Effects of Intercellular Adhesion of Tumor on Immune Escape / 医用生物力学

Objective To study the effect of intercellular adhesion of tumor cells on immune response of human body. Methods A tumor growth-cellular immune feedback model was developed based on cellular Potts model (CPM) to simulate the progression of tumor cells and the cellular immune feedback system, and the influence of adhesion between tumor cells on the immune system was analyzed. Results Under the condition of tumor intercellular adhesion with normal intensity, tumor cells could escape when the immune system was weak and be eliminated when the immune system was strong. Under the condition of tumor intercellular adhesion with low intensity, tumor cells could escape when the immune system was weak, while exhibited behavior of oscillation and could not be eliminated when the immune system was strong. Conclusions Higher adhesion between tumor cells inhibited escape of tumor cells from the immune system, while lower adhesion between tumor cells could effectively help the tumor escape killing from the immune system. When the tumor was extremely spread, the immune system could not completely eliminate tumor cells.

The role of lectin-like Ox-LDL receptor-1 on endothelial cell injury caused by human cytomegalovirus infection / 中华实验和临床病毒学杂志

Objective@#To investigate the role of lectin-like Ox-LDL receptor-1( LOX-1) in the activation and oxidative stress of cultured human umbilical vein endothelial cell(HUVEC) after human cytomegalovirus(HCMV) infection.@*Methods@#HUVEC were divided into four groups: HCMV, Control, Carrageenan, and HCMV+ Carrageenan. After HCMV AD169 infection, the supernatant of the culture was extracted, and cells were lysed. The levels of LOX-1 mRNA, intercellular adhesion molecule-1(ICAM-1) mRNA and vascular cellular adhesion molecule-1(VCAM-1) in HUVEC were measured by real-time PCR. And the content of nitrogen monoxidum(NO) of the supernatant was detected by nitrate reductase method accordingly.@*Results@#24 h after infection, the mRNA expression of LOX-1, ICAM-1 and VCAM-1 in HUVEC of HCMV infected group increased obviously compared to control, and NO quantity increased accordingly. The mRNA expression of LOX-1, ICAM-1 and VCAM-1 and the quantity of NO decreased after adding the LOX-1 inhibitor carrageenan. There was significant difference between groups(P<0.05).@*Conclusions@#HCMV may increase the mRNA expression of ICAM-1 and VCAM-1 and quantity of NO by upregulating the mRNA expresion of LOX-1, which may contribute to the formation of a therosclerosis(AS).

Biomimetic nanoparticles for inflammation targeting

There have been many recent exciting developments in biomimetic nanoparticles for biomedical applications. Inflammation, a protective response involving immune cells, blood vessels, and molecular mediators directed against harmful stimuli, is closely associated with many human diseases. As a result, biomimetic nanoparticles mimicking immune cells can help achieve molecular imaging and precise drug delivery to these inflammatory sites. This review is focused on inflammation-targeting biomimetic nanoparticles and will provide an in-depth look at the design of these nanoparticles to maximize their benefits for disease diagnosis and treatment.

Priming stem cells with protein kinase C activator enhances early stem cell-chondrocyte interaction by increasing adhesion molecules

