Emulsifying property,antioxidant activity,and bitterness of soybean protein isolate hydrolysate obtained by Corolase PP under high hydrostatic pressure

Enzymatic hydrolysis of proteins can enhance their emulsifying properties and antioxidant activities.However,the problem related to the hydrolysis of proteins was the generation of the bitter taste.Recently,high hydrostatic pressure(HHP)treatment has attracted much interest and has been used in several studies on protein modification.Hence,the study aimed to investigate the effects of enzymatic hydrolysis by Corolase PP under different pressure treatments(0.1,100,200,and 300 MPa for 1-5 h at 50℃)on the emulsifying property,antioxidant activity,and bitterness of soybean protein isolate hydrolysate(SPIH).As observed,the hydrolysate obtained at 200 MPa for 4 h had the highest emulsifying activity index(47.49 m^(2)/g)and emulsifying stability index(92.98%),and it had higher antioxidant activities(44.77%DPPH free radical scavenging activity,31.12%superoxide anion radical scavenging activity,and 61.50%copper ion chelating activity).At the same time,the enhancement of emulsion stability was related to the increase of zeta potential and the decrease of mean particle size.In addition,the hydrolysate obtained at 200 MPa for 4 h had a lower bitterness value and showed better palatability.This study has a broad application prospect in developing food ingredients and healthy foods.

Hmo1:A versatile member of the high mobility group box family of chromosomal architecture proteins

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.

Relationship of High Sensitivity C-Reactive Protein with Cardiovascular, Diabetic, and Hepatic Biomarkers

Biomarkers are early predictors of various disorders, circulating level of C-reactive protein is a sensitive biomarker of systemic inflammation and may also be associated with the development of diabetic, hepatic, and cardiovascular diseases. In the present study, we aimed to investigate the association between circulating levels of high sensitive C-reactive protein (hs-CRP) and various biomarkers for hepatic, diabetic, and cardiovascular health. The retrospective analysis included 438 individuals who were tested for these panels simultaneously at Vibrant America Clinical Laboratory. The study population included free-living individuals without any preexisting clinical conditions. Among the cardiovascular markers, a positive correlation and significant association was found between high levels of hs-CRP and serum levels of triglycerides (r = 0.0964, p −0.1423, p −0.1216, p < 0.0105) with circulating levels of hs-CRP. Among all the diabetic markers, glucose (r = 0.1547, p < 0.0011) and glycated serum protein (r = 0.1725, p < 0.0003) were positively correlated with circulating hs-CRP. In the hepatic panel, AST, a transaminase that plays a vital role in amino acid metabolism, was found to have a strong positive correlation with hs-CRP (r = 0.2139, p < 0.0001). In conclusion, the results clearly show the association of hs-CRP with diabetic, hepatic, and cardiovascular risk factors indicating its central value as a key marker for several lifestyle-associated disorders.

Suppressing high mobility group box-1 release alleviates morphine tolerance via the adenosine5'-monophosphate-activated protein kinase/heme oxygenase-1 pathway

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.

NMI,POLR3G and APIP are the key molecules connecting glaucoma with high intraocular pressure:a clue for early diagnostic biomarker candidates

AIM:To understand the molecular connectivity between the intraocular pressure(IOP)and glaucoma which will provide possible clues for biomarker candidates.METHODS:The current study uncovers the important genes connecting IOP with the core functional modules of glaucoma.An integrated analysis was performed using glaucoma and IOP microarray datasets to screen for differentially expressed genes(DEGs)in both conditions.To the selected DEGs,the protein interaction network was constructed and dissected to determine the core functional clusters of glaucoma.For the clusters,the connectivity of IOP DEGs was determined.Further,enrichment analyses were performed to assess the functional annotation and potential pathways of the crucial clusters.RESULTS:The gene expression analysis of glaucoma and IOP with normal control showed that 408 DEGs(277 glaucoma and 131 IOP genes)were discovered from two GEO datasets.The 290 DEGs of glaucoma were extended to form a network containing 1495 proteins with 9462 edges.Using ClusterONE,the network was dissected to have 12 clusters.Among them,three clusters were linked with three IOP DEGs[N-Myc and STAT Interactor(NMI),POLR3G(RNA Polymerase Ⅲ Subunit G),and APAF1-interacting protein(APIP)].In the clusters,ontology analysis revealed that RNA processing and transport,p53 class mediators resulting in cell cycle arrest,cellular response to cytokine stimulus,regulation of phosphorylation,regulation of type Ⅰ interferon production,DNA deamination,and cellular response to hypoxia were significantly enriched to be implicated in the development of glaucoma.Finally,NMI,POLR3G,and APIP may have roles that were noticed altered in glaucoma and IOP conditions.CONCLUSION:Our findings could help to discover new potential biomarkers,elucidate the underlying pathophysiology,and identify new therapeutic targets for glaucoma.

