Snake venom disintegrins update: insights about new findings

ABSTRACT Snake venom disintegrins are low molecular weight, non-enzymatic proteins rich in cysteine, present in the venom of snakes from the families Viperidae, Crotalidae, Atractaspididae, Elapidae, and Colubridae. This family of proteins originated in venom through the proteolytic processing of metalloproteinases (SVMPs), which, in turn, evolved from a gene encoding an A Disintegrin And Metalloprotease (ADAM) molecule. Disintegrins have a recognition motif for integrins in their structure, allowing interaction with these transmembrane adhesion receptors and preventing their binding to proteins in the extracellular matrix and other cells. This interaction gives disintegrins their wide range of biological functions, including inhibition of platelet aggregation and antitumor activity. As a result, many studies have been conducted in an attempt to use these natural compounds as a basis for developing therapies for the treatment of various diseases. Furthermore, the FDA has approved Tirofiban and Eptifibatide as antiplatelet compounds, and they are synthesized from the structure of echistatin and barbourin, respectively. In this review, we discuss some of the main functional and structural characteristics of this class of proteins and their potential for therapeutic use.

The role of integrin α4 in the anti-liver fibrosis effect of the sticky sugar amino acid extract of / 临床肝胆病杂志

Objective To investigate the mechanism of action of integrin α4 (ITGA4) in liver fibrosis based on the anti-liver fibrosis effect of sticky sugar amino acid (SSAA) in rats. Methods A rat model of liver fibrosis was induced by intraperitoneal injection of CCl 4 , and then colchicine and low-, middle-, and high-dose SSAA were used for intervention, with blank control group and SSAA group as control. After 12 weeks of experimental intervention, serum and liver samples were collected to measure the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and HE staining and Sirius Red staining were used to observe the pathological conditions of liver tissue; quantitative real-time PCR was used to measure the transcriptional level of ITGA4, integrin β1 (ITGB1), transforming growth factor-β1 (TGFβ1), alpha-smooth muscle actin (α-SMA), and TIMP2 in liver tissue; Western blot was used to measure the relative protein expression levels of ITGA4, ITGB1, TGFβ1, α-SMA, MMP2, TIMP1, and TIMP2; immunohistochemistry was used to observe the protein expression of TGFβ1 and α-SMA. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for comparison between two groups. Results There were significant increases in AST and ALT in the CCl 4 model group, and intervention with colchicine or low-, middle-, and high-dose SSAA reduced the levels of AST and ALT, with a significant difference between the CCl 4 model group and the other groups (all P < 0.05). HE staining and Sirius Red staining showed disordered structure of hepatic lobules and an increase in collagen fibers in the CCl 4 model group, and the structure of hepatic lobules was improved after intervention with colchicine or low-, middle-, and high-dose SSAA. The CCl 4 model group had significantly higher transcriptional levels of ITGA4, TGFβ1, α-SMA, and TIMP2 than the other groups, and there were significant reductions in the transcriptional levels of each factor after intervention with colchicine or SSAA, with a significant difference between the CCl 4 model group and the other groups (all P < 0.05). The CCl 4 model group had significantly higher protein expression levels of ITGA4, TGFβ1, α-SMA, TIMP2, and TIMP1 and a significantly lower protein expression level of MMP2 than the other groups, and intervention with colchicine or SSAA inhibited the expression of ITGA4, TGFβ1, α-SMA, TIMP2, and TIMP1 and promoted the expression of MMP2. Immunohistochemistry showed that the CCl 4 model group had significantly higher expression levels of TGFβ1 and α-SMA than the other groups, which was inhibited by intervention with colchicine or SSAA. The high-dose SSAA group had the most significant effect in reducing aminotransferases, improving lobular structure, and inhibiting the protein expression of liver fibrosis factors. Conclusion The high expression of ITGA4 in the liver is associated with the development of liver fibrosis, which is consistent with the increases in the expression of TGFβ1 and α-SMA. Inhibiting the expression of ITGA4 can provide more therapeutic targets for liver fibrosis and expand the anti-liver fibrosis mechanism of SSAA.

