The Serum Levels of Soluble Fas Ligand and Soluble Fas Receptor in Patients with chronic congestive heart failure

Objectives To investi gate the association of soluble Fas ligand( sFasL) and soluble Fas receptor( sFas) with human chronic con gestive heart failure( CHF) . Methods The serum level of sFasL and sFas in 33 patients with CHF (13 in cardiac function class Ⅱ, 17 in class Ⅲ, 3 in class Ⅳ, NYHA) was assessed with enzyme - linked immunosorbent assay, and was compared with that of 18 age - , blood pressure - matched patients with car diac function class Ⅰ (NYHA). Results There was no difference in the level of sFasL between the two groups [CHF group: 231. 50 + / - 84. 50 (cardiac function class Ⅱ216. 50 + / - 96. 00 , class Ⅲ 226. 80 + / - 85. 70, class Ⅳ 244. 00 + / - 73. 00) vs. cardiac function class I group: 217. 50 + /-89. 00 pg/mL, P>0. 05]. However, the level of sFas was significantly higher in the patients with CHF than those of cardiac function class I group [CHF group: 1353. 30 +/-507. 71 (cardiac function class Ⅱ 1154. 85 + /-371. 20 , class Ⅲ1412.88 + /-493. 62, classⅣ1875. 67 + / - 806. 10) vs. cardiac function class I group: 983. 11+/ -461. 26 pg/mL, P<0. 05 ] . Conclusions sFasL was not associated with human CHF. However, the elevation of serum level of sFas was proportion to the severity of human CHF. sFas may play an important role in the patho- genesis of human CHF.

In situ detection of tumor infiltrating lymphocytes expressing perforin and fas-ligand genes in human HCC

AIM To investigate the expression of perforin and fas ligand (fas L) of tumor infiltrating lymphocytes (TILs) in human hepatocellular carcinoma (HCC). METHODS By in situ hybridization and immunohistochemistry, the perforin and fas L gene expression of TILs was studied in 20 HCC cases. RESULTS Positive expression of perforin and fas L genes was detected in 16 HCC cases. One patient had expression of perforin and fas L genes in the majority of TILs and survived 1 5 years after tumor resection without HCC relapse. This seems that the presence of a large number of activated T cells might be beneficial for the antitumor immunity. In other cases, less than 10% of TILs were able to express perforin and fas L genes. CONCLUSION Although there were a number of T cells in HCC, only few of them were immunoactive and able to kill tumor cells. It seems important to promote further proliferation of these activated T cells in vitro or in vivo .

Enhancement of germ cell apoptosis induced by ethanol in transgenic mice overexpressing Fas Ligand

It was suggested that chronic ethanol exposure could result in testicular germ cell apoptosis, but the mechanism is still unclear. In the present study, we use a model of transgenic mice ubiquitously overexpressing human FasL to investigate whether Fas ligand plays a role in ethanol-induced testicular germ cell apoptosis. Both wild-type (WT)mice and transgenic (TG) mice were treated with acute ethanol (20% v/v) by introperitoneal injection for five times.After ethanol injection, WT mice displayed up-regulation of Fas ligand in the testes, which was shown by FITCconjugated flow cytometry and western blotting. Moreover, TG mice exhibited significantly more apoptotic germ cells than WT mice did after ethanol injection, which was demonstrated by DNA fragmentation, PI staining flow cytometry and TUNEL staining. In addition, histopathological examination revealed that degenerative changes of epithelial component of the tubules occurred in FasL overexpressing transgenic mice while testicular morphology was normal in wild-type mice after acute ethanol exposure, suggesting FasL expression determines the sensitivity of testes to ethanol in mice. In summary, we provide the direct evidences that Fas ligand mediates the apoptosis of testicular germ cells induced by acute ethanol using FasL transgenic mice.

Utility of adenovirus-mediated Fas ligand and bcl-2 gene transfer to modulate rat liver allograft survival

BACKGROUND: Expression of Fas ligand (FasL) on the graft by gene transduction is expected to introduce apoptosis to lymphocytes to protect rejection, but the FasL-expressing graft cells may also induce apoptosis as the graft usually expresses Fas antigens. In this study, a strong antiapoptotic gene, bcl-2, was cotransfected with the FasL gene in rat liver graft to protect against Fas- mediated cell death and to prolong recipient survival. METHODS: Orthotopic liver transplantation was done in a strain combination of DA to LEW rats. After donor vascular isolation, adenovirus-mediated FasL and bcl-2 genes were cotransfected in the liver graft. RESULTS: Intragraft expression of FasL mRNA was constitutively expressed after adenovirus-mediated transduction, although expression of FasL increased mildly in control grafts. Bcl-2 mRNA was highly expressed at 2 days after reperfusion. In contrast, lower expression of bcl-2 was observed in the control group. The average survival of the gene transferred allografts increased from (9.8+1.3) days to (18.5+8.7) days compared with the control group. CONCLUSION: Our results indicate that rat liver allografts can be protected against host immune responses by adenovirus-mediated FasL and bcl-2 transfection, and that bcl-2 expression prevents the graft from Fas-mediated apoptosis.

