Research progress on the molecular mechanism of periodontal pathogens promoting the development of cardiovascular diseases / 口腔疾病防治

@#Periodontitis is a multifactorial infectious and inflammatory disease occurring in tooth-supporting tissues. In recent decades, many studies have reported a potential relationship between periodontitis and cardiovascular disease, and periodontal pathogens are an important factor linking periodontitis and cardiovascular disease. In this review, we summarize updated preclinical studies and epidemiological evidence on the association of these two diseases. Moreover, possible mechanisms accounting for such links are introduced, including bacteremia and direct invasion of pathogens, endotoxemia caused by virulence factors of periodontal pathogens leading to systemic inflammation, abnormal lipid metabolism and oxidative stress, which further affect the inflammatory states of the cardiovascular system. The molecular mimicry theory and the intrinsic correlation of apolipoprotein E between periodontitis and cardiovascular disease require further study. Combined with existing studies, it is reasonable to assume that periodontal treatment and oral hygiene can reduce the risk of cardiovascular disease in patients with periodontitis. More studies are needed to focus on the molecular mechanism linking periodontal pathogens and cardiovascular diseases. These studies will provide evidence that periodontal pathogens directly invade the cardiovascular system or indirectly invade host cells as well as isolate and culture bacteria from the tissues of lesions. Studies should also explore how the local inflammatory state, periodontal pathogens and their products directly influence cardiovascular disease-related biomarkers (C-reactive protein, vascular endothelial growth factor, heat shock protein, etc.) and the mechanism. This information may provide a reference for the effective prevention and treatment of periodontitis and cardiovascular disease in the future.

Trastornos inmunitarios en paciente pediátrico con enfermedad de Behcet / Inmune disorders in a pediatric patient with Behcet's disease

Introducción: La enfermedad de Behcet es un proceso autoinflamatorio crónico que afecta arterias y venas de todos los calibres. Participan factores genéticos, microbianos e inmunológicos. Cursa con úlceras orales, genitales e inflamación ocular. Objetivo: Describir los trastornos inmunitarios en un paciente pediátrico con enfermedad de Behcet. Presentación del caso: Paciente masculino de 16 años de edad, con diagnóstico clínico de enfermedad de Behcet con marcadores serológicos de autoinmunidad negativa. Las inmunoglobulinas séricas exhibieron valores normales. Las subpoblaciones linfocitarias T CD3+CD4+ y CD3+CD8+ estuvieron elevadas. Las células B totales mostraron valores porcentuales normales, sin embargo, la subpoblación B CD5+CD19+ se encontró por encima de los valores referenciales. El paciente respondió favorablemente en relación con el curso de las infecciones a la terapia con inmunoestimulantes. Conclusiones: El tratamiento para la enfermedad de Behcet debe ser individualizado. Se debe tener en cuenta la gravedad del órgano afectado y el índice de recurrencias. Se requiere de un grupo interdisciplinario para llegar al adecuado control de la enfermedad.

Introduction: Behcet's disease is a chronic autoinflammatory process, of low frequency and unknown etiology that affects arteries and veins of all sizes, where genetic, microbial and immunological factors participate. It presents with oral and genital ulcers and ocular inflammation. Objective: To evaluate the immune disorders in a pediatric patient with Behcet's disease. Case presentation: A 16-year-old male patient with a clinical diagnosis of Behcet's disease with negative autoimmunity serological markers. Immunoglobulins exhibited normal values. CD3+CD4+ and CD3+CD8+T lymphocyte subpopulations were elevated. The B cells showed normal percentage values, however the CD5+CD19+ subpopulation B was found to be above the reference values. The patient responded favorably in relation to the course of the infections, to the therapy with immune stimulants. Conclusions: Treatment must be individualized, taking into account the severity of the affected organ and the recurrence rate. An interdisciplinary group is required to achieve adequate control of the disease.