Role of heat-shock proteins in infection of human adenocarcinoma cell line MCF-7 by tumor-adapted rotavirus isolates / Papel de las proteínas de choque térmico en la infección de la línea celular de adenocarcinoma humano MCF-7 por aislados de rotavirus adaptados a tumores

Abstract Background: Viruses are being used as alternative and complementary tools for treating cancers. Oncolytic viruses exhibit tumor tropism, ability to enhance anti-tumor immunity and ability to be used in combination with conventional chemotherapy and radiotherapy. We have recently selected some rotavirus isolates which are adapted to efficiently infect and kill tumor cell lines. Aim: We tested five tumor cell-adapted rotavirus isolates for their ability to infect the human adenocarcinoma cell line MCF-7. Methods: Cell surface membrane-associated proteins mediating virus particle attachment were characterized using ELISA, immunoprecipitation, FACS analysis, and antibody blocking. Results: It was found that heat shock proteins (HSPs) such as Hsp90, Hsp70, Hsp60, and Hsp40 are expressed on the cell surface forming complexes with protein disulfide isomerase (PDI), integrin β3, and heat shock cognate protein 70 (Hsc70) in lipid raft microdomains. Interaction of rotavirus isolates with these cellular proteins was further confirmed by a competition assay and an inhibition assay involving the HSPs tested. Conclusion: Our findings suggest that the tumor cell-adapted rotavirus isolates studied here offer a promising tool for killing tumor cells, thus encouraging further research into this topic, including animal models.

Resumen Antecedentes: Los virus se utilizan como herramientas alternativas y complementarias para el tratamiento del cáncer. Los virus oncolíticos exhiben tropismo por tumores, capacidad para intensificar la inmunidad antitumoral y la capacidad para utilizarse en combinación con quimioterapia y radioterapia convencionales. Recientemente, hemos seleccionado algunos aislamientos de rotavirus que están adaptados para infectar y eliminar de manera eficiente líneas de células tumorales. Objetivo: Se ensayaron cinco aislamientos de rotavirus adaptados a células tumorales para determinar su capacidad para infectar la línea celular de adenocarcinoma humano MCF-7. Métodos: Las proteínas asociadas a la membrana de la superficie celular que median la unión de partículas de virus se caracterizaron mediante ELISA, inmunoprecipitación, análisis FACS y bloqueo de anticuerpos. Resultados: Se encontró que las proteínas de choque térmico (HSPs) como Hsp90, Hsp70, Hsp60 y Hsp40 se expresan en la superficie celular formando complejos con la proteína disulfuro isomerasa (PDI), la integrina β3 y la proteína análoga de choque térmico 70 (Hsc70) en microdominios lipídicos (rafts). La interacción de los aislamientos de rotavirus con estas proteínas celulares se confirmó adicionalmente mediante un ensayo de competición y un ensayo de inhibición que incluía las HSP ensayadas. Conclusión: Nuestros hallazgos sugieren que los aislamientos de rotavirus adaptados a las células tumorales estudiados aquí ofrecen una herramienta prometedora para eliminar las células tumorales, lo que estimula más investigaciones sobre este tema, incluidos los modelos animales.

Effect of integrin ανβ3 on conjunctival scar formation after glaucoma filtration surgery in rats / 中华实验眼科杂志

