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https://www.readbyqxmd.com/read/28343277/pancreatic-alpha-cell-selective-deletion-of-tcf7l2-impairs-glucagon-secretion-and-counter-regulatory-responses-to-hypoglycaemia-in-mice
#1
Gabriela da Silva Xavier, Angeles Mondragon, Vishnou Mourougavelou, Céline Cruciani-Guglielmacci, Jessica Denom, Pedro Luis Herrera, Christophe Magnan, Guy A Rutter
AIMS/HYPOTHESIS: Transcription factor 7-like 2 (TCF7L2) is a high mobility group (HMG) box-containing transcription factor and downstream effector of the Wnt signalling pathway. SNPs in the TCF7L2 gene have previously been associated with an increased risk of type 2 diabetes in genome-wide association studies. In animal studies, loss of Tcf7l2 function is associated with defective islet beta cell function and survival. Here, we explore the role of TCF7L2 in the control of the counter-regulatory response to hypoglycaemia by generating mice with selective deletion of the Tcf7l2 gene in pancreatic alpha cells...
March 25, 2017: Diabetologia
https://www.readbyqxmd.com/read/28342873/relationships-of-braf-mutation-and-hmgb1-to-papillary-thyroid-carcinoma
#2
Xiaolei Guan, Ping Wang, Jingwei Chi, Shihua Zhao, Fei Wang
A poor papillary thyroid cancer (PTC) prognosis is strongly associated with the BRAF V600E mutation. During tumor progression, levels of the high mobility group box 1 (HMGB1) protein are often dysregulated. Results herein demonstrate that HMGB1 protein levels differ between tumor and adjacent non-tumor tissue and that HMGB1 mRNA levels were higher in wild-type BRAF PTC tissues than in BRAF V600E PTC tissues (2-△Ct 0.31 ± 0.25 vs. 0.16 ± 0.12; P < 0.05). HMGB1 protein levels also differed in the same manner (wild-type BRAF PTC tissues 0...
March 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28339089/hmgb1-induces-lung-fibroblast-to-myofibroblast-differentiation-through-nf%C3%A2-%C3%AE%C2%BAb%C3%A2-mediated-tgf%C3%A2-%C3%AE-1-release
#3
Qiong Wang, Jun Wang, Junfang Wang, Shanchao Hong, Feifei Han, Jingyu Chen, Guoqian Chen
The proinflammatory factor high‑mobility group box protein 1 (HMGB1) has been implicated in the pathogenesis of lung fibrosis; however, the role of HMGB1 in lung fibrosis remains unclear. It has previously been reported that nuclear factor (NF)‑κB and transforming growth factor (TGF)‑β1 may be involved in lung fibrosis. Therefore, the present study aimed to examine the potential molecular mechanisms that underlie HMGB1‑induced lung fibrosis via the regulation of NF‑κB and TGF‑β1. The results demonstrated that HMGB1 stimulation increased the activation of NF‑κB and the release of TGF‑β1, as well as the expression of α‑smooth muscle actin (α‑SMA) and collagen I in human lung fibroblasts in vitro...
March 23, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28338748/role-of-scavenger-receptors-as-damage-associated-molecular-pattern-receptors-in-toll-like-receptor-activation
#4
Kyoko Komai, Takashi Shichita, Minako Ito, Mitsuhiro Kanamori, Shunsuke Chikuma, Akihiko Yoshimura
Damage-associated molecular patterns (DAMPs) have been implicated in sterile inflammation in various tissue injuries. High-mobility group box 1 (HMGB1) is a representative DAMP, and has been shown to transmit signals through receptors for advanced glycation end products (RAGEs) and TLRs, including TLR2 and TLR4. HMGB1 does not, however, bind to TLRs with high affinity; therefore, the mechanism of HMGB1-mediated TLR activation remains unclear. In this study, we found that fluorescently labeled HMGB1 was efficiently internalized into macrophages through class A scavenger receptors...
February 24, 2017: International Immunology
https://www.readbyqxmd.com/read/28337869/knockdown-of-hmgb1-inhibits-cell-proliferation-and-induces-apoptosis-in-hemangioma-via-downregulation-of-akt-pathway
#5
C Pan, Y Wang, M K Qiu, S Q Wang, Y B Liu, Z W Quan, J M Ou
The high mobility group box 1 (HMGB1) as a conserved non-histone nuclear protein has been involved in a variety of biological processes of cancer, such as cell proliferation, apoptosis, angiogenesis and metastasis. Despite the increased expression of HMGB1 in many malignant tumors, the functions and molecular mechanisms by which HMGB1 contributes to the formation of hemangioma (HA) remain unclear. In the present study, immunohistochemistry was used to detect the expression levels of HMGB1 in different phases of human HAs...