EXPRESSION OF MATRIX METALLOPROTEINASE-7 AND FAS LIGAND: THEIR APOPTOSIS-INDUCING EFFECT ON GASTRIC CANCER CELLS

Objective: To investigate the expression of matrix metalloproteinase-7 (MMP-7) and Fas ligand (FasL) in gastric cancer and explore their role in progression of gastric cancer. Methods: Formalin-fixed paraffin and embedded tissues of primary gastric cancer and adjacent non-tumor mucosa from 113 cases were evaluated for MMP-7, FasL and Capase-3 expression by streptavidin-peroxidase (S-P) immunohistochemistry. The expression of the first two proteins in cancer cells of primary foci was compared with clinicopathological parameters of tumors. We also observed the correlation of MMP-7 and FasL expression with Caspase-3 expression in cancer cells of primary foci. Results: MMP-7 positive immunostaining was less frequently detected in adjacent epithelial cells than in cancer cells of primary foci of gastric cancer (P<0.05, 29.2% vs 69.0%), and so was FasL (P<0.05, 34.5% vs 54.0%). MMP-7 expression was associated with tumor size, Borrmann抯 classification, invasive depth, metastasis and TNM staging (P<0.05), but not with growth pattern, Lauren抯 classification, or histological classification (P>0.05). FasL expression was correlated with tumor size, invasive depth, metastasis, Lauren抯 classification, histological classification (P<0.05), while not with Borrmann抯 classification, TNM staging or growth pattern (P>0.05). Cancer cells of primary foci expressed less Caspase-3 than their adjacent epithelial cells (P<0.05, 32.7% vs 50.4%). There was an obvious correlation between FasL, MMP-7 and Caspase-3 expression in cancer cells of primary foci (P<0.05). Co-expression of MMP-7 and FasL paralleled with Caspase-3 expression in cancer cells of primary foci (P<0.05). Conclusion: MMP-7 and FasL expression was up-regulated in gastric carcinogenesis and was principally involved in progression of gastric cancer. FasL expression could reflect the differentiation of gastric cancer cells and underlie the molecular mechanisms of different pathways of gastric tumorigenesis. Co-expression of MMP-7 and FasL could have apoptosis-inducing effect on gastric cancer cells.

Action and mechanism of Fas and Fas ligand in immune escape of gallbladder carcinoma

AIM: To study the role of Fas and Fas ligand (FasL) in biological behaviors of gallbladder carcinoma, and their correlated action and mechanism in tumor escape.METHODS: Streptavidin-biotin-peroxidase immunohistochemistry technique was used to study the expression of Fas and FasL protein in 26 gallbladder carcinoma tissues,18 gallbladder adenoma tissues, 3 gallbladder dysplasia tissues and 20 chronic cholecystitis tissues. Apoptosis of the infiltrating lymphocytes in these tissues was studied by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) method. Expression of both proteins and apoptosis of the tumor infiltrating lymphocytes in cancer tissues of primary foci was compared with clinicopathological features of gallbladder carcinoma.RESULTS: The positive rates of Fas were not significantly different among carcinoma, adenoma, dysplasia and chronic cholecystitis. The positive rate of FasL in carcinoma was significantly higher than that in chronic cholecystitis (x2 = 4.89, P＜0.05). The apoptotic index (AI) in carcinoma was significantly higher than that in adenoma (t'= 4.19, P＜0.01) and chronic cholecystitis (t'= 8.06, P＜0.01). The AI was significantly lower in well-differentiated carcinoma and Nevin Ⅰ-Ⅲ carcinoma than that in poorly-differentiated carcinoma (t'= 2.63, P＜0.05) and Nevin Ⅳ-Ⅴ carcinoma(t'= 3.33, P＜0.01). The confidence interval (CI) ofinfiltrating lymphocytes in adenoma, chronic cholecystitis, well-differentiated carcinoma and Nevin Ⅰ-Ⅲ carcinoma wasvery significantly lower than that in carcinoma (t' = 6.99,P＜0.01), adenoma (t' = 3.66, P＜0.01), poorly-differentiated carcinoma (t' = 5.31, P＜0.01) and Nevin Ⅳ-Ⅴ carcinoma(t' = 3.76, P＜0.01), respectively. The CI of apoptosis of infiltrating lymphocytes in well-differentiated carcinoma was significantly lower than that in poorly-differentiated carcinoma (t = 2.52, P＜0.05), and was not significantly lower in Nevin Ⅰ-Ⅲ carcinoma than in Nevin Ⅳ-Ⅴ carcinoma (t = 1.42, P＞0.05). Apoptosis of infiltrating lymphocytes was not discovered in adenoma and chronic cholecystitis. CONCLUSION: FasL expressed in gallbladder carcinoma cells permits tumor cells to escape from immune surveillance of organism by inducing apoptosis in infiltrating lymphocytes of carcinoma tissues. Up-regulation of FasL expression plays an important role in invasive depth, histological classification and metastasis of gallbladder carcinoma.