Objective:To investigate the expression of integrin ανβ3 in conjunctival scar after glaucoma filtration surgery and to explore its role in the formation of filtering scar in rats.Methods:Fifty-five SPF male SD rats aged 6-8 weeks were selected to establish the model of glaucoma filtration surgery, and 15 unsuccessful modeling rats were excluded.The remaining rats were divided into control group, transforming growth factor (TGF) group, integrin ανβ3 receptor antagonist LM609 group and TGF+ LM609 group, with 10 rats in each group.The conjunctival flap of different groups was treated with cotton piece containing 0.9% sodium chloride, TGF-β2 (2 mg/ml), LM609 (40 μg/ml), TGF-β2 (2 mg/ml)+ LM609 (40 μg/ml) solution for two minutes, respectively, according to grouping.The intraocular pressure (IOP) was monitored with an iCARE tonometer before operation and at 3 days, 1 week, 2 weeks after operation, and the average IOP ratio ([postoperative IOP/preoperative IOP]×100%) was calculated.At 3 days, 1 week and 2 weeks after operation, slit lamp microscopy was used to observe the morphological changes of filtering blebs and calculate the survival rate of filtering blebs.Two weeks after operation, the operative eyeball tissues were removed and made into paraffin section.The inflammatory changes, fibrosis and collagen deposition of bulbar conjunctiva in the operation area were observed by hematoxylin-eosin staining and picric acid-sirius red staining, respectively.Western blot was used to detect the expression of integrin αν and β3.Immunohistochemical staining was used to detect the expression of integrin ανβ3 in the conjunctival tissue of operation area.The use and care of the rats complied with the Instruction Notions with Respect to Care for Laboratory by State Ministry of Science and Technology.The study protocol was approved by an Ethics Committee of The Daping Hospital, Army Medical University (No.2017-06).Results:The IOP of rats in each group was significantly decreased on the third day after operation compared with before operation, and gradually recovered to the preoperative level in the first to second week after operation.The mean IOP ratios of the control group, TGF group, LM609 group and TGF+ LM609 group were (101.80±4.44)%, (103.90±5.65)%, (94.10±7.45)% and (100.60±4.61)%, respectively, showing a statistically significant difference among them ( F=4.571, P=0.010). The mean IOP ratio of LM609 group was lower than that of the control group, TGF group and TGF+ LM609 group (all at P<0.05). Two weeks after operation, the filter blebs became flat and the bulbar conjunctival tissue was slightly thickened in the control group and TGF+ LM609 group, and bulbar conjunctival tissue was significantly thickened with a large number of blood vessels growing in the TGF group, and localized small filter blebs as well as less vascularization were seen in the LM609 group.The survival rate of filtering bleb in the TGF group was significantly lower than that in the control group, LM609 group and TGF+ LM609 group, and the survival rate of filtering bleb in the LM609 group was significantly higher than that in the control group and TGF+ LM609 group (all at P<0.05). Two weeks after operation, there were fewer infiltrated inflammatory cells and looser collagen fiber deposition in the conjunctival tissue in the LM609 group and TGF+ LM609 group compared with the TGF group.The relative expression levels of integrin αν and β3 under conjunctival tissue in the TGF group were significantly higher than those in the control group, LM609 group and TGF+ LM609 group (all at P<0.05). Immunohistochemical staining showed that integrin ανβ3-positive cells were mainly in the conjunctival tissue around the operation area and microtubules.The number of integrin ανβ3-positive cells in the conjunctival tissue of the operation area in the TGF group were significantly greater than those of other groups. Conclusions:Integrin ανβ3 is highly expressed in the scar of conjunctival tissue after filtering surgery in rats.The inhibition of integrin ανβ3 can reduce the deposition of fibers and prolong the survival of filtering blebs, suggesting that integrin ανβ3 may be involved in the formation of conjunctival scar.

Vedolizumabe no manejo das doenças inflamatórias intestinais: um estudo multicentrico observacional brasileiro / Vedolizumab in the management of inflammatory bowel diseases: a brazilian observational multicentric study

ABSTRACT BACKGROUND: There is scarce data regarding efficacy and safety of vedolizumab in inflammatory bowel diseases in Latin America. OBJECTIVE: To describe the first observational real-world experience with vedolizumab in Latin American inflammatory bowel diseases patients. METHODS: Retrospective observational multicentric study of patients with Crohn's disease (CD) and ulcerative colitis (UC) who used vedolizumab at any phase of their treatment. Clinical remission and response (according to Harvey-Bradshaw index for CD and Mayo score for UC), mucosal healing, need for surgery and adverse events were evaluated. RESULTS: A total of 90 patients were included (52 with CD and 38 with UC), the majority with previous exposure to anti-TNF agents (88.46% in CD and 76.31% in UC). In CD (as observed analysis) remission rates at weeks 12, 26 and 52 were 42.89% (21/49), 61.9% (26/42) and 46.15% (12/26), respectively. In UC, remission rates at weeks 12, 26 and 52 were 28.94% (11/38), 36.66% (11/30) and 41.17% (7/17). Mucosal healing rates were 36.11% in CD and 43.4% in UC. During the study period, 7/52 CD patients underwent major abdominal surgery and 4/38 UC patients needed colectomy. CONCLUSION: Vedolizumab was effective in induction and maintenance of clinical response and remission in CD and UC, with no new safety signs.

