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https://www.readbyqxmd.com/read/28812434/-pemetrexed-sildenafil-via-autophagy-dependent-hdac-down-regulation-enhances-the-immunotherapy-response-of-nsclc-cells
#1
Laurence Booth, Jane L Roberts, Andrew Poklepovic, Paul Dent
Pemetrexed is an approved therapeutic in NSCLC and ovarian cancer. Our studies focused on the ability of [pemetrexed + sildenafil] exposure to alter the immunogenicity of lung and ovarian cancer cells. Treatment of lung and ovarian cancer cells with [pemetrexed + sildenafil] in vitro rapidly reduced the expression of PD-L1, PD-L2 and ornithine decarboxylase (ODC), and increased the expression of Class I MHCA. In a cell-specific fashion, some cells also released the immunogenic nuclear protein HMGB1 into the extracellular environment...
August 16, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28810624/high-mobility-group-box-1-protein-attenuates-myocardial-ischemia-reperfusion-injury-via-inhibition-of-the-p38-mitogen-activated-protein-kinase-signaling-pathway
#2
Yan-Hong Zhou, Qian-Feng Han, Lan-Hua Wang, Tao Liu, Xiao-Yan Meng, Lei Wu, Tai Li, Yue-Ru Jiao, Heng-Chen Yao, De-Yong Zhang
The present study aimed to determine the effects of high mobility group box 1 protein (HMGB1) on myocardial ischemia reperfusion (I/R) injury in rats following acute myocardial ischemia and investigate the underlying molecular mechanisms of these effects. Male Wistar rats were randomly divided into the following groups (n=10/group): Sham operation; I/R; HMGB50 (50 ng/kg HMGB1 before I/R); HMGB100 (100 ng/kg HMGB1 before I/R); and HMGB200 (200 ng/kg HMGB1 before I/R). Serum cardiac troponin I (cTnI), interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels were subsequently measured...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810618/sivelestat-sodium-hydrate-improves-post-traumatic-knee-osteoarthritis-through-nuclear-factor-%C3%AE%C2%BAb-in-a-rat-model
#3
Xiaofeng Yu, Lijun Zhao, Zhiping Yu, Changzheng Yu, Jianfei Bi, Binglong Sun, Haibo Cong
As a specific inhibitor of neutrophil elastase, sivelestat sodium hydrate has primarily been used in the treatment of acute lung injury caused by various factors since its approval in 2002. Sivelestat sodium hydrate also improves post-traumatic knee osteoarthritis (KOA), although its underlying mechanisms of action have yet to be elucidated. The aim of the current study was to determine if sivelestat sodium hydrate improves post-traumatic KOA through nuclear factor (NF)-κB in a rat model. Treatment with sivelestat sodium hydrate significantly inhibited the induction of structural changes and significantly increased the vertical episode count and ipsilateral static weight bearing of the joint in KOA rats (all P<0...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810581/protective-effect-of-glycyrrhizin-on-myocardial-ischemia-reperfusion-injury-induced-oxidative-stress-inducible-nitric-oxide-synthase-and-inflammatory-reactions-through-high-mobility-group-box-1-and-mitogen-activated-protein-kinase-expression
#4
Xiangna Cai, Xin Wang, Jilin Li, Shuying Chen
Glycyrrhizin, which is a type of perennial leguminous caudex, has been used in various Asian countries, including P.R. China, India and Japan, for thousands of years. The present study was designed to investigate the protective effect of glycyrrhizin on myocardial ischemia/reperfusion (I/R) injury through oxidative stress, inducible nitric oxide synthase (iNOS), and inflammatory reactions via high-mobility group box 1 (HMGB1) and mitogen-activated protein kinase (MAPK) expression. Sprague-Dawley rats were divided into five groups: Sham; myocardial I/R injury + non-treated; myocardial I/R injury + 2 mg/kg glycyrrhizin; myocardial I/R injury + 4 mg/kg glycyrrhizin; and myocardial I/R injury + 10 mg/kg glycyrrhizin...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28807677/phosphodiesterase-4b-expression-plays-a-major-role-in-alcohol-induced-neuro-inflammation
#5
Diana V Avila, Scott A Myers, JingWen Zhang, Giorgi Kharebava, Craig J McClain, Hee-Yong Kim, Scott R Whittemore, Leila Gobejishvili, Shirish Barve
It is increasingly evident that alcohol-induced, gut-mediated peripheral endotoxemia plays a significant role in glial cell activation and neuro-inflammation. Using a mouse model of chronic alcohol feeding, we examined the causal role of endotoxin- and cytokine-responsive Pde4 subfamily b (Pde4b) expression in alcohol-induced neuro-inflammation. Both pharmacologic and genetic approaches were used to determine the regulatory role of Pde4b. In C57Bl/6 wild type (WT) alcohol fed (WT-AF) animals, alcohol significantly induced peripheral endotoxemia and Pde4b expression in brain tissue, accompanied by a decrease in cAMP levels...