January 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28329851/short-tslp-attenuates-toluene-diisocyanate-tdi-induced-airway-inflammation-and-inhibits-hmgb1-rage-and-long-tslp-expression
#6
Yanhong Wang, Yanqing Le, Wenqu Zhao, Yun Lin, Yue Wu, Changhui Yu, Jing Xiong, Fei Zou, Hangming Dong, Shaoxi Cai, Haijin Zhao
Short thymic stromal lymphopoietin (short TSLP), one of TSLP variants, exerts anti-inflammatory activities in endotoxin shock and colitis mouse models. Our latest work reported that short TSLP prevented house dust mite (HDM)-induced epithelial barrier disruption. Yet the role of short TSLP in toluene diisocyanate (TDI)-induced asthma is unknown. Male BALB/c mice were sensitized and challenged with TDI to generate a chemical-induced asthma model. Synthetic short TSLP peptides were given intranasally (i.n.) or intraperitoneally (i...
February 27, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28317284/mir-320a-regulates-high-mobility-group-box-1%C3%A2-expression-and-inhibits-invasion-and-metastasis-in-hepatocellular-carcinoma
#7
Guixiang Lv, Mingjuan Wu, Meijie Wang, Xiaochen Jiang, Jingli Du, Kaili Zhang, Dongliang Li, Ning Ma, Yahui Peng, Lujing Wang, Lingyun Zhou, Weiming Zhao, Yufei Jiao, Xu Gao, Zheng Hu
BACKGROUND & AIMS: Several studies have shown that miR-320a induces apoptosis, inhibits cell proliferation, and affects cell cycle progression as a tumor suppressor in many cancers. However, the involvement of miR-320a in the invasion and metastasis of hepatocellular carcinoma (HCC) is still unknown. METHODS: Endogenous miR-320a and high mobility group box 1 (HMGB1) expressions were assayed by real-time PCR. Luciferase activities were measured using a dual-luciferase reporter assay system...
March 19, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28317237/disruption-of-the-cx43-mir21-pathway-leads-to-osteocyte-apoptosis-and-increased-osteoclastogenesis-with-aging
#8
Hannah M Davis, Rafael Pacheco-Costa, Emily G Atkinson, Lucas R Brun, Arancha R Gortazar, Julia Harris, Masahiro Hiasa, Surajudeen A Bolarinwa, Toshiyuki Yoneda, Mircea Ivan, Angela Bruzzaniti, Teresita Bellido, Lilian I Plotkin
Skeletal aging results in apoptosis of osteocytes, cells embedded in bone that control the generation/function of bone forming and resorbing cells. Aging also decreases connexin43 (Cx43) expression in bone; and osteocytic Cx43 deletion partially mimics the skeletal phenotype of old mice. Particularly, aging and Cx43 deletion increase osteocyte apoptosis, and osteoclast number and bone resorption on endocortical bone surfaces. We examined herein the molecular signaling events responsible for osteocyte apoptosis and osteoclast recruitment triggered by aging and Cx43 deficiency...
March 19, 2017: Aging Cell
https://www.readbyqxmd.com/read/28303135/a-human-lin-cd123-cd127-low-population-endowed-with-ilc-features-and-migratory-capabilities-contributes-to-immunopathological-hallmarks-of-psoriasis
#9
Luz María Mora-Velandia, Octavio Castro-Escamilla, Andrés González Méndez, Cristina Aguilar-Flores, Martha Velázquez-Avila, María Isabel Tussié-Luna, Juan Téllez-Sosa, César Maldonado-García, Fermín Jurado-Santacruz, Eduardo Ferat-Osorio, Jesus Martínez-Barnetche, Rosana Pelayo, Laura C Bonifaz
Innate lymphoid cells (ILC) are members of a heterogeneous family with a lymphoid origin that mimics the T helper (Th) cytokine profile. ILC are involved in early effector cytokine-mediated responses during infections in peripheral tissues. ILC also play an important role in chronic skin inflammatory diseases, including psoriasis. Although classical ILC express CD127, it has been recently reported that the presence of non-classical CD127(-) ILC populations and an early ILC precursor (EILP) CD127(low). ILC development has predominately been investigated in mouse models...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28294475/sodium-tanshinone-iia-sulfonate-prevents-hypoxic-trophoblast-induced-endothelial-cell-dysfunction-via-targeting-hmgb1-release
#10
Min Zhao, Yaling Feng, Jianping Xiao, Jie Liang, Yongxiang Yin, Daozhen Chen
Preeclampsia (PE) is a serious blood pressure disorder of pregnancy. Systemic endothelial cell dysfunction, a hallmark of PE, is previously estimated to be induced by hypoxic trophoblast high mobility group box 1 (HMGB1). In the present study, we investigated the protective effect of sodium tanshinone IIA sulfonate (STS), the soluble form of tanshinone IIA isolated from danshen, against hypoxic trophoblast HMGB1-induced human umbilical vein endothelial cell (HUVEC) dysfunction. Our results showed that HMGB1 expression and release were significantly decreased in STS-treated hypoxic JEG-3 cells...
