Objective To investigate the protective effect of recombinant Schistosoma japonicum cystatin(rSj-Cys)against acute liver injury induced by lipopolysaccharide(LPS)and D-GalN in mice.Methods Adult male C57BL/6J mice with or without LPS/D-GaIN-induced acute liver injury were given intraperitoneal injections of rSj-Cys or PBS 30 min after modeling(n=18),and serum and liver tissues samples were collected from 8 mice in each group 6 h after modeling.The survival of the remaining 10 mice in each group within 24 h was observed.Serum levels of ALT,AST,TNF-α and IL-6 of the mice were measured,and liver pathologies was observed with HE staining.The hepatic expressions of macrophage marker CD68,Bax,Bcl-2 and endoplasmic reticulum stress(ERS)-related proteins were detected using immunohistochemistry or immunoblotting,and TUNEL staining was used to detect hepatocyte apoptosis.Results The survival rates of PBS-and rSj-Cys-treated mouse models of acute liver injury were 30%and 80%at 12 h and were 10%and 60%at 24 h after modeling,respectively;no death occurred in the two control groups within 24 h.The mouse models showed significantly increased serum levels of AST,ALT,IL-6 and TNF-α and serious liver pathologies with increased hepatic expressions of CD68 and Bax,lowered expression of Bcl-2,increased hepatocyte apoptosis,and up-regulated expressions of ERS-related signaling pathway proteins GRP78,CHOP and NF-κB p-p65.Treatment of the mouse models significantly lowered the levels of AST,ALT,IL-6 and TNF-α,alleviated liver pathologies,reduced hepatic expressions of CD68,Bax,GRP78,CHOP and NF-κB p-p65,and enhanced the expression of Bcl-2.In the normal control mice,rSj-Cys injection did not produce any significant changes in these parameters compared with PBS.Conclusion rSj-Cys alleviates LPS/D-GalN-induced acute liver injury in mice by suppressing ERS,attenuating inflammation and inhibiting hepatocyte apoptosis.

Objective To investigate the protective effect of recombinant Schistosoma japonicum cystatin(rSj-Cys)against acute liver injury induced by lipopolysaccharide(LPS)and D-GalN in mice.Methods Adult male C57BL/6J mice with or without LPS/D-GaIN-induced acute liver injury were given intraperitoneal injections of rSj-Cys or PBS 30 min after modeling(n=18),and serum and liver tissues samples were collected from 8 mice in each group 6 h after modeling.The survival of the remaining 10 mice in each group within 24 h was observed.Serum levels of ALT,AST,TNF-α and IL-6 of the mice were measured,and liver pathologies was observed with HE staining.The hepatic expressions of macrophage marker CD68,Bax,Bcl-2 and endoplasmic reticulum stress(ERS)-related proteins were detected using immunohistochemistry or immunoblotting,and TUNEL staining was used to detect hepatocyte apoptosis.Results The survival rates of PBS-and rSj-Cys-treated mouse models of acute liver injury were 30%and 80%at 12 h and were 10%and 60%at 24 h after modeling,respectively;no death occurred in the two control groups within 24 h.The mouse models showed significantly increased serum levels of AST,ALT,IL-6 and TNF-α and serious liver pathologies with increased hepatic expressions of CD68 and Bax,lowered expression of Bcl-2,increased hepatocyte apoptosis,and up-regulated expressions of ERS-related signaling pathway proteins GRP78,CHOP and NF-κB p-p65.Treatment of the mouse models significantly lowered the levels of AST,ALT,IL-6 and TNF-α,alleviated liver pathologies,reduced hepatic expressions of CD68,Bax,GRP78,CHOP and NF-κB p-p65,and enhanced the expression of Bcl-2.In the normal control mice,rSj-Cys injection did not produce any significant changes in these parameters compared with PBS.Conclusion rSj-Cys alleviates LPS/D-GalN-induced acute liver injury in mice by suppressing ERS,attenuating inflammation and inhibiting hepatocyte apoptosis.

Objective:To explore the potent effects of denatonium benzoate(DB)on Mas-related G protein-coupled receptor-B2(MrgprB2)-mediated rat mast cell degranulation.Methods:RBL-2H3 cells were treated with DB overnight,before challenged with MrgprB2 ligands substance P(SP).The release of β-hex from MrgprB2-activated RBL-2H3 was detected by substrate method.Detec-tion of LTC4,IL-6,TNF-α and cPLA2 activity were performed by ELISA.The Ca2+influx and the expression of RBL-2H3 MrgprB2 re-ceptors were measured by fluorescence assay.Results:The results showed 10 μmol/L,50 μmol/L,80 μmol/L,100 μmol/L DB treat-ments promoted β-hex and LTC4 releases from activated RBL-2H3,accompanied by increased Ca2+mobilization and cPLA2 activa-tion.DB treatments did not affect IL-6 and TNF-α LTC4 releases in MrgprB2-activated RBL-2H3,as well as the levels of MrgprB2 ex-pression in mast cells.Conclusion:Taken together,DB enhanced the MrgprB2-mediated RBL-2H3 degranulation in vitro,probably by up-regulating Ca2+mobilization in activated cells.