RESUMO CONTEXTO: Há escassez de dados sobre a eficácia e segurança do vedolizumabe nas doenças inflamatórias intestinais na América Latina. OBJETIVO: Descrever a primeira experiência observacional de mundo real com vedolizumabe em pacientes latino-americanos com doenças inflamatórias intestinais. MÉTODOS: Estudo retrospectivo multicêntrico observacional de pacientes com doença de Crohn (DC) e retocolite ulcerativa inespecífica (RCUI) que utilizaram vedolizumabe em qualquer fase de seu tratamento. Foram avaliadas a remissão e resposta clínicas (de acordo com o índice de Harvey-Bradshaw para DC e escore de Mayo para RCUI), cicatrização da mucosa, necessidade de cirurgia e eventos adversos. RESULTADOS: Foram incluídos 90 pacientes (52 com DC e 38 com RCUI), a maioria com exposição prévia a agentes anti-TNF (88,46% na DC e 76,31% na RCUI). Na DC (em análise conforme observado), as taxas de remissão nas semanas 12, 26 e 52 foram 42,89% (21/49), 61,9% (26/42) e 46,15% (12/26), respectivamente. Na RCUI, as taxas de remissão nas semanas 12, 26 e 52 foram de 28,94% (11/38), 36,66% (11/30) e 41,17% (7/17). As taxas de cicatrização da mucosa foram 36,11% na DC e 43,4% na RCUI. Durante o período do estudo, 7/52 pacientes com DC foram submetidos a cirurgia abdominal maior e 4/38 pacientes com RCUI necessitaram de colectomia. CONCLUSÃO: O vedolizumabe foi eficaz na indução e manutenção da resposta e remissão clínicas em população refratária na DC e RCUI, com perfil de segurança favorável.

Adipose-Derived Stem Cell Coculturing Stimulates Integrin-Mediated Extracellular Matrix Adhesion of Melanocytes by Upregulating Growth Factors

Coculture with adipose-derived stem cells (ADSCs) can stimulate proliferation and migration of melanocytes. To enhance outcomes of skin disorders caused by melanocyte loss or death, mixed transplantation with ADSCs has been suggested. However, role of cocultured ADSCs in proliferation and migration of melanocytes remains unclear. This study determined the effect of ADSCs on production of growth factors and expression levels of intergrins in primary culture of adult human melanocytes with or without ADSCs and in nude mice grafted with such melanocytes. Higher amounts of growth factors for melanocytes, such as bFGF and SCF were produced and released from ADSCs by coculturing with melanocytes. Relative levels of integrins β1, α5, and α6 as well as adhesion to fibronectin and laminin were increased in melanocytes cocultured with ADSCs. Such increases were inhibited by neutralization of bFGF or SCF. Relative levels of bFGF, SCF and integrins were increased in nude mice skin after grafting with melanocyte+ADSC cocultures. Collectively, these results indicate that ADSCs can stimulate proliferation and migration of melanocytes by increasing expression of integrins in melanocytes through upregulation of production/release of melanocyte growth factors such as bFGF and SCF.

Far-infrared radiation stimulates platelet-derived growth factor mediated skeletal muscle cell migration through extracellular matrix-integrin signaling

Despite increased evidence of bio-activity following far-infrared (FIR) radiation, susceptibility of cell signaling to FIR radiation-induced homeostasis is poorly understood. To observe the effects of FIR radiation, FIR-radiated materials-coated fabric was put on experimental rats or applied to L6 cells, and microarray analysis, quantitative real-time polymerase chain reaction, and wound healing assays were performed. Microarray analysis revealed that messenger RNA expressions of rat muscle were stimulated by FIR radiation in a dose-dependent manner in amount of 10% and 30% materials-coated. In 30% group, 1,473 differentially expressed genes were identified (fold change [FC] > 1.5), and 218 genes were significantly regulated (FC > 1.5 and p < 0.05). Microarray analysis showed that extracellular matrix (ECM)-receptor interaction, focal adhesion, and cell migration-related pathways were significantly stimulated in rat muscle. ECM and platelet-derived growth factor (PDGF)-mediated cell migration-related genes were increased. And, results showed that the relative gene expression of actin beta was increased. FIR radiation also stimulated actin subunit and actin-related genes. We observed that wound healing was certainly promoted by FIR radiation over 48 h in L6 cells. Therefore, we suggest that FIR radiation can penetrate the body and stimulate PDGF-mediated cell migration through ECM-integrin signaling in rats.