February 16, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28286920/blockade-of-notch-signaling-promotes-acetaminophen-induced-liver-injury
#11
Longfeng Jiang, Michael Ke, Shi Yue, Wen Xiao, Youde Yan, Xiaozhao Deng, Qi-Long Ying, Jun Li, Bibo Ke
Liver injury after experimental acetaminophen treatment is mediated both by direct hepatocyte injury through a P450-generated toxic metabolite and indirectly by activated liver Kupffer cells and neutrophils. This study was designed to investigate the role of Notch signaling in the regulation of innate immune responses in acetaminophen (APAP)-induced liver injury. Using a mouse model of APAP-induced liver injury, wild-type (WT) and toll-like receptor 4 knockout (TLR4 KO) mice were injected intraperitoneally with APAP or PBS...
March 13, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28286376/high-mobility-group-box-1-protein-and-outcomes-in-critically-ill-surgical-patients-requiring-open-abdominal-management
#12
Michelle S Malig, Craig N Jenne, Chad G Ball, Derek J Roberts, Zhengwen Xiao, Andrew W Kirkpatrick
Background. Previous studies assessing various cytokines in the critically ill/injured have been uninformative in terms of translating to clinical care management. Animal abdominal sepsis work suggests that enhanced intraperitoneal (IP) clearance of Damage-Associated Molecular Patterns (DAMPs) improves outcome. Thus measuring the responses of DAMPs offers alternate potential insights and a representative DAMP, High Mobility Group Box-1 protein (HMGB-1), was considered. While IP biomediators are being recognized in critical illness/trauma, HMGB-1 behaviour has not been examined in open abdomen (OA) management...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28285361/hmgb1-attenuates-tgf-%C3%AE-induced-epithelial-mesenchymal-transition-of-fadu-hypopharyngeal-carcinoma-cells-through-regulation-of-rage-expression
#13
Yanmei Li, Ping Wang, Jia Zhao, Haonan Li, Dahai Liu, Wei Zhu
Abnormal expression of high-mobility group box-1 (HMGB1) protein occurs in many tumors and is closely associated with tumor invasion and metastasis. However, a role for HMGB1 in epithelial-mesenchymal transition (EMT) in hypopharyngeal carcinoma has not been previously reported. We cultured cells of the hypopharyngeal carcinoma cell line FaDu in vitro and then treated them with 5 ng/ml TGF-β1 for 48 h to induce EMT. Vimentin, Snail, and HMGB1 expression patterns were then detected using immunofluorescence staining; HMGB1 mRNA and protein expression were verified by RT-PCR and western blot analyses...
March 11, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28280849/a-novel-synthetic-derivative-of-squamosamide-flz-inhibits-the-high-mobility-group-box-1-protein-mediated-neuroinflammatory-responses-in-murine-bv2-microglial-cells
#14
De-Chuan Li, Xiu-Qi Bao, Xiao-Liang Wang, Hua Sun, Dan Zhang
High mobility group box 1 (HMGB1) is a critical pro-inflammatory cytokine that contributes to the pathogenesis of various human diseases. FLZ, a squamosamide derivative, has been demonstrated to have neuroprotective effects in Parkinson's disease models and shows strong anti-inflammatory activity, while the precise mechanism remains unclear. Here, we investigated the anti-inflammatory mechanism of FLZ on HMGB1-mediated inflammatory responses. The effects of FLZ on HMGB1 release from microglial cells induced by lipopolysaccharide were first explored by Western blot assay and ELISA...