The effect of exogenous sugar solution and high concentration of CO_2 on the contents of sugar and protein of Betula platyphylla leaves

The content of total sugar, sucrose, fructose and protein in the leaves of3-yr.-old Betula platyphylla was measured after the treatment by three exogenous sugar solutions(sucrose, fructose, glucose) and three high concentrations of CO_2 (700, 1 400, 2 100 μL/L·L^(-1))for about a month in 1998. The results showed that spraying three exogenous sugar solutionsincreased markedly the content of sugar and protein of leaves under 700 μL·L^(-1) and 1 400μL·L^(-1) CO_2 The effect of spraying exogenous sucrose solution was the best among the threeexogenous sugars. The treatment of spraying exogenous sugar solution and 2 100 μL·L^(-1) CO_2constrained the accumulation of total sugar and protein of leaves. There was no difference inprotein content of leaves when spraying glucose and fructose solutions under 700 μL·L^(-1) and 1400 μL·L^(-1) CO_2. The treatment of 2 100 μL·L^(-1) CO_2 concentration significantly increasedthe contents of total sugar, sucrose, fructose, and protein of leaves compared with that of the 700μL·L^(-1) and 1 400 μL·L^(-1) CO_2 except the plants spraying fructose solution. There waspositive correlation between the content of sugar of leaves and CO_2 concentration when sprayingsame exogenous sugar solution.

Expression and Purification of Arabidopsis High Mobility Group B Protein Gene At2G34450 in Pichia pastoris

[Objective] The aim was to study the expression of Arabidopsis gene A/2G34450 in Pichia pastoris and to obtain recombinant Arabidopsis HMGB protein. [Method] The At2G34450 gene was cloned into yeast expression vector pPIC9K containing AOXl promoter and the sequences of secreting α-signal peptides. Recombinant plasmid was linearized by Sal l and transformed into P. pastoris GSl15 competent cells by electroporation. Positive integrated clones were screened out, and the At2G34450 protein was expressed under the induction of methanol. [Result] The At2G34450 protein was expressed in yeast medium through methanol induction. SDS-PAGE results showed that recombination product was At2G34450 protein. [Conclusion] At2G34450 protein was successfully expressed in the P. pastoris system for the first time, which paves a direct path to further research on the functions of HMGB family members.

The Expression and Functional Analysis of the Gene At2G34450 in High Mobility Group B Proteins from Arabidopsis thaliana

[Objective]To better understand the functions of High Mobility Group B （HMGB） proteins in the transcriptional regulation of plant stress responses.[Method]We cloned the At2G33450 gene encoding At2G34450 protein in Arabidopsis thaliana.Binary vectors carrying the above gene were transformed into Arabidopsis to detect the influences of environmental stimuli to transgenic Arabidopsis.[Result] Under salt or drought stress the transgenic Arabidopsis plants over-expressed At2G33450 displayed retarded germination and subsequent growth compared with wild-type plants.[Conclusion]Our results provide a novel basis for understanding the biological functions of HMGB protein family members that differently affect germination and seedling growth of Arabidopsis plants under various stress conditions.

High-mobility group box 1 protein and its role in severe acute pancreatitis

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.

High mobility group box-1 protein inhibits regulatory T cell immune activity in liver failure in patients with chronic hepatitis B

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.

