Research advances in the therapeutic potential of xanthine oxidoreductase inhibitors for periodontitis / 口腔疾病防治

@#Periodontitis is associated with abnormal purine metabolism, which is manifested by increased uric acid in host blood and increased expression of the purine-degrading enzyme, xanthine oxidoreductase (XOR), in periodontal tissues. Both XOR and uric acid are pro-oxidative and pro-inflammatory mediators under pathological conditions. Animal studies have found that injection of uric acid promotes the progression of periodontitis and that febuxostat (an XOR inhibitor) improves tissue destruction in periodontitis. Therefore, blocking the source of uric acid may be a therapeutic strategy to control the progression of periodontitis. In this article, the rationality of XOR inhibitors as potential therapeutic drugs for periodontitis is reviewed. The literature review results suggest that XOR inhibitors show antioxidative, anti-inflammatory, and anti-osteoclastic effects, and XOR inhibitors show clinical efficacy in the treatment of infectious, inflammatory and osteolytic diseases. Although there is no direct evidence to support the finding that XOR inhibitors can ameliorate periodontal microecological dysbiosis, these drugs can modulate intestinal microflora dysbiosis, and there is indirect evidence to support a beneficial effect of XOR inhibitors on periodontal microecological dysbiosis. In conclusion, XOR inhibitors may be used as immunomodulators for the adjuvant treatment of periodontitis by inhibiting inflammation, oxidative stress and anti-osteoclast effects.

Mechanism and immunotherapy of Kaposi sarcoma-associated herpesvirus and host immunity in the pathogenesis of Kaposi sarcoma / 国际肿瘤学杂志

Kaposi sarcoma is a multiple pigmented hemangioma of soft tissue. The etiology of Kaposi sarcoma is still unclear. Its occurrence is related to Kaposi sarcoma-related herpesvirus. Kaposi sarcoma-associated herpes virus plays an important role in the occurrence and development of Kaposi sarcoma by interfering with the pattern recognition receptors, complement system, or effecting on the immune cells directly to evasive host immune system. The immune modulators, immunotherapy of targeted drugs and vaccines are expected to be the new methods for the prevention and treatment of Kaposi sarcoma.

Research progress on the relationship between Fusobacterium nucleatum and periodontitis / 口腔疾病防治

@#Periodontitis is an infectious disease caused by a variety of microorganisms. Fusobacterium nucleatum is closely related to periodontitis with a high detection rate. Fusobacterium nucleatum is able to coaggregate with other microorganisms and attach and invade epithelial cells with the help of adhesins. It can also promote the occurrence and development of periodontal diseases and even systemic diseases by destroying periodontal tissues with virulence factors and metabolites and inducing a host immune response. However, at present, drugs assisting periodontal nonsurgical treatment clinically cannot target specific periodontal pathogens, such as Fusobacterium nucleatum, which may lead to problems such as dysbacteriosis or drug resistance. Therefore, studies on the pathogenic mechanism of Fusobacterium nucleatum provide new ideas for the prevention and treatment of periodontitis. The idea is to develop materials, drugs, or probiotics that target adhesins, virulence factors, and metabolites or cut off each pathogenic pathway of Fusobacterium nucleatum to inhibit its proliferation and inflammatory responses in deep periodontal pockets and achieve a balance with other oral microorganisms, and the host is beneficial for the control of periodontitis.

Cytokine Production in Cholangiocarcinoma Cells in Response to Clonorchis sinensis Excretory-Secretory Products and Their Putative Protein Components

Clonorchis sinensis is a carcinogenic human liver fluke that promotes hepatic inflammatory environments via direct contact or through their excretory-secretory products (ESPs), subsequently leading to cholangitis, periductal fibrosis, liver cirrhosis, and even cholangiocarcinoma (CCA). This study was conducted to examine the host inflammatory responses to C. sinensis ESPs and their putative protein components selected from C. sinensis expressed sequenced tag (EST) pool databases, including TGF-β receptor interacting protein 1(CsTRIP1), legumain (CsLeg), and growth factor binding protein 2 (CsGrb2). Treatment of CCA cells (HuCCT1) with the ESPs or bacterial recombinant C. sinensis proteins differentially promoted the secretion of proinflammatory cytokines (IL-1β, IL-6, and TNF-α) as well as anti-inflammatory cytokines (IL-10, TGF-β1, and TGF-β2) in a time-dependent manner. In particular, recombinant C. sinensis protein treatment resulted in increase (at maximum) of ~7-fold in TGF-β1, ~30-fold in TGF-β2, and ~3-fold in TNF-α compared with the increase produced by ESPs, indicating that CsTrip1, CsLeg, and CsGrb2 function as strong inducers for secretion of these cytokines in host cells. These results suggest that C. sinensis ESPs contribute to the immunopathological response in host cells, leading to clonorchiasis-associated hepatobiliary abnormalities of greater severity.

