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https://www.readbyqxmd.com/read/28636994/a-novel-ampk-activator-hernandezine-inhibits-lps-induced-tnf%C3%AE-production
#1
Ping Li, Xiaofang Li, Yonghong Wu, Manxiang Li, Xiaochuang Wang
Here, we found that hernandezine, a novel AMPK activator, inhibited LPS-induced TNFα expression/production in human macrophage cells (THP-1 and U937 lines). Activation of AMPK is required for hernandezine-induced anti-LPS response. AMPKα shRNA or dominant negative mutation (T172A) blocked hernandezine-induced AMPK activation, which almost completely reversed anti-LPS activity by hernandezine. Exogenous expression of the constitutively activate AMPKα (T172D, caAMPKα) also suppressed TNFα production by LPS...
June 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28635548/th-17-regulatory-cytokines-il-21-il-23-and-il-6-enhance-neutrophil-production-of-il-17-cytokines-during-asthma
#2
Rabih Halwani, Asma Sultana, Alejandro Vazquez-Tello, Amer Jamhawi, Abeer A Al-Masri, Saleh Al-Muhsen
BACKGROUND: In a subset of severe asthma patients, chronic airway inflammation is associated with infiltration of neutrophils, Th-17 cells and elevated expression of Th-17-derived cytokines (e.g., interleukin [IL]-17, IL-21, IL-22). Peripheral neutrophils from allergic asthmatics are known to express higher IL-17 cytokine levels than those from healthy subjects, but the regulatory mechanisms involved are not well understood. We hypothesize that Th-17 regulatory cytokines could modulate IL-17 expression in neutrophils...
March 2, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/28634283/phase-ib-study-of-utomilumab-pf-05082566-a-4-1bb-cd137-agonist-in-combination-with-pembrolizumab-mk-3475-in-patients-with-advanced-solid-tumors
#3
Anthony W Tolcher, Mario Sznol, Siwen Hu-Lieskovan, Kyriakos P Papadopoulos, Amita Patnaik, Drew Rasco, Donna Di Gravio, Bo Huang, Dhiraj Gambhire, Ying Chen, Aron Thall, Nuzhat Pathan, Emmett V Schmidt, Laura Q M Chow
Purpose:  This phase Ib study (NCT02179918) evaluated the safety, antitumor activity, pharmacokinetics, and pharmacodynamics of utomilumab, a fully human IgG2 mAb agonist of the T-cell costimulatory receptor 4-1BB/CD137 in combination with the humanized, PD-1-blocking IgG4 mAb pembrolizumab in patients with advanced solid tumors. <p>Experimental Design:  Utomilumab (0.45-5.0 mg/kg) and pembrolizumab (2 mg/kg) were administered intravenously every 3 weeks. Utomilumab dose escalation was conducted using the time-to-event-continual reassessment method...
June 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28633155/regional-anesthesia-and-pain-medicine-us-anesthesiology-resident-training-the-year-2015
#4
Joseph M Neal, Anne Gravel Sullivan, Richard W Rosenquist, Dan J Kopacz
BACKGROUND AND OBJECTIVES: The Anesthesiology Review Committee of the Accreditation Council for Graduate Medical Education sets core requirements for residency program accreditation. We periodically report and analyze the US anesthesiology residents' training experience in regional anesthesia and pain medicine. METHODS: Resident caseload, procedure, and pain medicine evaluation data were aggregated for the resident cohort who graduated in 2015. These data were analyzed for present-day experience and compared with previous reports from years 1980, 1990, and 2000 graduates...
July 2017: Regional Anesthesia and Pain Medicine
https://www.readbyqxmd.com/read/28630022/lamprey-metamorphosis-thyroid-hormone-signaling-in-a-basal-vertebrate
#5
REVIEW
Richard G Manzon, Lori A Manzon
As one of the most basal living vertebrates, lampreys represent an excellent model system to study the evolution of thyroid hormone (TH) signaling. The lamprey hypothalamic-pituitary-thyroid and reproductive axes overlap functionally. Lampreys have 3 gonadotropin releasing hormones and a single glycoprotein hormone from the hypothalamus and pituitary, respectively, that regulate both the reproductive and thyroid axes. TH synthesis in larval lampreys takes place in an endostyle that transforms into typical vertebrate thyroid tissue during metamorphosis; both the endostyle and follicular tissue have all the typical TH synthetic components found in other vertebrates...
