Effects of tumor derived exosomes on T cells markers expression / Efeitos de exossomos derivados de tumor na expressão de marcadores de células T

Exosomes are 30-120nm bio particles transferred from donor to recipient cells leading to modification in their regulatory mechanisms depending upon the coded message in the form of loaded biomolecule. Cancer cells derived exosomes the true representatives of the parent cells have been found to modify the tumor surrounding/distinct regions and participate in metastasis, angiogenesis and immune suppression. Tis study was aimed to study the effects of tumor mice derived exosomes on the normal mice spleen isolated T cells by using co-culture experiments and flow cytometer analysis. We mainly focused on some of the T cells population and cytokines including IFN-γ, FOXP3+ regulatory T (Treg) cells and KI67 (proliferation marker). Overall results indicated random changes in different set of experiments, where the cancer derived exosomes reduced the IFN-γ expression in both CD4 and CD8 T cells, similarly the Treg cells were also found decreased in the presence of cancer exosomes. No significant changes were observed on the Ki67 marker expression. Such studies are helpful in understanding the role of cancer exosomes in immune cells suppression in tumor microenvironment. Cancer exosomes will need to be validated in vivo and in vitro on a molecular scale in detail for clinical applications.

Os exossomos são biopartículas de 30-120 nm transferidas de células doadoras para células receptoras, levando à modificação em seus mecanismos reguladores, dependendo da mensagem codificada na forma de biomolécula carregada. Verificou-se que exossomos derivados de células cancerosas ­ os verdadeiros representantes das células-mãe ­ modificam as regiões circundantes / distintas do tumor e participam da metástase, angiogênese e imunossupressão. Este estudo teve como objetivo estudar os efeitos de exossomos derivados de camundongos com tumor nas células T isoladas de baço de camundongos normais, usando experimentos de cocultura e análise de citômetro de fluxo. Concentrou-se, principalmente, em algumas populações de células T e citocinas, incluindo IFN-γ, células T reguladoras FOXP3 + (Treg) e KI67 (marcador de proliferação). Os resultados gerais indicaram mudanças aleatórias em diferentes conjuntos de experimentos, em que os exossomos derivados de câncer reduziram a expressão de IFN-γ em células T CD4 e CD8, da mesma forma que as células Treg também foram encontradas diminuídas na presença de exossomos de câncer. Nenhuma mudança significativa foi observada na expressão do marcador Ki67. Esses dados são úteis para a compreensão do papel dos exossomos do câncer na supressão de células do sistema imunológico no microambiente tumoral. Exossomos de câncer precisarão ser validados in vivo e in vitro em escala molecular com detalhes para aplicações clínicas.

Effects of tumor derived exosomes on T cells markers expression

Abstract Exosomes are 30-120nm bio particles transferred from donor to recipient cells leading to modification in their regulatory mechanisms depending upon the coded message in the form of loaded biomolecule. Cancer cells derived exosomes the true representatives of the parent cells have been found to modify the tumor surrounding/distinct regions and participate in metastasis, angiogenesis and immune suppression. Tis study was aimed to study the effects of tumor mice derived exosomes on the normal mice spleen isolated T cells by using co-culture experiments and flow cytometer analysis. We mainly focused on some of the T cells population and cytokines including IFN-, FOXP3+ regulatory T (Treg) cells and KI67 (proliferation marker). Overall results indicated random changes in different set of experiments, where the cancer derived exosomes reduced the IFN- expression in both CD4 and CD8 T cells, similarly the Treg cells were also found decreased in the presence of cancer exosomes. No significant changes were observed on the Ki67 marker expression. Such studies are helpful in understanding the role of cancer exosomes in immune cells suppression in tumor microenvironment. Cancer exosomes will need to be validated in vivo and in vitro on a molecular scale in detail for clinical applications.

Resumo Os exossomos são biopartículas de 30-120 nm transferidas de células doadoras para células receptoras, levando à modificação em seus mecanismos reguladores, dependendo da mensagem codificada na forma de biomolécula carregada. Verificou-se que exossomos derivados de células cancerosas os verdadeiros representantes das células-mãe modificam as regiões circundantes / distintas do tumor e participam da metástase, angiogênese e imunossupressão. Este estudo teve como objetivo estudar os efeitos de exossomos derivados de camundongos com tumor nas células T isoladas de baço de camundongos normais, usando experimentos de cocultura e análise de citômetro de fluxo. Concentrou-se, principalmente, em algumas populações de células T e citocinas, incluindo IFN-, células T reguladoras FOXP3 + (Treg) e KI67 (marcador de proliferação). Os resultados gerais indicaram mudanças aleatórias em diferentes conjuntos de experimentos, em que os exossomos derivados de câncer reduziram a expressão de IFN- em células T CD4 e CD8, da mesma forma que as células Treg também foram encontradas diminuídas na presença de exossomos de câncer. Nenhuma mudança significativa foi observada na expressão do marcador Ki67. Esses dados são úteis para a compreensão do papel dos exossomos do câncer na supressão de células do sistema imunológico no microambiente tumoral. Exossomos de câncer precisarão ser validados in vivo e in vitro em escala molecular com detalhes para aplicações clínicas.

