The effects and mechanisms of Toll like receptors 4/9 mediating IL-10, IL-35 and TGF-β expressions by CD25+B cells from periodontitis individuals / 西安交通大学学报(医学版)

【Objective】 To analyze the expressions of IL-10, IL-35 and TGF-β in CD25+B cells from periodontitis individuals, and then establish how the activation of TLR4/9 affects the above processes. 【Methods】 SD rats were randomly divided into healthy group, primary periodontitis groups and severe periodontitis group; experimental models were performed by ligation. Expression of IL-10, IL-35 and TGF-β mRNA in CD25+B cells from gingiva and peripheral blood, expression and activation of TLR 2/4/7/9, MyD88, TRAF6 in gingival CD25+B cells were detected. The effect of TLRs/MyD88 on IL-10, IL-35 and TGF-β expressions and production were evaluated by cell culture experiments. 【Results】 CD25+B cells from gingiva of primary periodontitis individuals showed improved expression of IL-10 and TGF-β mRNA compared with the healthy ones (P<0.05); cells from peripheral blood did not present the same tendency. CD25+B cells from gingiva of severe periodontitis individuals showed improved expression of IL-10, IL-35 and TGF-β mRNA compared with the healthy ones (P<0.05), cells from peripheral blood showed higher IL-10 mRNA level than the healthy ones (P<0.05). Compared with healthy individuals, the expression and phosphorylation of TLR4/9 and MyD88 in CD25+B cells from gingiva of severe periodontitis individuals were increased (P<0.01). In cell culture experiments, TLR4 agonist promoted IL-10, IL-35 and TGF-β mRNA expression and IL-10 secretion (P<0.05); TLR9 agonist improved IL-10 and TGF-β mRNA expression and IL-10 secretion (P<0.05). The combined use of TLR4/9 agonist could increase the expression and secretion of all the detected indexes (P<0.05); MyD88 antagonism decrease the above effects (P<0.05). 【Conclusion】 The expressions of IL-10, IL-35 and TGF-β in gingiva CD25+B cells increase during periodontitis, which may be regulated by TLR4 /9-MyD88 pathway.

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.

Novel and potent inhibitors targeting DHODH are broad-spectrum antivirals against RNA viruses including newly-emerged coronavirus SARS-CoV-2

Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of the novel coronavirus SARS-CoV-2. Herein, we identified two potent inhibitors of human DHODH, S312 and S416, with favorable drug-likeness and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus, Zika virus, Ebola virus, and particularly against SARS-CoV-2. Notably, S416 is reported to be the most potent inhibitor so far with an EC of 17 nmol/L and an SI value of 10,505.88 in infected cells. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knock-out cells. This work demonstrates that both S312/S416 and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-regulation may have clinical potentials to cure SARS-CoV-2 or other RNA viruses circulating worldwide, no matter such viruses are mutated or not.

Role and mechanism of vitamin D in sepsis / 中华危重病急救医学

Sepsis is a life-threatening organ dysfunction caused by the host's imbalance in response to infection, which is still the leading cause of death in critically ill patients. In recent years, studies have found that vitamin D deficiency or insufficiency is common in critically ill patients, especially sepsis. The relationship between vitamin D and sepsis has attracted more and more attention. The mechanism of vitamin D in sepsis is described from the aspects of immune regulation, inflammation regulation, endothelial cell protection, carbon monoxide regulation, and receptor gene polymorphism, by analyzing the related literatures of vitamin D and sepsis in recent years in order to provide new ideas for clinical diagnosis and treatment of sepsis.

Progress of antimicrobial peptides cathelicidins in infection and immunology / 中华危重病急救医学

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.