June 16, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28627724/comparative-echogenicity-of-an-epidural-catheter-and-2-new-catheters-designed-for-ultrasound-guided-continuous-peripheral-nerve-blocks
#6
Daniel M Moy, T Edward Kim, T Kyle Harrison, Jody C Leng, Brendan Carvalho, Steven K Howard, Cynthia Shum, Alex Kou, Edward R Mariano
Visualization of the catheter during ultrasound-guided continuous nerve block performance may be difficult but is an essential skill for regional anesthesiologists. The objective of this in vitro study was to evaluate 2 newer catheters designed for enhanced echogenicity and compare them to a widely used catheter not purposely designed for ultrasound guidance. Outcomes were the numbers of first-place rankings among all 3 catheters and scores on individual echogenicity criteria as assessed by 2 blinded reviewers...
June 19, 2017: Journal of Ultrasound in Medicine: Official Journal of the American Institute of Ultrasound in Medicine
https://www.readbyqxmd.com/read/28623351/regulation-of-angiopoietin-signalling-by-soluble-tie2-ectodomain-and-engineered-ligand-trap
#7
Deborah O A Alawo, Tariq A Tahir, Marlies Fischer, Declan G Bates, Svetlana R Amirova, Nicholas P J Brindle
Angiopoietin-1 (Angpt1) is a glycoprotein ligand important for maintaining the vascular system. It signals via a receptor tyrosine kinase expressed on the surface on endothelial cells, Tie2. This receptor can undergo regulated ectodomain cleavage that releases the ligand-binding domain (sTie2) into the circulation. The concentration of sTie2 is increased in a range of conditions, including peripheral arterial disease and myocardial infarction, where it has been suggested to bind and block Angpt1 resulting in vascular dysfunction...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28623266/design-of-a-peripheral-building-block-for-h-bonded-dendritic-frameworks-and-analysis-of-the-void-space-in-the-bulk-dendrimers
#8
Cheng-Hua Lee, Dmitriy V Soldatov, Chung-Hao Tzeng, Long-Li Lai, Kuang-Lieh Lu
Three dendrimers, (t-Bu-G 2 N) 2 , CC(t-Bu-G 1 N) 3 and (t-Bu-G 1 N) 2 , with 3,5-di-tert-butyl amidobenzene as a common peripheral moiety were prepared in 64-83% yields and characterized. The bulk solids had high BET surface areas of 136-138 m(2)/g, which were similar for the three dendrimers in spite of their different molecular weight (ranging from 1791 to 2890). It was concluded that the peripheral amide groups do not imbed in the interstitial space of neighbouring dendrimer molecules but rather build a supramolecular architecture through strong intermolecular H-bonds...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28621630/evaluation-of-surgical-treatment-for-neuropathic-pain-from-neuroma-in-patients-with-injured-peripheral-nerves
#9
Valérie Decrouy-Duruz, Thierry Christen, Wassim Raffoul
OBJECTIVE Chronic neuropathic pain after peripheral nerve injury is a major clinical problem. Its management is difficult, and therapeutic approaches vary and include oral medication, neurostimulation, and surgery. The aim of this study was to assess the adequacy of surgical nerve revision in a large series of patients with long-term follow-up. METHODS The authors reviewed the charts of 231 patients (335 nerve injuries) who experienced neuropathic pain after peripheral nerve injury and underwent surgery for nerve revision at the authors' institution between 1997 and 2012...
June 16, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28620093/increased-interleukin-35-levels-in-patients-with-type-1-diabetes-with-remaining-c-peptide
#10
Daniel Espes, Kailash Singh, Stellan Sandler, Per-Ola Carlsson
OBJECTIVE: Many patients with long-standing type 1 diabetes have remaining functional β-cells. This study investigated immunological differences between patients with or without measurable remaining endogenous insulin production after ≥10 years duration of disease. RESEARCH DESIGN AND METHODS: Patients (n = 113; ≥18 years of age) with type 1 diabetes and with disease duration of ≥10 years were recruited at Uppsala University Hospital. Residual β-cell function was determined with an ultrasensitive C-peptide ELISA...