BACKGROUND: Osteoarthritis (OA) can be defined as degradation of articular cartilage of the joint, and is the most common degenerative disease. To regenerate the damaged cartilage, different experimental approaches including stem cell therapy have been tried. One of the major limitations of stem cell therapy is the poor post-transplantation survival of the stem cells. Anoikis, where insufficient matrix support and adhesion to extracellular matrix causes apoptotic cell death, is one of the main causes of the low post-transplantation survival rate of stem cells. Therefore, enhancing the initial interaction of the transplanted stem cells with chondrocytes could improve the therapeutic efficacy of stem cell therapy for OA. Previously, protein kinase C activator phorbol 12-myristate 13-acetate (PMA)- induced increase of mesenchymal stem cell adhesion via activation of focal adhesion kinase (FAK) has been reported. In the present study, we examine the effect PMA on the adipose-derived stem cells (ADSCs) adhesion and spreading to culture substrates, and further on the initial interaction between ADSC and chondrocytes. RESULTS: PMA treatment increased the initial adhesion of ADSC to culture substrate and cellular spreading with increased expression of adhesion molecules, such as FAK, vinculin, talin, and paxillin, at both RNA and protein level. Priming of ADSC with PMA increased the number of ADSCs attached to confluent layer of cultured chondrocytes compared to that of untreated ADSCs at early time point (4 h after seeding). CONCLUSION: Taken together, the results of this study suggest that priming ADSCs with PMA can increase the initial interaction with chondrocytes, and this proof of concept can be used to develop a non-invasive therapeutic approach for treating OA. It may also accelerate the regeneration process so that it can relieve the accompanied pain faster in OA patients. Further in vivo studies examining the therapeutic effect of PMA pretreatment of ADSCs for articular cartilage damage are required.

Role of HCMV infection in the activation and oxidative stress of cultured human umbilical vein endothelial cells / 中华实验和临床病毒学杂志

Objective@#To investigate the role of the activation and oxidative stress of cultured human umbilical vein endothelial cells (HUVEC) after HCMV infection.@*Methods@#HUVECs were divided into four groups: control, HCMV(+ ), after HCMV AD169 infection, and the supernatant of the culture was extracted, and the cells were lysed. The levels of vascular cellular adhesion molecule-1 (VCAM-1) in HUVEC were measured by real-time PCR. And the content of nitrogen monoxide (NO) of the supernatant was detected by nitrate reductasemethod accordingly.@*Results@#Twenty-four hours after infection, the mRNA expression of VCAM-1 in HUVECs of HCMV infected group increased obviously compared to control, and NO quantity increased accordingly and time-dependently. There was significant difference between groups(P<0.01).@*Conclusions@#HCMV increases the mRNA expression of VCAM-1 and quantity of NO, which may contribute to the formation of AS.

Transición epitelial-mesenquimal en la progresión del adenocarcinoma prostático / Epithelial-mesenquimal transition in the progression of prostatic adenocarcinoma / Transição epitélial-mesenquimal na progressão adenocarcinoma da próstata

Mundialmente, el adenocarcinoma prostático es el segundo cáncer diagnosticado en hombres y las metástasis son su principal complicación; se ha descrito la participación en su desarrollo de la transición epitelial-mesenquimal (TEM) proceso fundamental durante el desarrollo embrionario, la remodelación tisular y la cicatrización, que implica pérdida de las propiedades adhesivas y la polaridad epitelial y adquisición del fenotipo mesenquimal que aumenta la movilidad celular individual y permite el desarrollo de características invasivas. Este cambio en el comportamiento celular es mediado por una regulación molecular compleja en la que participa un gran número de vías de señalización, algunas actuando en forma independiente y otras interconectadas; la mayoría converge en el control de la expresión de la E-cadherina, cuya subregulación es el evento molecular clave en este proceso. Diversos estudios señalan una relación estrecha entre la TEM y el desarrollo y progresión de metástasis en carcinomas, pero ha sido menos ampliamente estudiada en el adenocarcinoma prostático. Los objetivos de esta revisión fueron: describir las bases moleculares y morfológicas de este proceso biológico y analizar la influencia de sus reguladores en la adquisición del fenotipo agresivo por las células tumorales, específicamente en lo que tiene que ver con la progresión del adenocarcinoma prostático.