Optimization of High-Protein Glutinous Rice Flour Production Using Response Surface Method

A response surface method was employed to study the effect of α-amylase concentration, hydrolysis temperature and time on the production of high protein glutinous rice flour(HPGRF). The suspension of glutinous rice flour(15%) that contained 6.52% protein was gelatinized and subsequently hydrolyzed by thermostable α-amylase. The hydrolysis yielded 0.144–0.222 g/g HPGRF with 29.4%–45.4% protein content. Hydrolysis time exerted a significant effect, while enzyme concentration and hydrolysis temperature showed insignificant effect on the protein content and production yield of HPGRF. The result of response surface method showed that the optimum condition for the production of HPGRF that contained at least 36% protein was treating gelatinized 15% glutinous rice flour suspension with 0.90 Kilo Novo α-amylase Unit(KNU)/g α-amylase at 80 oC for 99 min. By carrying out the predicted hydrolysis condition, HPGRF with 35.9% protein and 61.8% carbohydrates was resulted. The process yielded 0.172 g/g HPGRF. HPGRF contained higher amount of essential amino acids compared to glutinous rice flour. HPGRF had higher solubility and lower swelling power, and also showed no pasting peak compared with glutinous rice flour.

High Temperature During Rice Grain Filling Enhances Aspartate Metabolism in Grains and Results in Accumulation of AspartateFamily Amino Acids and Protein Components

Global warming causes the exacerbation of rice growing environment, which seriously affects rice growth and reproduction, and finally results in the decrease of rice yield and quality. We investigated the activities of aspartate metabolism enzymes in grains, and the contents of Aspartate-family amino acids and protein components to further understand the effects of high temperature （HT） on rice nutritional quality during rice grain filling. Under HT, the average activities of aspartate aminotransferase （AAT） and aspartokinase （AK） in grains significantly increased, the amino acid contents of aspartate （Asp）, lysine （Lys）, threonine （Thr）, methionine （Met） and isoleucine （lie） and the protein contents of albumin, globulin, prolamin and glutelin also significantly increased. The results indicated that HT enhanced Asp metabolism during rice grain filling and the enhancement of Asp metabolism might play an important role in the increase of Asp-family amino acids and protein components in grains. In case of the partial appraisal of the change of Asp-family amino acids and protein components under HT, we introduced eight indicators （amino acid or protein content, ratio of amino acid or protein, amino acid or protein content per grain and amino acid or protein content per panicle） to estimate the effects of HT. It is suggested that HT during rice grain filling was benefit for the accumulation of Asp-family amino acids and protein components. Combined with the improvement of Asp-family amino acid ratio in grains under HT, it is suggested that HT during grain filling may improve the rice nutritional quality. However, the yields of parts of Asp-family amino acids and protein components were decreased under HT during rice grain filling.

Novel insights for high mobility group box 1 proteinmediated cellular immune response in sepsis:A systemic review

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.

The effects of high temperature level on square Bt protein concen-tration of Bt cotton

Higher boll worm survival rates were detected after high temperature presented during square period in Bt cotton. The objective of this study was to investigate the effects of high temperature level on the Bt efficacy of two different types of Bt cotton cultivars at squaring stage. During the 2011 to 2013 cotton growth seasons, high temperature treatments ranged from 34 to 44°C in climate chambers, and field experiments under high temperature weather with various temperature levels were conducted to investigate the effects of the high temperature level on square Bt protein concentration and nitrogen metabolism. The climate chamber experiments showed that the square insecticidal protein contents reduced after 24 h elevated temperature treatments for both cultivars, whereas significant declines of the square insecticidal protein contents were detected at temperature 〉38°C, and only slightly numerical reductions were observed when temperature below 38°C. Similar high temperature responses were also observed at the two field experimental sites in 2013. Correspondingly, high temperature below 38°C seems have little effect on the square amino acid concentrations, soluble protein contents, glutamic-pyruvic transaminase（GPT） and glutamic-oxalacetic transaminase（GOT） activities as well as protease and peptidase activities; however, when the temperature was above 38°C, reduced soluble protein contents, enhanced amino acid concentrations, decreased GPT and GOT activities, bolstered protease and peptidase activities in square were detected. In general, the higher the temperature is（〉38°C）, the larger the changes for the above compound contents and key enzymes activities of the square protein cycle. The findings indicated that the unstable insect resistance of the square was related to high temperature level during square stage.