March 9, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28276514/the-human-mitochondrial-transcription-factor-a-is-a-versatile-g-quadruplex-binding-protein
#15
Sébastien Lyonnais, Aleix Tarrés-Soler, Anna Rubio-Cosials, Anna Cuppari, Reicy Brito, Joaquim Jaumot, Raimundo Gargallo, Marta Vilaseca, Cristina Silva, Anton Granzhan, Marie-Paule Teulade-Fichou, Ramon Eritja, Maria Solà
The ability of the guanine-rich strand of the human mitochondrial DNA (mtDNA) to form G-quadruplex structures (G4s) has been recently highlighted, suggesting potential functions in mtDNA replication initiation and mtDNA stability. G4 structures in mtDNA raise the question of their recognition by factors associated with the mitochondrial nucleoid. The mitochondrial transcription factor A (TFAM), a high-mobility group (HMG)-box protein, is the major binding protein of human mtDNA and plays a critical role in its expression and maintenance...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28276476/mir-193a-3p-interaction-with-hmgb1-downregulates-human-endothelial-cell-proliferation-and-migration
#16
Cheen P Khoo, Maria G Roubelakis, Jack B Schrader, Grigorios Tsaknakis, Rebecca Konietzny, Benedikt Kessler, Adrian L Harris, Suzanne M Watt
Circulating endothelial colony forming cells (ECFCs) contribute to vascular repair where they are a target for therapy. Since ECFC proliferative potential is increased in cord versus peripheral blood and to define regulatory factors controlling this proliferation, we compared the miRNA profiles of cord blood and peripheral blood ECFC-derived cells. Of the top 25 differentially regulated miRNAs selected, 22 were more highly expressed in peripheral blood ECFC-derived cells. After validating candidate miRNAs by q-RT-PCR, we selected miR-193a-3p for further investigation...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28275217/identification-of-proteins-interacting-with-cytoplasmic-high-mobility-group-box-1-during-the-hepatocellular-response-to-ischemia-reperfusion-injury
#17
Tianjiao Zhang, Weiwei Wei, Olaf Dirsch, Thomas Krüger, Chunyi Kan, Chichi Xie, Olaf Kniemeyer, Haoshu Fang, Utz Settmacher, Uta Dahmen
Ischemia/reperfusion injury (IRI) occurs inevitably in liver transplantations and frequently during major resections, and can lead to liver dysfunction as well as systemic disorders. High-mobility group box 1 (HMGB1) plays a pathogenic role in hepatic IRI. In the normal liver, HMGB1 is located in the nucleus of hepatocytes; after ischemia reperfusion, it translocates to the cytoplasm and it is further released to the extracellular space. Unlike the well-explored functions of nuclear and extracellular HMGB1, the role of cytoplasmic HMGB1 in hepatic IRI remains elusive...
January 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28270074/molecular-and-thermodynamic-studies-on-dna-triplex-formed-in-the-promoter-region-of-hmgb1-gene-as-a-selective-target-for-anticancer-drugs
#18
Neelam Lohani, Rajeswari Raja Moganty
HMGB1 (High Mobility Group Box-1) is a very versatile highly abundant architectural protein that plays multiple roles in human health and diseases. Under physiological condition it serves an amazing assortment of roles in different compartments of cell. The reported high expression of HMGB1 in almost all types of human cancers and inflammatory diseases make it a critical molecular therapeutic target. In the present study we have mobilized a proximal twenty one bp nucleotide (21RY) which is in the promoter region (-55 to-75) of hmgb1 gene and targeted it with triplex forming oligonucleotide (TFO) in combination with two widely used chemotherapeutic drugs actinomycin (ACT) and adriamycin (ADM)...
February 13, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28266599/double-stranded-rna-induces-inflammation-via-the-nf-%C3%AE%C2%BAb-pathway-and-inflammasome-activation-in-the-outer-root-sheath-cells-of-hair-follicles
#19
Jung-Min Shin, Dae-Kyoung Choi, Kyung-Cheol Sohn, Soo-Yeon Kim, Jeong Min Ha, Young Ho Lee, Myung Im, Young-Joon Seo, Chang Deok Kim, Jeung-Hoon Lee, Young Lee
Alopecia areata (AA), a chronic, relapsing, hair-loss disorder, is considered to be a T cell-mediated autoimmune disease. It affects approximately 1.7% of the population, but its precise pathogenesis remains to be elucidated. Despite the recent attention focused on the roles of inflammasomes in the pathogenesis of autoinflammatory diseases, little is known about inflammasome activation in AA. Thus, in this study, we investigated the pattern of NLRP3 inflammasome activation in the outer root sheath (ORS) cells of hair follicles...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28261206/the-hmgb1-cxcl12-complex-promotes-inflammatory-cell-infiltration-in-uveitogenic-t-cell-induced-chronic-experimental-autoimmune-uveitis
#20
Juan Yun, Guomin Jiang, Yunsong Wang, Tong Xiao, Yuan Zhao, Deming Sun, Henry J Kaplan, Hui Shao
It is largely unknown how invading autoreactive T cells initiate the pathogenic process inside the diseased organ in organ-specific autoimmune diseases. In experimental autoimmune uveitis (EAU) induced by uveitogenic, interphotoreceptor retinoid-binding protein (IRBP)-specific T cells (tEAU) in mice, we have previously reported that high mobility group box 1 (HMGB1) released as a consequence of the direct interaction between IRBP-specific T cells and retinal parenchymal cells is an early and critical mediator in induction of intraocular inflammation...
2017: Frontiers in Immunology
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