Worldwide, prostate adenocarcinoma is the second most frequently diagnosed cancer in men, and metastases are its most serious complication. The participation in its development of the epithelial-mesenchymal transition (EMT) has been described, a fundamental process during embryonic development, tissue remodeling and wound healing, which involves loss of adhesive properties and epithelial polarity, and acquisition of a mesenchymal phenotype with increasing cellular motility and invasive capability. This change in cellular behavior is mediated by a complex molecular regulation that includes a high number of signalization pathways acting independently or interconnected, many of them converging in the control of E-cadherin expression, whose regulation is the central molecular event of this process. Different studies support a tight link between EMT and progression and metastases development of carcinomas, but it has been less extensively studied in prostate adenocarcinoma. The aim of this review was to describe the molecular and morphological bases of this biological process, and to analyze the participation of regulators in the acquisition of an aggressive phenotype by tumor cells, specifically in regards to prostate adenocarcinoma progression.

Mundialmente, o adenocarcinoma prostático é o segundo câncer diagnosticado em homens e as metástases são sua principal complicação; descreveu-se a participação em seu desenvolvimento da transição epitélio-mesenquimal (TEM) processo fundamental durante o desenvolvimento embrionário, a remodelação tissular e a cicatrização, que implica perda das propriedades adesivas e a polaridade epitelial e aquisição do fenótipo mesenquimal que aumenta a mobilidade celular individual e permite o desenvolvimento de características invasivas. Esta mudança no comportamento celular é mediado por uma regulação molecular complexa na que participa um grande número de vias de sinalização, algumas atuando em forma independente e outras interconectadas; a maioria converge no controle da expressão da Ecadherin, cuja sub-regulação é o evento molecular clave neste processo. Diversos estudos assinalam uma relação estreita entre a TEM e o desenvolvimento e progressão de metástase em carcinomas, mas foi menos amplamente estudada no adenocarcinoma descrever as bases moleculares e morfológicas deste processo biológico e analisar a influência de seus reguladores na aquisição do fenótipo agressivo pelas células tumorais, especificamente em relação com a progressão do adenocarcinoma prostático.

Fisiopatología de la vaso-oclusión en la drepanocitosis / Pathophysiology of the vaso-occlusion in the sickle cell anemia

La vaso-oclusión en la drepanocitosis es una característica única entre las anemias hemolíticas. La idea de que el eritrocito falciforme induce el proceso vaso-oclusivo ha sido desechada y no cabe duda que el fenómeno ocurre debido a la adhesión de los hematíes deformables menos densos (reticulocitos de stress) al endotelio vascular activado en las vénulas post-capilares, proceso en el que participan moléculas de adhesión celular (MAC) eritrocitarias y vasculares así como un conjunto de factores plasmáticos; la externalización de la fosfatidilserina, la acción de la trombina, la expresión de factor tisular asociada a alteraciones del mecanismo de transporte catiónico, conjuntamente con la formación de agregados de banda 3 constituyen un conjunto de elementos cruciales en la explicación fisiopatológica de la vaso-oclusión y su relación con diferentes opciones terapéuticas.

The vaso-occlusion in the sickle cell anemia is only characteristic in the haemolytic anemias. The idea that the falciform erythrocyte induces the vaso-occlusive process has been abolished and without doubt the event is produced by the adhesion of the low density deformed erythrocytes ( stress reticulocytes ) to the active vascular endothelium in post-capillary venule participating in the process molecules of cellular adhesion ( erythrocytic and vascular) as well as a group of plasma factors; the external phosphatidilserine , the thrombine action , the expression of tissue factor associated to the disorders of the cationic transportation mechanism as well as the aggregates (band 3) are crucial elements in the pathophysiological explanation of vaso-occlusion and its relation to different therapeutic options.