Objective:To explore the prognostic value of tumor deposits (TD) by number and anatomical distribution in gastric cancer (GC) patients without lymph node metastasis.Methods:From Aug 2012 to Aug 2018 all 91 GC patients undergoing radical gastrectomy and without nodal metastasis at Yijishan Hospital of Wannan Medical College were enrolled in this study. Patients were divided into L1, L2, and L3 groups according to the number of TD and into Q1 and Q2 groups according to the anatomical regions of the TD.Results:The 3-year overall survival (OS) rates of groups L1, L2, and L3 were 58.9%, 52.1%, and 31.5%, respectively ( χ2=9.769, P=0.008). The 3-year OS rates of groups Q1 and Q2 were 58.9% and 7.1% ( χ2=46.310, P<0.001). The number of TD, their distribution, neural invasion, vascular invasion, tumor size, and pT stage were all related to prognosis by univariate analysis (all P<0.05). Tumor size>4 cm ( HR=2.460, 95% CI:1.307-4.629, P=0.005), distribution of TD (non-perigastric)( HR=3.959, 95% CI:2.077-7.545, P<0.001), neural invasion ( HR=4.299,95% CI:1.953-9.461, P<0.001), and pT 4 stage ( HR=2.283, 95% CI:1.250-4.171, P=0.007) were independent risk factors for prognosis by multivariate analysis. Conclusion:The distribution of TD (non-perigastric) is an independent risk factor for poor prognosis in gastric cancer patients after radical gastrectomy and with negative lymph node metastasis.

Inflammatory reaction dominated by defense response will arise against infection and trauma. As an important proinflammatory cytokine, high mobility group box 1 (HMGB1) is widely expressed in all nuclear cells to mediate the inflammatory response. However, the biological functions of HMGB1 in inflammation vary depending on the type of HMGB1 protein modification and the localization in the cell. HMGB1 protein will be modified as acetylation of lysine residues, methylation of lysine residues, oxidation of cysteine residues, phosphorylation of serine residues, glycosylation of asparagine residues, adenosine diphosphate-ribosylation and lactylation of the protein in the nucleus, migrate from the nucleus to the cytoplasm, and release into the extracellular compartment. Extracellular HMGB1 can bind to receptors for advanced glycation end products (RAGE) and Toll-like receptors, activate cells and regulate inflammatory responses. The authors review the research progress in regulatory mechanism of HMGB1 in inflammation response from aspects of its post-translational modifications, releases, biological roles and binding receptors, hoping to provide theoretical basis for finding the targets of inflammation intervention.

PURPOSE: Details of patients hospitalized for asthma exacerbation in mainland China are lacking. To improve disease control and reduce economic burden, a large sample survey among this patient population is indispensable. This study aimed to investigate the clinical characteristics and outcomes of such patients.METHODS: A retrospective study was conducted on patients hospitalized for asthma exacerbation in 29 hospitals of 29 regions in mainland China during the period 2013 to 2014. Demographic features, pre-admission conditions, exacerbation details, and outcomes were summarized. Risk factors for exacerbation severity were analyzed.RESULTS: There were 3,240 asthmatic patients included in this study (57.7% females, 42.3% males). Only 28.0% used daily controller medications; 1,287 (39.7%) patients were not currently on inhaled corticosteroids. Acute upper airway infection was the most common trigger of exacerbation (42.3%). Patients with severe to life-threatening exacerbation tended to have a longer disease course, a smoking history, and had comorbidities such as hypertension, chronic obstructive pulmonary disease (COPD), and food allergy. The multivariate analysis showed that smoking history, comorbidities of hypertension, COPD, and food allergy were independent risk factors for more severe exacerbation. The number of patients hospitalized for asthma exacerbation varied with seasons, peaking in March and September. Eight patients died during the study period (mortality 0.25%).CONCLUSIONS: Despite enhanced education on asthma self-management in China during recent years, few patients were using daily controller medications before the onset of their exacerbation, indicating that more educational efforts and considerations are needed. The findings of this study may improve our understanding of hospital admission for asthma exacerbation in mainland China and provide evidence for decision-making.
Adrenal Cortex Hormones ; Asthma ; China ; Comorbidity ; Disease Progression ; Education ; Female ; Food Hypersensitivity ; Hospitalization ; Humans ; Hypertension ; Inpatients ; Medication Adherence ; Mortality ; Multivariate Analysis ; Pulmonary Disease, Chronic Obstructive ; Retrospective Studies ; Risk Factors ; Seasons ; Self Care ; Smoke ; Smoking

