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Hmo1:A versatile member of the high mobility group box family of chromosomal architecture proteins
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作者 Xin Bi 《World Journal of Biological Chemistry》 2024年第1期1-10,共10页
Eukaryotic chromatin consisting of nucleosomes connected by linker DNA is organized into higher order structures,which is facilitated by linker histone H1.Formation of chromatin compacts and protects the genome,but al... Eukaryotic chromatin consisting of nucleosomes connected by linker DNA is organized into higher order structures,which is facilitated by linker histone H1.Formation of chromatin compacts and protects the genome,but also hinders DNA transactions.Cells have evolved mechanisms to modify/remodel chromatin resulting in chromatin states suitable for genome functions.The high mobility group box(HMGB)proteins are non-histone chromatin architectural factors characterized by one or more HMGB motifs that bind DNA in a sequence nonspecific fashion.They play a major role in chromatin dynamics.The Saccharomyces cerevisiae(yeast hereafter)HMGB protein Hmo1 contains two HMGB motifs.However,unlike a canonical HMGB protein that has an acidic C-terminus,Hmo1 ends with a lysine rich,basic,C-terminus,resembling linker histone H1.Hmo1 exhibits characteristics of both HMGB proteins and linker histones in its multiple functions.For instance,Hmo1 promotes transcription by RNA polymerases I and II like canonical HMGB proteins but makes chromatin more compact/stable like linker histones.Recent studies have demonstrated that Hmo1 destabilizes/disrupts nucleosome similarly as other HMGB proteins in vitro and acts to maintain a common topological architecture of genes in yeast genome.This minireview reviews the functions of Hmo1 and the underlying mechanisms,highlighting recent discoveries. 展开更多
关键词 Hmo1 high mobility group box proteins CHROMATIN Chromatin remodeling Gene regulation Ribosomal DNA Ribosomal protein genes DNA damage response Linker histone
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Bone marrow-derived mesenchymal stem cell-derived exosomeloaded miR-129-5p targets high-mobility group box 1 attenuates neurological-impairment after diabetic cerebral hemorrhage 被引量:1
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作者 Yue-Ying Wang Ke Li +5 位作者 Jia-Jun Wang Wei Hua Qi Liu Yu-Lan Sun Ji-Ping Qi Yue-Jia Song 《World Journal of Diabetes》 SCIE 2024年第9期1979-2001,共23页
BACKGROUND Diabetic intracerebral hemorrhage(ICH)is a serious complication of diabetes.The role and mechanism of bone marrow mesenchymal stem cell(BMSC)-derived exosomes(BMSC-exo)in neuroinflammation post-ICH in patie... BACKGROUND Diabetic intracerebral hemorrhage(ICH)is a serious complication of diabetes.The role and mechanism of bone marrow mesenchymal stem cell(BMSC)-derived exosomes(BMSC-exo)in neuroinflammation post-ICH in patients with diabetes are unknown.In this study,we investigated the regulation of BMSC-exo on hyperglycemia-induced neuroinflammation.AIM To study the mechanism of BMSC-exo on nerve function damage after diabetes complicated with cerebral hemorrhage.METHODS BMSC-exo were isolated from mouse BMSC media.This was followed by transfection with microRNA-129-5p(miR-129-5p).BMSC-exo or miR-129-5poverexpressing BMSC-exo were intravitreally injected into a diabetes mouse model with ICH for in vivo analyses and were cocultured with high glucoseaffected BV2 cells for in vitro analyses.The dual luciferase test and RNA immunoprecipitation test verified the targeted binding relationship between miR-129-5p and high-mobility group box 1(HMGB1).Quantitative polymerase chain reaction,western blotting,and enzyme-linked immunosorbent assay were conducted to assess the levels of some inflammation factors,such as HMGB1,interleukin 6,interleukin 1β,toll-like receptor 4,and tumor necrosis factorα.Brain water content,neural function deficit score,and Evans blue were used to measure the neural function of mice.RESULTS Our findings indicated that BMSC-exo can promote neuroinflammation and functional recovery.MicroRNA chip analysis of BMSC-exo identified miR-129-5p as the specific microRNA with a protective role in neuroinflammation.Overexpression of miR-129-5p in BMSC-exo reduced the inflammatory response and neurological impairment in comorbid diabetes and ICH cases.Furthermore,we found that miR-129-5p had a targeted binding relationship with HMGB1 mRNA.CONCLUSION We demonstrated that BMSC-exo can reduce the inflammatory response after ICH with diabetes,thereby improving the neurological function of the brain. 展开更多
关键词 Bone marrow mesenchymal stem cells Exosome Diabetic cerebral hemorrhage Neuroinflammation MicroRNA-129-5p high mobility group box 1
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High mobility group box 1 in the central nervous system:regeneration hidden beneath inflammation
