Progress in Biomechanics and Mechanobiology of Dendritic Cells / 医用生物力学

Dendritic cells (DCs) are now known as the most powerful antigen-presenting cells in vivo, with efficient antigen uptaking, and processing capabilities. They can present antigens to naïve T cells in secondary lymphoid tissues, thereby induce immune response or tolerance, and play a key role in initiating and amplifying innate and adaptive immunity. DCs experience complex chemical and mechanical microenvironment changes and show different mechanophenotypes and immunophenotypes in the process of exerting their physiological functions. Deeply understanding the chemical and mechanical factors that regulate the mechanophenotypes and immunophenotypes of DCs is a prerequisite for using DCs to treat immune related diseases. In this review, the progress in the biomechanics and mechanobiology research of DCs was mainly introduced, and their potential applications and future development directions in the treatment of immune related diseases were explored.

First report of deep crypt secretory cells in ascending colon in chinchilla (Chinchilla lanigera): a histological and histochemical study / Primer reporte de células secretoras de criptas profundas en colon ascendente en chinchilla (Chinchilla lanigera): un estudio histológico e histoquímico

SUMMARY: The normal morphology of the colon differs among mammal species.The ascending colon presents several types of cells, responsible for carrying different functions for this organ. Among them, the mucus-secreting cells ensure the integrity of the mucosa, local defense, protection against different external factors, inflammatory diseases, cancer, etc. The ascending colon from 5 adult male chinchillas were processed for paraffin embedding and stained with three methods: Goldner's trichrome, PAS reaction, and Alcian blue staining procedure. The results showed that the structure of the ascending colon is similar to the one described in other species, i.e. mucosa, submucosa, muscularis externa, and serosa. Regarding the mucus-secreting cells present in the deeper part of the mucosal crypts (deep crypt secretory or DCS cells) turned out to be different not only morphologically from the surface goblet cells but also regarding the type of mucus synthesized. DCS cells have a multivacuolated, faintly stained cytoplasm with moderately PAS-positive reaction and intensely positive reaction to Alcian blue stain. The mean surface of DCS cells was 521.6 μm2 as compared to 437.9 μm2 for goblet cells (p<0.05). In conclusion, our study describes for the first time in chinchilla (Chinchilla lanigera) the presence of formerly known non-goblet or vacuolated cells, and recently entitled DCS cells in the glandular epithelium of the colon. The understanding of morphological peculiarities in chinchilla may serve as a good basis to understand the pathophysiology of various conditions that may arise.

RESUMEN: La morfología normal del colon es diferente entre las especies de mamíferos. El colon ascendente presenta varios tipos de células, encargadas de llevar varias funciones a este órgano. Entre ellos, las células secretoras aseguran la integridad de la mucosa, defensa local, protección frente a diferentes factores externos, enfermedades inflamatorias, cáncer, etc. Se procesaron para su inclusión en parafina el colon ascendente de 5 chinchillas machos adultos y se tiñeron con tres métodos: tricrómico de Goldner, reacción PAS y Azul de Alcian. Los resultados mostraron que la estructura de del colon ascendente es similar a la descrita en otras especies, es decir, mucosa, submucosa, muscular externa y serosa. Las células secretoras de la mucosa presente en la parte más profunda de las criptas mucosas (células secretoras de la cripta profunda o células DCS) resultaron ser diferentes morfológicamente de las células caliciformes superficiales, con citoplasma levemente teñido con reacción PAS positiva moderada y reacción intensamente positiva a Azul de Alcian. La superficie media de las células DCS fue de 521,6 μm2 en comparación con 437,9 μm2 de las células caliciformes (p <0,05). En conclusión, nuestro estudio describe por primera vez en chinchilla (Chinchilla lanigera) la presencia de células no caliciformes o vacuoladas anteriormente conocidas, y recientemente denominadas células DCS en el epitelio glandular del colon. La comprensión de las peculiaridades morfológicas de la chinchilla puede servir como una buena base para comprender la fisiopatología de las diversas afecciones.