Recent advances in preclinical research of renal xenotransplantation and selection of potential recipients in the future / 中华器官移植杂志

After continuous efforts from generations of transplant surgeons, kidney transplantation (KT) has become an optimal treatment for end-stage renal disease.However, an imbalance between supply and demand of organs has always restricted the development of KT.For this clinical dilemma, xenotransplantation is expected to become one practical alternative for alleviating organ shortage.This review summarized recent literature reports of kidney xenotransplantation and the latest cases of pig-to-human kidney and heart transplantations.Also clinical transformations and applications of kidney xenotransplantation were discussed.

Respuesta inmune e inmunosupresión en pacientes con ventilación mecánica por infección por SARS-CoV-2 / Immune response and immune suppression in patients with mechanical ventilation secondary to SARS-CoV-2 infection / Resposta imune e imunossupressão em pacientes com ventilação mecânica devido à infecção por SARS-CoV-2

Resumen Introducción: La pandemia por SARS-CoV-2 ha inspirado intriga sobre la respuesta inmune a dicho virus, especialmente en pacientes graves con síndrome de dificultad respiratoria aguda (SDRA). Este estudio describe el comportamiento de la respuesta inmune, la inmunosupresión y sus desenlaces en los pacientes con ventilación mecánica (VM). Material y métodos: Cohorte prospectiva. Del 23 de marzo al 31 de diciembre de 2020 se recolectó información basal, parámetros ventilatorios, gasométricos y estudios de laboratorio de todos los pacientes mayores de 18 años que recibieron VM por COVID-19 con registros hasta el día 15 de VM. Se dividieron los grupos en pacientes vivos a los 90 días y defunciones. Resultados: Registramos 218 pacientes, con mortalidad de 23%. En el día 1 de VM, los pacientes no presentaron diferencias en conteos celulares o reactantes de fase aguda, excepto dímero D de 1,020 (705-1,711) vs 1,328 (940-2,340) ng/dL p = 0.035. En el análisis de regresión lineal de efectos mixtos se observaron diferencias cronológicas estadísticamente significativas en leucocitos y proteína C reactiva (PCR) concordante con la elevación de la presión de distensión alveolar (PDalv). No se encontró asociación con mortalidad en el uso de tocilizumab 2.20 (0.279-17.358) y corticosteroides 0.54 (0.229-1.273) en riesgos proporcionales de Cox al día 1 de VM. Durante los 15 días de VM los pacientes que fallecieron recibieron dosis más altas de corticosteroides, dosis mayores de 150 mg/día equivalente a prednisona se asocian a mortalidad. Conclusiones: Existe evolución cronológica similar en elevación de PCR, leucocitos y elevación de la PDalv, las cuales se explican por la disminución de la distensibilidad pulmonar estática (Cstat) y la presión positiva al final de la espiración total (PEEP total). El uso de tocilizumab no tuvo asociación con la mortalidad y dosis equivalentes a prednisona entre 100-150 mg/día se asocian a mejores resultados.

Abstract Introduction: The SARS-CoV-2 pandemic has inspired interest in the immune response to the virus, especially in severe patients with acute respiratory distress syndrome (ARDS). The study describes the behaviour of the immune response, immune suppression, and their results in patients under mechanical ventilation (MV). Material and methods: Prospective cohort. From March 23rd to December 31st, 2020, we recollected basal information, MV parameters, blood gas analysis and laboratory studies of all the patients over 18 years who received MV secondary to COVID-19. We registered 15 continuous days of MV. We divided the groups in patients alive at day 60 and deaths. Results: We included 218 patients with a mortality of 23%. In day 1 of MV, the patients didn't have any differences in cell counts or acute phase reactants, except for D Dimer (705-1,711) vs 1,328 (940-2,340) ng/dL p = 0.035. In mixed effects linear regressions, we found statistically significant chronological differences in C reactive protein (CPR) and leucocyte count, concordant with the elevation of the driving pressure (DP). In the Cox regression we found no association with tocilizumab and corticosteroids with mortality on day 1 of MV. Patients who died received higher doses of corticosteroids throughout the 15 days of MV, with doses equivalent to prednisone over 150 mg/day are associated with mortality. Conclusions: There is a similar chronological behaviour in the elevation of acute phase reactants and the elevation con DP with no elevation of Vt, which can be explained by the drop of total PEEP and Cstat. There was no association with the use of tocilizumab and mortality, and a dose of 100-150 mg/día of equivalent of prednisone was associated with better results.