June 15, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28617615/association-between-pnpla3-gene-polymorphisms-and-risk-of-hepatitis-b-virus-related-hepatocellular-carcinoma-in-han-population-in-china-a-case-control-study
#11
Xia Gao, Wenxuan Liu, Lei Yang, Xiaolin Zhang, Ning Ma, Liqin Wang, Lina Yan, Longmei Tang, Haitao Yang, Dianwu Liu
BACKGROUND AND AIM: Several recent studies showed that the genetic polymorphisms in the PNPLA3 region (rs738408, rs738409, rs2294918, rs2294919 and rs2281135) were with related to various kinds of liver diseases. We analyzed the five single-nucleotide polymorphisms (SNPs) for major HBV outcomes in Han Chinese. METHODS: A total of 2410 samples were involved and peripheral blood samples were collected in this study. The SNPs in the PNPLA3 region were genotyped by using Matrix-assisted laser desorption/ionization time of flight mass spectrometry...
June 15, 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28616651/comparison-of-efficacy-of-transversus-abdominis-plane-block-and-iliohypogastric-ilioinguinal-nerve-block-for-postoperative-pain-management-in-patients-undergoing-inguinal-herniorrhaphy-with-spinal-anesthesia-a-prospective-randomized-controlled-open-label-study
#12
Onur Okur, Zeki Tuncel Tekgul, Nazif Erkan
PURPOSES: The purpose of this study was to compare the effects of lateral abdominal transversus abdominis plane block (TAP block) and iliohypogastric/ilioinguinal nerve block (IHINB) under ultrasound guidance for postoperative pain management of inguinal hernia repair. Secondary purposes were to compare the complication rates of the two techniques and to examine the effects of TAP block and IHINB on chronic postoperative pain. METHODS: This was a prospective randomized controlled open-label study...
June 14, 2017: Journal of Anesthesia
https://www.readbyqxmd.com/read/28614301/microglia-dependent-synapse-loss-in-type-i-interferon-mediated-lupus
#13
Allison R Bialas, Jessy Presumey, Abhishek Das, Cees E van der Poel, Peter H Lapchak, Luka Mesin, Gabriel Victora, George C Tsokos, Christian Mawrin, Ronald Herbst, Michael C Carroll
Systemic lupus erythematosus (SLE) is an incurable autoimmune disease characterized by autoantibody deposition in tissues such as kidney, skin and lungs. Notably, up to 75% of patients with SLE experience neuropsychiatric symptoms that range from anxiety, depression and cognitive impairment to seizures and, in rare cases, psychosis-collectively this is referred to as central nervous system (CNS) lupus. In some cases, certain autoantibodies, such as anti-NMDAR or anti-phospholipid antibodies, promote CNS lupus...
June 14, 2017: Nature
https://www.readbyqxmd.com/read/28609678/glucocorticoid-mediated-activation-of-gsk3%C3%AE-promotes-tau-phosphorylation-and-impairs-memory-in-type-2-diabetes
#14
Aditi Dey, Shuai Hao, Marlena Wosiski-Kuhn, Alexis M Stranahan
Type 2 diabetes is increasingly recognized as a risk factor for Alzheimer's disease, but the underlying mechanisms remain poorly understood. Hyperphosphorylation of the microtubule-associated protein tau has been reported in rodent models of diabetes, including db/db mice, which exhibit insulin resistance and chronically elevated glucocorticoids due to leptin receptor insufficiency. In this report, we investigated endocrine mechanisms for hippocampal tau phosphorylation in db/db and wild-type mice. By separately manipulating peripheral and intrahippocampal corticosterone levels, we determined that hippocampal corticosteroid exposure promotes tau phosphorylation and activates glycogen synthase kinase 3β (GSK3β)...
May 19, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28608253/femoral-nerve-block-with-propofol-sedation-versus-general-anesthesia-in-patients-with-severe-cardiac-dysfunction-undergoing-autologous-myoblast-sheet-transplantation
#15
Kenta Okitsu, Takeshi Iritakenishi, Akira Iura, Michioki Kuri, Yuji Fujino
PURPOSE: Regional anesthesia is more favorable than general anesthesia in patients with severe comorbidity; however, data on the superiority of peripheral nerve blocks over general anesthesia in patients with severe cardiac dysfunction are lacking. We aimed to demonstrate that peripheral nerve blocks reduce perioperative analgesic requirements and promote faster recovery compared to general anesthesia. METHODS: We retrospectively evaluated intraoperative blood pressure, perioperative medications, and postoperative recovery in patients who underwent skeletal muscle harvesting for autologous myoblast sheet transplantation...