High sensitivity C-reactive protein and cardfiac resynchronization therapy in patients with advanced heart failure

Background The data on the prognostic values of high sensitivity C-reactive protein （hsCRP） levels in patients with advanced symp-tomatic heart failure （HF） receiving cardiac resynchronization therapy （CRT） are scarce. The aim of present study was to investigate the association of serum hsCRP levels with left ventricle reverse remodeling after six months of CRT as well as long-term outcome. Methods A total of 232 CRT patients were included. The assessment of hsCRP values, clinical status and echocardiographic data were performed at baseline and after six months of CRT. Long-term follow-up included all-cause mortality and hospitalizations for HF. Results During the mean follow-up periods of 31.3 ± 31.5 months, elevated hsCRP （〉3 mg/L） prior to CRT was associated with a significant 2.39-fold increase （P=0.006） in the risk of death or HF hospitalizations. At 6-month follow-up, patients who responded to CRT showed significant reductions or maintained low in hsCRP levels （–0.5 ± 4.1 mg/L reduction） compared with non-responders （1.7 ± 6.1 mg/L increase, P=0.018）. Com-pared with patients in whom 6-month hsCRP levels were reduced or remained low, patients in whom 6-month hsCRP levels were increased or maintained high experienced a significantly higher risk of subsequent death or HF hospitalizations （Log-rank P〈0.001）. The echocardio-graphic improvement was also better among patients in whom 6-month hsCRP levels were reduced or remained low compared to those in whom 6-month hsCRP levels were raised or maintained high. Conclusions Our findings demonstrated that measurement of baseline and follow-up hsCRP levels may be useful as prognostic markers for timely potential risk stratification and subsequent appropriate treatment strategies in patients with advanced HF undergoing CRT.

Effect on proliferation and apoptosis of retinoblastoma cell by RNA inhibiting high mobility group protein box-1 expression

AIM： To investigate the effect of high mobility group protein box-1 （HMGB1） siRNA on proliferation and apoptosis of retinoblastoma （Rb） cells.METHODS： The expression of HMGB1 in Rb cells were detected by real-time polymerase chain reaction （RT-PCR） and Western blot. Chemically synthesized HMGB1 siRNA was transfected into Y79 cells. The inhibitory rate was also examined by RT-PCR and Western blot. After HMGB1 siRNA transfection, the cell proliferation was analyzed by MTT, and cell apoptosis was detected by Caspase-3 active detection kit. Cell cycle distribution and apoptosis were detected by flow cytometry. RESULTS： The expression of HMGB1 significantly elevated in Rb cells （P〈0.01）. After transfected by siRNA, the HMGB1 protein level of Y79 cells was significantly reduced （P〈0.01）. After siRNA interference HMGB1, the proportion of proliferating cells reduced, and the proportion of quiescent cells increased （P〈0.05）. In addition, apoptosis rate of Y79 cells increased from 2.03% to 9.10% after interfering with HMGB1 siRNA （P〈0.05）.CONCLUSION： Specific HMGB1 siRNA can inhibit the expression of HMGB1. The effect may be attributed to inhibit the proliferation and promote cell apoptosis.

High mobility group protein 1: A collaborator in nucleosome dynamics and estrogen-responsive gene expression