Resumo Introdução: A pandemia de SARS-CoV-2 inspirou intrigas sobre a resposta imune ao referido vírus, especialmente em pacientes gravemente doentes com síndrome do desconforto respiratório do adulto (SDRA). Este estudo descreve o comportamento da resposta imune, imunossupressão e seus desfechos em pacientes em ventilação mecânica (VM). Material e métodos: Coorte prospectiva. De 23 de março a 31 de dezembro de 2020, foram coletadas informações basais, parâmetros ventilatórios e gasométricos e estudos laboratoriais de todos os pacientes maiores de 18 anos que receberam VM para COVID-19 com registros até o dia 15 de VM. Os grupos foram divididos em pacientes vivos em 90 dias e óbitos. Resultados: Registramos 218 pacientes, com mortalidade de 23%. No dia 1 de VM, os pacientes não apresentaram diferenças na contagem de células ou reagentes de fase aguda, exceto dimero D 1020 (705-1711) vs 1328 (940-2340) ng/dL p = 0.035. Na análise de regressão linear dos efeitos mistos, observam-se diferenças cronológicas estatisticamente significativas nos leucócitos e na proteína C reativa (PCR), consistentes com o aumento da pressão de distensão alveolar (PDalv). Não foi encontrada associação com mortalidade no uso de tocilizumab 2.20 (0.279-17.358) e corticoide 0.54 (0.229-1.273) nos riscos proporcionais de COX no 1o dia de VM. Durante os 15 dias de VM, os pacientes que foram a óbito receberam doses maiores de corticosteróides, doses a partir de 150 mg/dia equivalentes a prednisona estão associadas à mortalidade. Conclusões: Há evolução cronológica semelhante em PCR e leucócitos elevados e PDalv elevados, explicados pela diminuição da complacência pulmonar estática (Cstat) e da pressão positiva ao final da expiração total (PEEPtotal). O uso de tocilizumab não foi associado à mortalidade e doses equivalentes à prednisona entre 100-150 mg/dia estão associadas a melhores resultados.

Progress on biomarkers of EB virus-related posttransplant lymphoproliferative disease / 器官移植

Posttransplant lymphoproliferative disease (PTLD) is a series of heterogeneous lymphoproliferative diseases and a severe complication after solid organ transplantation in children. Over 70% of PTLD is associated with Epstein-Barr virus (EBV). EBV-related B-cell lymphoma is also the main malignant tumor after pediatric organ transplantation. EBV-related PTLD is still a challenge in pediatric solid organ transplantation, which is mainly caused by immune function damage induced by immune suppression after transplantation. However, the specific mechanism remains elusive. In recent years, biomarkers have been developed to guide the diagnosis and individualized treatment of EBV-related PTLD, which possesses excellent application prospect. In this article, research progresses on the incidence of EBV-related PTLD in solid organ transplantation and its biomarkers were reviewed, aiming to explore novel ideas for clinical diagnosis and treatment.

Study of Serum Albumin Level in Subjects with HIV Infection, in Relation to CD 4 Count, as a Marker of Immune Suppression

Introduction: HIV/AIDS Infection is one of the commonlyencountered illness in our setup. It causes morbidity andmortality worldwide, and the number of HIV-infected patientshas increased dramatically in the past decade. Current studyaimed to record serum albumin level in patients suffering fromHIV infection.Material and methods: A total of 175 subjects were studiedover a period of 3 months. History and examination weredone according to the proforma after taking written informedconsent. Routine investigations included CD 4 Count andLFT. All data were entered in the master chart and analysedusing SPSS Version 20 softwareResults: Out of 175 subjects majority were in age group of 41to 50 years (30.4%) with mean age around 42 years and 101subjects were males (57.7%). Low serum albumin was foundin 67.2% of subjects. 12% of the subjects had CD 4 Count ofless than 100 and among subjects with CD 4 Count of lessthan 100, 76% of the subjects had low serum albumin whichwas statistically significant with p value of 0.003.Conclusion: From the study can conclude that in HIV /AIDSpatients serum albumin levels correlate with CD 4 counts andcan be used as a marker of immune suppression.

Kampo and Cancer Immunity in the Era of Immune Checkpoint Inhibitors / 日本東洋医学雑誌

Kampo medicine is well known to play an important role in cancer therapy, especially as a supportive therapy. We literally investigated the significance of Kampo medicine on antitumor effect including our data in the era that cancer immunotherapy using immune checkpoint inhibitors is a main stream. Up to now, many reports have been published regarding the mechanism of Kampo medicine on augmentation of immunity, particularly innate immunity. Regarding the effect of Kampo medicine on cancel of immune suppression by cancer, a few reports have been published including our data that juzentaihoto reduced regulatory T cell ratio in advanced pancreas cancer patients. Interestingly, a certain kind of Kampo medicine has possibility to induce immune tolerance in murine cardiac transplant model through increased regulatory T cells, and to suppress intestinal inflammation by anticancer drug by functioning immune checkpoint (PD-1). We hope that Kampo medicine would be proved to possibly regulate immune function from the viewpoint of immune checkpoint in the near future.