Role and mechanism of vitamin D in sepsis / 中华危重病急救医学

Sepsis is a life-threatening organ dysfunction caused by the host's imbalance in response to infection, which is still the leading cause of death in critically ill patients. In recent years, studies have found that vitamin D deficiency or insufficiency is common in critically ill patients, especially sepsis. The relationship between vitamin D and sepsis has attracted more and more attention. The mechanism of vitamin D in sepsis is described from the aspects of immune regulation, inflammation regulation, endothelial cell protection, carbon monoxide regulation, and receptor gene polymorphism, by analyzing the related literatures of vitamin D and sepsis in recent years in order to provide new ideas for clinical diagnosis and treatment of sepsis.

Progress of antimicrobial peptides cathelicidins in infection and immunology / 中华危重病急救医学

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.

Mast cell-derived exosomes at the stimulated acupoints activating the neuro-immune regulation / 中国结合医学杂志

Exosomes are cell-derived vesicles that take part in intercellular signaling. Research has shown that acupuncture is closely related to affecting the functions of the mast cells in the local region of the acupoint, and stimulating the afferent nerve. Mast cells have a connection with the conduction within the meridians, and play an important role in immuno-regulation. The 'synapse-like' connection between the mast cells and nerve endings is the basis for the exchange of information between these two tissues. Exosome mediates mast exchange of information between mast cells and the nerves, starting the process of neuro-immuno regulation. Therefore, we propose that mast cell-derived exosomes mediate the neuro-immuno regulation at the local site of acupuncture, and this is one of the key factors resulting in the effectiveness of acupuncture.

A study on the effect of whole cranberry powder on immune function of ICR mice in vivo / 预防医学

Objective Toevaluatetheeffectsofwholecranberrypowder(Pacranpowder)onimmunefunctionsofICR miceinvivo.Methods FemaleICRmice(18-22g)wererandomlydividedintocontrolgroupandlow,mediumandhigh dose groups of whole cranberry powder (83,1 66,and 332 mg/kgbw).Whole cranberry powder was treated with by gavage for 30 days continuously.Control mice were treated with distilled water only.Their immune functions were analyzed, including serum hemolysin analysis, antibody -producing cells (APCs ), conA -induced splenic lymphocyte transformation,SRBC-induced delayed type hypersensitivity,natural killer cell activity assay,peritoneal macrophages phagocytosed chicken red blood cells (CRBC),carbon clearance test and thymus or spleen /body weight ratio.Results Ascomparedwiththecontrols,wholecranberrypowdertreatmentincreasedthenumberofplagueformingcells(PFCs)at 83 mg/kgbw group(P<0.05 ).There were no statistical difference in the total production of antibodies,the activity of conA-induced splenic lymphocyte transformation,the left-hind voix pedis thickness,NK cytoactivity,the phagocytosis index and ratio of peritoneal macrophages, the carbon clearance ability between the groups treated with different concentrationsofwholecranberrypowderandthecontrolgroup(P>0.05).Conclusion Wholecranberrypowdercan enhance mouse the number of plague forming cells (PFCs).

Comparison of the immunoregulatory effects of Radix Millettia Speciosa and Radix Millettia Championi on immunosuppressed mice / 西安交通大学学报(医学版)

Objective To compare the immunoregulatory effects of Radix Millettia Speciosa (RM Speciosa) and Radix Millettia Championi (RM Championi)on immunosuppressed mice.Methods Kunming mice were randomly divided into normal control group,CTX model group,LMS positive group,RM Speciosa groups and RM Championi groups (20,10 and 5 g/kg).The mice were treated respectively with drug or NS once a day for consecutive 20 days.Mice in the other groups were injected intraperitoneally with CTX at days 8,10 and 12 to establish immunosuppressed mice model except the normal group.The changes of body weight,immune organ weight,white blood cell (WBC)number,carbon particle clearance capability of macrophages and delayed type hypersensitivity (DTH)of mice in all groups were determined and compared.Results Compared with that in CTX group,the WBC number was significantly increased (P0.05).Conclusion Both RM Speciosa and RM Championi can improve the immune function of CTX-induced immunosuppressed mice,and RM Speciosa is slightly superior to RM Championi in improving specific cellular immunity.