High mobility group protein 1(HMGB1) is a multifunctional protein that interacts with DNA and chromatin to influence the regulation of transcription, DNA replication and repair and recombination. We show that HMGB1 alters the structure and stability of the canonical nucleosome(N) in a nonenzymatic,adenosine triphosphate-independent manner. As a result, the canonical nucleosome is converted to two stable, physically distinct nucleosome conformers. Although estrogen receptor(ER) does not bind to its consensus estrogen response element within a nucleosome, HMGB1 restructures the nucleosome to facilitate strong ER binding. The isolated HMGB1-restructured nucleosomes(N' and N'') remain stable and exhibit a number of characteristics that are distinctly different from the canonical nucleosome. These findings complement previous studies that showed(1) HMGB1 stimulates in vivo transcriptional activation at estrogen response elements and(2) knock down of HMGB1 expression by siR NA precipitously reduced transcriptional activation. The findings indicate that a major facet of the mechanism of HMGB1 action involves a restructuring of aspects of the nucleosome that appear to relax structural constraints within the nucleosome. The findings are extended to reveal the differences between ER and the other steroid hormone receptors. A working proposal outlines mechanisms that highlight the multiple facets that HMGB1 may utilize in restructuring the nucleosome.

Correlation of Enhancement Degree on Contrast-enhanced Ultrasound with Histopathology of Carotid Plaques and Serum High Sensitive C-Reactive Protein Levels in Patients Undergoing Carotid Endarterectomy

This study was undertaken to investigate the correlation of the enhancement degree on contrast-enhanced ultrasound(CEUS) with the histopathology of carotid plaques and the serum high sensitive C-reactive protein(hs-CRP) levels in patients undergoing carotid endarterectomy(CEA). Carotid CEUS was performed preoperatively in 115 patients who would undergo CEA, and the enhancement degree of the carotid plaques was evaluated by both the visual semiquantitative analysis and the quantitative time-intensity curve analysis. Serum hs-CRP levels were detected using the particle-enhanced immunoturbidimetric assay also before the operation. Additionally, the carotid plaque samples were subjected to histopathological examination postoperatively. The density of neovessels and the number of macrophages in the plaques were assessed by immunohistochemistry. The results showed that among the 115 patients, grade 0 plaque contrast enhancement was noted in 35 patients, grade 1 in 48 patients and grade 2 in 32 patients. The degree of plaque enhancement, the density of neovessels, the number of macrophages, and the hs-CRP levels were highest in the grade 2 patients. Correlation analysis showed that the enhancement degree of the carotid plaques was closely related to the immunohistochemical parameters of the plaques and the serum hs-CRP levels. It was suggested that the carotid plaque enhancement on CEUS can be used to evaluate the vulnerability of carotid plaques.

Inflammatory response and immune regulation of high mobility group box-1 protein in treatment of sepsis

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.

Myeloperoxidase and High-Sensitivity C-Reactive Protein for Predicting Major Adverse Cardiovascular Events in Patients with Coronary Heart Disease

Background: Research has shown that high-sensitivity C-reactive protein (hs-CRP) is a major inflammatory marker for prediction of acute coronary syndrome (ACS). Myeloperoxidase (MPO) also plays an important role in atherosclerosis initiation and development. In present study, the major adverse cardiovascular events (MACEs) of patients with coronary heart disease (CHD) were investigated. Methods: MPO, hs-CRP and ACS-related risk factors from 201 ACS (78 AMI and 123 UAP) and 210 non-ACS (84 SAP and 126 non-CHD) patients confirmed by coronary angiography were detected, and the data were analyzed with receiver operating characteristic (ROC) curve and Spearman’s correlation coefficients. MACEs of 285 CHD patients were investigated during the 4-year period follow-up from March 2010 to May 2014. Results: The areas under ROC curve for diagnosing ACS were 0.888 (95% CI 0.843 - 0.933) for MPO, and 0.862 (95% CI 0.815-0.910) for hs-CRP, respectively. There were significantly correlations between MPO and hs-CRP in both ACS and non-ACS groups. Regarding to ACS patients, both MPO and hs-CRP were positively correlated with BMI, TC, TG, LDL-C and Hcy. Prospective study demonstrated that the incidences of MACEs associated significantly with elevated MPO baseline level (yes vs no, OR 7.383, 95% CI 4.095 - 13.309) and high hs-CRP baseline level (yes vs no, OR 4.186, 95% CI 2.469 - 7.097) in CHD patients. Conclusions: The present study provides the epidemiological evidence that elevated baseline MPO and hs-CRP levels are both valuable predictors of MACEs in CHD patients. MPO and hs-CRP would prompt the progression of atherosclerosis and development from SAP to ACS.