Association between Up-regulation of Fas Ligand Expression and Apoptosis of Tumor-infiltrating Lymphocytes in Human Breast Cancer

In order to study the significance of FasL expression in immune escape of breast cancer, FasL protein expression and the number of tumor-infiltrating lymphocytes （TILs） in 40 specimens of breast cancer were detected by immunohistochemitry. The expression of FasL mRNA was measured by in situ hybridization in the consecutive tissue slices of 40 breast cancers respectively. By using terminal deoxynucleotidyl transferase-mediaed dUTP nick end labeling （TUNEL）, apoptotic cells were detected in 40 specimens of breast cancer. The expression of FasL was detected in all 40 specimens to varying degrees. In the consecutive tissue slices, the location of expression of FasL protein corresponded with that of FasL mRNA. In those with FasL extensive expression, the number of TILs was less （P〈0.05）, the apoptotic index （AI） of TILs was higher and the AI of tumor cells was lower （P〈0.01） than those with FasL weak expression respectively. The AI of TILs was correlated with that of tumor cells （r=-0.629, P〈0.01）. In conclusion, breast cancer cells can induce the apoptosis of TILs through the expression of FasL, which can counterattack the immune system. This may be a mechanism of immune evasion in breast cancer.

Study on the Expression of Fas Ligand on the Surfaces of Human Cytotrophoblasts in Normal Pregnancy

To further study the mechanism of maternal-fetal immune tolerance, the expression of Fas ligand (FasL) on the surfaces of human cytotrophoblasts in normal pregnancy was detected by using immunohistochemical method. High precise color-image measure system for immuno-histo- chemistry was used to quantitatively analyze the expression of FasL. The results showed that FasL were expressed on the surfaces of placental cytotrophoblasts throughout normal pregnancy. The variance among the first, second and term pregnant stages was also detected. It was suggested that the expression of FasL on the surfaces of placental cytotrophoblasts might play an important role both in the maintenance of pregnancy and in the normal development of fetus. The maternal speific T cell apoptosis induced by Fas/FasL is one of the significant mechanisms of maternal-fetal immune tolerance.

Effects of Ureaplasma Urealyticum on Fas Ligand Expression in Rat Sertoli Cell

To investigate the effect of ureaplasma urealyticum (UU) on the expression of Fas ligand (FasL) on rat Sertoli cell Materials & Method Isolated rat Sertoli cells were infected by living UU, UU super- natants, inactivated UU, then Fluorescence Activated Cell Sorter and observed fluores- cence microscopy were used to assay for the FasL expression on the surface of Sertoli cells. Results UU infection could increase the expression of FasL in Sertoli cell. Conclusion The functional expression of FasL is related to the immune privilege and can give the immune regulation on the testis.