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作者 Hanki Kim Bum Jun Kim +4 位作者 Seungyon Koh Hyo Jin Cho Xuelian Jin Byung Gon Kim Jun Young Choi 《Neural Regeneration Research》 SCIE CAS 2025年第1期107-115,共9页
High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the ex... High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain injury.Several drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system disorders.Although it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system disorders.In this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory role.Research targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1. 展开更多
关键词 central nervous system damage-associated molecular pattern ethyl pyruvate glycyrhizzin high mobility group box 1 INFLAMMATION neural stem cells NEURODEVELOPMENT oligodendrocyte progenitor cells redox status REGENERATION
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Suppressing high mobility group box-1 release alleviates morphine tolerance via the adenosine5'-monophosphate-activated protein kinase/heme oxygenase-1 pathway
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作者 Tong-Tong Lin Chun-Yi Jiang +10 位作者 Lei Sheng Li Wan Wen Fan Jin-Can Li Xiao-Di Sun Chen-Jie Xu Liang Hu Xue-Feng Wu Yuan Han Wen-Tao Liu Yin-Bing Pan 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第9期2067-2074,共8页
Opioids,such as morphine,are the most potent drugs used to treat pain.Long-term use results in high tolerance to morphine.High mobility group box-1(HMGB1) has been shown to participate in neuropathic or inflammatory p... Opioids,such as morphine,are the most potent drugs used to treat pain.Long-term use results in high tolerance to morphine.High mobility group box-1(HMGB1) has been shown to participate in neuropathic or inflammatory pain,but its role in morphine tolerance is unclear.In this study,we established rat and mouse models of morphine tolerance by intrathecal injection of morphine for 7 consecutive days.We found that morphine induced rat spinal cord neurons to release a large amount of HMGB1.HMGB1 regulated nuclear factor κB p65 phosphorylation and interleukin-1β production by increasing Toll-like receptor 4receptor expression in microglia,thereby inducing morphine tolerance.Glycyrrhizin,an HMGB1 inhibito r,markedly attenuated chronic morphine tole rance in the mouse model.Finally,compound C(adenosine 5’-monophosphate-activated protein kinase inhibitor) and zinc protoporphyrin(heme oxygenase-1 inhibitor)alleviated the morphine-induced release of HMGB1 and reduced nuclear factor κB p65 phosphorylation and interleukin-1β production in a mouse model of morphine tolerance and an SH-SY5Y cell model of morphine tole rance,and alleviated morphine tolerance in the mouse model.These findings suggest that morphine induces HMGB1 release via the adenosine 5’-monophosphate-activated protein kinase/heme oxygenase-1 signaling pathway,and that inhibiting this signaling pathway can effectively reduce morphine tole rance. 展开更多
关键词 adenosine 5’-monophosphate-activated protein kinase heme oxygenase-1 high mobility group box-1 INTERLEUKIN-1Β MICROGLIA morphine tolerance NEUROINFLAMMATION neuron nuclear factor-κB p65 Toll-like receptor 4
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High mobility group box 1 protein(HMGB1)as an immune-modulating factor for polarization of human T lymphocytes 被引量:6
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作者 Lifeng Huang Yongming Yao +3 位作者 Haidong Meng Xiaodong Zhao Ning Dong Yan Yu 《Journal of Geriatric Cardiology》 SCIE CAS CSCD 2008年第2期117-122,共6页
Objective This study was performed to investigate the effect of high mobility group box-1 protein(HMGB1)on immune function of human T lymphocytes in vitro and explore its potential role in cell-mediated immune dysfunc... Objective This study was performed to investigate the effect of high mobility group box-1 protein(HMGB1)on immune function of human T lymphocytes in vitro and explore its potential role in cell-mediated immune dysfunction.Methods Fresh blood was obtained from healthy adult volunteers and peripheral blood mononuclear cells(PBMCs)were isolated,then rhHMGB1 was added to PBMCs.Four-color flow cytometric(FCM)analysis was used for the measurement of intracellular cytokine including interleukin IL-4 and interferon IFN-?ELISA kits were employed for the determination of IL-2 and sIL-2R protein levels in cell culture supernatants.Results(1)Different stimulating time and dosage of rhHMGB1 did not alter the number of IFN-αpositive cells(Th1).rhHMGB1 stimulation provoked a dose-dependent and time-dependent increase in Th2 subset and decrease in ratio of Th1 to Th2.(2)Compared with the untreated cells,when the cells were coincubated with rhHMGB1(10-100ng/ml)for 12 hrs,protein release of IL-2 and sIL-2R were significantly up-regulated.At 48 hrs,in contrast,protein production was relatively lower in cells after exposure to 100-1000 ng/ml rhHMGB1.Conclusions These findings demonstrated that HMGB1 has a dual influence on immune functions of human T lymphocytes. 展开更多