Expression of Fermintin family homologous protein 2 in non-small cell lung cancer and its clinical significance / 中华病理学杂志

Objective@#To investigate the expression of Fermintin family homologous protein 2 (FERMT2) in non-small cell lung cancer and its clinical significance.@*Methods@#Seventy-two patients with non-small cell lung cancer were collected at Xinxiang Central Hospital, Henan Province, from January 2015 to January 2017.There were 48 male and 24 female patients, the age ranged from 37 to 78 years (mean 58 years). The expression of FERMT2 in tumor samples and para-cancerous tissues were detected by immunohistochemistry. Protein and mRNA expression of FERMT2 were detected by Western blot and real-time fluorescence quantitative PCR, respectively. Western blot method was also used to detect integrin-related protein expression, including integrin beta 1 (CD29), vascular cell adhesion molecule (VCAM1), and mobile related protein-1 (MRP1).@*Results@#Immunohistochemistry showed that the positive rates of FERMT2 expression were 81.9%(59/72)in carcinoma tissue and 15.4%(11/72) in para-cancerous tissues, and the difference was statistically significant (P<0.01). Positive FERMT2 expression was different in tumors at different tumor stages: 11/17 at stage Ⅰ, 16/20(80.0%)at stage Ⅱ, 17/20(85.0%)at stage Ⅲ, and 15/15 at stage Ⅳ, and there was a significant difference between each stage (P<0.01). By real-time PCR and Western blot, the expression of FERMT2 in non-small cell lung cancer tissues was significantly higher than that of para-cancerous tissue (P<0.01). The expression levels of integrin related proteins (integrin β1, VCAM1 and MRP1) in tumor tissues were significantly higher than those in para-cancerous tissues, and positively correlated with the expression of FERMT2 (r=0.531, P<0.01; r=0.483, P<0.01; r=0.612, P<0.01).@*Conclusions@#FERMT2 is highly expressed in non-small cell lung carcinomas. Its expression is closely correlated with the tumor clinical stage. It is hypothesized that FERMT2 may promote tumor metastasis through interactions with integrin-like protein.

Research on the correlation between mechanical signaling molecules of hypertrophic scar and post injury time in burn patients in scar remodeling stage / 中华烧伤杂志

Objective@#To analyze the correlation between integrin β1, focal adhesion kinase (FAK), extracellular signal-regulated kinase 1/2 (ERK1/2) of hypertrophic scar (HS) and post injury time in burn patients in scar remodeling stage.@*Methods@#Thirty-four patients with 34 HS specimens admitted to Department of Burns and Plastic Surgery of Chengdu No.2 Hospital and Institute of Burn Research of the First Affiliated Hospital of Army Medical University (originally the Third Military Medical University) from May 2013 to April 2016 were recruited by convenient sampling method, and normal skin specimens were obtained from donor sites of another 6 patients from the above-mentioned departments who had scar resection and skin grafting for this cross-sectional and observational study. Vancouver Scar Scale (VSS) was used to assess the height, vascularity, pigmentation, and pliability of scars. Diasonograph was used to assess scar thickness. Immunohistochemical method was used to observe the expressions of integrin β1, FAK, and ERK1/2 in dermis and epidermis of scar and normal skin. Correlations between the post injury time and the scar thickness, the post injury time and the expressions of integrin β1, FAK, and ERK1/2 in epidermis of scar, the post injury time and the expressions of integrin β1, FAK, and ERK1/2 in dermis of scar, the expressions of integrin β1, FAK, and ERK1/2 in dermis and those in epidermis of scar were analyzed by Pearson correlation analysis. Locally estimated scatterplot smoothing curve fitting line was used to demonstrate the non-linear regression relationship between the expressions of integrin β1, FAK, and ERK1/2 in dermis and those in epidermis of scar, the scar thickness and the post injury time.@*Results@#(1) The total VSS score of scars of patients was (8.3±2.3) points, with height scored (2.2±0.7) points, vascularity scored (2.0±0.8) points, pigmentation scored (2.3±0.7) points, and pliability scored (1.9±0.7) points. The thickness of scar was (2.8±1.1) mm. (2) The expressions of integrin β1, FAK, and ERK1/2 in dermis and epidermis of scar were more than those in normal skin. (3) There was significantly positive correlation between the scar thickness and the post injury time (r=0.39, P<0.05). There was significantly positive correlation between the expression of integrin β1 in epidermis of scar and the post injury time (r=0.33, P<0.05). There were no significantly correlations between the expressions of FAK and ERK1/2 in epidermis of scar and the post injury time (r=-0.03, -0.04, P>0.05). There was significantly negative correlation between the expression of FAK in dermis of scar and the post injury time (r=-0.34, P<0.05). There were no significantly correlations between the expressions of integrin β1 and ERK1/2 in dermis of scar and the post injury time (r=0.07, -0.23, P>0.05). There were significantly positive correlation between the expressions of integrin β1, FAK, and ERK1/2 in dermis and those in epidermis of scar (r=0.70, 0.60, 0.64, P<0.01). (4) The expressions of integrin β1, FAK, and ERK1/2 in dermis and epidermis of scar were changed from downtrend in 1 to 2 months post injury to uptrend in 2 to 3 months post injury, which reached the peak around 3 to 4 months post injury. Hereafter the expressions of mechanical signaling molecules in epidermis of scar were gradually declined, while the expressions of mechanical signaling molecules in dermis of scar were at a quite high level within half a year post injury. Scar thickness was steadily increased after 1 month post injury.@*Conclusions@#In scar remodeling stage of burn patients, the HS thickness increases continuously along with the increasing post injury time in the early stage of scar formation. The vulnerability of integrin β1, FAK, and ERK1/2 of HS to external mechanical stimuli increases gradually within 4 months post injury.