Changes and significance of T lymphocyte subsets and cytokines in hyperlipidemia-induced acute pancreatitis / 中华急诊医学杂志

Objective:To explore the characteristics of T lymphocyte subsets and cytokines in hyperlipidemia-induced acute pancreatitis (HLAP) and its prognostic value.Methods:This study included 184 patients with acute pancreatitis (AP) admitted to the First Affiliated Hospital of Xiamen University from January 2018 to May 2021. Based on disease etiology, there were 92 HLAP cases and 92 non-hyperlipidemia-induced AP (NHLAP) cases. Stratified by disease severity according to 2012 Atlanta classification criteria, the patients were divided into the severe subgroup (SAP) and non-severe subgroup (NSAP). Peripheral venous blood samples were taken from all patients on day 1, 3, and 5 after admission. T lymphocyte subsets were determined by flow cytometry, and cytokines were detected by flow fluorometry. The number of CD4 +% and CD8 +% and the expression of cytokines were compared by Student’s t test or Mann-Whitney U analysis. Logistic regression analyses were performed to identify risk factors for severe AP, and a receiver operating characteristic (ROC) curve was constructed to predict severe AP. Statistical significance was taken as P<0.05. Results:Compared with the NHLAP group, patients in the HLAP group had lower CD4 +%, while higher levels of IL-2 on day 1 ( P<0.05), and had also lower CD4 +%, while higher levels of IL-4, IL-6, and IL-10 on day 3 ( P<0.05). Furthermore, IL-6 and IL-10 levels of the HLAP group were significantly increased compared to the NHLAP group on day 5 ( P<0.05). IL-10 levels in the SAP subgroup were significantly higher than those in the NSAP subgroup on day 1 ( P<0.05). Compared with the NSAP subgroup, the SAP subgroup had elevated levels of IL-2, IL-4, IL-6, IL-10 and IFN-γ on day 3 (all P<0.05), and had lower CD4 +%, while increased levels of IL-6 and IL-10 on day 5 (all P<0.05). Multivariate Logistic regression analysis showed that IL-10 was an immune indicator of independent risk factor for severe AP in the HLAP group on day 1 ( OR=1.139, 95% CI: 1.038-1.251, P<0.05). Finally, ROC analysis showed that the area under the curve of IL-10 to assess HLAP with severe AP was 0.772, and the best cut-off value for predicting severe AP was 5.6 pg/mL, with a sensitivity of 83.3% and a specificity of 68.8%. Conclusions:Changes of CD4 +% and cytokines are different between the HLAP and NHLAP groups. IL-10 can be used as a predictor of early disease severity in patients with HLAP.

Aspectos inmunológicos relacionados con la reinfección por SARS-CoV-2 / Immunological aspects related to re-infection by SARS-CoV-2

A finales de 2019 una nueva cepa de coronavirus (SARS-CoV-2) ocasiona una notable crisis mundial. Los esfuerzos del personal sanitario se han centrado en conocer la novel enfermedad y buscar la manera de frenar las curvas de contagio para en un futuro contar con inmunidad por vacunas. La inmunidad ante la primoinfección mediada por Linfocitos B ha reportado pérdida de inmunoglobulinas en cuestión de semanas. Estas características en el genotipo de la enferme- dad abren la posibilidad de reinfección por cepas distintas. Contados reportes a nivel mundial describen reinfección, los que tuvieron curso clínico leve al determinar algún factor protector luego de la primoinfección. La real posibilidad de volver a enfermarse por COVID-19 enciende las alarmas sobre la respuesta en el control de la pandemia, con las vacunas que están cerca de expenderse y representa un nuevo campo de estudio en la presente emergencia sanitaria.

At the end of 2019, a new strain of coronavirus (SARS-CoV-2) causes a notable global crisis. The efforts of health personnel have focused on learning about the novel disease and finding a way to slow down the contagion curves to have immunity from vaccines in the future. Immunity to primary B lymphocyte-mediated infection has reported loss of immunoglobulins in a matter of weeks. These characteristics in the genotype of the disease open the possibility of reinfection by different strains. Counted reports worldwide describe reinfection, which had a mild clinical course when determining some protective factor after the primary infection. The real possibility of getting sick again from COVID-19 raises the alarms about the response in the control of the pandemic, with the vaccines that are close to being distributed and represents a new field of study in the current health emergency.

Immunomodulatory properties of bone marrow mesenchymal stem cells

Bone marrow mesenchymal stem cells (BM-MSCs) are multipotent progenitor cells of mesodermal originpossessing multilineage differentiation potential and ease of expansion in vitro. Over the years, these cells havegained attention owing to their potential in cell-based therapies in treating various diseases. In particular, thewide spectrum of immunoregulatory/immunomodulatory role of MSCs in various clinical conditions hasgained immense attention. The immunomodulatory properties of BM-MSCs are mediated by either cell–cellcontact (interactions with various immune cells in a context-dependent manner), paracrine mode of action orextracellular vesicles, making them a potential option as immunosuppressants/immunomodulators in treatingvarious clinical conditions. A plethora of studies have demonstrated that MSCs do so by exhibiting a profoundeffect on various immune cells for example they can inhibit the proliferation of T cells, B cells, and naturalkiller cells; modulate the activities of dendritic cells and induce regulatory T cells both in vitro and in vivo. Inthis review we aim at briefly elucidating the characteristics of BM-MSCs, specifically addressing the currentunderstanding on the hypoimmunogeneticity and immunomodulatory properties of the same with specificreference to their interactions with B cells, T cells, Dendritic cells and natural killer cells. We also aim atreviewing the secretory profile and their role in some clinical conditions that have shown promising outcomes.