关键词 high mobility group box-1 protein IMMUNITY T lymphocytes TH1/TH2
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Clinical signification of high-mobility group box 1protein(HMGB1) expression in infiltrating ductalcarcinoma breast tissue
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作者 Baoping Chang Xiao Wang +5 位作者 Songsou Gao Bianfeng Zhao Wanli Wang Shaohua Yang Qian Chu Shiying Yu 《The Chinese-German Journal of Clinical Oncology》 CAS 2014年第5期215-219,共5页
Objective: Exploring the clinical signification of high-mobility group box 1 protein(HMGB1) expression in infiltrating ductal carcinoma(IDC) breast tissue. Methods: The expression of HMGB1 protein in IDC breast tissue... Objective: Exploring the clinical signification of high-mobility group box 1 protein(HMGB1) expression in infiltrating ductal carcinoma(IDC) breast tissue. Methods: The expression of HMGB1 protein in IDC breast tissue was detected by immunohistochemistry, and the relations among size of tumour, lymph node metastasis, clinical staging, estrogen receptor(ER), progesterone receptor(PR) and human epidermal growth factor receptor 2(HER-2) were also analyzed. Results: Fortysix cases out of 60 cases of IDC breast tissue showed positive or strong positive HMGB1 expression(76.67%), statistical significance was observed between HMGB1 expression with clinical staging(P < 0.01), lymph node metastasis(P < 0.01), breast cancer ER(P < 0.05) and HER-2(P < 0.05), however same conclusion can not be drawn between HMGB1 with either size of tumour or PR expression(P > 0.05) in IDC breast tissue. Spearman analysis showed negative correlation between HMGB1 expression and ER, and positive correlation between HMGB1 expression and clinical staging, lymph node metastasis together with HER-2. Conclusion: It's promising that HMGB1 expression in IDC tissue can be one of biological indicators of poor prognosis. 展开更多
关键词 infiltrating ductal carcinoma (IDC) high-mobility group box 1 protein (hmgb1) clinical staging lymph node estrogen receptor (ER) human epidermal growth factor receptor 2 (HER-2)
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High-mobility group box 1 protein and its role in severe acute pancreatitis 被引量:27
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作者 Xiao Shen Wei-Qin Li 《World Journal of Gastroenterology》 SCIE CAS 2015年第5期1424-1435,共12页
The high mobility group box 1(HMGB1),which belongs to the subfamily of HMG-1/-2,is a highly conserved single peptide chain consisting of 215 amino acid residues with a molecular weight of approximately 24894 Da.HMGB1 ... The high mobility group box 1(HMGB1),which belongs to the subfamily of HMG-1/-2,is a highly conserved single peptide chain consisting of 215 amino acid residues with a molecular weight of approximately 24894 Da.HMGB1 is a ubiquitous nuclear protein in mammals and plays a vital role in inflammatory diseases.Acute pancreatitis is one of the most common causes of acute abdominal pain with a poor prognosis.Acute pancreatitis is an acute inflammatory process of the pancreas(duration of less than six months),for which the severe form is called severe acute pancreatitis(SAP).More and more studies have shown that HMGB1 has a bidirectional effect in the pathogenesis of SAP.Extracellular HMGB1 can aggravate the pancreatic inflammatory process,whereas intracellular HMGB1 has a protective effect against pancreatitis.The mechanism of HMGB1 is multiple,mainly through the nuclear factor-κB pathway.Receptors for advanced glycation endproducts and toll-like receptors(TLR),especially TLR-2 and TLR-4,are two major types of receptors mediating the inflammatory process triggered by HMGB1 and may be also the main mediators in the pathogenesis of SAP.HMGB1 inhibitors,such as ethyl pyruvate,pyrrolidine dithiocarbamate and Scolopendra subspinipes mutilans,can decrease the level of extracellular HMGB1 and are the promising targets in the treatment of SAP. 展开更多
关键词 high mobility group box 1 protein INHIBITORS Infla
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High mobility group box-1 protein inhibits regulatory T cell immune activity in liver failure in patients with chronic hepatitis B 被引量:23
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作者 Wang, Lu-Wen Chen, Hui Gong, Zuo-Jiong 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS 2010年第5期499-507,共9页
