BACKGROUND Accumulating studies indicated that maintain nuclei homeostasis was deemed to the protective factors for the occurrence of cancer.Thus,high-mobility group box 1(HMGB1)might influence the risk and poorer pro...BACKGROUND Accumulating studies indicated that maintain nuclei homeostasis was deemed to the protective factors for the occurrence of cancer.Thus,high-mobility group box 1(HMGB1)might influence the risk and poorer prognoses of colorectal cancer(CRC).AIM This study was designed to investigate whether HMGB1 polymorphisms influence the risk and lymph node metastasis(LNM)of CRC.METHODS Firstly,we designed an investigation with 1003 CRC patients and 1303 cancer-free controls to observe whether HMGB1 rs1412125 T>C and rs1045411 C>T SNPs could influence the risk of cancer.Subsequently,we carried out a correlation-analysis to assess whether these SNPs could alter the risk of LNM.RESULTS The current investigation suggested a relationship of HMGB1 rs1412125 SNP with the increased susceptibility of CRC.In a subgroup analysis,our findings suggested that this SNP could enhance an occurrence of CRC in≥61 years,non-drinker and body mass index<24 kg/m2 subgroups.However,we found that there was null association between HMGB1 rs1412125 SNP and LNM,even in different CRC region.These observations were confirmed by calculating the power value(more than 0.8).The association of HMGB1 rs1045411 C>T SNP with CRC risk and LNM was not found in any compare.CONCLUSION This study highlights a possible association between HMGB1 rs1412125 polymorphism and the increased risk of CRC.In the future,more studies should be conducted to explore HMGB1 rs1412125 polymorphism in relation to CRC development.展开更多
AIM:To explore the role of high-mobility group box 1 (HMGB1) protein during liver fibrogenesis and investigate the functional effects of HMGB1 gene silencing in hepatic stellate cells (HSCs) using siRNA.METHODS:Hepati...AIM:To explore the role of high-mobility group box 1 (HMGB1) protein during liver fibrogenesis and investigate the functional effects of HMGB1 gene silencing in hepatic stellate cells (HSCs) using siRNA.METHODS:Hepatic fibrosis in rats was induced through serial subcutaneous injections of dimethylnitrosamine,and expression of HMGB1 was detected by immunohistochemistry.HMGB1 siRNAs were developed and transiently transfected into HSC-T6 cells using Lipofectamine 2000.HMGB1 expression was evaluated by real-time polymerase chain reaction (PCR) and Western blotting analysis.Expression of α-smooth muscle actin (α-SMA) and collagen typesⅠand Ⅲ was evaluated by real-time PCR.Cell proliferation and the cell cycle were determined using the methyl thiazolyl tetrazolium method.Finally,collagen content in HSC supernatant was evaluated by an enzyme-linked immunosorbent assay.RESULTS:The results showed that HMGB1 was upregulated during liver fibrosis and that its expression was closely correlated with the deposition of collagen.siRNA molecules were successfully transfected into HSCs and induced inhibition of HMGB1 expression in a time-dependent manner.Moreover,HMGB1 siRNA treatment inhibited synthesis of α-SMA and collagen types Ⅰ and Ⅲ in transfected HSCs.CONCLUSION:This study suggests a significant functional role for HMGB1 in the development of liver fibrosis.It also demonstrates that downregulation of HMGB1 expression might be a potential strategy to treat liver fibrosis.展开更多
Objective： To investigate the antibacterial mechanism of high-mobility group nucleosomal-binding domain 2 （HMGN2） on Escherichia coil K12, focusing on the antibacterial and antibiofilm formation effects. Its chemot...Objective： To investigate the antibacterial mechanism of high-mobility group nucleosomal-binding domain 2 （HMGN2） on Escherichia coil K12, focusing on the antibacterial and antibiofilm formation effects. Its chemotactic activity on human neutrophils was also investigated. Methods： Human tissue-derived HMGN2 （tHMGN2） was extracted from fresh uterus fiber cystadenoma and purified by HPl100 reversed-phase high-performance liquid chromatography （RP-HPLC）. Recombinant human HMGN2 （rHMGN2） was generated in E. coil DE3 carrying PET-32a- c（＋）-HMGN2. Antibacterial activity of HMGN2 was determined using an agarose diffusion assay and minimum inhibitory concentration （MIC） of HMGN2 was determined by the microdilution broth method. Bacterial membrane permeability assay and DNA binding assay were performed. The antibiofilm effect of HMGN2 was investigated using a crystal violet assay and electron microscopy scanning. The activating effect and chemotactic activity of