August 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28806702/hmgb1-redox-during-sepsis
#6
Wasan Abdulmahdi, Devika Patel, May M Rabadi, Tala Azar, Edson Jules, Mark Lipphardt, Rameen Hashemiyoon, Brian B Ratliff
During sepsis, the alarmin HMGB1 is released from tissues and promotes systemic inflammation that results in multi-organ damage, with the kidney particularly susceptible to injury. The severity of inflammation and pro-damage signaling mediated by HMGB1 appears to be dependent on the alarmin's redox state. Therefore, we examined HMGB1 redox in kidney cells during sepsis. Using intravital microscopy, CellROX labeling of kidneys in live mice indicated increased ROS generation in the kidney perivascular endothelium and tubules during lipopolysaccharide (LPS)-induced sepsis...
August 4, 2017: Redox Biology
https://www.readbyqxmd.com/read/28806152/chicken-hmgb1-monoclonal-antibody
#7
(no author information available yet)
No abstract text is available yet for this article.
August 2017: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/28804542/significant-association-of-trem-1-with-hmgb1-tlrs-and-rage-in-the-pathogenesis-of-insulin-resistance-in-obese-diabetic-populations
#8
Saravanan Subramanian, Pradeep K Pallati, Poonam Sharma, Devendra K Agrawal, Kalyana C Nandipati
Activated cell surface and intracellular receptors lead to insulin resistance in obesity. Among these receptors, triggering receptors expressed on myeloid cells (TREM)-1, toll like receptors (TLRs), and receptors for advanced glycation end products (RAGE) play a significant role in the induction of inflammatory response in innate immunity. TREM-1 potentially amplifies TLRs and RAGE synergistically with DNA-binding high-mobility group box 1 (HMGB-1). The objective of the study was to analyze the association between TREM-1/DAP12 and HMGB-1, RAGE and TLRs in obesity-induced insulin resistance...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28802057/hmgb1-released-by-autophagic-cancer-associated-fibroblasts-maintains-the-stemness-of-luminal-breast-cancer-cells
#9
Xi-Long Zhao, Yong Lin, Jun Jiang, Zhuo Tang, Shuai Yang, Lu Lu, Yan Liang, Xue Liu, Jiao Tan, Xu-Gang Hu, Qin Niu, Wen-Juan Fu, Ze-Xuan Yan, De-Yu Guo, Yi-Fang Ping, Ji Ming Wang, Xia Zhang, Hsiang-Fu Kung, Xiu-Wu Bian, Xiao-Hong Yao
Cancer stem/initiating cells (CSCs/CICs) and their microenvironmental niche play a vital role in malignant tumour recurrence and metastasis. Cancer associated fibroblasts (CAFs) are major components of the niche of breast cancer initiating cells (BCICs) and their interactions may profoundly affect breast cancer progression. Autophagy has been considered as a critical process for CIC maintenance, but whether it is involved in the cross-talk between CAFs and CICs to affect tumourigenesis and pathological significance remains elusive...
August 12, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28798347/tonebp-nfat5-haploinsufficiency-attenuates-hippocampal-inflammation-in-high-fat-diet-streptozotocin-induced-diabetic-mice
#10
Jong Youl Lee, Eun Ae Jeong, Kyung Eun Kim, Chin-Ok Yi, Zhen Jin, Jung Eun Lee, Dong Hoon Lee, Hyun Joon Kim, Sang Soo Kang, Gyeong Jae Cho, Wan Sung Choi, Soo Youn Choi, H Moo Kwon, Gu Seob Roh
Recent studies have shown that overexpression of tonicity-responsive enhancer binding protein (TonEBP) is associated with many inflammatory diseases, including diabetes mellitus, which causes neuroinflammation in the hippocampus as well as hepatic steatosis. However, the exact mechanism in diabetic neuroinflammation is unknown. We report that haploinsufficiency of TonEBP inhibits hepatic and hippocampal high-mobility group box-1 (HMGB1) expression in diabetic mice. Here, mice were fed a high-fat diet (HFD) for 16 weeks and received an intraperitoneal injection of 100 mg/kg streptozotocin (STZ) and followed by continued HFD feeding for an additional 4 weeks to induce hyperglycemia and hepatic steatosis...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28795668/-immune-intervention-of-human-umbilical-cord-mesenchymal-stem-cells-on-sepsis-rats
#11
Hewei Zhang, Xiaoxu Cui, Tao Fang, Qiang Fu
OBJECTIVE: To investigate the effect of human umbilical cord mesenchymal stem cells (UC-MSCs) on immune cells and inflammatory factors in septic rats. METHODS: 184 male Sprague-Dawley (SD) rats were divided into normal control group (n = 8), sham operation group (n = 48), sepsis model group (n = 64), and UC-MSCs treatment group (n = 64). An animal model of sepsis was produced by cecal ligation and puncture (CLP). In the UC-MSCs treatment group 1 mL UC-MSCs (2×10(6)/mL) were injected intraperitoneally at 1 hour after the model establishment; the sham operation group and the sepsis model group were given the same amount of saline...