BACKGROUND: Liver failure in chronic hepatitis B (CHB) patients is a severe, life-threatening condition. Intestinal endotoxemia plays a significant role in the progress to liver failure. High mobility group box-1 (HMG... BACKGROUND: Liver failure in chronic hepatitis B (CHB) patients is a severe, life-threatening condition. Intestinal endotoxemia plays a significant role in the progress to liver failure. High mobility group box-1 (HMGB1) protein is involved in the process of endotoxemia. Regulatory T (Treg) cells maintain immune tolerance and contribute to the immunological hyporesponsiveness against HBV infection. However, the roles of HMGB1 and Treg cells in the pathogenesis of liver failure in CHB patients, and whether HMGB1 affects the immune activity of Treg cells are poorly known at present, and so were explored in this study. METHODS: The levels of HMGB1 expression were detected by ELISA, real-time RT-PCR, and Western blotting, and the percentage of CD4(+)CD25(+)CD127(low) Treg cells among CD4(+) cells was detected by flow cytometry in liver failure patients with chronic HBV infection, CHB patients, and healthy controls. Then, CD4(+)CD25(+)CD127(low) Treg cells isolated from the peripheral blood mononuclear cells from CHB patients were stimulated with HMGB1 at different concentrations or at various intervals. The effect of HMGB1 on the immune activity of Treg cells was assessed by a suppression assay of the allogeneic mixed lymphocyte response. The levels of forkhead box P3 (Foxp3) expression in Treg cells treated with HMGB1 were detected by RT-PCR and Western blotting. RESULTS: A higher level of HMGB1 expression and a lower percentage of Treg cells within the population of CIA(+) cells were found in liver failure patients than in CHB patients (82.6+/-20.1 mu g/L vs. 34.2+/-13.7 mu g/L; 4.55+/-1.34% vs. 9.52+/-3.89%, respectively). The immune activity of Treg cells was significantly weakened and the levels of Foxp3 expression were reduced in a dose- or time-dependent manner when Treg cells were stimulated with HMGB1 in vitro. CONCLUSIONS: The high level of HMGB1 and the low percentage of Treg cells play an important role in the pathogenesis of liver failure in patients with chronic HBV infection. Moreover, HMGB1 can weaken the immune activity of Treg cells. It is suggested that effectively inhibiting HMGB1 expression could be a feasible way to treat liver failure by suppressing endotoxemia and enhancing Treg cell activity. 展开更多
关键词 high mobility group box-1 protein regulatory T cells chronic hepatitis B liver failure
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Novel insights for high mobility group box 1 proteinmediated cellular immune response in sepsis:A systemic review 被引量:20
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作者 Li-feng Huang Yong-ming Yao Zhi-yong Sheng 《World Journal of Emergency Medicine》 CAS 2012年第3期165-171,共7页
High mobility group box 1 protein (HMGB1) is a highly conserved, ubiquitous protein in the nuclei and cytoplasm of nearly all cell types. HMGB1 is secreted into the extracellular milieu and acts as a proinflammatory... High mobility group box 1 protein (HMGB1) is a highly conserved, ubiquitous protein in the nuclei and cytoplasm of nearly all cell types. HMGB1 is secreted into the extracellular milieu and acts as a proinflammatory cytokine. In this article we reviewed briefly the cellular immune response mediated by HMGB1 in inflammation and sepsis. This systemic review is mainly based on our own work and other related reports HMGB1 can actively affect the immune functions of many types of cells including T lymphocytes, regulatory T cells (Tregs), dendritic cells (DCs), macrophages, and natural killer cells (NK cells). Various cellular responses can be mediated by HMGB1 which binds to cell-surface receptors [e.g., the receptor for advanced glycation end products (RAGE), Toll-like receptor (TLR)2, and TLR4]. Anti-HMGB1 treatment, such as anti-HMGB1 polyclonal or monoclonal antibodies, inhibitors (e.g., ethyl pyruvate) and antagonists (e.g., A box), can protect against sepsis lethality and give a wider window for the treatment opportunity. HMGB1 is an attractive target for the development of new therapeutic strategies in the treatment of patients with septic complications. 展开更多
关键词 high mobility group box 1 protein SEPSIS Immunological effect CYTOKINE Signal transduction
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Inflammatory response and immune regulation of high mobility group box-1 protein in treatment of sepsis 被引量:7
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作者 Qing-yang Liu Yong-ming Yao 《World Journal of Emergency Medicine》 SCIE CAS 2010年第2期93-98,共6页