HMGN2 on neutrophils were determined using a nitroblue tetrazolium （NBT） reduction assay and Transwell chamber cell migra- tion assay, respectively. Results： HMGN2 showed a relatively high potency against Gram-negative bacteria E. coli and the MIC of HMGN2 was 16.25 μg/ml. Elevated bacterial membrane permeability was observed in HMGN2-treated E. coil K12. HMGN2 could also bind the bacterial plasmid and genomic DNA in a dose-dependent manner. The antibiofilm effect of HMGN2 on E. coil K12 was confirmed by crystal violet staining and scanning electron microscopy. However, the activating effects and chemotactic effects of HMGN2 on human neutrophils were not observed. Con- clusions： As an antimicrobial peptide （AMP）, HMGN2 possessed a good capacity for antibacterial and antibiofilm activities on E. coil K12. This capacity might be associated with disruption of the bacterial membrane and combination of DNA, which might affect the growth and viability of E. coil.展开更多
BACKGROUND Necrotising enterocolitis(NEC)is a critical gastrointestinal emergency affecting premature and low-birth-weight neonates.Serum amyloid A(SAA),procalcitonin(PCT),and high-mobility group box 1(HMGB1)have emer...BACKGROUND Necrotising enterocolitis(NEC)is a critical gastrointestinal emergency affecting premature and low-birth-weight neonates.Serum amyloid A(SAA),procalcitonin(PCT),and high-mobility group box 1(HMGB1)have emerged as potential biomarkers for NEC due to their roles in inflammatory response,tissue damage,and immune regulation.AIM To evaluate the diagnostic value of SAA,PCT,and HMGB1 in the context of NEC in newborns.METHODS The study retrospectively analysed the clinical data of 48 newborns diagnosed with NEC and 50 healthy newborns admitted to the hospital.Clinical,radiological,and laboratory findings,including serum SAA,PCT,and HMGB1 Levels,were collected,and specific detection methods were used.The diagnostic value of the biomarkers was evaluated through statistical analysis,which was performed using chi-square test,t-test,correlation analysis,and receiver operating characteristic(ROC)analysis.RESULTS The study demonstrated significantly elevated levels of serum SAA,PCT,and HMGB1 Levels in newborns diagnosed with NEC compared with healthy controls.The correlation analysis indicated strong positive correlations among serum SAA,PCT,and HMGB1 Levels and the presence of NEC.ROC analysis revealed promising sensitivity and specificity for serum SAA,PCT,and HMGB1 Levels as potential diagnostic markers.The combined model of the three biomarkers demonstrating an extremely high area under the curve(0.908).CONCLUSION The diagnostic value of serum SAA,PCT,and HMGB1 Levels in NEC was highlighted.These biomarkers potentially improve the early detection,risk stratification,and clinical management of critical conditions.The findings suggest that these biomarkers may aid in timely intervention and the enhancement of outcomes for neonates affected by NEC.展开更多
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
AIM:To evaluate the prognostic value of high-mobility group box 1(HMGB1) expression in intrahepatic cholangiocarcinoma(IHCC) and the possible underlying mechanism.METHODS:Tissue microarray was constructed from 65 IHCC...AIM:To evaluate the prognostic value of high-mobility group box 1(HMGB1) expression in intrahepatic cholangiocarcinoma(IHCC) and the possible underlying mechanism.METHODS:Tissue microarray was constructed from 65 IHCC patients.Immunohistochemistry was performed to validate expression of HMGB1 and Vascular endothelial growth factor C(VEGF-C).Realtime PCR and Western blot analyses were used to study transcript and protein levels.The interaction between HMGB1 and VEGF-C was evaluated by si RNA,real-time PCR,and enzyme-linked immuno assays.The correlation between HMGB1 expression and other clinicopathologic parameters was analyzed byχ2 test,and the univariate as well as multivariate analyses were accomplished by Kaplan-Meier method and Coxregression model,respectively.RESULTS:Overall,overexpression of HMGB1 was found in 38/65(58.8%)IHCCs,whereas VEGF-C overexpression was present in 30/65(46.2%)cases.Overexpression of HMGB1 was significantly correlated with lymphatic microvessel density(P=0.031,r=0.268)and VEGF-C expression(P=0.041,r=0.254).With univariate analysis,both HMGB1(P=0.001)and VEGF-C(P=0.004)were identified to be significantly associated with overall survival rate.Multivariateanalysis indicated that HMGB1 could be served as an unfavorable independent prognostic factor in IHCCs(P=0.005).si RNA knockdown of HMGB1 inhibited transforming growth factor-β-induced epithelialmesenchymal transition(EMT)by elevating E-Cadherin expression and reducing expression of N-Cadherin,Vimentin and Snail in RBE cells.Further in vitro study revealed that HMGB1 silencing significantly decreased the level of VEGF-C,whereas the recombinant HMGB1increased the VEGF-C level in RBE cells(both P<0.05),which suggested that HMGB1 could promote lymphatic microvessel density,and subsequently lymphatic invasion,via promoting VEGF-C expression.CONCLUSION:Our results define an important role of HMGB1 in the progression of cholangiocarcinoma,and HMGB1 may serve as a prognostic marker for IHCC patients.展开更多