Polymeric Nanoparticles Containing Both Antigen and Vitamin D₃ Induce Antigen-Specific Immune Suppression

The active form of vitamin D3, 1,25-dihydroxyvitamin D₃ (aVD₃), is known to exert beneficial effects in the treatment of autoimmune diseases because of its immunosuppressive effects. However, clinical application of aVD₃ remains limited because of the potential side effects, particularly hypercalcemia. Encapsulation of aVD₃ within biodegradable nanoparticles (NPs) would enhance the delivery of aVD₃ to antigen presenting cells, while preventing the potential systemic side effects of aVD₃. In the present study, polymeric NPs containing ovalbumin (OVA) and aVD₃ (NP[OVA+aVD₃]) were prepared via the water-in-oil-in-water double emulsion solvent evaporation method, after which their immunomodulatory effects were examined. Bone marrow-derived immature dendritic cells (DCs) treated with NP(OVA+aVD₃) did not mature into immunogenic DCs but were converted into tolerogenic DCs, which express low levels of co-stimulatory molecules and MHC class II molecules, produce lower levels of pro-inflammatory cytokines while increasing the production of IL-10 and TGF-β, and induce the generation of Tregs. Intravenous injection with NP(OVA+aVD₃) markedly suppressed the generation of OVA-specific CTLs in mice. Furthermore, OVA-specific immune tolerance was induced in mice orally administered with NP(OVA+aVD₃). These results show that biodegradable NPs encapsulating both antigen and aVD₃ can effectively induce antigen-specific immune suppression.

Persistent inflammation, immune-suppression and catabolism syndrome secondary to sepsis in elderly patients in medical intensive care unit:a retrospective study / 中华老年医学杂志

Objective To investigate the clinical characteristics,risk factors and prognosis of patients with persistent inflammation,immune-suppression and catabolism syndrome(PICS)secondary to sepsis in medical intensive care unit(MICU)in initial stage,in order to increase the understanding of PICS and provide the reference experience for the early screening of high-risk patients.Methods A total of 298 elderly patients diagnosed as sepsis admitted into MICU from Aug.2013 to Dec.2016 were retrospectively studied.Of them,97 patients meeting inclusion criteria were ultimately enrolled and separated into the PICS group and the non-PICS group.General and clinical data and laboratory indexes at first day admitted into MICU were compared between the two groups.The indexes between the two groups were analyzed statistically by multivariate logistic regression analysis.The survival-time distributions were estimated by Kaplan-Meier model,and the difference in prognosis was compared between the two groups.Results Of 97 patients,36 patients (37.1％)met the diagnosis of PICS.The acute physiological function and chronic health evaluation Ⅱ (APACHE Ⅱ) score had a significant difference between the two groups(27.7±5.8 vs.22.9±6.0,P＜0.01).The grade of acute gastrointestinal injury(AGI)were significantly higher in the PICS group than in the non-PICS group(P ＜0.05).Platelet counts,helper T cell counts and CD4+/CD8+ ratios were significantly lower in the PICS group than in the non-PICS group[(164.39 ± 84.29) × 109/L vs.(235.16 ± 126.89) × 109/L,(238.97± 181.11)/μl vs.(385.93±308.22)/μl,(1.58 ± 1.13) vs.(2.12± 1.23),all P ＜0.05)].Multivariable logistic regression analysis revealed that APACHE Ⅱ score was an independent risk factor for PICS and its optimal cut-off value for predicting PICS was 26.5.Kaplan-Meier analysis showed that the overall survival was poorer in the PICS group than in non-PICS group in the whole observation phase.The further Kaplan-Meier analysis on survival time of subdivisions showed that the survival of patients at 90-day and 180-day after admission and in stage 1-3 during one year had significant differences between the two groups (P ＜ 0.05).While the survival of patients at 28-day after admission had no significant difference between the two groups(P＞0.05).Conclusions The elderly patients with persistent inflammation,immune-suppression,and catabolism syndrome(PICS) secondary to sepsis in medical intensive care unit(MICU)show the higher levels of APACHE Ⅱ score and AGI grade,and lower values of platelet counts,CD4+ T cell counts and CD4+/CD8+ ratio in initial stage.And APACHE Ⅱ score is an independent risk factor for PICS in elderly sepsis patients,and the optimal cut-off value of APACHE Ⅱ score for predicting PICS is 26.5.The prognosis for advanced stage and long term prognosis are poor.It is essential to use APACHE Ⅱ and so on,to timely identify and intervene PICS.