Sepsis is an infection induced systemic inflammatory response syndrome and is a major cause of morbidity as well as mortality in intensive care units. A growing body of evidence suggests that the activation of a proin... Sepsis is an infection induced systemic inflammatory response syndrome and is a major cause of morbidity as well as mortality in intensive care units. A growing body of evidence suggests that the activation of a proinflammatory cascade is responsible for the development of immune dysfunction, susceptibility to severe sepsis and septic shock. The present theories of sepsis as a dysregulated inflammatory response and immune function, as manifested by excessive release of inflammatory mediators such as high mobility group box 1 protein (HMGB1), are supported by increasing studies employing animal models and clinical observations of sepsis. HMGB1, originally described as a DNA-binding protein and released passively by necrotic cells and actively by macrophages/monocytes, has been discovered to be one of essential cytokines that mediates the response to infection, injury and inflammation. A growing number of studies still focus on the inflammation-regulatory function and its contribution to infectious and inflammatory disorders, recent data suggest that HMGB1 formation can also markedly influence the host cell-mediated immunity, including T lymphocytes and macrophages. Here we review emerging evidence that support extracellular HMGB1 as a late mediator of septic complications, and discuss the therapeutic potential of several HMGBl-targeting agents in experimental sepsis. In addition, with the development of traditional Chinese medicine in recent years, it has been proven that traditional Chinese herbal materials and their extracts have remarkable effective in treating severe sepsis. In this review, we therefore provide some new concepts of HMGBl-targeted Chinese herbal therapies in sepsis. 展开更多
关键词 SEPSIS Inflammatory mediators high mobility group box 1 protein
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Scolopendra subspinipes mutilans protected the ceruleininduced acute pancreatitis by inhibiting high-mobility group box protein-1 被引量:7
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作者 Il-Joo Jo Gi-Sang Bae +7 位作者 Kyoung-Chel Park Sun Bok Choi Won-Seok Jung Su-Young Jung Jung-Hee Cho Mee-Ok Choi Ho-Joon Song Sung-Joo Park 《World Journal of Gastroenterology》 SCIE CAS 2013年第10期1551-1562,共12页
AIM:To evaluate the inhibitory effects of Scolopendra subspinipes mutilans(SSM) on cerulein-induced acute pancreatitis(AP) in a mouse model.METHODS:SSM water extract(0.1,0.5,or 1 g/kg) was administrated intraperitonea... AIM:To evaluate the inhibitory effects of Scolopendra subspinipes mutilans(SSM) on cerulein-induced acute pancreatitis(AP) in a mouse model.METHODS:SSM water extract(0.1,0.5,or 1 g/kg) was administrated intraperitoneally 1 h prior to the first injection of cerulein.Once AP developed,the stable cholecystokinin analogue,cerulein was injected hourly,over a 6 h period.Blood samples were taken 6 h later to determine serum amylase,lipase,and cytokine levels.The pancreas and lungs were rapidly removed for morphological examination,myeloperoxidase assay,and real-time reverse transcription polymerase chain reaction.To specify the role of SSM in pancreatitis,the pancreatic acinar cells were isolated using collagenase method.Then the cells were pre-treated with SSM,then stimulated with cerulein.The cell viability,cytokine productions and high-mobility group box protein-1(HMGB-1) were measured.Furthermore,the regulating mechanisms of SSM action were evaluated.RESULTS:The administration of SSM significantly attenuated the severity of pancreatitis and pancreatitis associated lung injury,as was shown by the reduction in pancreatic edema,neutrophil infiltration,vacuolization and necrosis.SSM treatment also reduced pancreatic weight/body weight ratio,serum amylase,lipase and cytokine levels,and mRNA expression of multiple inflammatory mediators such as tumor necrosis factor-α and interleukin-1β.In addition,treatment with SSM inhibited HMGB-1 expression in the pancreas during AP.In accordance with in vivo data,SSM inhibited the cerulein-induced acinar cell death,cytokine,and HMGB-1 release.SSM also inhibited the activation of c-Jun NH2-terminal kinase,p38 and nuclear factor(NF)-κB.CONCLUSION:These results suggest that SSM plays a protective role during the development of AP and pancreatitis associated lung injury via deactivating c-Jun NH2-terminal kinase,p38 and NF-κB. 展开更多
关键词 SCOLOPENDRA subspinipes mutilans CYTOKINES Acute PANCREATITIS high-mobility group box protein-1
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Role of high mobility group box protein 1 in depression:A mechanistic and therapeutic perspective 被引量:1
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作者 Shu Wang Yu-Guang Guan +1 位作者 Yan-Hua Zhu Min-Zhong Wang 《World Journal of Psychiatry》 SCIE 2022年第6期779-786,共8页
As a common and serious psychiatric disorder,depression significantly affects psychosocial functioning and quality of life.However,the mechanism of depression is still enigmatic and perplexing,which limits its precise... As a common and serious psychiatric disorder,depression significantly affects psychosocial functioning and quality of life.However,the mechanism of depression is still enigmatic and perplexing,which limits its precise and effective therapeutic methods.Recent studies demonstrated that neuroinflammation activation plays an important role in the pathophysiology of depression.In this respect,high mobility group box 1(HMGB1)may be a possible signaling inducer of neuroinflammation and can be a potential mechanistic and therapeutic target for depression.Herein,we review recent studies on the mechanistic and therapeutic targets of HMGB1 in depression and propose potential perspectives on this topic. 展开更多