AIM: To investigate the inflammatory amplification effect of high-mobility group box 1(HMGB1) in Aspergillus fumigatus(A. fumigatus) keratitis and the relationship between lectin-like oxidized low-density lipoprotein ...AIM: To investigate the inflammatory amplification effect of high-mobility group box 1(HMGB1) in Aspergillus fumigatus(A. fumigatus) keratitis and the relationship between lectin-like oxidized low-density lipoprotein receptor 1(LOX-1) and HMGB1 in keratitis immune responses.METHODS: Phosphate buffer saline(PBS), and Boxb were injected into BALB/c mice subconjunctivally before the corneas were infected with A. fumigatus. RAW264.7 macrophages and neutrophils were pretreated with PBS and Boxb to determine the HMGB1 inflammatory amplification effects. Abdominal cavity extracted macrophages were pretreated with Boxb and Poly(I)(a LOX-1 inhibitor) before A. fumigatus hyphae stimulation to prove the the relationship between the two molecules. LOX-1, interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), macrophage inflammatory protein-2(MIP-2) and IL-10 were assessed by polymerase chain reaction and Western blot.RESULTS: Pretreatment with Boxb exacerbated corneal inflammation. In macrophages and neutrophils, A. fumigatus induced LOX-1, IL-1β, TNF-α and MIP-2 expression in Boxb group was higher than those in PBS group. Poly(I) treatments before infection alleviated the proinflammatory effects of Boxb in abdominal cavity extracted macrophages. Pretreatment with Boxb did not influence Dectin-1 mRNA levels in macrophages and neutrophils.CONCLUSION: In fungal keratitis, HMGB1 is a proinflammatory factor in the first line of immune response. HMGB1 mainly stimulates neutrophils and macrophages to produce inflammatory cytokines and chemokines during the immune response. LOX-1 participates in HMGB1 induced inflammatory exacerbation in A. fumigatus keratitis.展开更多
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
Background Sepsis is a leading cause of death in the intensive care units. The late inflammatory cytokine, high-mobility group box 1 （HMGB1）, plays a critical role in sepsis. In the present study, we investigated th...Background Sepsis is a leading cause of death in the intensive care units. The late inflammatory cytokine, high-mobility group box 1 （HMGB1）, plays a critical role in sepsis. In the present study, we investigated the association between the serum HMGB1 levels and the severity of organ injury in the lipopolysaccharide-induced sepsis in rats. Methods To produce an animal model of sepsis with different degree of organ injury, animals were treated with three different doses of lipopolysaccharide （4, 8 and 16 mg/kg）, and the animals in control group were treated with the same volume of the vehicle （saline）. The levels of serum HMGB1 were measured at 0, 2, 4, 8, 16, 24, 32 and 48 hours after lipopolysaccharide （LPS） or vehicle injection, meanwhile the biochemical and histopathological indicators for the severity of organ injury were assessed. Results The level of HMGB1 had a positive, high correlation with the abnormal changes of serum cardiac troponin I, alanine aminotransferase, aspartate aminotransferase, creatinine and blood urea nitrogen, as well as the pathologic scores of heart, lung, liver and kidney. Conclusions The level of serum HMGB1 is highly correlated with the severity of sepsis in rats, suggesting that HMGB1 could serve as a valuable adjunct in the diagnosis and management of sepsis.展开更多