Wuhutang Alleviates Respiratory Syncytial Virus-induced Asthma in Mice by Inhibiting STAT3 Protein and Regulating Dendritic Cell Autophagy / 中国实验方剂学杂志

Objective:To investigate the therapeutic mechanism of Wuhutang on respiratory syncytial virus （RSV）-induced asthma in mice and its influence on the expression of signal transducer and activator of transcription 3 （STAT3） in lung tissue. Method:One hundred female BALB/c mice of SPF grade were randomly divided into a normal group and an experimental group. After successful modeling via aerosol inhalation of RSV and ovalbumin （OAV）， the mice in the experimental group were further randomized into the following seven groups： model， positive control （dexamethasone， 1.82 mg·kg^-1）， STAT3 inhibitor （STATTIC， 3.75 mg·kg^-1）， STAT3 inducer （colivelin， 1.0 mg·kg^-1）， and low-， medium-， and high-dose （1.6， 3.2， and 6.4 g·kg^-1， respectively） Wuhutang groups. The corresponding drugs were administered for two weeks， followed by the detection of airway reactivity using a small animal ventilator， the pathological changes in lung tissue， mucus secretion by goblet cells and collagen deposition in airway were observed by hematoxylin-eosin （HE）， periodic acid-Schiff （PAS） and Masson staining， the serum levels of interleukin-6 （IL-6）， IL-10， and IL-17 were detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression levels of TGF-<italic>β</italic>₁ and <italic>α</italic>-SMA in lung tissue were detected by fluorescence-based real-time polymerase chain reaction （Real-time PCR）， autophagosomes present in lung tissue were examined by transmission electron microscopy， the protein expression levels of ATG5 and SQSTM1 in dendritic cells （DCs） and STAT3 and p-STAT3 in lung tissue were detected by Western blot. Result:The airway reactivity of the model group was enhanced in contrast to that in the model group （<italic>P<</italic>0.01）， manifested as inflammatory cell infiltration around the lung tissue， excessive metaplasia of goblet cells， and extensive deposition of airway collagen， the expression levels of serum IL-6 and IL-17 were increased （<italic>P<</italic>0.01）， while that of IL-10 declined （<italic>P<</italic>0.01）， the mRNA expression levels of TGF-<italic>β</italic>₁ and <italic>α</italic>-SMA were elevated （<italic>P</italic><0.01）， the number of autophagosomes in the lung tissue increased. The protein expression levels of ATG5， STAT3， and p-STAT were up-regulated， while that of SQSTM1 was down-regulated （<italic>P<</italic>0.01）. Compared with the model group， Wuhutang and STATTIC significantly reduced the airway hyperresponsiveness of asthmatic mice （<italic>P<</italic>0.05， <italic>P<</italic>0.01）， alleviated RSV-induced pathological changes in lung tissue， reduced the contents of serum IL-6 and IL-17 （<italic>P<</italic>0.01）， increased serum IL-10 and ATG5 in DCs （<italic>P<</italic>0.01）， down-regulated the mRNA expression levels of TGF-<italic>β</italic>₁ and <italic>α</italic>-SMA as well as the protein expression levels of SQSTM1， STAT3 and p-STAT3 （<italic>P<</italic>0.05，<italic>P<</italic>0.01）， and elevated the number of autophagosomes. Conclusion:Wuhutang relieves airway inflammation， improves airway remodeling and reduces airway hyperresponsiveness in RSV-induced asthmatic mice by inhibiting STAT3 protein and up-regulating DC autophagy in lung tissue.

Uptake and trafficking of different sized PLGA nanoparticles by dendritic cells in imiquimod-induced psoriasis-like mice model

Psoriasis is an autoimmune inflammatory disease, where dendritic cells (DCs) play an important role in its pathogenesis. In our previous work, we have demonstrated that topical delivery of curcumin-loaded poly (lactic-

The effects of agmatine on the apoptosis of immune cells in septic rats / 中华急诊医学杂志