Modulation of the adhesion of neutrophils to endothelium and the expression of intercellular adhesion molecule 1 in endothelial cells by one small peptide interfering with IgG-FcγR interaction / 中华肾脏病杂志

Objective To investigate the effects of tg19320,a small peptide,interfering with IgG-FcγR interaction on the adhesion of neutrophils to endothelium and the expression of intercellular adhesion molecule 1 (ICAM-1)in endothelial cells and its possible mechanism.Methods Tg19320 was prepared by solid-phase peptide synthesis.ANCA IgG was isolated from the serum of active ANCA-associated systemic vasculitis(AASV)patients.When primary human umbilical vein endothelial cells(HUVEC)grew into connuence in cytokine-free eonditions,the cells were stimulated with TNF-α,human normal IgG,ANCA IgG and ANCA IgG+tg19320 respectively.HUVEC were pretreated with tg19320 for 45 minutes before being stimulated by ANCA IgG.Non-activated neutrophils was added to treat HUVEC and adhesion was measured by cell count.The expression of ICAM-1 mRNA and protein was assessed by real-time PCR and Western blot respectively.Soluble ICAM-1(sICAM-1)was determined using ELISA technique.Phosphorylation of IκB-α was assessed by Western blot. Results ANCA IgG significantly up-regulated the expression of ICAM-1 in HUVEC and promoted sICAM-1 release(P＜0.05),and TNF-α enhanced the effect of ANCA.These effects were almost completely abolished by tgl9320 both at protein and mRNA level.Furthermore,ANCA IgG increased the IκB-α phosporylation in HUVEC and tg19320could inhibit the effect. Conclusions ANCA IgG can modulate the expression of ICAM-1 and sICAM-1 release in endothelial cells.FcγR probably play a critical role in the ICAM-1 expression up-regulated by ANCA,which is mediated in part through NF-κB signaling pathway.Tg19320 has protective effect on endothelium in AASV in vitro.

Estudo das características físico-químicas e biológicas pela adesão de osteoblastos em superfícies de titânio modificadas pela nitretação em plasma / Study of physical-chemical and osteoblast adhesion characteristics of titanium surfaces modified by plasma nitriding

INTRODUÇÃO: Superfícies de titânio modificadas por diferentes métodos foram estudadas com base nos parâmetros físicos e químicos de caracterização superficial e sua influência no comportamento de células pré-osteoblásticas (MC3T3) in vitro. MÉTODOS: Discos de titânio comercialmente puro grau II foram submetidos a três métodos de modificação de superfície (polimento, nitretados em plasma em configuração planar e gaiola catódica). As diferentes superfícies foram caracterizadas para observar o efeito do processamento na estrutura da camada superficial, na rugosidade e molhabilidade. Ensaios de adesão e proliferação celular usando linhagens de células pré-osteoblásticas MC3T3 foram realizados para avaliar o efeito das novas superfícies no comportamento celular in vitro. RESULTADOS: Os resultados demonstraram que a nitretação em plasma na configuração de gaiola catódica produz superfícies mais rugosas (p<0,02) e com menores ângulos de contato com a água. CONCLUSÕES: A adesão celular é maior nas superfícies mais rugosas do que nas superfícies polidas (p<0,05) e reagem de modo diferente a composição química do substrato e à topografia da superfície.

PURPOSE: The aim of this study was to evaluated the physico-chemical properties of different titanium surfaces modified by means of low temperature plasma nitridind on rat osteoblast cell adhesion and proliferation. METHODS: Pure Titanium discs grade II was submitted to three different surface preparations (polishing, glow discharge plasma nitriding in planar and cathodic cage configurations). Surface parameters as roughness, wettability and chemichal composition was determined to compare influency of gas mixture on the modified surface material properties. Cellular morphology was observed by scanning electron microscopy. To evaluate the effect of the surface on cellular response, osteoblast cells (MC3T3) adhesion and proliferation was quantified and data analised by Kruskal-Wallis and Friedman statistical tests. RESULTS: plasma nitriding discs shows rougher surfaces( p<0,02) in cathodic cage configuration and lower contact angle values. MC3T3 cells attached on rough surfaces produced by cathodic cage configuration was statistically significant p<0,05 compared to polished discs. CONCLUSIONS: Glow discharge plasma nitriding improve titanium surface roughness and wettability. MC3T3 cell adhesion behavior is related to substrate chemical composition and topography.