Background:Sepsis is a common severe complication in major burn victims and is characterized by a dysregulated systemic response to inflammation.YTH domain family 2(YTHDF2),a wellstudied N6-methyladenosine(m6A)reader ...Background:Sepsis is a common severe complication in major burn victims and is characterized by a dysregulated systemic response to inflammation.YTH domain family 2(YTHDF2),a wellstudied N6-methyladenosine(m6A)reader that specifically recognizes and binds to m6A-modified transcripts to mediate their degradation,is connected to pathogenic and physiological processes in eukaryotes,but its effect on sepsis is still unknown.We aimed to discover the effects and mechanisms of YTHDF2 in sepsis.Methods:Quantitative reverse transcription-polymerase chain reaction(qRT-PCR)and western blot analyses were used to measure the expression of YTHDF2,the interleukin 6 receptor(IL-6R),high-mobility group box-1(HMGB1),Janus kinase 2(JAK2)and signal transducer and activator of transcription 1(STAT1)under different in vitro conditions.Enzyme-linked immunosorbent assays were utilized to evaluate the expression of HMGB1,IL-6,IL-1βand tumor necrosis factor-α.To confirm that YTHDF2 specifically targets IL-6R mRNA,RNA immunoprecipitation and dual-luciferase reporter assays were performed.Finally,we utilized a mouse model of lipopolysaccharide(LPS)-induced sepsis to verify the effects of YTHDF2 in vivo.Results:According to our findings,YTHDF2 was expressed at a low level in peripheral blood mononuclear cells from septic mice and patients as well as in LPS-induced RAW264.7 cells.Overexpression of YTHDF2 alleviated the inflammatory response by inhibiting HMGB1 release and JAK2/STAT1 signalling in LPS-stimulated cells.Mechanistically,YTHDF2 suppressed JAK2/STAT1 signalling by directly recognizing the m6A-modified site in IL-6R and decreasing the stability of IL-6R mRNA,thereby inhibiting HMGB1 release.In vivo experiments showed that YTHDF2 played a protective role in septic mice by suppressing the IL-6R/JAK2/STAT1/HMGB1 axis.Conclusions:In summary,these findings demonstrate that YTHDF2 plays an essential role as an inhibitor of inflammation to reduce the release of HMGB1 by inhibiting the IL-6R/JAK2/STAT1 pathway,indicating that YTHDF2 is a novel target for therapeutic interventions in sepsis.展开更多
High-mobility group box-1(HMGB1)is an architectural chromosomal protein with various roles depending on its cellular localization.Extracellular HMGB1 functions as a prototypical damage-associated molecular pattern tha...High-mobility group box-1(HMGB1)is an architectural chromosomal protein with various roles depending on its cellular localization.Extracellular HMGB1 functions as a prototypical damage-associated molecular pattern that triggers inflammation and adaptive immune responses,mediated by specific cell surface receptors,including receptors for advanced glycation end products and toll-like receptors.Post-translational modifications of HMGB1 significantly impact various cellular processes that contribute to the pathogenesis of liver diseases.Recent studies have highlighted the close relationship between HMGB1 and the pathogenesis of acute liver injuries,including acetaminophen-induced liver injury,hepatic ischemia-reperfusion injury,and acute liver failure.In chronic liver diseases,HMGB1 plays a role in nonalcoholic fatty liver disease,alcohol-associated liver disease,liver fibrosis,and hepatocellular carcinoma.Targeting HMGB1 as a therapeutic approach,either by inhibiting its release or blocking its extracellular function,is a promising strategy for treating liver diseases.This review aimed to summarize the available evidence on HMGB1’s role in liver disease,focusing on its multifaceted signaling pathways,impact on disease progression,and the translation of these findings into clinical interventions.展开更多
Strained-Si0.73Ge0.27 channels are successfully integrated with high-R/metal gates in p-type metai-oxide- semi- conductor field effect transistors （pMOSFETs） using the replacement post-gate process. A silicon cap an...Strained-Si0.73Ge0.27 channels are successfully integrated with high-R/metal gates in p-type metai-oxide- semi- conductor field effect transistors （pMOSFETs） using the replacement post-gate process. A silicon cap and oxide inter layers are inserted between Si0.73Ge0.27 and high-κ dielectric to improve the interface. The fab- ricated Si0.73Ge0.27 pMOSFETs with gate length of 3Onto exhibit good performance with high drive current （~428μA/μm at VDD = 1 V） and suppressed short-channel effects （DIBL^77mV/V and SS^90mV/decade）. It is found that the enhancement of effective hole mobility is up to 200% in long-gate-length Si0.73Ge0.27-channel pMOSFETs compared with the corresponding silicon transistors. The improvement of device performance is reduced due to strain relaxation as the gate length decreases, while 26% increase of the drive current is still obtained for 30-nm-gate-length Si0.73Ge0.27 devices.展开更多
基金Supported by the Major Project of Changzhou Science and Technology Bureau,No.CJ20220255.