Objective:By establishing the rats model of sepsis induced by endotoxin, exploring the effects of agmatine on the apoptosis of splenocyte and dendritic cells in the septic rats.Methods:SD rats ( healthy and clean, male, 90) were randomly(random number) divided into control groups, endotoxin groups and agmatine groups, 30 rats per group. The control groups were injected with normal saline via femoral vein (10 mL/kg), endotoxin groups were injected with lipopolysaccharide via femoral vein (10 mg/kg), agmatine groups were injected with lipopolysaccharide via femoral vein (10 mL/kg) and intraperitoneal injected of agmatine (200 mg/kg).The three groups were randomly selected 10 rats separately at 0 h, 12 h, 24 h (marked as 0 h, 12 h, 24 h subgroups, n=10) , anesthetized to death. Weigh the spleen; HE staining was used to observe the pathological changes of the spleen; The cell apoptosis of splenocyte and dendritic cells were detected by flow cytometry. The results were statistically analyzed using SPSS 17.0 software, analyzed by independent sample t test, P<0.05 was considered statistically significant. Results:The weights (g) of spleen in 12 h (1.2633±0.0652) , 24 h (1.5576±0.0711) subgroups of the endotoxin groups were increased significantly than the corresponding subgroups[(0.8876±0.0361),(0.9079±0.0425)]of the control groups ( P<0.05) , the 12 h (1.1052±0.0585) , 24 h (1.3262±0.0682) subgroups of the agmatine groups were decreased significantly than the corresponding subgroups of the endotoxin groups ( P<0.05) . HE staining showed that the spleen tissue inflammatory reaction in the endotoxin groups were worse than the control group ( P<0.05) , the agmatine groups were better than the endotoxin group ( P<0.05) . The apoptosis rates of the splenocyte[(13.31±1.26)、(19.53±1.68)]and dendritic cells[(19.5±1.52)、(16.09±1.15)]in the spleen from 12 h, 24 h subgroups of the endotoxin groups were significantly higher than the corresponding subgroups[(6.27±0.71),(6.01±0.67) and (4.99±0.51)、(5.30±0.66)]of the control groups ( P<0.05) , the 12 h[(9.19±0.95),(12.19±1.25)], 24 h [(12.71±1.19),(10.76±1.09)subgroups of the agmatine groups were significantly lower than the corresponding subgroups of the endotoxin groups ( P<0.05) ; The apoptosis rates of the splenocyte in the 24 h subgroups of the endotoxin groups and the agmatine groups were significantly higher than the 12 h subgroups of the same group ( P<0.05) , but the apoptosis rates of the dendritic cells were significantly lower than the 12h subgroups of the same group ( P<0.05) . Conclusion:The apoptosis of splenocyte and dendritic cells were closely related to the occurrence and development of sepsis, Agmatine could inhibit the apoptosis of splenocyte and dendritic cells the rats with sepsis.

LMP2-DC Vaccine Elicits Specific EBV-LMP2 Response to Effectively Improve Immunotherapy in Patients with Nasopharyngeal Cancer / 生物医学与环境科学（英文）

Objective@#To evaluate the safety and effectiveness of a vaccine based on latent membrane protein 2 (LMP2) modified dendritic cells (DCs) that boosts specific responses of cytotoxic T lymphocytes (CTLs) to LMP2 before and after intradermal injection in patients with nasopharyngeal carcinoma (NPC).@*Methods@#DCs were derived from peripheral blood monocytes of patients with NPC. We prepared LMP2-DCs infected by recombinant adenovirus vector expressing LMP2 (rAd-LMP2). NPC patients were immunized with 2 × 10 @*Results@#We demonstrated that DCs derived from monocytes displayed typical DC morphologies; the expression of LMP2 in the LMP2-DCs vaccine was confirmed by immunocytochemical assay. Twenty-nine patients with NPC were enrolled in this clinical trial. The LMP2-DCs vaccine was well tolerated in all of the patients. Boosted responses to LMP2 peptide sub-pools were observed in 18 of the 29 patients with NPC. The follow-up data of 29 immunized patients from April, 2010 to April 2015 indicated a five-year survival rate of 94.4% in responders and 45.5% in non-responders.@*Conclusion@#In this pilot study, we demonstrated that the LMP2-DCs vaccine is safe and effective in patients with NPC. Specific CTLs responses to LMP2 play a certain role in controlling and preventing the recurrence and metastasis of NPC, which warrants further clinical testing.