Mesenchymal stem cells and immune disorders: from basic science to clinical transition / 医学前沿

As a promising candidate seed cell type in regenerative medicine, mesenchymal stem cells (MSCs) have attracted considerable attention. The unique capacity of MSCs to exert a regulatory effect on immunity in an autologous/allergenic manner makes them an attractive therapeutic cell type for immune disorders. In this review, we discussed the current knowledge of and advances in MSCs, including its basic biological properties, i.e., multilineage differentiation, secretome, and immunomodulation. Specifically, on the basis of our previous work, we proposed three new concepts of MSCs, i.e., "subtotipotent stem cell" hypothesis, MSC system, and "Yin and Yang" balance of MSC regulation, which may bring new insights into our understanding of MSCs. Furthermore, we analyzed data from the Clinical Trials database ( http://clinicaltrials.gov ) on registered clinical trials using MSCs to treat a variety of immune diseases, such as graft-versus-host disease, systemic lupus erythematosus, and multiple sclerosis. In addition, we highlighted MSC clinical trials in China and discussed the challenges and future directions in the field of MSC clinical application.

miRNA-124 in immune system and immune disorders / 中国药理学与毒理学杂志

In recent years, miR-124 has emerged as a critical modulator of immunity and inflammation. Here, we summarize studies on the function and mechanism of miR-124 in the immune system and immunity-related diseases. They indicated that miR-124 exerts a crucial role in the development of immune system, regulation of immune responses, and inflammatory disorders. It is evident that miR-124 may serve as an informative diagnostic biomarker and therapeutic target in the future.

Expressions of Th1-Th2-Th17 cytokines in mice chronic viral myocarditis / 中国免疫学杂志

Objective:To investigate the expressions of Th 1-Th2-Th17 cytokines in the coxsackievirus B 3-induced mice chronic viral myocarditis(VMC).Methods:BALB/c mice were intraperitoneally(i.p) infected with increased CVB3 for establishing chronic VMC models.Control mice were treated with phosphate-buffered saline(PBS)i.p.Cardiac tissues were obtained 8 weeks after CVB3 in-jection,myocardial histopathologic changes were observed by HE and Masson staining .Th1-Th2-Th17 cytokines in plasma were detected by protein array technology , and their cardiac mRNA expressions were measured by RT-PCR.Results: Compared with the control group,levels of IL-2,IL-5,IL-10,IL-13,IL-17,IL-6,IL-22,IL-21 and TGF-βobviously increased in chronic VMC group (P all<0.05). Conclusion:The imbalance of Th1-Th2-Th17 cytokines may play an important roles in the pathogenesis of chronic VMC .

Expression of leukocyte-associated immunoglobulin-like receptor on Treg cells in children with immune thrombocytopenia / 中华实用儿科临床杂志