文摘BACKGROUND Accumulating studies indicated that maintain nuclei homeostasis was deemed to the protective factors for the occurrence of cancer.Thus,high-mobility group box 1(HMGB1)might influence the risk and poorer prognoses of colorectal cancer(CRC).AIM This study was designed to investigate whether HMGB1 polymorphisms influence the risk and lymph node metastasis(LNM)of CRC.METHODS Firstly,we designed an investigation with 1003 CRC patients and 1303 cancer-free controls to observe whether HMGB1 rs1412125 T>C and rs1045411 C>T SNPs could influence the risk of cancer.Subsequently,we carried out a correlation-analysis to assess whether these SNPs could alter the risk of LNM.RESULTS The current investigation suggested a relationship of HMGB1 rs1412125 SNP with the increased susceptibility of CRC.In a subgroup analysis,our findings suggested that this SNP could enhance an occurrence of CRC in≥61 years,non-drinker and body mass index<24 kg/m2 subgroups.However,we found that there was null association between HMGB1 rs1412125 SNP and LNM,even in different CRC region.These observations were confirmed by calculating the power value(more than 0.8).The association of HMGB1 rs1045411 C>T SNP with CRC risk and LNM was not found in any compare.CONCLUSION This study highlights a possible association between HMGB1 rs1412125 polymorphism and the increased risk of CRC.In the future,more studies should be conducted to explore HMGB1 rs1412125 polymorphism in relation to CRC development.
基金Supported by The Select and Train Outstanding Young Teach-ers Foundation of Shanghai,No.jdy08086WUJieping Experimental Diagnosis of Liver Disease Medical Foundation,No.LDWMF-SY-2011B009
文摘AIM:To explore the role of high-mobility group box 1 (HMGB1) protein during liver fibrogenesis and investigate the functional effects of HMGB1 gene silencing in hepatic stellate cells (HSCs) using siRNA.METHODS:Hepatic fibrosis in rats was induced through serial subcutaneous injections of dimethylnitrosamine,and expression of HMGB1 was detected by immunohistochemistry.HMGB1 siRNAs were developed and transiently transfected into HSC-T6 cells using Lipofectamine 2000.HMGB1 expression was evaluated by real-time polymerase chain reaction (PCR) and Western blotting analysis.Expression of α-smooth muscle actin (α-SMA) and collagen typesⅠand Ⅲ was evaluated by real-time PCR.Cell proliferation and the cell cycle were determined using the methyl thiazolyl tetrazolium method.Finally,collagen content in HSC supernatant was evaluated by an enzyme-linked immunosorbent assay.RESULTS:The results showed that HMGB1 was upregulated during liver fibrosis and that its expression was closely correlated with the deposition of collagen.siRNA molecules were successfully transfected into HSCs and induced inhibition of HMGB1 expression in a time-dependent manner.Moreover,HMGB1 siRNA treatment inhibited synthesis of α-SMA and collagen types Ⅰ and Ⅲ in transfected HSCs.CONCLUSION:This study suggests a significant functional role for HMGB1 in the development of liver fibrosis.It also demonstrates that downregulation of HMGB1 expression might be a potential strategy to treat liver fibrosis.
基金supported by the National Natural Science Foundation of China(Nos.30470763,81470931,and 31401188)the China Medical Board of New York(No.98-861)the Youth Foundation of Sichuan University(No.2014SCU11042),China
文摘Objective： To investigate the antibacterial mechanism of high-mobility group nucleosomal-binding domain 2 （HMGN2） on Escherichia coil K12, focusing on the antibacterial and antibiofilm formation effects. Its chemotactic activity on human neutrophils was also investigated. Methods： Human tissue-derived HMGN2 （tHMGN2） was extracted from fresh uterus fiber cystadenoma and purified by HPl100 reversed-phase high-performance liquid chromatography （RP-HPLC）. Recombinant human HMGN2 （rHMGN2） was generated in E. coil DE3 carrying PET-32a- c（＋）-HMGN2. Antibacterial activity of HMGN2 was determined using an agarose diffusion assay and minimum inhibitory concentration （MIC） of HMGN2 was determined by the microdilution broth method. Bacterial membrane permeability assay and DNA binding assay were performed. The antibiofilm effect of HMGN2 was investigated using a crystal violet assay and electron microscopy scanning. The activating effect and chemotactic activity of HMGN2 on neutrophils were determined using a nitroblue tetrazolium （NBT） reduction assay and Transwell chamber cell migra- tion assay, respectively. Results： HMGN2 showed a relatively high potency against Gram-negative bacteria E. coli and the MIC of HMGN2 was 16.25 μg/ml. Elevated bacterial membrane permeability was observed in HMGN2-treated E. coil K12. HMGN2 could also bind the bacterial plasmid and genomic DNA in a dose-dependent manner. The antibiofilm effect of HMGN2 on E. coil K12 was confirmed by crystal violet staining and scanning electron microscopy. However, the activating effects and chemotactic effects of HMGN2 on human neutrophils were not observed. Con- clusions： As an antimicrobial peptide （AMP）, HMGN2 possessed a good capacity for antibacterial and antibiofilm activities on E. coil K12. This capacity might be associated with disruption of the bacterial membrane and combination of DNA, which might affect the growth and viability of E. coil.