June 12, 2017: Journal of Anesthesia
https://www.readbyqxmd.com/read/28607575/spatholobus-suberectus-exhibits-antidiabetic-activity-in-vitro-and-in-vivo-through-activation-of-akt-ampk-pathway
#16
Peijun Zhao, Md Badrul Alam, Seok-Hyun Lee, Young-Jun Kim, Seul Lee, Hongyan An, Hee-Jeong Choi, Hyeong-U Son, Chul-Hong Park, Hyo-Hyun Kim, Sang-Han Lee
Glucose deposition in peripheral tissue is an important parameter for the treatment of type 2 diabetes mellitus. The aim of this study was to investigate the effects of Spatholobus suberectus (Ss) on glucose disposal in skeletal muscle cells and additionally explore its in vivo antidiabetic potential. Treatment of ethanolic extract of S. suberectus (EeSs) significantly enhanced the glucose uptake, mediated through the enhanced expression of GLUT4 in skeletal muscle via the stimulation of AKT and AMPK pathways in C2C12 cells...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28602535/periarticular-injections-in-knee-and-hip-arthroplasty-where-and-what-to-inject
#17
Jeremy A Ross, Anna C Greenwood, Phillip Sasser, William A Jiranek
BACKGROUND: Periarticular injections have become a valuable adjunct to multimodal pain control regimens after knee and hip arthroplasties. Injection techniques vary greatly among surgeons with little standardization of practice. METHODS: We performed an extensive literature search to determine where nociceptive pain fibers are located in the hip and the knee and also to explore the pharmacology of periarticular cocktail ingredients. RESULTS: Large concentrations of nociceptors are present throughout the various tissues of the knee joint with elevated concentrations in the infrapatellar fat pad, fibrous capsule, ligament insertions, periosteum, subchondral bone, and lateral retinaculum...
May 11, 2017: Journal of Arthroplasty
https://www.readbyqxmd.com/read/28601696/anticipatory-processing-in-social-anxiety-investigation-using-attentional-control-theory
#18
Rachel A Sluis, Mark J Boschen, David L Neumann, Karen Murphy
BACKGROUND AND OBJECTIVES: Cognitive models of social anxiety disorder (SAD) emphasize anticipatory processing as a prominent maintaining factor occurring before social-evaluative events. While anticipatory processing is a maladaptive process, the cognitive mechanisms that underlie ineffective control of attention are still unclear. The present study tested predictions derived from attentional control theory in a sample of undergraduate students high and low on social anxiety symptoms...
June 1, 2017: Journal of Behavior Therapy and Experimental Psychiatry
https://www.readbyqxmd.com/read/28600292/adam10-interacting-tetraspanins-tspan5-and-tspan17-regulate-ve-cadherin-expression-and-promote-t-lymphocyte-transmigration
#19
Jasmeet S Reyat, Myriam Chimen, Peter J Noy, Justyna Szyroka, G Ed Rainger, Michael G Tomlinson
The recruitment of blood leukocytes across the endothelium to sites of tissue infection is central to inflammation, but also promotes chronic inflammatory diseases. A disintegrin and metalloproteinase 10 (ADAM10) is a ubiquitous transmembrane molecular scissor that is implicated in leukocyte transmigration by proteolytically cleaving its endothelial substrates. These include VE-cadherin, a homotypic adhesion molecule that regulates endothelial barrier function, and transmembrane chemokines CX3CL1 and CXCL16, which have receptors on leukocytes...
June 9, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28600151/splenomegaly-myeloid-lineage-expansion-and-increased-osteoclastogenesis-in-osteogenesis-imperfecta-murine
#20
Brya G Matthews, Emilie Roeder, Xi Wang, Hector Leonardo Aguila, Sun-Kyeong Lee, Danka Grcevic, Ivo Kalajzic
Osteogenesis imperfecta (OI) is a disease caused by defects in type I collagen production that results in brittle bones. While the pathology is mainly caused by defects in the osteoblast lineage, there is also elevated bone resorption by osteoclasts resulting in high bone turnover in severe forms of the disease. Osteoclasts originate from hematopoietic myeloid cells, however changes in hematopoiesis have not been previously documented in OI. In this study, we evaluated hematopoietic lineage distribution and osteoclast progenitor cell frequency in bone marrow, spleen and peripheral blood of osteogenesis imperfecta murine (OIM) mice, a model of severe OI...
June 7, 2017: Bone
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