IL-12 reverses inhibitory effect of cisplatin on immune function of human NK cells and its mechanism / 中国肿瘤生物治疗杂志

@# Objective: To investigate the reverse effect and mechanism of IL-12 on chemotherapeutic medicine suppressing the immune function of NK cells. Methods: Purified NK cells were stimulated with PMAplus Ionomycin in the presence or absent of Cisplatin (DDP) and IL-12. The levels of IFN-γ and TNF-α in culture supernatants were detected by enzyme-linked immunosorbent assay (ELISA); The content of IFN-γ and TNF-α, TRAIL (TNF-related apoptosis inducing ligand) and transcription factors including T-bet and p-STAT-4 in NK cells were analyzed by Flow cytometry. The cytotoxicity of purified NK cells (pretreated with/without chemotherapeutics and IL-12 for 48 h) to Jurkat cells was measured by Flow cytometry. Results: Chemotherapeutics significantly inhibited the production of IFN-γ, TNF-α and the expression of TRAILin NK cells, which were significantly reversed by IL-12 (P<0.05 or P<0.01). Further study revealed that chemotherapeutics down-regulated while IL-12 reversed the expression of p-STAT4 to restore cytokine production. In addition, DDP also inhibited but IL-12 recovered the cytotoxicity of NK cells against tumor cells by inducing the expression of TRAIL (P<0.05 or P<0.01). Conclusion: Chemotherapeutics inhibited the cytotoxicity of NK cells and its secretion of cytokines (IFNγ and TNF-α), which were reversed by IL-12 via up-regulating TRAIL and p-STAT-4; this might provide experimental evidence for the clinical application of IL-12 for rebuild the immune function of tumor patients receiving chemotherapy.

Vacunación en adultos / Vaccination in adults

ResumenIntroducción:cada año, miles de adultos mueren por causa de enfermedades prevenibles mediante vacunación. Sin embargo, la aplicación de vacunas en adultos es muy baja a nivel mundial por múltiples razones, incluyendo los altos costos de implementación.Objetivos:discutir las recomendaciones nacionales e internacionales de inmunización de personas mayores de 18 años, incluyendo las poblaciones con alto riesgo de adquirir infecciones inmunoprevenibles y resumirlas en un esquema recomendado para vacunación de adultos en general, y personas con elevado nivel de riesgo.Métodos:se efectuó una revisión no sistemática de bibliografía médica y científica publicada entre 2000 y 2017, concerniente a vacunación en adultos. Así mismo, se compararon los esquemas de inmunización vigentes en América y Europa.Conclusiones:las recomendaciones para vacunación en adultos se basan principalmente en edad, condiciones médicas subyacentes, estilo de vida, inmunizaciones previas, características epidemiológicas locales y viajes. La necesidad de aplicar un esquema de vacunación adecuado a la población general y a poblaciones con factores de riesgo, representa una medida de gran importancia en un sistema de salud funcional. En este sentido, la adecuada asesoría e información provenientes del personal de salud constituyen un predictor clave en la inmunización de adultos.

AbstractIntroduction:Every year thousands of adults die from vaccine preventable disease worldwide. Nevertheless, the vaccine application rates maintain in relative low levels for multiple reason, including high costs of the implementation of vaccination programs.Objectives:Discuss national and international existing immunization schemes for adult persons, including high risk populations for the acquisition of immune preventable infections and resume this knowledge in vaccination schemes for adults in general and high risk populationMethods:A nonsystematic revision of medical and scientific literature related to adult vaccination topics from the years 2000 to 2017 was performed. As well, a comparison between actual vaccination schemes from American and European countries has been realized.Conclusion:Vaccination recommendations are based in multiple factors like age, individual medical history, lifestyle, formerly applied vaccinations, local epidemiologic criteria end traveling activity.The application of adequate vaccination scheme for both, adults in general and an adaptation for persons with elevated risk factors, represents a crucial element for effective health system. Therefore, the adequate assessing and information provided by medical personnel represents a key factor in successful vaccination and disease prevention.

Relationship between tumor metastasis with T cell subsets and cytokines in patients with primary hepatocellular carcinoma / 重庆医学

Objective To investigate the correlation between tumor metastasis with T cell subsets and cytokines in the pa tients with primary hepatocellular carcinoma (HCC).Methods Ninety-seven cases of primary HCC were prospectively collected from January 2014 to January 2016 and assigned into the metastasis group (38 cases) and non-metastasis group(59 cases) according to whether suffering from metastasis.Surgical specimens were obtained from all pauents and flow cytometry was used to detect the CD4+,CD8+ T cell proportion in HCC tissue,paracancerous tissues and peripheral blood.Moreover,ELISA was adopted to detect the peripheral blood IL-6,IL-10,TNF-α and IFN-γ levels.Results Compared with the non-metastasis group,the CD4+ T cell proportion of HCC tissue in the metastasis group was significantly increased(P=0.02),while the CD8+ T cells were significantly decreased (P=0.015).There was no statistical difference in CD4+ T cells proportion in the paracancerous tissue between the two groups (P=0.328).However the CD8+ T cells proportion of paracancerous tissue in the metastasis group was significantly higher than that in the non-metastasis group (P=0.021).There was no statistically significant difference in the proportion of CD8+ T cells in peripheral blood of the two groups (P=0.362).The proportion of CD4+ T cells in peripheral blood of the metastatic group was significantly lower than that in non-metastasis group (P=0.032).When compared with non-metastasis group,the metastasis group got a decreased level of peripheral blood IL-6 (P =0.012);while the IL-10 level was significantly increased (P =0.006);the TNF-α level and IFN-γ level were significantly decreased(P=0.000,P=0.035).Conclusion The patients with primary HCC have obvious T cell subsets and cytokines imbalance.