文摘BACKGROUND Necrotising enterocolitis(NEC)is a critical gastrointestinal emergency affecting premature and low-birth-weight neonates.Serum amyloid A(SAA),procalcitonin(PCT),and high-mobility group box 1(HMGB1)have emerged as potential biomarkers for NEC due to their roles in inflammatory response,tissue damage,and immune regulation.AIM To evaluate the diagnostic value of SAA,PCT,and HMGB1 in the context of NEC in newborns.METHODS The study retrospectively analysed the clinical data of 48 newborns diagnosed with NEC and 50 healthy newborns admitted to the hospital.Clinical,radiological,and laboratory findings,including serum SAA,PCT,and HMGB1 Levels,were collected,and specific detection methods were used.The diagnostic value of the biomarkers was evaluated through statistical analysis,which was performed using chi-square test,t-test,correlation analysis,and receiver operating characteristic(ROC)analysis.RESULTS The study demonstrated significantly elevated levels of serum SAA,PCT,and HMGB1 Levels in newborns diagnosed with NEC compared with healthy controls.The correlation analysis indicated strong positive correlations among serum SAA,PCT,and HMGB1 Levels and the presence of NEC.ROC analysis revealed promising sensitivity and specificity for serum SAA,PCT,and HMGB1 Levels as potential diagnostic markers.The combined model of the three biomarkers demonstrating an extremely high area under the curve(0.908).CONCLUSION The diagnostic value of serum SAA,PCT,and HMGB1 Levels in NEC was highlighted.These biomarkers potentially improve the early detection,risk stratification,and clinical management of critical conditions.The findings suggest that these biomarkers may aid in timely intervention and the enhancement of outcomes for neonates affected by NEC.
基金Supported by a grant from the Innovation Foundation of Excellent Intellectuals in Henan Province(No.2109901)
文摘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.
基金Supported by National Natural Science Foundation of China No.81072110 and No.81171951grants from Independent Innovation Foundation of Shandong University,No.2010TB012Scientific Research Foundation for Returned Scholars,Ministry of Education of China
文摘AIM:To evaluate the prognostic value of high-mobility group box 1(HMGB1) expression in intrahepatic cholangiocarcinoma(IHCC) and the possible underlying mechanism.METHODS:Tissue microarray was constructed from 65 IHCC patients.Immunohistochemistry was performed to validate expression of HMGB1 and Vascular endothelial growth factor C(VEGF-C).Realtime PCR and Western blot analyses were used to study transcript and protein levels.The interaction between HMGB1 and VEGF-C was evaluated by si RNA,real-time PCR,and enzyme-linked immuno assays.The correlation between HMGB1 expression and other clinicopathologic parameters was analyzed byχ2 test,and the univariate as well as multivariate analyses were accomplished by Kaplan-Meier method and Coxregression model,respectively.RESULTS:Overall,overexpression of HMGB1 was found in 38/65(58.8%)IHCCs,whereas VEGF-C overexpression was present in 30/65(46.2%)cases.Overexpression of HMGB1 was significantly correlated with lymphatic microvessel density(P=0.031,r=0.268)and VEGF-C expression(P=0.041,r=0.254).With univariate analysis,both HMGB1(P=0.001)and VEGF-C(P=0.004)were identified to be significantly associated with overall survival rate.Multivariateanalysis indicated that HMGB1 could be served as an unfavorable independent prognostic factor in IHCCs(P=0.005).si RNA knockdown of HMGB1 inhibited transforming growth factor-β-induced epithelialmesenchymal transition(EMT)by elevating E-Cadherin expression and reducing expression of N-Cadherin,Vimentin and Snail in RBE cells.Further in vitro study revealed that HMGB1 silencing significantly decreased the level of VEGF-C,whereas the recombinant HMGB1increased the VEGF-C level in RBE cells(both P<0.05),which suggested that HMGB1 could promote lymphatic microvessel density,and subsequently lymphatic invasion,via promoting VEGF-C expression.CONCLUSION:Our results define an important role of HMGB1 in the progression of cholangiocarcinoma,and HMGB1 may serve as a prognostic marker for IHCC patients.