Function of tumor-associated macrophages in gastric cancer / 中国肿瘤临床

Macrophages are a diverse phenotype that has important functions in inherent and adaptive immunity. Macrophage ac-tivation has two distinct states of polarization:the classically activated (M1) and the alternatively activated (M2) macrophage pheno-types in different micro-environments. M2 macrophages exert an immuno-regulatory activity that is associated with the induction of Th2 responses. The macrophages can infiltrate in the tumor micro-environment, and is also known as tumor-associated macrophages (TAMs). TAMs show the M2 macrophage phenotypes that have been associated with tumor neo-vascularization, infiltration, and metas-tasis. This review aims to investigate the importance of the immuno-regulatory activity of TAM in the carcinogenesis of gastric cancers.

Effects of Xinzhi Bimin Capsule on cytokines in serum and expression of related genes in nasal mucosa of rat model with allergic rhinitis / 中草药

Objective: To explore the effects of Xinzhi Bimin Capsule (XBC) on the contents of interleukin (IL)-5 and IL-13 in serum and the expression of eotaxin, CCR3, and signal transducers and activators of transcription-6 (STAT6) in nasal mucosa of rat models with allergic rhinitis, and to identify the mechanism of pharmacodynamic action. Methods: The allergic rhinitis rat model was established using ovalbumin, and forty rats were randomly divided into four groups, model, normal control, XBC (1.8 g/kg), and Biyankang Tablet (1.8 g/kg, positive control) groups. The rats were administered once daily for 10 d. The contents of IL-5 and IL-6 were detected by ELISA, and the expression of positive cell of eotaxin, CCR3, and STAT6 in nasal mucosa was detected in semi quantity by in situ hybridization (ISH) method. Results: The expression of STAT6 in nasal mucosa and the levels of IL-5 and IL-13 in blood serum were markedly lower in XBC group than those in the model and positive control groups (P < 0.05). Conclusion: XBC could reduce the expression of eotaxin, CCR3, and STAT6 in nasal mucosa of rats and down-regulate the contents of IL-5 and IL-13 in serum, so as to decrease the eosinophil infiltration and to treat allergic rhinitis in rats.

Pathogenesis of immune dysfunction in septic and immunoregulation therapy / 临床儿科杂志

The pathogenesis of immune dysfunction in septic has been summarized in this review.Innate immune response toward pathogens is initiated by pattem recognition receptor (PRR) such as Toll-like receptor (TLR) .Inflammatory cytokines derived from innate immune response not only cause inflammatory response.but also trigger adaptive immune responses through inducing the differentiation of naive T cell into Th1, Th2, CD4~+CD25~+Foxp3~+ regulatory T cells (Treg), and Th17 cells. Adaptive immune response might suppress or enhance inflammatory response.Abnormal activation of innate/adaptive immune responses may coexist in sepsis, resulting in immune dysfunction.Logical and adequate approach of immunoregulation therapy to sepsis may be to suppress PRR persistent activation by eliminating endogenous or exogenous ligands, as well as to avoid excessive inhibition of immune responses to infection.

Antioxidation and Immuno-regulation Effects of Jiawei Zhisou Powder on Hypersensitive Asthma Mice / 中药新药与临床药理

Objective To study the antioxidation and immuno-regulation effects of the active fraction in Jiawei Zhisou Powder.Methods Hypersensitive asthma mice were established by the miscible liquids of ovalbumin(OA)and Al(OH)3.The influences of the powder on the contents of SOD and MDA in the serum and lung tissue of mice were observed and the contents of IL-4 and IFN-?in supernatant of mouse spleen cells cultured in vitro were measured by enzyme-linked immunosorbent assay.And Jiawei Zhisou Powder and dexamethasone were administered to normal mice respectively,then the immune organs weight were measured and the spleen and thymus indexes of mice were calculated.Results Compared with the normal group,the contents of SOD and IFN-?were significantly decreased,while MDA and IL-4 contents were obviously enhanced in asthma group(P