Salidroside regulates DC through TLR4 to increase the lethality of T cells to lung cancer 3LLcells / 中国肿瘤生物治疗杂志

@#Objective： ：To investigatetheeffectofsalidroside(SAL)onthephenotype of dendritic cells (DCs) and the antitumor ability of cytotoxic T lymphocytes (CTL). Methods： ：Lewis lung cancer cell line 3LL, wild type (WT) C57BL/6 mice and TLR4-/- C57BL/6 mice were chosen for this study. Mice bone marrow derived DC precursor cells were obtained to differentiate into immature DCs, which were harvested on the sixth day of culture. CD11c+ DCs were obtained by magnetic beads screening, and further divided into PBS group, SAL group and lipopolysaccharide (LPS) group.After being cultured for 48 h, the effects of SAL on surface molecules and phagocytosis of DCs as well as the efffect of TLR4 pathway on the killing effect of T cells were detected by Fow cytometry. Results： ： Compared with PBS group, expressions of DC surface molecules CD80, CD86 and MHC Ⅱ significantly increased (all P<0.05), phagocytosis significantly decreased (P<0.05), and TLR4 expression level significantly increased (P<0.01) in SAL group; Compared with WT group, after being treated with SAL or LPS, the expressions of DC surface molecules CD80, CD86 and MHC Ⅱ decreased significantly in TLR4-/- group (all P<0.05); ComparedwithPBSgroup,theactivatedCTLinSALgroupexhibited a significantly elevated killing effect against lung cancer 3LLcells (P<0.05). Conclusion：SAL can induce DC maturation by regulating TLR4, thus improving the killing ability of T cells.

DC-SIGN molecules promote EV71 infection in dendritic cells in vitro / 临床检验杂志

Objective@#To investigate the influence of dendritic cell specific intercellular adhesion molecule-3 grabbing non integrin (DC-SIGN) expression on the infection of enterovirus type 71 (EV71) for dendritic cells (DCs) and 293T cells. @*Methods@#Peripheral blood mononuclear cells (PBMCs) were isolated from human peripheral blood by gradient density centrifugation and induced to DCs. The DC-SIGN gene was amplified by polymerase chain reaction (PCR) for construction of transient expression vector pLB-DC-SIGN which was then transfected into 293T cells using Lipofectamine TM 2000. After 293T cell and 293T-pLB-DC-SIGN was infected with EV71, EV71 mRNA was identified by fluorescence quantitative PCR. EV71/VP1 was identified by western blot. After the expression of DC-SIGN on DCs was blocked by yeast mannan, EV71 mRNA was identified by fluorescence quantitative PCR and EV71/VP1 was identified by western blot. @*Results@#EV71 viral load and EV71/VP1 expression level in 293T cells overexpressed DC-SIGN was significantly higher than that of control 293T, while the viral load and EV71/VP1 expression level in DCs blocked with DC-SIGN inhibitor was lower than that of control DCs (P＜0.05). @*Conclusion@#DC-SIGN may be one of the receptors of EV71 who promote EV71 infection in DCs and 293T cells in vitro.

The Farsi translation, reliability and validity of the Death Concern Scale / Tradução, confiabilidade e validade da Death Concern Death para a língua persa

Abstract Introduction: Death concern is a conscious contemplation of the reality of death combined with a negative evaluation of that reality. The Death Concern Scale (DCS) is related to thinking, and death fear or anxiety about death. The aim of the present study was to develop a Farsi version of the DCS and to explore its psychometric properties in a sample of Iranian nurses. Methods: A cross-sectional study was conducted to investigate the reliability, validity, and factorial structure of the Farsi version of the DCS in a convenience sample of 106 Iranian nurses in two hospitals in Tehran, Iran. The nurses completed the DCS, the Collett-Lester Fear of Death Scale (CLFDS), the Death Anxiety Scale (DAS), the Reasons for Death Fear Scale (RDFS), the Death Depression Scale (DDS), and the Death Obsession Scale (DOS). Results: For the DCS, Cronbach's α was 0.77, the Spearman-Brown coefficient 0.63, the Guttman split-half coefficient 0.62, and two-week test-retest reliability 0.77. The DCS correlated at 0.51 with the CLFDS, 0.52 with the DAS, 0.34 with the RDFS, 0.40 with the DDS, and 0.48 with the DOS, indicating good construct and criterion-related validity. The results of an exploratory factor analysis for the DCS identified seven factors, accounting for 64.30% of the variance and indicating considerable heterogeneity in the content of the items. Conclusions: The Farsi version of the DCS has good validity and reliability, and it can be used in clinical, educational, and research settings to assess death concerns in the Iranian society.