关键词 NEUROINFLAMMATION DEPRESSION high mobility group box 1 Mechanism Review PERSPECTIVE
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Effect of high mobility group box-1 protein on immune cells and its regulatory mechanism 被引量:1
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作者 Ying-yi LUAN Feng-hua YAO +3 位作者 Qing-hong ZHANG Xiao-mei ZHU Ning DONG Yong-ming YAO 《中国应用生理学杂志》 CAS CSCD 2012年第6期548-554,共7页
High mobility group box-1 protein(HMGB1),which is a nuclear protein,participates in chromatin architecture and transcriptional regulation.When released from cells,HMGB1 also plays a well-established role as a pro-infl... High mobility group box-1 protein(HMGB1),which is a nuclear protein,participates in chromatin architecture and transcriptional regulation.When released from cells,HMGB1 also plays a well-established role as a pro-inflammatory mediator during innate immune responses to injury.In the initial stage of injury,there is a release of large quantities of early pro-inflammatory mediators to initiate or perpetuate immune responses against pathogens,but this pro-inflammatory period is transient,and it is followed by a prolonged period of immune suppression.At present,several lines of evidences have suggested that HMGB1 is a late cytokine provoking delayed endotoxin morbidity,which may enhance the production of early proinflammatory mediators,and it can contribute potently to the activation of different immune cells and play a role in the development of host cell-mediated immunity.The biology of HMGB1 has been extensively studied as a pro-inflammatory cytokine of systemic inflammation,however,this review will attempt to provide a summary of the effects of HMGB1 on different immune cells and its regulatory mechanism in acute insults. 展开更多
关键词 免疫细胞 调控机制 核蛋白 迁移率 hmgb1 炎症介质 基因转录调控 免疫反应
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Relationship of plasma homocysteine, soluble intercellular adhesion molecule-1, high mobility group box 1 protein with carotid intima-media thickness in elderly patients with type 2 diabetes mellitus
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作者 Zhijie Cai Jun Xue +4 位作者 Xiaohui Ma Peifeng Chen Biao Ge Yuying Zhang Zhihui Dong 《Discussion of Clinical Cases》 2022年第1期9-12,共4页
Objective:To explore the relationship of plasma homocysteine(Hcy),soluble intercellular adhesion molecule-1(sICAM-1)and high mobility group box 1 protein(HMGB1)with carotid intima-media thickness(c-IMT)in elderly pati... Objective:To explore the relationship of plasma homocysteine(Hcy),soluble intercellular adhesion molecule-1(sICAM-1)and high mobility group box 1 protein(HMGB1)with carotid intima-media thickness(c-IMT)in elderly patients with type 2 diabetes mellitus.Methods:A total of 100 elderly patients who were diagnosed as type 2 diabetes mellitus in Baogang Hospital of Inner Mongolia from June 2017 to May 2020 were chosen as research objects.According to c-IMT,they were divided into the normal group(n=35),the mild to moderate group(n=41)and the severe group(n=24).The expression levels of plasma Hcy,sICAM-1 and HMGB1 were compared between groups respectively.Pearson’s correlation coefficient was used to analyze the relationship of plasma Hcy,sICAM-1,HMGB1 with c-IMT.Results:The comparison in plasma Hcy,sICAM-1,HMGB1 and c-IMT among the three groups of patients was of statistical significance(p<.05).The results of correlation analysis showed that the expression levels of plasma Hcy,sICAM-1 and HMGB1 were positively correlated with c-IMT in elderly patients with type 2 diabetes mellitus(r=.627,.598,.614;p<.05).Conclusions:The expression levels of plasma Hcy,sICAM-1 and HMGB1 are abnormally increased in elderly patients with type 2 diabetes mellitus,and related to c-IMT,which can provide a strong evidence for clinical diagnosis and treatment by detecting their levels in clinical practice. 展开更多
关键词 Type 2 diabetes mellitus Carotid intima-media thickness HOMOCYSTEINE Soluble intercellular adhesion molecule-1 high mobility group box 1 protein
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HMGB1中和抗体抑制细胞焦亡改善系统性红斑狼疮小鼠肺损伤的机制研究 被引量:1
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作者 李鸣远 孟岩 武云 《医学分子生物学杂志》 CAS 2024年第1期39-44,50,共7页