Progression of studies on virulence factors and pathogenesis of Bordetella pertussis / 中华实用儿科临床杂志

In 1906,it was confirmed that the pertussis was caused by Bordetella pertussis (BP).Virulence factors of BP had been studied widely for over a hundred years,however,the pertussis pathology remains largely unknown.The development of a baboon model will promote the study of the pathogenesis of BP infection and disease,and the understanding about the pathogenesis is helpful for the prevention and therapeutics of pertussis.

Effect of Inhibition of Uygur Fomes Officinalis Polysaccharides on Antioxidant Capacity and Exercise Immunity / 世界科学技术-中医药现代化

This study was aimed to investigate the effects of Fomes officinalis polysaccharides (FoP) on exercise-induced fatigue and exercise immune suppression in mice with FoP induced by exercise fatigue and unbalanced exercise immunity.Through treadmill exercise,the long-term exercise immune suppression model fatigue was established.Different doses of FoP were used in the animal experiment.The experimental animal were randomly divided into the positive control group,negative control group,low dose FoP (20 mg· kg-1) + exercise group,middle dose FoP (40 mg· kg-1) + exercise group,and the high dose FoP (80 mg· kg-1) + exercise group.The intragastric administration was given 6 days per week for 8 weeks.Treadmill exercise was administered during these 8 weeks.After 8 weeks,the samples were sacrificed.The levels of malondialdehyde (MDA),superoxide dismutase (SOD),hemoglobin (HB) and creatine kinase (CK) were detected by kit.And the relative expression of IL-4mRNA,INF-γmRNA was detected by RT-PCR.The results showed that compared with the positive control group,FoP can significantly improve the level of HB in mice,the level of serum CK in each FoP dose group was significantly decreased;compared with the positive control group,FoP group can significantly eliminate MDA with no significant difference among different FoP dose groups.The contents of SOD in serum of different dose FoP group and the negative control group were significantly higher than that of the positive control group.The IL-4 mRNA/INF-γ mRNA ratio of different dose FoP group were in basic equilibrium.It was concluded that Uygur FoP can effectively promote the body fatigue recovery,accelerate the clearance of free radicals,and improve the antioxidant ability and immune status.

Progress in pharmacological effects and clinical applications of berberine / 中国药理学与毒理学杂志

Berberine is an isoquinoline alkaloid isolated from Rhizoma Coptidis and Cortex Phellodendri,which has a long medical history in China.Recent studies have indicated that berberine has multiple pharmacological activities including anti-inflammatory,anti-microorganisms,anti-cancer,cardiac protection,glucose lowering,regulating lipid metabolism and immune suppression.Berberine has been used for the treatment of intestinal infectious diseases for many years.With the continuous progress of the research,it is reported that berberine has many new clinical applications,including treatment of the cardiovascular disease,metabolic syndrome and its complications,cancers,abdominal adhesions and chlamydia trachomatis infection.This review is intended to introduce the role of berberine in various aspects of pharmacological effects,molecular mechanisms and clinical applications.

Vacunación de pacientes adultos receptores de trasplante de células madre hematopoyéticas: Perspectiva de Costa Rica / Vaccination of adult patients receiving hematopoietic stem cell transplantation: Perspective of Costa Rica

In this article the present recommendations for immunization of adult patients who received hematopoietic stem cell transplantation -a common procedure in therapy of many types of hematological diseases and serious inborn defects of the immune system- are reviewed and discussed. Patients that undergo this kind of transplantation procedure exhibit, compared to the general population, an elevated susceptibility of immune-preventable infections, due to loss of the humoral and cellular protective immunity. A revaccination strategy for transplanted patients can result in a significant diminution of morbidity and mortality related to the treatment of these diseases. Few data are published about the duration and magnitude of the vaccination response in this specific population of patients. Moreover, deviation from international guidelines recommendations for post-transplant immune prophylaxis can be observed frequently, partly as a result of the absence of specific vaccines in some countries. Multiple factors as intensity of the pharmacologic immune suppression, myeloablative regimen, administration of monoclonal and polyclonal antibodies, duration of the post-transplant period or the presence of graft-versus-host disease (GVHD), can influence the immune response and establish special considerations for certain biological agents, as observed in case of living attenuated virus composed vaccines. This conditions are responsible for the fact that an optimal time point for vaccination of transplanted patients remains not clearly defined. More specific studies about the underlying immunological mechanisms during immunocompromised periods are necessary to understand better the immunogenicity and security of existing vaccines. The development of innovative vaccines as well can induce certain advances in the post-transplant therapy.