Resumo Introdução: A preocupação com a morte é uma contemplação consciente da realidade da morte combinada com uma avaliação negativa dessa realidade. A Death Concern Scale (DCS) aborda o pensamento, o medo da morte ou a ansiedade em relação à morte. O objetivo deste estudo foi desenvolver uma versão da DCS na língua persa e explorar suas propriedades psicométricas em uma amostra de enfermeiros iranianos. Métodos: Um estudo transversal foi conduzido para investigar a confiabilidade, validade e estrutura fatorial da versão persa da DCS em uma amostra de conveniência de 106 enfermeiros iranianos em dois hospitais de Teerã, no Irã. Os enfermeiros completaram os seguintes instrumentos: DCS, Collett-Lester Fear of Death Scale (CLFDS), Death Anxiety Scale (DAS), Reasons for Death Fear Scale (RDFS), Death Depression Scale (DDS) e Death Obsession Scale (DOS). Resultados: Para a DCS, o α de Cronbach foi 0,77, o coeficiente de Spearman-Brown 0,63, o coeficiente split-half de Guttman 0,62 e a confiabilidade teste-reteste de duas semanas 0,77. A DCS apresentou correlação de 0,51 com CLFDS, 0,52 com DAS, 0,34 com RDFS, 0,40 com DDS e 0,48 com a DOS, indicando a qualidade do construto e a validade dos critérios relacionados. Os resultados de uma análise fatorial exploratória para a DCS identificaram sete fatores, respondendo por 64,30% da variância e indicando uma heterogeneidade considerável no conteúdo dos itens. Conclusões: A versão persa da DCS tem boa validade e confiabilidade e pode ser usada em contextos clínicos, educacionais e de pesquisa para avaliar preocupação com a morte na sociedade iraniana.

In vitro method for skin sensitization based on dendritic cell activation / 中国比较医学杂志

Allergy contact dermatitis is a type IV delayed type hypersensitivity that is induced by exogenous compounds and involves many cell types. Traditional animal testing uses guinea pigs or mice as a model. With progress of the adverse outcome pathway(AOP)on skin sensitization, a concept for development of alternative methods based on a molecular initiating event and key events is provided. Dendritic cell(DC)activation plays a key role in the AOP. Many alternative methods have been developed,with several methods validated and accepted as guidance for assays. This paper examines DC screening, characteristics of test parameters, and limitations and applicability of DC-derived methods. Progress on interactions between DCs and other cells, co-culture systems, and the human body-on-a-chip will also be introduced. Altogether,this paper will provide information for optimization of in vitro alternative methods for sensitization detection.

CD11c+DCs promote the occurrence and development of psoriasis-like morbidity in K14-VEGF transgenic mice / 基础医学与临床

Objective To investigate the auxoaction and mechanism of CDllc+DCs on psoriasis. Methods CDllc+ DCs in the psoriasis-like lesions were confirmed by immunofluorescence double staining experiments. The CD1lc+ DCs were subcutaneously injected into the neck skin of transgenic mice without disease. The clinical features were observed and assessed with PASI score every day. The ear and back skin were checked by HE stained. At the same time, the T lymphocyte and DCs of bone marrow, spleen, submandibular lymph nodes and blood were analyzed by flow cytometry, and the T lymphocyte in the skin lesions were analyzed by immunofluorescence. The heart, liver, spleen, lungs and kindey were HE stained. Results In the psoriasis-like lesions, about 90％ CDllc+ cells expressed CDllc. HE test showed that the thickness of the skin layer was significant different between the experimental group (ear: 29±4 μm; back: 25±3 μm) and the control group(ear: 11±2 μm; back: 9±1 μm) (P＜0.01). CD3 + CD4+ T lymphocyte cells in the blood of the experimental mice (17.87％) were decreased significantly (P＜0.01) compared with the control group mice (31.77％). The numbers of Thl and Th17 cells from bone marrow, spleen, submaxillary lymph nodes and blood, as the same as CD1lc+DCs from bone marrow and submaxillary lymph nodes, were decreased in the experimental mice compared with the control group mice (P＜0.01). The number of CD4﹢T cells, CD8+T cells, IL-17a+cells and IFN-γ+cells in the skin lesions from the experimental group all were higher than that from the control group (P＜0.01). And the vessels in the lesions of the experimental group were higher than that in the control group (P＜0.01). Conclusions CD1 lc+CD1 lc+DCs may play an important role in the occurrence and development of psoriasis by increasing the T lymphocyte and the blood vessel in the skins of K14-VEGF transgenic mice.