Immunosuppressive mechanism of Hypoderma lineatum secreted serine esterase, a potential modulatory method used to inhibit transplant rejection

Background: Although immunosuppressive therapies have made organ transplantation a common medical procedure worldwide, chronic toxicity has a major issue for long-term treatment. One method to improve therapies and methods is the application of immunomodulatory agents from parasites such as Hypoderma lineatum. Hypodermin A (HA) is a serine esterase secreted by the larvae of Hypoderma lineatum, several studies demonstrated its immunosuppressive mechanism in vitro, and recently we discovered that HA inhibits the expression of interferon (IFN)-γ and interleukin (IL)-2 and activates IL-10 expression. Therefore, we hypothesized that it might be a potential agent used to block allograft rejections. However, most studies of the immunosuppressive mechanisms associated with HA were undertaken at the cellular level. In order to augment these studies, we evaluated the immunosuppressive effects of HA in vivo using an HA transgenic mouse model. Result: Our results revealed similar findings to those reported by in vitro studies, specifically that HA induced prostaglandin E2 expression, downregulated IFN-γ and IL-2 expression, and promoted IL-10 secretion via E-type prostanoid receptor 4. Additionally, we observed that HA overexpression inhibited lipopolysaccharide-induced TLR4 activation. These findings provide insight into a new potential agent capable of blocking graft rejection. Conclusion: Our founding suggested that HA-related treatment could be a promising option to improve the viability of grafts in human.

Progress of research in the regulatory mechanism of enterovirus 71 in host immune response / 国际儿科学杂志

Virus infection can cause a variety of host immune response to prevent the spreading of virus.Innate immunity is the first line of defense to resist to virus infection in host.After the virus enters,the macrophage phagocytoses and process of virus antigen.On the other hand,it activates the innate antiviral immune response.The expression of interferon after EV71 infection may be associated with cell specific response.Most studies have shown that EV71 can inhibit the expression of interferon to achieve immune escape.Then antigen presenting cells present antigens to T/B lymphocytes,once specific T/B lymphocytes are activated by antigen,they will be activated,proliferated,diferentiated to immunologic effector cells,which secrete antibodies,cytokines,cell toxicity of medium,ultimately,develop immunological effect.Both humoral immunity and cellular immunity are activated in EV71 infection,and play an important role in mediating protection effect.Cellular immunity may be associated with the clinical outcome of EV71 infection.The EV71-specific neutralizing antibody generated by the humoral immunity plays a key role in protective immunity,but the antibody response level is not correlated with disease severity.In addition,virus infection can induce cell apoptosis to prevent the virus proliferation and the spreading of progeny virus.

Serum antibody & Th2 cytokine profiles in patients with cystic echinococcosis.

Background & objectives: Human cystic echinococcosis (CE), caused by Echinococcus granulosus, is one of the most important and widespread parasitic zoonoses. T helper cell-2 (Th2) dominated immunity in CE is associated with increased susceptibility to the disease, while T helper cell-1 (Th1) cell activation is assumed to induce protective immunity. Hence, in order to investigate in vivo Th2 cell activation and serum complement levels, the present study was aimed to detect serum levels of specific IgG, IgE, interleukin (IL)-4, IL-10, C3c and C4 in confirmed CE patients. Methods: Specific IgG levels in serum was measured by enzyme linked immunosorbent assay using recombinant E. granulosus antigen-B/2 (RecEg-AgB/2) and serum IgE, IL-4, IL-10, C3c and C4 were quantified by nephelometry in 45 surgically confirmed patients with CE, and 10 healthy controls. Results: Specific IgG (P<0.0001), IgE (P<0.05), IL-4 (P=0.0197) and IL-10 (P<0.01) levels were significantly elevated in CE cases compared to healthy controls. IL-4 could be detected in 34 patients (75.55%) and six controls (60%) in a low concentration. The IgE concentration was elevated (>120 U/ml) in 36 (80%) cases of CE and in one healthy control. Interpretation & conclusion: Our results showed higher C3c and C4 levels in CE patients than healthy controls. No significant association was found between IgE concentrations and cytokine levels. The results of this study point to a cytokine profile suggestive of Th2 cell dominance in vivo in CE.

The Effect of Iron Depletion on the Monocytic Adhesion, Differentiation and SR-A Expression / 대한해부학회지

Maintenance of cellular iron homeostasis is a prerequisite for proliferation and differentiation of cells, and is also a central role in the regulation of immune function. Monocyte-macrophages play an important roles in host defense, particularly in the inflammatory process of acute and chronic disease. The reason that an iron is important in these cell is because an iron is indispensable in a generation of hydroxyl radical for bacterium killing. Because of the role of iron in the monocytic THP-1 cell differentiation is not become clear, we investigated whether THP-1 cell can differentiate to macrophage-like cell using of iron and iron chelator which cause iron depletion. The cell differentiation was not able to observe by iron treatment, by the way, the cell adhesion was increased in DFO treated monocyte and cellular pseodopodial extension, change of a nucleus-cytoplasmic ratio were showed in Differential interference contrast (DIC) and Giemsa staining, and it was inhibited by ferric citrate (FC). Increased polystyrene bead phagocytosis by DFO treatment of THP-1 cell were detected through FACS and rhodamine-phallodin staining. The SR-A expression, which was a cell differentiation marker, was increased by DFO treatment of THP-1 cell. These results suggest that iron depletion by DFO can promote THP-1 cell diffentiation into macrophage-like cell, and this may carrying out important role in the immune response.