Effect of integrin-linked kinase towards matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 in the process of TGF-β1-induced epithelial-mesenchymal transition of renal tubular cell / 中国医师杂志

Objective To investigate the possible regulating effect of integrin-linked kinase (ILK) towards matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 (MMP-9/TIMP-1) ratio in the process of transforming growth factor-β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) in human kidney proximal tubular epithelial (HK-2) cells.Methods HK-2 cells were cultured and stimulated with 10 ng/ml TGF-β1.Specific ILK-small interfering RNA (ILK-siRNA) was used to inhibit ILK expression.The characteristic epithelial marker (E-cadherin) and mesenchymal marker (α-SMA) of EMT were examined by Real-time reverse transcription polymerase chain reaction (real-time RT-PCR) and Western blot.The expressions of ILK,MMP-9,and TIMP-1 were also examined,to determine the regulating effect of ILK towards MMP-9/TIMP-1 ratio.Results In the HK-2 cells cultured with TGF-β1,the expression of E-cadherin decreased,and α-SMA expression increased;overexpression of ILK and an abnormal changing of MMP-9/TIMP-1 ratio were observed.ILK inhibition by ILK-siRNA could adjust MMP-9/TIMP-1 ratio to near normal.Meanwhile,the overexpressed ILK and α-SMA were decreased.Conclusions Our data indicates that ILK-siRNA successfully inhibits ILK expression,which regulates the MMP-9/TIMP-1 ratio in HK-2 cells.The inhibition of ILK expression suppresses TGF-β1-induced EMT partially.

Role of β₁-Integrin in Colorectal Cancer: Case-Control Study / 이화의대지

OBJECTIVES: In the metastatic process, interactions between circulating tumor cells (CTCs) and the extracellular matrix or surrounding cells are required. β1-integrin may mediate these interactions. The aim of this study was to investigate whether β1-integrin is associated with the detection of CTCs in colorectal cancer. METHODS: We enrolled 30 patients with colorectal cancer (experimental group) and 30 patients with benign diseases (control group). Blood samples were obtained from each group, carcinoembryonic antigen (CEA) mRNA for CTCs marker and β1-integrin mRNA levels were estimated by using reverse transcription-polymerase chain reaction, and the results were compared between the two groups. RESULTS: CEA mRNA was detected more frequently in colorectal cancer patients than in control patients (P=0.008). CEA mRNA was significantly reduced after surgery in the colorectal cancer patients (P=0.032). β1-integrin mRNA was detected more in colorectal cancer patients than in the patients with benign diseases (P<0.001). In colorectal cancer patients, expression of β1-integrin mRNA was detected more for advanced-stage cancer than for early-stage cancer (P=0.033) and was significantly decreased after surgery (P<0.001). In addition, expression of β1-integrin mRNA was significantly associated with that of CEA mRNA in colorectal cancer patients (P=0.001). CONCLUSION: In conclusion, β1-integrin is a potential prognostic factor following surgical resection in colorectal cancer patients. β1-integrin may be a candidate for use as a marker for early detection of micrometastatic tumor cells and for monitoring the therapeutic response in colorectal cancer patients.