Effects of crude antigen and excretory-secretory products of Clonorchis sinensis on T cells / 中国人兽共患病学报

We investigated the roles of the crude antigen(CA) of Clonorchis sinensis and excretory secretory products (ESPs) in the polarization of Th1 and Th2 cells.Bone marrow-derived cells were generated from BALB/c mice and isolated into immature DCs;immature DCs were then treated with either CA (CA stimulated group),ESPs (ESPs stimulated group),LPS (positive control group) or PBS (negative control group) for 24 hours.Then the CD4+T cells were isolated from mouse spleen by using anti mouse-CD4 Microbeads,and further cocultured with stimulated DCs for another 72 hours.The purities of DCs and CD4+ T cells were evaluated by flow cytometry and the expressing levels of T-bet mRNA and GATA-3 mRNA were detected by real-time PCR.ELISA was used to detect the levels of IFN-γ and IL-4 cytokines in the supernatant.mRNA levels of T-bet and GATA-3 in the ESPs group were higher than those in PBS-stimulated group (P＜0.05).The concentrations of IFN-γ and IL-4 cytokines in the culture were increased in the ESPs group,compared with PBS stimulated group(P＜0.05).IFN-γ but not IL-4 was increased in CA group (P＜0.05).The results implied that CA might play a role in Th1 type immune response,and ESPs likely play roles in both Th1 and Th2 immune responses.

Near-infrared diffuse correlation spectroscopy for early diagnosis of chronic periodontitis / 实用口腔医学杂志

Objective:To study the feasibility of the early diagnosis of chronic periodontitis using near-infrared diffuse correlation spectroscopy(DCS).Methods:30 subjects were inclded.The relative gingival blood flow(GBF) at the labial,mesial and distal healthy gingiva(the control) or the gingiva with periodontitis of maxillary anterior teeth was respectively measured by DCS before periodontal treatment,a week and a month after treatment.Results:The GBF of healthy gingiva group,gingivitis group and periodontitis group was 129.73 ± 10.70,95.51 ± 11.83 and 67.84 ± 13.05 respectively.Periodontal indexes were decreased and the relative GBF increased significantly 1 week and 1 month after treatment.Gingival index and sulcus bleeding index were respectively correlated to relative GBF(r =-0.902,r =-0.893).Conclusion:Near-infrared diffuse correlation spectroscopy can non-invasively detect the relative gingival blood flow in different stages of chronic periodontitis,it may be a method of early diagnosis of chronic periodontitis.

Clinical significance of VEGF expression in colon cancer tissue and dendritic cells in colon carcinoma and correlation analysis of serum VEGF and DCs activa-tion / 中国免疫学杂志

Objective:To investigate the clinic significance of vascular endothelial cell growth factor ( VEGF) expression and dendritic cells ( DCs ) infiltration in colon cancer tissues , and to analysis the correlation between the sera VEGF with DCs activation.Methods:The expressions of VEGF and S-100 protein in colon carcinoma tissue and pericarcinous tissue were determined by immumohistochemistry.The serum VEGF level of colon carcinoma patients in preoperation and healthy subjects was detected using ELISA.Peripheral blood monocytes were isolated in preoperative patients and healthy subjects and induced to DCs by TNF -αin vitro.The surface expression of CD 83 in DCs was assayed with flow cytometry.Results: Expression of VEGF protein positive in colon carcinoma tissue was significantly higher than the pericarcinous tissue (P<0.01),while S-100 positive expression of colon carcinoma tissue was significantly lower than the pericarcinous tissue ( P<0.01 ).The serum VEGF level in colon carcinoma patients was significantly higher than healthy subjects ( P<0.01 ) ,while the CD83 level in peripheral blood DCs was significantly lower than healthy subjects ( P<0.01 ).The expression of VEGF and S-100 protein in colon carcinoma tissue was correlated with tumor differentiation , stage and lymph node metastasis ( P<0.01 ).The expression of VEGF was inversely correlated with S-100 ( P<0.01 ) in colon carcinoma tissue , while positively correlated with the serum VEGF ( P<0.01 ) and inversely correlated with DCs activation.The infiltration degree of DCs was inversely correlated with serum VEGF , and positively correlated with the DCs activation.Conclusion:VEGF expression in colon carcinoma tissue and DCs infiltration co-participate in the progress of colon cancer ,and VEGF could inhibit the infiltration and activation of DCs.

