume was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and brain water content was also evaluated...
January 5, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28012960/heme-oxygenase-ho-1-induction-prevents-endoplasmic-reticulum-stress-mediated-endothelial-cell-death-and-impaired-angiogenic-capacity
#14
Hatem Maamoun, Matshediso Zachariah, John H McVey, Fiona R Green, Abdelali Agouni
Most of diabetic cardiovascular complications are attributed to endothelial dysfunction and impaired angiogenesis. Endoplasmic Reticulum (ER) and oxidative stresses were shown to play a pivotal role in the development of endothelial dysfunction in diabetes. Hemeoxygenase-1 (HO-1) was shown to protect against oxidative stress in diabetes; however, its role in alleviating ER stress-induced endothelial dysfunction remains not fully elucidated. We aim here to test the protective role of HO-1 against high glucose-mediated ER stress and endothelial dysfunction and understand the underlying mechanisms with special emphasis on oxidative stress, inflammation and cell death...
December 21, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28011945/orexin-a-modulates-ins-1e-cell-proliferation-and-insulin-secretion-via-extracellular-signal-regulated-kinase-and-transient-receptor-potential-channels
#15
M Skrzypski, N Khajavi, S Mergler, M Billert, D Szczepankiewicz, T Wojciechowicz, K W Nowak, M Z Strowski
Orexins A (OXA) and B (OXB) control energy homeostasis by regulating food intake, energy expenditure and sleep-wake cycle. Several studies showed that OXA stimulates insulin secretion and proliferation of beta cells. However, mechanisms of action are still not well understood. Here, we investigated whether ERK and transient receptor potential channels (TRPs) play a role in mediating the effect of OXA on cell growth, insulin production, and secretion using the established INS-1E cell line. Cell proliferation was measured using BrdU assay...
October 2016: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28011640/regulation-of-ulk1-expression-and-autophagy-by-stat1
#16
Alexander A Goldberg, Bernard Nkengfac, Anthony M J Sanchez, Nikolay Moroz, Salman T Qureshi, Antonis E Koromilas, Shuo Wang, Yan Burelle, Sabah N Hussain, Arnold S Kristof
Autophagy involves the lysosomal degradation of cytoplasmic contents for regeneration of anabolic substrates during nutritional or inflammatory stress. Its initiation occurs rapidly after inactivation of the protein kinase mammalian target of rapamycin (mTOR) (or mechanistic target of rapamycin), leading to dephosphorylation of Unc-51-like kinase 1 (ULK1) and autophagosome formation. Recent studies indicate that mTOR can, in parallel, regulate the activity of stress transcription factors, including signal transducer and activator of transcription-1 (STAT1)...
February 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27999941/extracellular-phosphates-enhance-activities-of-voltage-gated-proton-channels-and-production-of-reactive-oxygen-species-in-murine-osteoclast-like-cells
#17
Guangshuai Li, Katsuyuki Miura, Miyuki Kuno
Osteoclasts are highly differentiated bone-resorbing cells and play a significant role in bone remodelling. In the resorption pit, inorganic phosphate (Pi) concentrations increase because of degradation of hydroxyapatite. We studied effects of extracellular Pi on voltage-gated H(+) channels in osteoclast-like cells derived from a macrophage cell line (RAW264). Extracellular Pi (1.25-20 mM) increased the H(+) channel currents dose dependently and reversibly. The Pi-induced increases were attenuated by removal of extracellular Na(+) and by phosphonoformic acid, a blocker of Na(+)-dependent Pi transporters...
December 21, 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27998718/camkii-mediated-phosphorylation-of-glun2b-regulates-recombinant-nmda-receptor-currents-in-a-chloride-dependent-manner
#18
Steven J Tavalin, Roger J Colbran
Some forms of long-term synaptic plasticity require docking of Ca(2+)/calmodulin-dependent protein kinase II α (CaMKIIα) to residues 1290-1309 within the intracellular C-terminal tail of the N-methyl-d-aspartate (NMDA) receptor GluN2B subunit. The phosphorylation of Ser1303 within this region destabilizes CaMKII binding. Interestingly, Ser1303 is a substrate for CaMKII itself, as well as PKC and DAPK1, but these kinases have been reported to have contradictory effects on the activity of GluN2B-containing NMDA receptors...
March 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/27994435/pkr-promotes-choroidal-neovascularization-via-upregulating-the-pi3k-akt-signaling-pathway-in-vegf-expression
#19
Manhui Zhu, Xiaojuan Liu, Shengcun Wang, Jin Miao, Liucheng Wu, Xiaowei Yang, Ying Wang, Lihua Kang, Wendie Li, Chen Cui, Hui Chen, Aimin Sang
PURPOSE: The aim of this study was to investigate the functions of dsRNA-activated protein kinase (PKR) in choroidal neovascularization (CNV) and related signaling pathways in the production of vascular endothelial growth factor (VEGF). METHODS: A chemical hypoxia model of in vitro RF/6A cells, a rhesus choroid-retinal endothelial cell line, was established by adding cobalt chloride (CoCl2) to the culture medium. PKR, phosphophosphatidylinositol 3-kinase (p-PI3K), phosphoprotein kinase B (p-Akt), and VEGF protein levels in RF/6A cells were detected with western blotting...
2016: Molecular Vision
https://www.readbyqxmd.com/read/27991911/inhibition-of-infarction-induced-sympathetic-innervation-with-endothelin-receptor-antagonism-via-a-pi3k-gsk-3%C3%AE-dependent-pathway
#20
T-M Lee, Nen-Chung Chang, Shinn-Zong Lin
Although endothelin (ET)-1 has been shown to upregulate nerve growth factor (NGF) expression, the molecular mechanisms are largely unknown. Phosphatidylinositol 3-kinase (PI3K)/Akt/glycogen synthase kinase (GSK)-3β signal has been implicated in the regulation of NGF. We investigated whether selective ET receptor blockers attenuated cardiac sympathetic reinnervation through restoring PI3K/Akt/GSK-3β activity. After ligation of the left anterior descending artery, male Wistar rats were randomized to either vehicle, atrasentan (an ETA receptor antagonist) or A-192621 (an ETB receptor antagonist) for 4 weeks...
December 19, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
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