基金Supported by the National Natural Science Foundation of China(No.81470609 No.81500695+5 种基金 No.81700800 No.81870632 No.81800800)Natural Science Foundation of Shandong Province(No.ZR2017BH025 No.ZR2017MH008 No.ZR2013HQ007)
文摘AIM: To investigate the inflammatory amplification effect of high-mobility group box 1(HMGB1) in Aspergillus fumigatus(A. fumigatus) keratitis and the relationship between lectin-like oxidized low-density lipoprotein receptor 1(LOX-1) and HMGB1 in keratitis immune responses.METHODS: Phosphate buffer saline(PBS), and Boxb were injected into BALB/c mice subconjunctivally before the corneas were infected with A. fumigatus. RAW264.7 macrophages and neutrophils were pretreated with PBS and Boxb to determine the HMGB1 inflammatory amplification effects. Abdominal cavity extracted macrophages were pretreated with Boxb and Poly(I)(a LOX-1 inhibitor) before A. fumigatus hyphae stimulation to prove the the relationship between the two molecules. LOX-1, interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), macrophage inflammatory protein-2(MIP-2) and IL-10 were assessed by polymerase chain reaction and Western blot.RESULTS: Pretreatment with Boxb exacerbated corneal inflammation. In macrophages and neutrophils, A. fumigatus induced LOX-1, IL-1β, TNF-α and MIP-2 expression in Boxb group was higher than those in PBS group. Poly(I) treatments before infection alleviated the proinflammatory effects of Boxb in abdominal cavity extracted macrophages. Pretreatment with Boxb did not influence Dectin-1 mRNA levels in macrophages and neutrophils.CONCLUSION: In fungal keratitis, HMGB1 is a proinflammatory factor in the first line of immune response. HMGB1 mainly stimulates neutrophils and macrophages to produce inflammatory cytokines and chemokines during the immune response. LOX-1 participates in HMGB1 induced inflammatory exacerbation in A. fumigatus keratitis.
基金Supported by National Research Foundation of Korea grant funded by the Korea government MEST,No. 2010-0029498
文摘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.
基金This work was supported by the grants from the National Natural Science Foundation of China （No.30471675, No.30672041 and No.30725039） the National Natural Science Foundation of Shaanxi Province （No.2004KI7-GI5） and the National Natural Science Foundation of PLA （No.06G086）.We are grateful to Drs. LI Qing and HUI Yan-ping （Department of Pathology, Fourth Military Medical University） for assisting in histopathological analysis+1 种基金 to Dr. SHANG Lei （Department of Health Statistics, Fourth Military Medical University） for his help in the statistics analysis to Dr. LIU Shan-lu （Department of Microbiology and Immunology, McGill University） for his insightful comments.
文摘Background Sepsis is a leading cause of death in the intensive care units. The late inflammatory cytokine, high-mobility group box 1 （HMGB1）, plays a critical role in sepsis. In the present study, we investigated the association between the serum HMGB1 levels and the severity of organ injury in the lipopolysaccharide-induced sepsis in rats. Methods To produce an animal model of sepsis with different degree of organ injury, animals were treated with three different doses of lipopolysaccharide （4, 8 and 16 mg/kg）, and the animals in control group were treated with the same volume of the vehicle （saline）. The levels of serum HMGB1 were measured at 0, 2, 4, 8, 16, 24, 32 and 48 hours after lipopolysaccharide （LPS） or vehicle injection, meanwhile the biochemical and histopathological indicators for the severity of organ injury were assessed. Results The level of HMGB1 had a positive, high correlation with the abnormal changes of serum cardiac troponin I, alanine aminotransferase, aspartate aminotransferase, creatinine and blood urea nitrogen, as well as the pathologic scores of heart, lung, liver and kidney. Conclusions The level of serum HMGB1 is highly correlated with the severity of sepsis in rats, suggesting that HMGB1 could serve as a valuable adjunct in the diagnosis and management of sepsis.
基金The National Natural Science Foundation of China(82072171 and 81873935)provided funding for this work.