目的探究高迁移率族蛋白1(high-mobility group box 1,HMGB1)中和抗体对系统性红斑狼疮(systemic lupus erythematosus,SLE)小鼠肺损伤的影响及机制。方法30只MRL/lpr小鼠随机分为MRL/lpr组、MRL/lpr+HMGB1中和抗体(anti-HMGB1)组、MRL/... 目的探究高迁移率族蛋白1(high-mobility group box 1,HMGB1)中和抗体对系统性红斑狼疮(systemic lupus erythematosus,SLE)小鼠肺损伤的影响及机制。方法30只MRL/lpr小鼠随机分为MRL/lpr组、MRL/lpr+HMGB1中和抗体(anti-HMGB1)组、MRL/lpr+MCC950组,每组10只,另取10只野生型C57BL/6小鼠作为对照组,给药4周。苏木精-伊红(HE)染色和马松三色(Masson)染色观察各组小鼠肺组织病理学变化及胶原纤维沉积情况,酶联免疫吸附法(ELISA)检测各组小鼠肺泡灌洗液中白细胞介素-1β(IL-1β)、IL-6、IL-18及肿瘤坏死因子-α(TNF-α)含量,免疫荧光染色观察各组小鼠肺组织内核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)荧光表达,蛋白质免疫印记(Western blotting)检测各组小鼠肺组织中HMGB1及NLRP3、凋亡相关斑点样蛋白(ASC)、含半胱氨酸的天冬氨酸蛋白水解酶-1(Caspase-1)、gasdermin D(GSDMD)的蛋白表达水平。结果与对照组比较,MRL/lpr组小鼠肺组织呈现严重病理损伤症状,胶原纤维沉积面积显著增加(P<0.05),肺泡灌洗液中IL-1β、IL-6、IL-18、TNF-α含量显著升高(P<0.05),肺组织内NLRP3平均荧光强度显著增加(P<0.05),HMGB1蛋白相对表达量及NLRP3、ASC、Caspase-1、GSDMD蛋白相对表达量均显著上调(P<0.05);与MRL/lpr组比较,MRL/lpr+anti-HMGB1组和MRL/lpr+MCC950组小鼠肺组织损伤得到明显改善,胶原纤维沉积面积显著减少(P<0.05),肺泡灌洗液中IL-1β、IL-6、IL-18、TNF-α含量显著降低(P<0.05),肺组织内NLRP3平均荧光强度显著减小(P<0.05),同时,肺组织中HMGB1蛋白相对表达量及NLRP3、ASC、Caspase-1、GSDMD蛋白相对表达量均显著下调(P<0.05)。结论HMGB1中和抗体能够改善SLE模型小鼠肺损伤,该作用可能是通过抑制细胞焦亡实现的。 展开更多
关键词 系统性红斑狼疮 肺损伤 高迁移率族蛋白1 细胞焦亡
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血清HMGB1、CCL20、HSP27水平与慢性牙周炎患者牙周病变程度的相关性分析 被引量:1
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作者 王伟新 张丽娜 《河南医学研究》 CAS 2024年第2期252-255,共4页
目的探讨血清高迁移率族蛋白1(HMGB1)、CC趋化因子配体20(CCL20)、热休克蛋白27(HSP27)水平与慢性牙周炎(CP)患者牙周病变程度的相关性。方法选取2021年9月至2023年8月在新乡医学院第一附属医院诊治的60例CP患者纳入观察组,根据1∶1原则... 目的探讨血清高迁移率族蛋白1(HMGB1)、CC趋化因子配体20(CCL20)、热休克蛋白27(HSP27)水平与慢性牙周炎(CP)患者牙周病变程度的相关性。方法选取2021年9月至2023年8月在新乡医学院第一附属医院诊治的60例CP患者纳入观察组,根据1∶1原则,另选取同期牙周健康者60例纳入对照组。比较两组及不同牙周病变程度CP患者血清HMGB1、CCL20、HSP27水平,分析各指标水平与CP牙周病变程度的相关性及联合诊断价值,并分析不同血清水平患者发生CP的危险度。结果观察组血清HMGB1、CCL20、HSP27水平高于对照组(P<0.05);不同牙周病变程度CP患者血清HMGB1、CCL20、HSP27水平比较:轻度<中度<重度,且各指标水平与牙周病变程度均呈正相关(P<0.05);入院时HMGB1、CCL20、HSP27水平联合诊断CP的曲线下面积(AUC)为0.905,最佳诊断敏感度为91.67%,特异度为88.33%,约登指数0.800,且各指标高水平患者发生CP的危险度是低水平的1.105倍、1.034倍、1.105倍(P<0.05)。结论HMGB1、CCL20、HSP27在CP患者血清中呈异常高表达,各指标水平与牙周病变程度均呈正相关,且联合检测对CP具有较高诊断价值,可作为临床诊断CP、评估牙周病变程度的有效指标。 展开更多
关键词 高迁移率族蛋白1 CC趋化因子配体20 热休克蛋白27 慢性牙周炎
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Delayed ethyl pyruvate therapy attenuates experimental severe acute pancreatitis via reduced serum high mobility group box 1 levels in rats 被引量:23
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作者 Zhi-Yong Yang Yan Ling Tao Yin Jing Tao Jiong-Xin Xiong He-Shui Wu Chun-You Wang 《World Journal of Gastroenterology》 SCIE CAS CSCD 2008年第28期4546-4550,共5页
AIM: To investigate the effect of delayed ethyl pyruvate (EP) delivery on distant organ injury, survival time and serum high mobility group box 1 (HMGB1) levels in rats with experimental severe acute pancreatitis... AIM: To investigate the effect of delayed ethyl pyruvate (EP) delivery on distant organ injury, survival time and serum high mobility group box 1 (HMGB1) levels in rats with experimental severe acute pancreatitis (SAP). METHODS: A SAP model was induced by retrograde injection of artificial bile into the pancreatic ducts of rats. Animals were divided randomly into three groups (n = 32 in each group): sham group, SAP group and delayed EP treatment group. The rats in the delayed EP treatment group received EP (30 mg/kg) at 12 h, 18 h and 30 h after induction of SAP. Animals were sacrificed, and samples were obtained at 24 h and 48 h after induction of SAP. Serum HMGB1, aspartate arninotransferase (AST), alanine arninotransferase (ALT), blood urea nitrogen (BUN), and creatinine (Cr) levels were measured. Lung wet-to-dry-weight (W/D) ratios and histological scores were calculated to evaluate lung injury. Additional experiments were performed between SAP and delayed EP treatment groups to study the influence of EP on survival times of SAP rats. RESULTS: Delayed EP treatment significantly reduced serum HMGB1 levels, and protected against liver, renal and lung injury with reduced lung W/D ratios (8.22 ±0.42 vs 9.76 ± 0.45, P 〈 0.01), pulmonary histological scores (7.1 ± 0.7 vs 8.4 ± 1.1, P 〈 0.01), serum AST (667 ± 103 vs 1 368 ± 271, P 〈 0.01), ALT (446 ± 91 vs 653 ± 98, P 〈 0.01) and Cr (1.2 ± 0.3 vs 1.8 ± 0.3, P 〈 0.01) levels. SAP rats had a median survival time of 44 h. Delayed EP treatment significantly prolonged median survival time to 72 h (P 〈 0.01). CONCLUSION: Delayed EP therapy protects against distant organ injury and prolongs survival time via reduced serum HMGBllevels in rats with experimental SAP. EP may potentially serve as an effective new therapeutic option against the inflammatory response and multiple organ dysfunction syndrome (MODS) in SAP patients. 展开更多
关键词 Severe acute pancreatitis Ethyl pyruvate high mobility group box 1 multiple organ dysfunction syndrome Survival time
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miR-141-3p靶向调控HMGB1对LPS诱导的A549细胞损伤的影响
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作者 龙光文 张谦 +2 位作者 杨秀林 孙鸿鹏 吉春玲 《安徽医科大学学报》 CAS 北大核心 2024年第1期85-91,共7页