Objective:To determine the effects of cytochrome P450 1A1 (CYP1A1) on nitric oxide (NO) production in lipopolysaccharide (LPS)-induced macrophages and the underlying mechanism.Methods:The peritoneal macrophages (PMs) were isolated from healthy C57BL/6 mice and stimulated with 10 mg/L LPS to establish inflammatory response model. The CYP1A1 mRNA and protein expressions in the cells were determined. The mouse macrophages RAW264.7 cell line with CYP1A1 overexpression (CYP1A1/RAW) were cultured in vitro, and they were stimulated by 10 mg/L LPS at logarithmic phase. The negative control-expressed RAW264.7 cells (NC/RAW) were established. The protein and mRNA expressions of activator protein-1 (AP-1) and inducible nitric oxide synthase (iNOS) in the cells as well as the content of NO in the cell supernatant were determined. The RAW264.7 cells were cultured in vitro, and they were stimulated by 10 mg/L LPS and 100 nmol/L 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE] only or in combination at logarithmic phase. The blank control group was set up. The expression of iNOS mRNA in the cells and NO content in the cell supernatant were determined to observe whether the effect of CYP1A1 on LPS induced NO production in macrophages was related to 12(S)-HETE produced by metabolism. The RAW264.7 cells with CYP1A1 overexpression and hydroxylase activity mutation (CYP1A1m/RAW) were cultured in vitro, and they were stimulated by 10 mg/L LPS at logarithmic phase. The CYP1A1/RAW cell control group was set up. The iNOS mRNA expression in the cells and NO content in the cell supernatant were determined to observe the effect of hydroxylase activity of CYP1A1 in regulating NO production in macrophages. Results:Compared with the phosphate buffered saline (PBS) control group, the CYP1A1 mRNA expressions were elevated significantly from 2 hours after LPS stimulation and reached a peak at 12 hours [CYP1A1 mRNA (2 -ΔΔCt): 6.41±0.98 vs. 1.00±0.00, P < 0.05], while CYP1A1 protein expressions were increased from 6 hours after LPS stimulation and reached a peak at 24 hours, suggesting that CYP1A1 expression might be involved in LPS-induced macrophage over-activation. Compared with NC/RAW+LPS group, the iNOS mRNA expressions and NO contents both increased in CYP1A1/RAW+LPS group and reached a peak after 12 hours and 24 hours, respectively [12-hour iNOS mRNA (2 -ΔΔCt): 54.42±8.21 vs. 24.22±3.89, 24-hour NO (μmol/L): 66.52±4.09 vs. 41.42±2.09, both P < 0.05], while the iNOS protein expression and AP-1 phosphorylation also enhanced, suggesting that CYP1A1 might increase NO production by promoting AP-1 activation and iNOS expression. LPS and 12(S)-HETE stimulation only or in combination had no effect on iNOS mRNA expression and NO production, and no significant difference was found between the 12 (S)-HETE+LPS group and LPS group [12-hour iNOS mRNA (2 -ΔΔCt): 34.24±4.07 vs. 34.35±4.01, 24-hour NO (μmol/L): 44.02±3.14 vs. 44.56±3.21, both P > 0.05], suggesting that the regulation of CYP1A1 on NO production might not be induced by 12 (S)-HETE. There was no significant difference in the iNOS mRNA expressions or NO content between the CYP1A1m/RAW+LPS group and CYP1A1/RAW+LPS group [12-hour iNOS mRNA (2 -ΔΔCt): 52.11±6.84 vs. 50.21±5.19, 24-hour NO (μmol/L): 60.42±4.14 vs. 52.01±5.12, both P > 0.05], suggesting that CYP1A1 hydroxylase activity deficiency showed no effect on NO production. Conclusions:LPS stimulation significantly increases CYP1A1 expression in macrophages. CYP1A1 overexpression promotes NO production by activated macrophages through AP-1/iNOS pathway, while hydroxylase-deficiency or 12(S)-HETE has no effect on this regulation.

Infection is one of the main causes of death in clinical patients, and multi-drug resistance leads to ineffective treatment with conventional antibiotics. Therefore, it is imperative to develop new anti-infective drugs. Antimicrobial peptides cathelicidins are cationic host defense peptides found in many organisms. It has been demonstrated by in vivo and in vitro studies that antimicrobial peptides cathelicidins not only show broad-spectrum antibacterial activity and high sensitivity to drug-resistant bacteria, but also have a good guiding effect on the immune response. This paper summarizes the reports of antimicrobial peptides cathelicidins in recent years, highlighting their research achievements in antibiosis, anti-inflammatory, chemotaxis regulation and phagocytosis, providing new ideas for the treatment of infection-related diseases.

Severe trauma or massive deep burn can cause significant immunosuppression associated with sepsis and multiple organ failure. Dendritic cell (DC), as the professional antigen presenting cells and activating factor of immune response, plays an extraordinary role in initiating and regulating congenital and adaptive immune response. The quantity, functional changes, relevant molecular mechanisms and reverse measures of DC after trauma/burn were reviewed in order to intensively study the changes of DC after trauma/burn and provide a reference for exploring effective intervention measures for trauma/burn.

Infectious and inflammatory diseases are important diseases threatening human health. Without timely control, a series of complications will occur in patients, such as sepsis, inflammatory factor storm, and even lead to death. It has been found that cytochrome P4501A1 (CYP1A1) plays a key role in the development of infectious and inflammatory diseases through aromatic hydrocarbon receptor (AhR) dependent and non-dependent pathways in different cells and organs induced by different substances. The non AhR dependent regulatory mechanism of CYP1A1 and the different roles of CYP1A1 in infection and inflammation is reviewed in order to provide reference for further research on the relationship between CYP1A1 and infection and inflammation.