August 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28789951/hepatoprotective-activities-of-rosmarinic-acid-against-extrahepatic-cholestasis-in-rats
#12
Shih-Yi Lin, Ya-Yu Wang, Wen-Ying Chen, Su-Lan Liao, Su-Tze Chou, Ching-Ping Yang, Chun-Jung Chen
Though rosmarinic acid possesses nutritional, pharmaceutical, and toxic properties and shows therapeutic potential on liver diseases, its therapeutic effects against cholestatic liver diseases have not been proven. Using an extrahepatic cholestasis rat model by bile-duct ligation (BDL), daily oral administration of rosmarinic acid showed improvement effects on liver histology, serum biochemicals, ductular reaction, oxidative stress, inflammation, and fibrosis. Rosmarinic acid alleviated BDL-induced transforming growth factor beta-1 (TGF-β1) production and hepatic collagen deposition, and the anti-fibrotic effects were accompanied by reductions in matrix-producing cells and Smad2/3...
August 5, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28771884/hmgb2-expression-is-associated-with-transition-from-a-quiescent-to-an-activated-state-of-adult-neural-stem-cells
#13
Ayaka Kimura, Taito Matsuda, Atsuhiko Sakai, Naoya Murao, Kinichi Nakashima
BACKGROUND: Although quiescent neural stem cells (NSCs) in the adult hippocampus proliferate in response to neurogenic stimuli and subsequently give rise to new neurons continuously throughout life, misregulation of NSCs in pathological conditions, including aging, leads to the impairment of learning and memory. High mobility group B family 1 (HMGB1) and HMGB2, HMG family proteins that function as transcriptional activators through the modulation of chromatin structure, have been assumed to play some role in the regulation of adult NSCs; however, their precise functions and even expression patterns in the adult hippocampus remain elusive...
August 2, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28769106/lipoxin-a4-and-its-analog-suppress-inflammation-by-modulating-hmgb1-translocation-and-expression-in-psoriasis
#14
Xinxin Liu, Xin Wang, Xiaoru Duan, Devesh Poorun, Juntao Xu, Song Zhang, Lu Gan, Mengwen He, Ke Zhu, Zhangyin Ming, Feng Hu, Hongxiang Chen
Psoriasis is a chronic inflammatory skin disease that affects 2-3% of the global population, and there is still no known possibility of a cure. Lipoxin A4 (LXA4), an endogenous lipoxygenase-derived eicosanoid mediator, has potent dual pro-resolving and anti-inflammatory properties. BML-111 (5(S)-6(R)-7-trihydroxyheptanoic acid methyl ester), a lipoxin receptor agonist, has been previously confirmed to be equivalent to LXA4 in the anti-inflammatory processes. High mobility group box 1 (HMGB1) serves as an inflammatory cytokine when secreted extracellularly in psoriatic lesions and is involved in the development of psoriasis...
August 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28765610/high-mobility-group-box-1-protein-level-as-a-novel-biomarker-for-the-development-of-peri-implant-disease
#15
Jinpan Liu, Ronghui Li, Tongjun Liu, Xiaohui Rausch-Fan, Mingguo Wang
Peri-implant disease is a chronic inflammation of the soft and hard tissues around a dental implant, resulting from bacterial infection. Recent evidence indicates that some pro-inflammatory cytokines and chemokines released by immunocytes are substantially responsible for the progress and consequence of inflammation. High mobility group box 1 (HMGB1) is released into the extracellular matrix and acts as a key pro-inflammatory factor during injury, necrosis and inflammation. A higher concentration of HMGB1 has been found in gingival crevicular fluid from inflammatory gingival tissue than from healthy sites...