目的探讨miR-141-3p通过靶向调控高迁移率族蛋白1(HMGB1)对脂多糖(LPS)诱导的A549细胞损伤的影响。方法以Ⅱ型肺泡上皮细胞来源的A549细胞作为研究对象,将miR-141-3p mimics、mimics NC、HMGB1基因过表达质粒(pcDNA3.1-HMGB1)和空载质粒... 目的探讨miR-141-3p通过靶向调控高迁移率族蛋白1(HMGB1)对脂多糖(LPS)诱导的A549细胞损伤的影响。方法以Ⅱ型肺泡上皮细胞来源的A549细胞作为研究对象,将miR-141-3p mimics、mimics NC、HMGB1基因过表达质粒(pcDNA3.1-HMGB1)和空载质粒(Vector)分别或共转染至A549细胞中,再采用10μg/ml LPS处理24 h。细胞计数试剂盒8(CCK-8)检测各组细胞增殖活性;比色法检测各组细胞培养上清液中乳酸脱氢酶(LDH)活性;流式细胞术检测各组细胞凋亡水平;酶联免疫吸附测定法(ELISA)检测各组细胞中白介素(IL)-1β、IL-6和肿瘤坏死因子α(TNF-α)水平;双荧光素酶报告基因实验验证miR-141-3p与HMGB1之间的靶向调控关系。结果LPS干预后,A549细胞增殖活性及细胞中miR-141-3p表达水平降低(P<0.05),细胞凋亡率升高(P<0.05),细胞中IL-1β、IL-6、TNF-α水平及上清液中LDH活性升高(P<0.05)。过表达miR-141-3p可增强LPS处理后的A549细胞增殖活性(P<0.05),降低细胞凋亡率及细胞中IL-1β、IL-6、TNF-α水平和上清液中LDH活性(P<0.05)。然而,HMGB1基因过表达可逆转miR-141-3p对LPS诱导A549细胞损伤的改善作用。双荧光素酶报告基因实验证实,HMGB1是miR-141-3p下游靶基因。结论miR-141-3p可抑制LPS诱导的A549细胞凋亡,降低炎症因子表达水平,改善A549细胞损伤,其作用机制可能与靶向调控HMGB1表达有关。 展开更多
关键词 Ⅱ型肺泡上皮细胞 A549 脂多糖 miR-141-3p 高迁移率族蛋白1
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Expression of high mobility group protein B1 in the lungs of rats with sepsis 被引量:6
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作者 Qiao-meng Qiu Zhong-wang Li +5 位作者 Lu-ming Tang Qi Sun Zhong-qiu Lu Huan Liang Guang-liang Hong Meng-fang Li 《World Journal of Emergency Medicine》 SCIE CAS 2011年第4期302-306,共5页
BACKGROUND: Vibrio vulnifi cus inside the body could activate the NF-!B signaling pathwayand initiate the inflammatory cascade. The lung is one of the earliest organs affected by sepsisassociated with acute lung inju... BACKGROUND: Vibrio vulnifi cus inside the body could activate the NF-!B signaling pathwayand initiate the inflammatory cascade. The lung is one of the earliest organs affected by sepsisassociated with acute lung injury. High mobility group protein B1 (HMGB1) is an important late-actingpro-infl ammatory cytokine involving in the pathophysiology of sepsis. It is also involved in the injuryprocess in the lung, liver and intestine. There has been no report on the involvement of HMGB1 inVibrio vulnifi cus sepsis-induced lung injury.METHODS: Sixty rats were randomly divided into a normal control group (group A, n=10) anda Vibrio vulnificus sepsis group (group B, n=50). Sepsis was induced in the rats by subcutaneousinjection of Vibrio vulnificus (concentration 6×108 cfu/mL, volume 0.1 mL/100g)) into the left lowerlimbs. The rats in group B were sacrifi ced separately 1, 6, 12, 24, and 48 hours after the infection.Their lungs were stored as specimens, lung water content was measured, and lung pathology wasobserved under a light microscope. The expressions of the HMGB1 gene and protein in the lungswere detected by RT-PCR and Western blot. Data were analyzed with one-way analysis of variance(ANOVA) and the LSD method for pair-wise comparison between the two groups. P〈0.05 wasconsidered statistically signifi cant.RESULTS: Compared to group A (0.652±0.177), HMGB1 mRNA expression in the lungs ofgroup B was signifi cantly higher at 0 hour (1.161±0.358, P=0.013), 24 hours (1.679±0.235, P=0.000),and 48 hours (1.258±0.274, P=0.004) (P〈0.05), and peaked at 24 hours. Compared to group A(0.594±0.190), HMGB1 protein expression at 6 hours (1.408±0.567, P=0.026) after infection wassignificantly increased (P〈0. 05), and peaked at 24 hours (2.415±1.064, P=0.000) after infection.Compared to group A (0.699±0.054), lung water content was significantly increased at 6 hours(0.759±0.030, P=0.001),12 hours (0.767±0.023, P=0.000), 24 hours (0.771±0.043, P=0.000) and 48hours (0.789±0.137, P=0.000) after infection (P〈0.05). Compared to group A, pathological changesat 12 hours in group B indicate marked pulmonary vascular congestion, interstitial edema andinfl ammatory infi ltration. Alveolar cavity collapse and boundaries of the alveolar septum could not beclearly identifi ed.CONCLUSION: Vibrio vulnifi cus sepsis can lead to injury in rat lungs, and increased HMGB1expression in lung tissue may be one of the mechanisms for injury from Vibrio vulnifi cus sepsis. 展开更多
关键词 VIBRIO VULNIFICUS SEPSIS LUNG injury high mobility group protein B1 REVERSETRANSCRIPTION polymerase chain reaction Western blot LUNG water content Histopathology
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HMGB1及血清炎性因子与轻度胃肠炎伴良性惊厥发病机制的关系
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作者 陈辉 陈勇 +3 位作者 章静静 查剑 王蕊艳 钟建民 《实用临床医学(江西)》 CAS 2024年第3期42-46,共5页
目的 探讨高迁移率族蛋白B1(HMGB1)及白介素(IL)-1β、IL-2R、IL-6、IL-8及肿瘤坏死因子α(TNF-α)与轻度胃肠炎伴良性惊厥(CwG)发病机制的关系。方法 选取2022年1月至2023年11月期间在江西省儿童医院就诊的CwG患儿30例(CwG组)和同期轻... 目的 探讨高迁移率族蛋白B1(HMGB1)及白介素(IL)-1β、IL-2R、IL-6、IL-8及肿瘤坏死因子α(TNF-α)与轻度胃肠炎伴良性惊厥(CwG)发病机制的关系。方法 选取2022年1月至2023年11月期间在江西省儿童医院就诊的CwG患儿30例(CwG组)和同期轻度急性胃肠炎(AGE)不伴有惊厥的患儿30例(对照组)。采集2组急性期和恢复期的静脉血,采用酶联免疫吸附法(ELISA)检测血清HMGB1水平;采用化学发光法检测血清IL1β、IL2R、IL6、IL8、TNF-α水平。结果 在急性期,CwG组的血清HMGB1、IL-6、IL-8、TNF-α水平均显著高于对照组(P<0.001),而血清IL-1β、IL-2R水平与对照组比较差异无统计学意义(P>0.05)。CwG组的惊厥发作次数、惊厥发作总时间、病程均与血清HMGB1、IL-6、IL-8、TNF-α水平成正相关(P<0.05或P<0.001),且血清HMGB1、IL-6、IL-8、TNF-α水平之间相互呈正相关(P<0.05或P<0.001)。CwG组恢复期HMGB1、IL-6、IL-8、TNF-α水平均较急性期下降(P<0.05);2组在恢复期时HMGB1、IL-1β、IL-2R、IL-6、IL-8、TNF-α水平比较差异无统计学意义(P>0.05)。结论 HMGB1介导的免疫炎症网络与CwG的发病过程密切相关,血清HMGB1、IL-6、IL-8、TNF-α水平与CwG急性期的惊厥严重程度及病程转归显著相关。 展开更多
关键词 高迁移率族蛋白B1 炎症 轻度胃肠炎 惊厥 儿童
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