El presente artículo revisa las recomendaciones actuales para la inmunización de pacientes adultos que han recibido trasplante de células madre hematopoyéticas, procedimiento común en la terapia de muchas patologías hematológicas y defectos congénitos del sistema inmune. Los pacientes que reciben este tipo de tratamiento son más susceptibles a infecciones inmunoprevenibles que la población general debido a la pérdida de la inmunidad protectora tanto humoral como celular con posterioridad al trasplante. De esta manera, la revacunación de los receptores de trasplante representa una estrategia importante para reducir la morbilidad y mortalidad asociadas con esas enfermedades. Sin embargo, se conoce poco sobre la duración y magnitud de la respuesta inmunológica generada por las vacunas en esta población. Además, aunque existen guías internacionales consensuadas en inmunoprofilaxis post-trasplante, frecuentemente ocurren desviaciones en las prácticas recomendadas por múltiples motivos, incluyendo la no disponibilidad de ciertas vacunas en algunos sistemas de salud. Factores como la intensidad de la inmunosupresión farmacológica, el régimen mieloablativo empleado, la administración de anticuerpos monoclonales y policlonales, la duración de la fase neutropénica en el período posterior al trasplante y la presencia de enfermedad injerto versus hospedero (graft-versus-host disease, GVHD) pueden influenciar la respuesta inmunitaria y establecer consideraciones especiales para ciertos agentes como es el caso de las vacunas compuestas por virus vivos atenuados. Estas condiciones contribuyen a que el momento oportuno de inicio de las inmunizaciones en los receptores de trasplante aún no se encuentre bien definido. Se requieren más estudios específicos acerca de los mecanismos inmunológicos subyacentes durante los estados de inmunocompromiso para entender mejor la inmunogenicidad y seguridad de las vacunas existentes en dichos contextos. El desarrollo de vacunas innovadoras puede también inducir avances en la terapia post-trasplante.

Changed percentage of myeloid-derived suppressor cells in the peripheral blood of prostate cancer patients and its clinical implication / 中华男科学杂志

<p><b>Objective</b>To investigate the changes in the percentage of myeloid-derived suppressor cells (MDSCs) in the peripheral blood of prostate cancer (PCa) patients and explore the correlation of MDSCs and their subsets with the prognosis of PCa.</p><p><b>METHODS</b>Using flow cytometry, we determined the percentage of MDSCs and the levels of Arg-1, iNOS and PD-L1 in the peripheral blood of 32 PCa patients and 25 healthy controls, detected the distribution of CD14+ Mo-MDSC and CD15+ PMN-MDSC subsets, and analyzed the correlation between the obtained parameters and the prognosis of PCa.</p><p><b>RESULTS</b>Compared with the healthy controls, the PCa patients showed significant increases in the percentage of MDSCs (P<0.01) and levels of Arg-1, iNOS and PD-L1 in the peripheral blood. Statistically significant differences were observed in the distribution of the CD14+ Mo-MDSC and CD15+ PMN-MDSC subsets between the two groups（60.4% vs 72.2%, 29.5% vs 18.8%） (P<0.05). The percentages of MDSCs and Mo-MDSCs were remarkably correlated with the total survival rate of the PCa patients (P=0.025 and 0.017).</p><p><b>CONCLUSIONS</b>The percentages of MDSCs and CD14+ Mo-MDSCs in the peripheral blood were correlated with the prognosis of PCa, which may provide a target or some evidence for the clinical treatment of PCa.</p>

Metabolic analysis of immune suppression mice based on NMR / 中国药理学通报

Aim Toanalyzethecharacteristicsofser-um metabolites in immune suppression mice by using 1HNMR-basedmetabonomics.Methods Twentymale Kunming(KM)mice were randomly divided into two groups:normal group and cyclophosphamide (Cy ) model group.Cy model group was given Cy to induce immune suppression.NMR technology was used to find out the variability of serum metabolites by the method ofOPLS-DA.Results Comparedwithnormalgroup, Cy model group showed a significant decrease in the serum levels of glutamine,glycolprotein,unsaturated lipid,VLDL,LDL,acetone and showed a significant increase in the serum levels of leucine,alanine,tyro-sine, histidine, lactate, glycine, creatine, me-theionine,valine,β-hydrocxy butyrate and carnitine. Conclusions Immunesuppressionmiceareimbal-anced in metabolic network.These findings indicate that lipid metabolism-related metabolites are de-creased,however,β-oxidation of fatty acid,proteoly-sis and glycolysis level are increased.

