Disruption of Histamine-H1R signaling exacerbates cardiac microthrombosis after periodontal disease via TLR4/NFκB-p65 pathway.

Periodontal disease is a chronic inflammatory disease that is highly correlated with cardiovascular disease(CVD). Histamine has been proven to participate in the pathophysiological processes of cardiovascular disease and oral inflammation. However, the role of histamine in the development of cardiac microthrombosis caused by periodontal disease has not been fully elucidated. We established a murine periodontal inflammation model by injecting lipopolysaccharide (LPS) or Porphyromonas gingivalis (P. gingivalis). In order to examine the effect of histamine/H1R signaling on cardiac injury after periodontal disease, we used histidine decarboxylase- knockout (HDC-/-) mice and histamine 1 receptor (H1R) antagonist. Our results demonstrated that LPS-induced periodontal inflammation significantly increased CD11b+Gr-1+ neutrophils in the peripheral blood and myocardial interstitium. Histamine deficiency resulted in further increases in P. gingivalis, neutrophils, inflammatory cytokines, and cardiac microthrombosis in the myocardium of HDC-/- mice compared to wild-type (WT) mice. Mechanistic analysis showed that blocking H1R could synergistically interact with LPS, further increasing the phosphorylation of p65, exacerbating the inflammatory response of neutrophils and endothelial cell damage. Conclusively, the disruption of histamine-H1R signaling exacerbates cardiac microthrombosis after periodontal disease via TLR4/NFκB-p65 pathway. Our findings not only reveal a link between periodontal inflammation and myocardial injury but also provided some thoughts for the use of H1R antagonist in clinical practice.

Expression Levels of WNT Signaling Pathway Genes During Early Tooth Development.

It is known to all that Wnt signaling pathway plays an important role in the early development of tooth. Our previous research found that Wnt signaling pathway played crucial roles in dental development, and mutations in antagonist of Wnt signaling pathway may lead to the formation of supernumerary teeth. However, the expression pattern of Wnt signaling molecules in early development of tooth, especially genes with stage specificity, remains unclear. Hence, we applied RNA-seq analysis to determine the expression levels of wnt signal molecules at five different stages of rat first molar tooth germ. In addition, after literature review we summarized the function of Wnt signaling molecules during tooth development and the relationship between Wnt signaling molecules variation and tooth agenesis. Our research may have implications for exploring the role of Wnt signaling molecules in different stages of tooth development.

Chinese expert consensus on interventional diagnosis and management of acquired digestive-respiratory tract fistulas (second edition).

Acquired digestive-respiratory tract fistulas occur with abnormal communication between the respiratory tract and digestive tract caused by a variety of benign or malignant diseases, leading to the alimentary canal contents in the respiratory tract. Although various departments have been actively exploring advanced fistula closure techniques, including surgical methods and multimodal therapy, some of which have gotten good clinical effects, there are few large-scale evidence-based medical data to guide clinical diagnosis and treatment. The guidelines update the etiology, classification, pathogenesis, diagnosis, and management of acquired digestive-respiratory tract fistulas. It has been proved that the implantation of the respiratory and digestive stent is the most important and best treatment for acquired digestive-respiratory tract fistulas. The guidelines conduct an in-depth review of the current evidence and introduce in detail the selection of stents, implantation methods, postoperative management and efficacy evaluation.

Histamine deficiency deteriorates LPS-induced periodontal diseases in a murine model via NLRP3/Caspase-1 pathway.

Histamine is a versatile biogenic amine, generated by the unique enzyme histidine decarboxylase (Hdc). Accumulating evidence has proven that histamine plays important roles in numerous biological and pathophysiological processes. However, the role and mechanism of Hdc/Histamine signaling in periodontal diseases remain unclear. In our current study, the concentration of histamine increased in the serum, and Hdc gene expression was upregulated in the gingiva of WT mice with LPS-induced periodontal inflammation. With Hdc-GFP mice, we identified that Hdc/GFP in the periodontium was expressed in CD11b+ myeloid cells, rather than in tryptase-positive mast cells. Hdc-expressing CD11b+Gr-1+ neutrophils significantly increased in the peripheral blood of Hdc-GFP mice one day after LPS injection. Lack of histamine in Hdc-/- mice not only promoted the activation and infiltration of more CD11b+ cells into the peripheral blood but also upregulated mRNA expression levels of IL-1ß, IL-6, MCP-1and MMP9 in the gingiva compared to WT mice one day after LPS stimulation. 28 days after LPS treatment, we observed that Hdc-/- mice exhibited more alveolar bone loss and more osteoclasts than WT mice, which was slightly ameliorated by the administration of exogenous histamine. In vivo and in vitro mechanistic studies revealed that the mRNA expression levels of proinflammatory cytokines and protein levels of NLRP3, Caspase-1, and cleaved-Caspase-1 were upregulated after blocking histamine receptor 1 and 2, especially histamine receptor 1. Taken together, CD11b+Gr-1+ neutrophils are the predominant Hdc-expressing sites in periodontal inflammation, and deficiency of endogenous histamine in Hdc-/- mice exacerbates the destruction of the periodontium. Disruption of the histamine/H1R/H2R axis aggravates the inflammatory immune response via NLRP3/Casapse-1 pathway.

Rapid diagnosis of a complex oral mucosal infection using metagenomic next-generation sequencing: a case report.

The most commonly used methods for pathogen detection and identification in oral mucosal infectious diseases are DNA or RNA quantitative polymerase chain reaction detection, bacterial or fungal cultures, and immunohistochemical analysis. These traditional methods are time-consuming and can only detect one specific targeted pathogen at a time. An efficient and sensitive method with higher species richness is urgently needed. Metagenomic next-generation sequencing (mNGS) is a new method of pathogen detection with high efficiency and sensitivity. In this case report, mNGS was used to identify the pathogens in oral mucosal tissues of a patient with complex oral mucosal infections and oral leukoplakia. Candida albicans, human gamma herpesvirus 4, and many other pathogens were identified using this method. For complex oral mucosal infections, mNGS is a more efficient and sensitive approach that can replace conventional detection methods.

The relationship between KRAS gene mutations and HLA class I antigen downregulation in the metastasis of non-small cell lung cancer.

OBJECTIVE: To investigate the association between v-Ki-ras2 Kirsten rat sarcoma viral oncogene homologue (KRAS) gene mutations and levels of human leucocyte antigen (HLA) class I antigen in primary lung tumours and metastatic lymph nodes of patients with non-small cell lung cancer (NSCLC). METHODS: Patients with NSCLC undergoing tumour resection were enrolled. KRAS codon 12 mutations were analysed in normal lung and lymph node tissue, primary lung tumours and metastatic lymph nodes using polymerase chain reaction-restriction fragment length polymorphism analysis. HLA class I antigen immunostaining was examined using flow cytometry. RESULTS: A total of 65 patients participated in the study. All normal lung tissues had positive HLA class I antigen immunostaining. The majority of primary lung tumours (56/65) and all of the metastatic lymph nodes (31/31) had downregulated HLA class I antigen immunostaining. There was a positive correlation between downregulated HLA class I antigen in primary tumours and metastatic lymph nodes. There was a negative correlation between KRAS codon 12 mutations and the level of HLA class I antigen in primary and metastatic tumours. CONCLUSIONS: KRAS codon 12 mutations appear to be important in the downregulation of HLA class I antigen in NSCLC. Abnormal activation of the oncogenic KRAS pathway might provide a new treatment target for NSCLC.