Infecção por leishmania modula a ativação de Beta-1 integrinas e altera a cinética do espalhamento celular de monócitos sobre fibronectina/Leishmania infection modulates the activation of Beta-1 integrins and alters the kinetics of monocyte cell spread on fibronectin / Leishmania infection modulates the activation of beta-1 integrins and alters the kinetics of monocyte cell spread on fibronectin / Leishmania infection modulates the activation of beta-1 integrins and alters the kinetics of monocyte cell spread on fibronectin

A leishmaniose é considerada como um grupo de doenças, causadas por parasitos do gênero Leishmania. O gênero inclui mais de 20 espécies de parasitos que são transmitidas ao homem pela picada da fêmea, infectada, dos insetos da família dos flebotomíneos e as diferentes espécies estão associadas a diferentes manifestações clínicas da doença. Uma característica marcante na infecção é a presença de macrófagos infectados no sítio de inoculação do parasito e em órgãos internos do hospedeiro. Estudos prévios, demonstraram que a infecção de fagócitos mononucleares com Leishmania amazonensis, L. infantum ou L. braziliensis promove uma diminuição na adesão celular ao tecido conjuntivo inflamado da pele. Esta diminuição da adesão é decorrente, principalmente, de mecanismos envolvidos na regulação da molécula VLA-4, uma integrina da família beta 1 que se liga à VCAM-1...

Leishmaniasis is considered a group of diseases, caused by parasites of the genus Leishmania. The genus includes more than 20 species of parasites that are transmitted to humans by the bite of vector female insect, of the phlebotomine family, and the different species are associated with different clinical manifestations of the disease. A striking feature of infection is the presence of infected macrophages at the site of inoculation of the parasite and internal organs of the host. Previous studies have demonstrated that infection of mononuclear phagocytes with Leishmania amazonensis, L. infantum or L. braziliensis promotes a decrease in cellular adhesion to the inflamed connective tissue of the skin. This decrease in adhesion results mainly from mechanisms involved in the regulation of the VLA-4 molecule, a beta 1 integrin that binds to VCAM-1...

The role of Cyr61 in tumors and its clinical application / 中华检验医学杂志

Cyr61/CCN1 is a secreted extracellular matrix ( ECM) protein, which has been shown to regulate a multitude of cellular responses.Many researches indicate that Cyr61 plays important roles in oncogenesis and development of tumor and is considered to be a novel potential oncogene.This review would provide a comprehensive summary about the roles of Cyr61 in the diagnosis and treatment of tumor.

Research progress of integrin β1 effect in cardiovascular diseases / 心血管康复医学杂志

As important adhesion molecule on cell surface,integrin is a kind of important receptor family. It′s im- portant role is to mediate intercellular adhesion and adhesion between cells and extracellular matrix,also regulate proliferation,differentiation,migration of cells and tissue remodeling,and plays an important role in maintaining cellular form and growth.The present article made a short review about research progress of integrin β1 effect in cardiovascular diseases in recent years.

Progress in integrin in acute leukemia / 白血病·淋巴瘤

Acute leukemia (AL) is an early hematopoietic stem/progenitor cell malignant cloning disease.Minimal residual disease and drug resistance are considered to be the origin of relapse and refractory.Recently,more and more evidences have shown that the interaction between leukemia cells and stromal cells or extracellular matrix in the bone marrow microenvironment can promote their survival,and enhance the resistance to conventional chemotherapy drugs.Integrin is the major molecule mediating the adhesion between leukemia cells and extracellular matrix (cellular and non cellular components),which plays a key role in cell proliferation,survival and other biological processes;however,the mechanism is not fully understood yet.This paper will review molecular mechanisms of the relationship between integrin and AL discovered recently.

Effect of integrin-linked kinase in heart disease / 心血管康复医学杂志

Interin-linked kinase (ILK)is a kind of effector of intra-and extracellular biological signal transduction,partici-pating in the formation of multiple signal pathways,it plays an important role for occurrence and development of heart dis-eases such as cardiac hypertrophy,coronary heart disease,viral myocarditis,dilated cardiomyopathy etc..