Cell-mediated immune suppression effect of rocket kerosene through dermal exposure in mice / 解放军医学杂志

ObjectiveTo study the effect of cell-mediated immune suppression effect of rocket kerosene (RK) through dermal application in mice. MethodsSkin delayed type hypersensitivity (DTH) was used to observe the relation of the RK amount the skin exposed and the cellular immune inhibitory function. Different amount of the undiluted fuel was smeared directly onto the dorsal skin of mice. Mice in negative and positive control groups were treated with acetone. After the last exposure, all the mice except those in negative control group were allergized by evenly smearing with 1% dinitrofluorobenzene (DNFB) solution on their dorsum. Five days after allergy, 1% DNFB solution was smeared onto right ear of all mice to stimulate the allergic reaction. Twenty-four hours after attack, the auricle swelling, spleen index and thymus index in corresponding mice were determined. In the first series of experiments, different dosages of RK were applied once, and the ICR mice were randomly divided into negative control group, positive control group and experimental group (0.5ml/kg.BW×1, 1ml/kg.BW×1 and 2ml/kg.BW×1 group). In the second series of experiments, the certain and same dosage of RK was applied for different times, and the ICR mice were randomly divided into negative control group, positive control group and experimental group (0.5ml/kg.BW×1, 0.5mL/kg.BW×2, 0.5ml/kg.BW×3, 0.5ml/kg.BW×4 and 0.5mL/kg.BW×5 group). In the third series of experiments, the different dosages of RK were applied more than once, and the ICR mice were randomly divided into negative control group, positive control group and experimental group (0.5ml/kg.BW×5, 1ml/kg.BW×5 and 2ml/kg.BW×5 group). Lymphocyte proliferation experiment in vitro was conducted to observe the persistent time of the cell-mediated immune suppression in mice by RK dermal exposure. The lymphocyte proliferation induced by concanavalin A (Con A) was analyzed by MTT assay, and T lymphocyte subsets (CD3+, CD4+ and CD8+) in peripheral blood and spleen lymphocyte cell cycle were analyzed by flow cytometry. ResultsRK dermal exposure (1ml/kg.BW×1) alleviated the ear edema, suppressed the spleen index elevation and thymus index reduction caused by DNFB sensitization in ICR mice, and the suppression effect increased with exposed dosage and time increasing. RK dermal exposure (1ml/kg.BW×1) suppressed ConAinduced spleen lymphocyte proliferation, and the effect persisted for 20d (P+/CD8+ ratio in peripheral blood was lower in RK group than in negative control group (P<0.05). ConclusionDermal exposure of RK may have cell-mediated immunotoxicity.

Signal pathway defects of Toll-like receptors 2-p38 mitogen activated protein kinase signal pathway defects and immune suppression in children with measles / 中华实用儿科临床杂志

Objective To investigate the expression of Toll-like receptors 2 (TLR2) mRNA,p38 mitogen activated protein kinase(p38 MAPK) mRNA and cytokine in peripheral blood of children with measles and to study the effect and possible mechanism for TLR2-p38 MAPK signal pathway defects on immune suppression in the children with measles during acute phase.Methods Thirty children with measles hospitalized in the department of infectious diseases from June 2012 to July 2013 were enrolled into the measles group,and 30 healthy children were chosen as the healthy control group.The mRNA expressions of TLR and p38 MAPK in peripheral blood mononuclear cells (PBMC) were detected by reverse transcription-polymerase chain reaction (RT-PCR).The protein levels of interferon-γ (IFN-γ),tumor necrosis factor-β (TNF-β),interleukin (IL)-12,IL-6 and IL-10 in plasma were measured by using enzyme linked immunosorbent assay (ELISA),and flow cytometry (FCM)was applied to detect the percentage of lymphocyte subpopulation.The serum IgG,IgA and IgM levels were detected by velocity scatter turbidimetry.Results (1) The expressions of TLR2 mRNA and p38 MAPK mRNA in the measles group were both significantly lower than those in the healthy control group (all P ＜ 0.05).(2) Compared with the healthy control group,the protein levels of IFN-γ,TNF-β and IL-12 in the plasma of the measles group decreased significantly (all P ＜ 0.05),and the levels of IL-6 and IL-10 increased significantly(all P ＜ 0.05).(3)Compared with the healthy control group,the percentage of CD3 +,CD4 +,CD4 +/CD8 + ratio and the level of IgG and IgA in the measles group decreased significantly(all P ＜ 0.05),and the percentage of CD19 + increased significantly(P ＜ 0.05),but there was no any significant change in the percentage of CD8 + and the level of IgM (all P ＞ 0.05).Conclusions The mRNA expressions of TLR2 and p38 MAPK are low in PBMC in the measles children during acute phase.There are different degrees of suppression of cell immunity,humoral immune and cytokines disorder in children with measles.Defects of TLR2-p38 MAPK signal pathway may cause the formation of measles immune suppression.