Objective To observe the expression of leukocyte-associated immunoglobulin(Ig)-like receptor-1 (LAIR-1) on Treg cells in children with immune thrombocytopenia (ITP) and the level of soluble LAIR-1 (sLAIR-1),LAIR-2 in peripheral blood,and to discuss the possible role of LAIR in the pathogenesis of childhood ITP.Methods The levels of LAIR-1 on Treg cells of peripheral blood were measured in 36 children with ITP by using flow cytometry.Plasma levels of sLAIR-1 and LAIR-2 were measured by adopting enzyme-linked immunosorbent assay(ELISA).Real-time PCR was used to measure both LAIR-1 mRNA and LAIR-2 mRNA.Twenty-eight healthy children served as the healthy control group.Results The expression of Treg cells in children with ITP was significantly lower than that in the healthy control group [(2.05 ± 0.85) ％ vs (3.04 ± 1.03) ％,t =4.198,P ＜ 0.001].The expression rate of LAIR-1 on Treg cells and tyrosine phosphatase-2 (SHP-2) in children with ITP group had no statistically significant difference with the healthy control group [(71.18 ± 13.36) ％ vs (67.69 ± 13.07)％,t=1.045,P＞0.05;(1.20 ± 0.97) ％ vs (0.85 ±0.66)％;t=1.718,P＞0.05].The levels of sLAIR-1 and LAIR-2 in plasma in children with ITP group were increased significantly than those in the healthy control group [(20.53 ±4.32) μg/L vs (17.51 ± 5.15) μg/L,t =2.424,P ＜0.05;(5.83 ± 1.08) μg/L vs (5.19 ± 1.24) μg/L,t =2.267,P ＜ 0.05].The LAIR-1 mRNA expression level in children with ITP group was significantly increased compared with the healthy control group (t =2.851,P ＜ 0.05),but not the LAIR-2 mRNA expression level (t =1.715,P ＞ 0.05).Conclusions The expression of Treg cells in children with ITP is decreased,and it may be associated with the onset of ITP,and it may suggest that LAIR-1 does not play a leading role in Treg cells when ITP occurrs.And the levels of sLAIR-1,LAIR-2 in plasma are both increased,suggesting that LAIR-1,LAIR-2 may be one of the factors of immune disorders in children with ITP.

Progress of pathogenesis of aplastic anemia / 国际儿科学杂志

Aplastic anemia is an acquired bone marrow failure syndrome,characterized by an empty bone marrow,pancytopenia,as well as anemia,bleeding,infection syndrome.The pathogenesis of aplastic anemia has not yet been completely clear.Some of the proposed causes include hematopoietic stem/ progenitor cell deficiency,immune disorders,and abnormalities in the hematopoietic microenvironment.In recent years,further clinical and experimental studies have accumulated to recognize the pathogenesis of aplastic anemia.

Haptoglobin study in myasthenia gravis / Estudo sobre a haptoglobina na miastenia grave

OBJECTIVE: A cross-sectional study of haptoglobin (Hp) in myasthenia gravis (MG) was designed, with the objective to identify its values and correlate them with different disease status. METHOD: 46 patients were enrolled in the study, all having disease severity established according to the quantitative myasthenia gravis strength scores (QMGSS). Based on the functional scale determined by Myasthenia Gravis Foundation of America (MGFA) recommendations, patients were classified as having: complete stable remission (CSR; n=10); minimal manifestations-0 (MM0; n=6), minimal manifestations-1 (MM1; n=4); pharmacological remission (PR; n=6). Two other groups participated: thymomatous patients (T; n=10) and patients without imunosuppression or thymectomy, until the assessment for Hp (WIT; n=10). Hp dosage was done by immunonephelometry, blindly to clinical data. Student's t-test, Anova test and linear regression were employed for statistical analyses. RESULTS: Statistically significant differences occurred between CSR+MM0xWIT groups (86.62x157.57, p<0.001) and PR+MM1xWIT groups (73.93x157.57, p<0.001). Linear regression showed correlation between Hp levels and QMGSS (r=0.759, p<0.001). CONCLUSION: Our results suggest that Hp may be useful in clinical practice as a disease severity marker in MG.

OBJECTIVO: Desenhou-se estudo transversal sobre a haptoglobina (Hp) na miastenia grave (MG) com o objetivo de identificar seus valores e correlacioná-los a diferentes condições na doença. MÉTODO: 46 pacientes foram incluídos, todos tendo a gravidade da doença estabelecida segundo escores internacionais (QMGSS). Os pacientes tiveram seu estado funcional determinado de acordo com a Myasthenia Gravis Foundation of América (MGFA) e classificados em: remissão completa estável (CSR; n=10); mínima manifestação-0 (MM0; n=6), mínima manifestação-1 (MM1; n=4); remissão farmacológica (PR; n=6). Dois outros grupos participaram: pacientes timomatosos (T; n=10) e pacientes sem imunossupressão ou timectomia, até o momento da inclusão no estudo (WIT; n=10). A dosagem de Hp foi realizada por imunonefelometria, de modo cego quanto à clínica. As análises estatísticas incluíram o teste de Student, Anova e regressão linear. RESULTADOS: Observou-se diferença significativa entre os grupos CSR+MM0xWIT (86,62x157,57, p<0,001) e entre PR+MM1xWIT (73,93x157,57, p<0,001). A regressão linear mostrou correlação positiva entre os valores de Hp e os escores QMGSS (r=0,759, p<0,001). CONCLUSÃO: O estudo sugere que valores altos de Hp se correlacionaram a maior gravidade da MG.