文摘Background:Sepsis is a common severe complication in major burn victims and is characterized by a dysregulated systemic response to inflammation.YTH domain family 2(YTHDF2),a wellstudied N6-methyladenosine(m6A)reader that specifically recognizes and binds to m6A-modified transcripts to mediate their degradation,is connected to pathogenic and physiological processes in eukaryotes,but its effect on sepsis is still unknown.We aimed to discover the effects and mechanisms of YTHDF2 in sepsis.Methods:Quantitative reverse transcription-polymerase chain reaction(qRT-PCR)and western blot analyses were used to measure the expression of YTHDF2,the interleukin 6 receptor(IL-6R),high-mobility group box-1(HMGB1),Janus kinase 2(JAK2)and signal transducer and activator of transcription 1(STAT1)under different in vitro conditions.Enzyme-linked immunosorbent assays were utilized to evaluate the expression of HMGB1,IL-6,IL-1βand tumor necrosis factor-α.To confirm that YTHDF2 specifically targets IL-6R mRNA,RNA immunoprecipitation and dual-luciferase reporter assays were performed.Finally,we utilized a mouse model of lipopolysaccharide(LPS)-induced sepsis to verify the effects of YTHDF2 in vivo.Results:According to our findings,YTHDF2 was expressed at a low level in peripheral blood mononuclear cells from septic mice and patients as well as in LPS-induced RAW264.7 cells.Overexpression of YTHDF2 alleviated the inflammatory response by inhibiting HMGB1 release and JAK2/STAT1 signalling in LPS-stimulated cells.Mechanistically,YTHDF2 suppressed JAK2/STAT1 signalling by directly recognizing the m6A-modified site in IL-6R and decreasing the stability of IL-6R mRNA,thereby inhibiting HMGB1 release.In vivo experiments showed that YTHDF2 played a protective role in septic mice by suppressing the IL-6R/JAK2/STAT1/HMGB1 axis.Conclusions:In summary,these findings demonstrate that YTHDF2 plays an essential role as an inhibitor of inflammation to reduce the release of HMGB1 by inhibiting the IL-6R/JAK2/STAT1 pathway,indicating that YTHDF2 is a novel target for therapeutic interventions in sepsis.
基金supported by grants from the Natural Science Foundation of China(82070611)the Guangzhou Science and Technology Plan Projects(2023B03J1287)+2 种基金the Guangdong Medical Science and Technology Research Fund(A2021304)the Five-Year Plan of the Third Affiliated Hospital of Sun Yat-sen University(2024W106)the Shandong Provincial Natural Science Foundation(ZR2024QH660).
文摘High-mobility group box-1(HMGB1)is an architectural chromosomal protein with various roles depending on its cellular localization.Extracellular HMGB1 functions as a prototypical damage-associated molecular pattern that triggers inflammation and adaptive immune responses,mediated by specific cell surface receptors,including receptors for advanced glycation end products and toll-like receptors.Post-translational modifications of HMGB1 significantly impact various cellular processes that contribute to the pathogenesis of liver diseases.Recent studies have highlighted the close relationship between HMGB1 and the pathogenesis of acute liver injuries,including acetaminophen-induced liver injury,hepatic ischemia-reperfusion injury,and acute liver failure.In chronic liver diseases,HMGB1 plays a role in nonalcoholic fatty liver disease,alcohol-associated liver disease,liver fibrosis,and hepatocellular carcinoma.Targeting HMGB1 as a therapeutic approach,either by inhibiting its release or blocking its extracellular function,is a promising strategy for treating liver diseases.This review aimed to summarize the available evidence on HMGB1’s role in liver disease,focusing on its multifaceted signaling pathways,impact on disease progression,and the translation of these findings into clinical interventions.
基金Supported by the National Basic Research Program of China under Grant No 2011CBA00605the National Natural Science Foundation of China under Grant No 61404165
文摘Strained-Si0.73Ge0.27 channels are successfully integrated with high-R/metal gates in p-type metai-oxide- semi- conductor field effect transistors （pMOSFETs） using the replacement post-gate process. A silicon cap and oxide inter layers are inserted between Si0.73Ge0.27 and high-κ dielectric to improve the interface. The fab- ricated Si0.73Ge0.27 pMOSFETs with gate length of 3Onto exhibit good performance with high drive current （~428μA/μm at VDD = 1 V） and suppressed short-channel effects （DIBL^77mV/V and SS^90mV/decade）. It is found that the enhancement of effective hole mobility is up to 200% in long-gate-length Si0.73Ge0.27-channel pMOSFETs compared with the corresponding silicon transistors. The improvement of device performance is reduced due to strain relaxation as the gate length decreases, while 26% increase of the drive current is still obtained for 30-nm-gate-length Si0.73Ge0.27 devices.