Expressão imuno-histoquimico das integranas a2B1, a3B1, e a5B1, em mucosa oral norma hiperplasia fibroepitalial inflamatória oral e displasia epitelial oral

Este estudo se propôs analisar através da técnica da estreptoavidina-biotina a expressão imuno-histoquímica das integrinas α2ß1, α3ß1 e α5ß1 em 11 espécimes de mucosa oral normal (MON), 16 de hiperplasia fibroepitelial inflamatória oral (HFIO) e 25 de displasia epitelial oral (DEO) (16 leves, 2 moderadas e 7 graves), procurando determinar se existe alteração qualitativa na expressão destas integrinas e se a mesma guarda relação com as modificações sofridas pelo epitélio oral. Para a integrina α2ß1 a maioria dos espécimes exibiu uma marcação predominantemente intensa e difusa nos contatos intercelulares e no citoplasma celular das camadas basal e suprabasal, sem diferença desse perfil entre os diferentes tipos de espécimes, porém com uma tendência a fraca ou perda da expressão em 21.1% das DEOs, sendo todos os espécimes que não expressaram marcação para este heterodímero DEOs graves. Para a integrina α3ß1 a maioria da amostra exibiu uma marcação fraca ou ausente predominantemente em camada basal. A integrina α5ß1 exibiu uma forte marcação difusa nos contatos intercelulares e citoplasmática na camada suprabasal, com diferença apenas na intensidade de marcação entre os tipos de espécimes, residindo essa diferença nas DEOs, onde 12 (48%) espécimes exibiram uma fraca marcação. Concluiu-se que as integrinas avaliadas podem estar envolvidas nas interações célula-célula e célula-MEC que garantem a diferenciação celular e manutenção do arranjo estrutural tecidual. A variável expressão da integrina α5ß1 nas DEOs, poderia sugerir, respectivamente, um papel dessa molécula na sobrevida celular, com o intuito de perpetuar o fenótipo alterado nessas lesões, ou uma ação supressora desse fenótipo devido à falta de interação desta molécula com a fibronectina da MEC (AU).

The objective of this study was perform by the streptoavidin-biotin technique an immunohistochemical analysis of α2ß1, α3ß1 e α5ß1 integrins in 11 normal oral mucosa (NOM), 16 oral inflammatory fibroepithelial hyperplasia (OIFH) and 25 oral epithelial dysplasia (OED) (16 mild, 2 moderates and 7 severe), to determine if exists qualitative alteration in the expression of these integrins and if this guard relation with the oral epithelial modifications. It was observed that for the α2ß1 integrin the majority of the sample showed a predominantly intense labeling diffusely distributed in the intercellular contacts and the cytoplasm of cells of the basal and suprabasal layers, without difference of this profile between the different types of specimens, however with a trend to weak or loss of expression in 21.1% of the OEDs, being all the specimens that had not expressed this heterodimer, severe OEDs. For the α3ß1 integrin the majority of the sample showed a weak or absent labeling in basal layer. The α5ß1 integrin showed a predominant strong diffuse labeling in the intercellular contacts and cytoplasm in the suprabasal layer, with difference only in the labeling intensity between the types of specimens, inhabiting this difference in the OEDs, where 12 (48%) specimens had shown a weak labeling. It was concluded that the evaluated integrins can be involved in the cell-cell, cell-ECM interactions modulating the cellular differentiation and maintenance of the epithelial structural arrangement. The variable expression of the α5ß1 integrin in the OEDs, could suggest, respectively, a role of this molecule in the cellular survival, with intention to perpetuate the modified phenotype in these lesions, or a suppressor role on the modified phenotype due to lack of interaction of this molecule with the fibronectina of the MEC (AU).