Up-regulation of Fas Ligand Expression by Sirtuin 1 in both Flow-restricted Vessels and Serum-stimulated Vascular Smooth Muscle Cells

Objective To study the role of sirtuin 1 （SIRT1） in Fas ligand （FasL） expression regulation during vascular lesion formation and to elucidate the potential mechanisms. Methods SIRT1 and FasL protein levels were detected by Western blotting in either mouse arteries extract or the whole rat aortic vascular smooth muscle cell （VSMC） lysate. Smooth muscle cell （SMC）-specific human SIRT1 transgenic （Tg） C57BL/6 mice and their littermate wild-type （WT） controls underwent complete carotid artery ligation （ligation groups） or the ligation-excluded operation （sham groups）. The carotid arteries were collected 1 day after operation. Reverse transcription-polymerase chain reaction was performed to detect the mRNA levels of SIRT1 and FasL. Luciferase reporter assays were performed to detect the effect of WT-SIRT1, a dominant-negative form of SIRT1 （SIRT1H363Y）, and GATA-6 on the promoter activity of FasL. Flow cytometry assay was applied to measure the hypodiploid DNA content of VSMC so as to monitor cellular apoptosis. Results SIRTI was expressed in both rat aortic VSMCs and mouse arteries. Forced SIRT1 expression increased FasL expression both in injured mouse carotid arteries 1 day after ligation （P〈0.001） and VSMCs treated with serum （P〈0.05 at the transcriptional level, P〈0.001 at the protein level）. No notable apoptosis was observed. Furthermore, transcription factor GATA-6 increased the promoter activity of FasL （P〈0.001）. The induction of FasL promoter activity by GATA-6 was enhanced by WT-SIRT1 （P〈0.001）, while SIRT1H363Y significantly relieved the enhancing effect of WT-SIRT1 on GATA-6 （P〈0.001）. Conclusions Overexpression of SIRT1 up-regulates FasL expression in both flow-restricted mouse carotid arteries and serum-stimulated VSMCs. The transcription factor GATA-6 participates in the transcriptional regulation of FasL expression by SIRT 1.

A fast and in-depth self-reconstruction of anion ligands optimized CoFe-based pre-catalysts for water oxidation

The design of efficient and robust non-precious metal electrocatalysts towards oxygen evolution reaction(OER)is of great value for developing green energy technologies.The in-situ formed high-valence(oxy)hydroxides species during the reconstruction process of pre-catalysts are recognized as the real contributing sites for OER.However,pre-catalysts generally undergo a slow and inadequate self-reconstruction.Herein,we reported a PO^(3-)_(4)optimized CoFe-based OER catalysts with amorphous structure,which enables a fast and deep reconstruction during the OER process.The amorphous structure induced by ligands PO^(3-)_(4)is prone to evolution and further form active species for OER.The electron interaction between metal sites can be modulated by electron-rich PO^(3-)_(4),which promotes generation of high active CoOOH.Simultaneously,the etching of PO^(3-)_(4)from the pre-catalysts during the catalytic process is in favor of accelerating the self-reconstruction.As a result,as-prepared precatalyst can generate high active CoOOH at a low potential of 1.4 V and achieve an in-depth reconstructed nanosheet structure with abundant OER active sites.Our work provides a promising design of pre-catalysts for realizing efficient catalysis of water oxidation.

EXPRESSION OF Fas LIGAND IN HUMAN COLON CANCER CELL LINES

Objective: To investigate the expression of Fas ligand in human colon carcinoma cell lines. Methods: A total of six human colon cancer cell lines were examined for the expression of Fas ligand mRNA and cell surface protein by using RT-PCR and flow cytometry respectively. Results: The results showed that Fas ligand mRNA was expressed in all of the six cancer cell lines and Fas ligand cell surface protein was expressed in part of them. Conclusion: These data suggest that Fas ligand was expressed, at least in part, in human colon cancer cell lines and might facilitate to escape from immune surveillance of the host.

Apoptosis of Leukemia Cells Induced by CD34^+ Cells Transferred Exogenous Fas Ligand

To assess the value of CD34 + cells transferred exogenous Fas ligand (FasL) in inducing apoptosis of human leukemic cells, the CD34 + cells transfected with F asL or without, pretreated with mitomycin C, was mixed with leukemic cell line U937 cells in presence or absence of daunorubicin (DNR) or cytosine arabinoside (Ara C). After l8 h, apoptosis of cells was detected by FCM and TUNEL. Induced for l8 h by CD34 + cells transfected with FasL or without, the ratio of apoptos is of U937 cells was (5.0±1.3) %, (10.8±0.6) % ( P < 0.01), respectively. Induced by FasL +CD34 ++DNR, FasL +CD34 ++Ara C, the ratio was (13.4±1.0) % ( P < 0.05), (17.9±1.3)% ( P <0.01), respectively. The result demonstrated that CD34 + cells transfected with exogenous FasL could induce apoptosis of human leukemic cells and showed a cytotoxic synergistic effect when used in combination with chemotherapeutic drugs, suggesting that it was possible to develop a new method in treatment of leukemia.