Regulatory Mechanism of Integrins on Pancreatic Cancer Cells and Progress in their Application / 胃肠病学

Integrins are a family of cell adhesion receptors that mediate cell-cell and cell-extracellular matrix adhesion, and interact with cytokines through a bidirectional signal transduction,thus regulating the biological behavior of pancreatic cancer cells,such as proliferation,apoptosis,invasion,and migration etc. Molecular and animal studies indicated that integrins targeted methods might benefit the early diagnosis and drug therapy of pancreatic cancer,which offered a new approach for the study of diagnosis and treatment of pancreatic cancer.

Construction of RGD-TAT modified liposomes and evaluation of its targeting on glioma / 中国生化药物杂志

Objective To construct RGD-TAT modified liposomes(RGD-TAT-LPs)and evaluate its glioma targeting efficiency.Methods RGD-TAT-LPs was constructed by film-ultrasonic method,its appearance,particle size and Zeta potential were mearsured. Cellular uptake of LPs,TAT-LPs, RGD-LPs and RGD-TAT-LPs was used to evaluate the affinity to C6 cells.C6 cells were xenografted in athymic mice to establish the animal model,which were used to evaluate the distribution of liposomes in vivo. Results The particle diameter of RGD-TAT-LPs was (1 16.5 ±1 1.3 )nm,and its Zeta potential was (23.2 ±3.5 )mV. Cellular uptake experiments demonstrated the cell uptake efficiency of RGD-TAT-LPs by C6 cells were 2.9-fold,2.3-fold and 4.7-fold than that of RGD-LPs,TAT-LPs and LPs respectively. The in vivo imaging showed that RGD-TAT-LPs had the strongest fluorescence intensity in brain. Conclusion The RGD-TAT-LPs might serve as a promising delivery system of antitumor drugs.

Cytoskeleton and mechanical signal transduction / 中国组织工程研究

BACKGROUND:cells under mechanical stimulation can achieve their biological functions by converting mechanical signals into chemical signals through certain signal transduction mechanism. As the fibrous framework throughout a cell, cytoskeleton is one of the critical components in this process. OBJECTIVE:Through systemical y analyzing the role of the cytoskeleton in mechanical signal transduction, to provide a potential therapeutic target for the clinical treatment of cytoskeleton related diseases. METHODS:In order to search relevant articles about the mechanics mechanism of signal transduction of cytoskeleton from PubMed and CNKI databases (from 1990 to 2012), a computer-based search was performed, using the key words of“cytoskeleton, microtubules, microfilaments, intermediate filaments, mechanical stimulation, signal transduction”in English and Chinese, respectively. After eliminating literatures which were irrelevant to research purpose or containing a similar content, 48 articles were chosen for further analysis. RESULTS AND CONCLUSION:Mechanical stimulation plays an important role in cellproliferation, development and apoptosis. With the gradual understanding of the biological function of cytoskeleton, people have found that cytoskeleton is one of the critical components in the process of the mechanical signal transduction. After getting mechanical stimulation, cytoskeleton can be reorganized through Rho, protein kinase C, integrin and mitogen-activated protein kinase signaling pathways, then converting the mechanical stimulation to chemical signals and finishing its biological functions final y.

CCL18 for promoting breast cancer SK-3rd cells invasion via integrin aggregation / 重庆医学

Objective To explore the role of integrin in CCL18 for promoting breast cancer SK-3 rd cells invasion and migration process to illuminate the molecular mechanism of CCL 18 for promoting breast cancer SK-3 rd cells invasion and migration process . Methods The flow cytometry was adopted to detect CCL18-induced integrin aggregation ;Western blot was used to detect the focal adhesion kinase(FAK ) activation ,the infiltrating migrationin experiment was adopted to determine the invasion and migration of SK-3rd cells and the siRNAs transfection was used to detect the expression of silence integrin β1 .Results CCL18 promoted the in-tegrinβ1 aggregation in breast cancer SK-3rd cell surface and further promoted the integrin-mediated phosphorylated activation of FAK .Under the reaction of CCL18 ,the cells number of SK-3rd cellular invasion and migration was increased by ten times (P<0 .01) ,which was obviously decreased by siRNA silenced integrin β1 .Conclusion CCL18 promotes breast cancer invasion and mi-gration via integrin aggregation .