Diagnostic significance of dendritic cells for chronic obstructive pulmonary dis-ease / 中国免疫学杂志

Objective:To detect the levels of dendritic cells(DCs)in peripheral blood of patients with acute exacerbations of chronic obstructive pulmonary disease(AECOPD)and explore the relationship between the content of DCs with AECOPD.Methods:The levels of DCs subsets( mDCs and pDCs) in peripheral blood with thirty-four cases of AECOPD and fifteen cases of healthy persons were measured by flow cytometry with four-color fluorescent analysis;and the pulmonary function tests in every subjects were evaluated by spirometry.Results:Compared with the control group,the levels of mDCs and pDCs inAE COPD groups with GOLDⅠ,GOLDⅡ, GOLDⅢand ClassⅣwere significantly higher( P<0.05) ,and with the severity of lung function in AECOPD patients,the levels were also increased( P<0.05).Conclusion:The levels of mDCs and pDCs inAE COPD patients were higher and significantly correlated with the severity of the disease,suggesting that DCs may be involved in the inflammation reaction process of COPD.

Effects of miR-30 a on cell cycle and dendritic cell-suppressive function of MSCs / 中国免疫学杂志

Objective:Mesenchymal stem cells( MSCs) have self-renewal capacity and potential to differentiate into the cells.It was reported that the expression of miR-30a changed in some immune diseases.But it remains unclear the effect of miR-30a on the im-munoregulatory functions of MSCs.Here we studied the impact of miR-30a on the phenotype,cell viability,apoptosis,cell cycle and im-munoregulatory functions of MSCs.Methods: The mixed enzyme methods were used for the isolation of human umbilical cord MSCs.Flow cytometry(FCM)was used to investigate the effect of overexpressed miR-30a on the phenotype of MSCs.CCK-8 was used to examine the cell viability of miR-30a-overexpressed MSCs.Annexin V/PI was used for the detection of apoptosis of MSCs.Q-PCR and Western blot were used to investigate the effect of miR-30a on the expression of Cyclin E2( CCNE2).CCNE2 was one putative target of miR-30a predicted by Targetscan database.The effects of miR-30a-overexpressed MSCs on the maturation of dendritic cells(DCs)were determined.Results:Overexpression of miR-30a blocked the cell cycle of MSCs in the G0/G1 phase by inhibiting the expression of CCNE2,but did not affect the phenotype, cell viability and apoptosis of MSCs.When co-cultured with DCs, although MSCs down-regulated the expression of CD40 and CD86 on DCs,overexpression of miR-30a more significantly enhanced the suppressive impact of MSCs on the maturation of DCs.Conclusion: miR-30a affects the cell cycle of MSCs and enhances its immunosuppressive effect on DCs.

Circulating Dendritic Cells with their Dual Function are the Link Connecting Lymphatic Tissue and Brain.

Aims: The objective of the paper is to reveal the sources in which the data about the main characteristics of the DCs have been shown and prove the theses of the “Theory of Duality of Protective Systems” (TDPS) formulated earlier. Study Design: To compare the own DCs data with later DCs data of other authors. Place and Duration of Study: Department of Human Anatomy of Novosibirsk State Medical University and Scientific Research Institute of Clinical and Experimental Lymphology, Novosibirsk, between December 1986 and November 1998. Methodology: DCs were obtained from central lymph of thoracic duct (cistern chyle), intestinal and liver lymph, bone morrow, thymus, spleen, mesenteric lymph, adrenal, palatine tonsils and CNS/brain of general anesthetized rabbits and rats. The cistern chyle, liver and mesenteric lymphatic vessels were punctured with original glass micropipettes. Scrapes specimens from the organs (as smears) were studied by light and electronic microscopes. Percentage of DCs was calculated. Results: The DCs migrate from different organs of lymphatic/immune systems, periphery blood, skin, mucous membranes and brain to lymphatic drainage, then into blood via thoracic duct. The data induced the author to formulate the TDPS. The theses of TDPS are: 1. Lymphatic and immune systems guard an organism against any antigen and at the same time defend antigen structures of the organism, the brain. 2. These functions and the relation of the systems with brain are realized by DCs. DCs of lymph nodes, thymus, spleen, adrenal, red marrow, palatine tonsils, skin and brain are the same as DCs of peripheral and central lymph. The DCs migrate from different organs of the systems, periphery blood, skin, mucous membranes and brain to lymphatic drainage, then to blood. Thus, they circulate. 3. The DCs of central lymph are a special system, which plays an important role in regulation of homeostasis. Conclusion: The TDPS formulated in 1998 is proved by modern research.