EXPRESSION OF PERFORIN AND FAS LIGAND IN INFILTRATING CELLS OF MURINE MYOCARDIUM INFECTED WITH COXSACKIEVIRUS B3

Purpose. To clarify the role of perforin-and Fas ligand (L)-mediated cytotoxicity pathogenesis of viral myocarditis. Materials and methods. Forty balb/c mice were randomly divided into experimental group (n = 20) and control group (n = 20), and inoculated intraperitoneally with coxsackievirus B3(CVB3) and Eagle’s solu- tion without CVB3, respectively. The mice were sacrificed and their hearts were removed at day 7 post-in- oculation. Expression of perform and FasL were detected with immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization. Results. (1)Perform-and FasL-positiye cells were demonstrated in experimental murine hearts by im- munohistochemistry, however, no cells were discovered in control murine hearts; (2) The examination of RT-PCR showed the positive ratios of perform and FasL mRNA in myocardium were significantly higher in experimental group (100% and 100 % ) than that in control group (20% and 30 %, P<0.05); (3)Positive signals of perform and FasL mRNA were found in myocardium of all the experimental mice by in situ hybridization, but nothing was detected in control group. Conclusion. Perform and FasL can be expressed in infiltrating cells in murine myocardium with acute myocarditis caused by CVB3, suggesting perform and FasL might play an important role in pathogenesis of viral myocarditis.

Mechanism of counterattack of colorectal cancer cell by Fas/Fas ligand system

AIM： To determine the role of Fas/Fas ligand （FasL） in the immune escape of colon cancer cells. METHODS： Immunohistochemistry was used to observe the expression of Fas and FasL in the tissues of colon cancer patients. In situ hybridization was used to detect the localization of FasL mRNA expression in cancer tissues. Terminal deoxynucleotide transferase-mediated dUTP nick end labeling （TUNEL） assay and CD45 staining were performed to detect the apoptosis of tumor-infiltrating lymphocytes （TILs）. Co-culture assays of colon cancer cells （SW480） and Jurkat cells （Fas-sensitive cells） were performed to observe the counterattack of colon cancer cells to lymphocytes. RESULTS： Of 53 cases of colon carcinomas, 23 cases （43.4%） expressed Fas which was significantly lower as compared to the normal colonic mucosa （73.3%, P〈0.01）, and 45 cases （84.9%） of colon carcinomas expressed FasL, whereas only two cases （3.75%） in normal mucosa expressed FasL. FasL expression in the colon cancer cells was found to be associated with increased cell death of TIEs. The apoptotic rate of TIL in the FasL-positive staining regions of tumor cells was significantly higher than that in the FasL-negative staining region （54.84±2.79% vs 25.73±1.98%, P〈0.01）. The co-culture of SW480 cells and Jurkat cells confirmed the function of FasL on the SW480 cells. The apoptotic rates of Jurkat cells were found to be related with the amount of SW480 cells. CONCLUSION： Colon cancer cells can escape the immune surveillance and killing via decreasing Fas expression, and can counterattack the immune system via increasing FasL expression. Fas/FasL can serve as potential targets for effective antitumor therapy.

CHANGES OF SOLUBLE FAS AND SOLUBLE FAS LIGANDIN SERUM AND PERITONEAL FLUID OF INFERTILEPATIENTS WITH ENDOMETRIOSIS

Objective To evaluate the relationship between levels of soluble Fas(sFas)and soluble Fas ligand(sFasL)in serum and peritoneal fluid of endometriosis-associated infertility. Methods The soluble Fas ligand and soluble Fas levels in serum and peritoneal fluid of 20 infertile patients with endometriosis were assessed with enzyme-linked immunosorbent assay, and were compared with 14 infertile patients due to chronic pelvic infectious disease and 16 fertile controls. Results The sFasL levels were significantly higher in infertile patients with endometriosis(175.09 ± 80.55 pg/mL in serum and 284.50 ± 152.38 pg/mL in peritoneal fluid)than those of infertile controls (88.47 ± 43.55 pg/mL in serum and 17.30 ± 9.62 pg/mL in peritoneal fluid)and fertile controls(16.13 ± 11.75 pg/mL in serum and 8.84 ± 2.31 pg/mL in peritoneal fluid). In contrast, as for the sFas levels, infertile patients with endometriosis(828.60 ± 429.65 pg/mL in serum and 349.61 ± 288.89 pg/mL in peritoneal fluid)did not show any significant difference compared with those in infertile patients resulting from pelvic infectious disease(868.75 ± 570.48 pg/mL in serum and 181.76 ± 157.78 pg/mL in peritoneal fluid)and fertile control(822.26 ± 129.12 pg/mL in serum and 318.42 ± 145.16 pg/mL in peritoneal fluid). Conclusions Based upon these results, high level of sFasL in serum and peritoneal fluid and thus apoptosis mediated by it may be implicated in the mechanism involved in endometriosis-related infertility.