August 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28761710/differential-expression-of-alarmins-s100a9-il-33-hmgb1-and-hif-1%C3%AE-in-supraspinatus-tendinopathy-before-and-after-treatment
#16
Michael J Mosca, Andrew J Carr, Sarah J B Snelling, Kim Wheway, Bridget Watkins, Stephanie G Dakin
BACKGROUND: Alarmins, endogenous molecules released on tissue damage have been shown to play an important role in inflammatory musculoskeletal conditions including fracture repair andrheumatoid arthritis. However, the contribution of alarmins to the pathogenesis of tendon disease is not fully understood. METHODS: We investigated expression of alarmin proteins (S100A9, high-mobility group box 1 (HMGB1) and interleukin-33 (IL-33) and hypoxia-inducible factor 1α (HIF-1α), a subunit of an oxygen sensitive transcription factor, in three cohorts of human supraspinatus tissues: healthy (n=6), painful diseased (n=13) and post-treatment pain-free tendon samples (n=5)...
2017: BMJ Open Sport & Exercise Medicine
https://www.readbyqxmd.com/read/28755860/dynamic-and-accurate-assessment-of-acetaminophen-induced-hepatotoxicity-by-integrated-photoacoustic-imaging-and-mechanistic-biomarkers-in-vivo
#17
Nathalie Brillant, Mohamed Elmasry, Neal C Burton, Josep Monne Rodriguez, Jack W Sharkey, Stephen Fenwick, Harish Poptani, Neil R Kitteringham, Christopher E Goldring, Anja Kipar, B Kevin Park, Daniel J Antoine
The prediction and understanding of acetaminophen (APAP)-induced liver injury (APAP-ILI) and the response to therapeutic interventions is complex. This is due in part to sensitivity and specificity limitations of currently used assessment techniques. Here we sought to determine the utility of integrating translational non-invasive photoacoustic imaging of liver function with mechanistic circulating biomarkers of hepatotoxicity with histological assessment to facilitate the more accurate and precise characterization of APAP-ILI and the efficacy of therapeutic intervention...
July 26, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28755135/macrophage-derived-hmgb1-as-a-pain-mediator-in-the-early-stage-of-acute-pancreatitis-in-mice-targeting-rage-and-cxcl12-cxcr4-axis
#18
Yuhei Irie, Maho Tsubota, Hiroyasu Ishikura, Fumiko Sekiguchi, Yuka Terada, Toshifumi Tsujiuchi, Keyue Liu, Masahiro Nishibori, Atsufumi Kawabata
Extracellular high mobility group box 1 (HMGB1) activates the receptor for advanced glycation end products (RAGE) or Toll-like receptor 4 (TLR4) and forms a heterocomplex with CXCL12 that strongly activates CXCR4, promoting inflammatory and pain signals. In the present study, we investigated the role of HMGB1 in pancreatic pain accompanying cerulein-induced acute pancreatitis in mice. Abdominal referred hyperalgesia accompanying acute pancreatitis occurred within 1 h after 6 hourly injections of cerulein. The anti-HMGB1 neutralizing antibody or recombinant human soluble thrombomodulin (rhsTM), known to inactivate HMGB1, abolished the cerulein-induced referred hyperalgesia, but not pancreatitis itself...
July 28, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28754974/blockade-of-high-mobility-group-box-1-attenuates-intestinal-mucosal-barrier-dysfunction-in-experimental-acute-pancreatitis
#19
Xia Chen, Hong-Xian Zhao, Chao Bai, Xiang-Yu Zhou
The release of inflammatory cytokines, that plays a dominant role in local pancreatic inflammation and systemic complications in severe acute pancreatitis (SAP). High-mobility group box 1 (HMGB1) is implicated in the mechanism of organ dysfunction and bacterial translocation in SAP. This current study aims to investigate possible role of HMGB1 in the intestinal mucosal barrier dysfunction of SAP, and the effect of anti-HMGB1 antibody treatment in intestinal mucosal injury in SAP. Our data revealed that the HMGB1 expression was significantly increased in AP mice induced by caerulein and LPS, and the inhibition of HMGB1 played a protective role in intestinal mucosal barrier dysfunction, reduced the serum level of other proinflammatory cytokines include IL-1β, IL-6, TNF-α...
July 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28752362/necrostatin-1-protects-against-d-galactosamine-and-lipopolysaccharide-induced-hepatic-injury-by-preventing-tlr4-and-rage-signaling
#20
Seok-Joo Kim, Sun-Mee Lee
Fulminant hepatic failure (FHF) is a life-threatening clinical syndrome results in massive inflammation and hepatocyte death. Necroptosis is a regulated form of necrotic cell death that is emerging as a crucial control point for inflammatory diseases. The kinases receptor interacting protein (RIP) 1 and RIP3 are known as key modulators of necroptosis. In this study, we investigated the impact of necroptosis in the pathogenesis of FHF and molecular mechanisms, particularly its linkage to damage-associated molecular pattern (DAMP)-mediated pattern recognition receptor (PRR) signaling pathways...
July 27, 2017: Inflammation
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