The clinical significance of the epithelial cellular adhesion molecule(Ep-CAM)expression in esophageal squamous cell carcinoma(SCC) / 肿瘤研究与临床

Objective To evaluate the clinical significance of epithelial cellular adhesion molecule (Ep-CAM)expression in esophageal squamous cell carcinoma(SCC).Methods The Ep-CAM expression was immunohistochemically investigated in 70 normal esophageal mucosas,SCCs and 72 lymph nodes.Results Ep-CAM expression was observed in 94.3% of the tumors,but no expression in the normal mucosa.The Ep- CAM expression was not significantly different between different tumor scales and tumors invading depths,its expression level was relevant with the tumors differentiation and lymph node metastases(P

Analysis of Clinical Data about Qingfei Huatan Tongluo Method in Treating 34 Patients of COPD at Acute Stage / 中国中医药信息杂志

0.05),the clinical control rate were 67.65% and 52.94% (P

Pilot study on measurement of sICAM-1 and sE-selectin in patients with chronic hepatitis C to judge response to treatment / 中华检验医学杂志

Objective To investigate the levels of sICAM 1 and sE selectin in patients with chronic hepatitis(CHC) and to study their roles in judge of response to IFN ? 2b treatment. Methods sICAM 1 and sE selectin levels were measured in 32 cases of CHC before and after treatment of IFN ? 2b by enzyme linked immunosorbent assay(ELISA), levels of HCV RNA was detected by quantitative PCR and serum ALT activity was also detected. Results Levels of sICAM 1 and sE selectin in CHC patients were significantly higher than those in normal controls(P

Antioxidant Vitamin Supplementation and Levels of Circulating Cellular Adhesion Molecules / 대한임상병리학회지

BACKGROUND: The oxidative modification of lipids and the endothelial expression of adhesion molecules are key events in the pathogenesis of atherosclerosis. The appropriate antioxidants that protected and slowed the progression of the disease were reported. We measured the antioxidant enzyme activities and the levels of soluble cellular adhesion molecules in order to evaluate whether antioxidant vitamin supplementation affected the oxidative changes and the expression of cellular adhesion molecules. METHODS: Seventy-seven patients participated in a randomized, double blind, placebo-controlled trial. The test group (38 patients) was given antioxidant vitamin doses including a daily dose of vitamin C 500 mg, beta-carotene 15 mg, vitamin E 400 IUs, and selenium 50 microgram, The control group (44 patients) received placeboes for three months. We measured the vitamin serum levels, intercellular adhesion molecules-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin and activities of erythrocyte enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPX) before and at 3 months after supplementation. RESULTS: After supplementation, the serum vitamin levels increased significantly (P<0.05) and the activity of the erythrocyte SOD significantly increased by 0.85 unit/mg hemoglobin (P<0.05) in the test group. Soluble ICAM-1, VCAM-1 and E-selectin levels did not change significantly in the test group after supplementation. CONCLUSIONS: These results suggest that the antioxidant vitamin supplementation may affect erythrocyte SOD activity, but not soluble cellular adhesion molecule levels.

The research progress of carcino-embryonic antigen related cellular adhesion molecule 1 / 中国癌症杂志

Carcino-embryonic antigen related cellular adhesion molecule 1(CEACAM1),used to be called CD66a, biliar glyeoprotein(BGP) or C-CAM,is a glucoprotein expressed on the surface of cells, a member of the carcino-embryonic antigen family(CEA) and an adhesion molecule of immunoglobulin superfamily. It is widely expressed on the epithelial cells and vascular endothelial cells.CEACAM1 inhibits tumor growth and epithelial cell proliferation, induces apoptosis of epithelial cells, inhibits activation and proliferation of T lymphocytes, stimulates proliferation of B lymphocytes, inhibits the cytotoxic effects of T cells and NK cells, delays apoptosis of granulocytes and monocytes, inhibits the activity of tumor-infiltrating lymphocytes, stimulates invasion of tumor cells and motility of endothelial cells, promotes blood vessel angiogenesis, and modulates vascular remodeling, so it has many important biological functions.