Recent advances in the anti-HCV mechanisms of interferon

Interferon (IFN) in combination with ribavirin has been the standard of care (SOC) for chronic hepatitis C for the past few decades. Although the current SOC lacks the desired efficacy, and 4 new direct-acting antiviral agents have been recently approved, interferons are still likely to remain the cornerstone of therapy for some time. Moreover, as an important cytokine system of innate immunity, host interferon signaling provides a powerful antiviral response. Nevertheless, the mechanisms by which HCV infection controls interferon production, and how interferons, in turn, trigger anti-HCV activities as well as control the outcome of HCV infection remain to be clarified. In this report, we review current progress in understanding the mechanisms of IFN against HCV, and also summarize the knowledge of induction of interferon signaling by HCV infection.

Gene cloning and sequence analysis of diketide CoA synthase in Amomum villosum / 中草药

Objective: To clone the full length cDNA encoding diketide CoA synthase (DCS) gene which plays an important role in curcumin biosynthesis pathway in Amomum villosum, and to provide the basis for the further studies on biosynthesis and gene regulation of curcumin. Methods: According to the annotation of root transcriptome of A. villosum, primers were designed and cDNA of DCS gene was cloned from A. villosum by PCR. Results: The complete coding sequence of DCS gene was 1 170 bp and it encoded a protein of 389 amino acids. The deduced DCS amino acid sequence exhibited 96% identity to the DCS of Curcumae Longae and 66%-69% identity to the chalcone synthase (CHS) of Narcissus tazetta. Phylogenetic analysis on the amino acid sequence of DCS with those of other plants showed that DCS was closely related to Curcumae Longae. Conclusion: The DCS gene is cloned from A. villosum for the first time. This research lays a foundation for studying the gene expression pattern and regulatory functions of DCS in curcumin biosynthesis.

Effect of Kidney-tonification, Spleen-invigoration and Detoxification Methods on T lymphocytes Mediated by Peripheral Blood DCs in Chronic HBV Infection Patients / 世界科学技术-中医药现代化

This study was aimed to compare the effect of traditional Chinese medicine ( TCM ) treatment method of kidney-tonification, spleen-invigoration and detoxification on T lymphocytes of patients with chronic HBV infec-tion, which were mediated by peripheral blood dendritic cells (DCs). Ten patients with chronic HBV infection and eight healthy controls were included in this study. DCs were differentiated from PBMCs which were isolated from their peripheral blood, incubated and induced. Then, the DCs were interfered by plasma of medicine through the treatment methods of kidney-tonification, spleen-invigoration and detoxification. Models of interaction were estab-lished. Expressions of CD3+, CD4+, CD8+, CD8+CD28+, CD8+PD-1 of DCs and T cells were detected by FACS; and the levels of IFN-γ in supernatants were detected by ELISA. The results showed that the kidney-tonification plasma, spleen-invigoration plasma, detoxification plasma deal with HBcAg in load DCs incubated T lymphocytes. The CD3+ and CD4+ expression rate were increased; the CD8+ and CD8+PD-1 expression were reduced; IFN-γ level was increased; but only the Liuweidihuang Tang group was with significant difference compared to the model group (P < 0.05); the CD8+CD28+ expression rate was increased in the Sijunzi Tang and Liuweidihuang Tang group compared to the model group ( P < 0 . 05 ) . It was concluded that to a certain extent , the treatment method of kidney-tonification, spleen-invigoration and detoxification can restore the function of peripheral blood DCs in chronic HBV infection patients in order to restore its downstream T lymphocyte function. Among these treatment methods, the optimal method is kidney-tonification.