Expression of Fas ligand and Caspase-3 contributes to formation of immune escape in gastric cancer

AIM: To study the role of Fas ligand (FasL) and Caspase-3expression in carcinogenesis and progression of gastric cancer and molecular mechanisms of relevant immune escape.METHODS: FasL and Caspase-3 expression was studied in adjacent epithelial cells, cancer cells and lymphocytes of primary foci, and cancer cells of metastatic foci from 113 cases of gastric cancer by streptavidin-biotin-peroxidase (S-P) immunohistochemistry. Expression of both proteins in cancer cells of primary foci was compared with clinicopathological features of gastric cancer. The relationship between FasL expression in cancer cells and Caspase-3expression in cancer cells or infiltrating lymphocytes of primary foci was investigated.RESULTS: Cancer cells of primary foci expressed FasL in 53.98 % (61/113) of gastric cancers, more than their adjacent epithelial cells (34.51%, 39/113) (P=0.003, X2=8.681), while the expression of Caspase-3 in cancer cells of primary foci was detected in 32.74 % (37/113) of gastric cancers, less than in the adjacent epithelial cells (50.44 %, 57/113)(P=0.007, X2=7.286). Infiltrating lymphocytes of the primary foci showed positive immunoreactivity to Caspase-3 in 70.80 % (80/113) of gastric cancers, more than their corresponding adjacent epithelial cells (P=0.001, X2=10.635)or cancer cells of primary foci (P=0.000, X2=32.767). FasL was less expressed in cancer cells of metastases (51.16 %,22/43) than in those of the corresponding primary foci (81.58 %, 31/38) (P=0.003, X2=9.907). Conversely,Caspase-3 was more expressed in cancer cells of metastases (58.14 %, 25/43) than in those of the corresponding primary foci (34.21%, 13/38) (P=0.031, X2=4.638). FasL expression was significantly correlated with tumor size (P=0.035,rs=0.276), invasive depth (P=0.039, rs=0.195), metastasis (P=0.039, rs=0.195), differentiation (P=0.015, rs=0.228)and Lauren′s classification (P=0.038, rs=0.196), but not with age or gender of patients, growth pattern or TNM staging of gastric cancer (P＞0.05). In contrast, Caspase-3 expression showed no correlation with any dinicopathological parameters described above in cancer cells of the primary foci (P＞0.05).Interestingly, FasL expression in primary gastric cancer cells paralleled to Caspase-3 expression in infiltrating lymphocytes of the primary foci (P=0.016, X2=5.825).CONCLUSION: Up-regulated expression of FasL and downregulated expression of Caspase-3 in cancer cells of primary foci play an important role in gastric carcinogenesis. As an effective marker to reveal the biological behaviors, FasL is implicated in differentiation, growth, invasion and metastasis of gastric cancer by inducing apoptosis of infiltrating lymphocytes. Chemical substances derived from the primary foci and metastatic microenvironment can inhibit the growth of metastatic cells by enhancing Caspase-3 expression and diminishing FasL expression.

Gene Expression of Fas,Soluble Fas and Fas-Ligand in Thyroid Tissues and Thyrocytes from Patients with Graves′ Disease

ObjectiveTo investigate Fas,soluble Fas(sFas)and Fas ligand(Fas L)gene expression in thyroid tissues and thyrocytes from patients with Graves disease(GD)and to find the interrelationship between apoptosis and pathogenesis of GD. MethodsThyroid tissues were obtained from 7 GD patients and 3 healthy subjects who died accidentally. Thyrocytes were cultured in Eagle′s medium. Total RNA was isolated from thyroid tissues and cultured thyrocytes. The cDNA was prepared by reverse transcription and amplified for Fas,sFas and Fas L by polymerase chain reaction(PCR). ResultsFas and sFas mRNA were detected in all samples from both GD and normal thyroid tissues and thyrocytes,but Fas L mRNA was only found in GD thyroid tissues and thyrocytes. Semi quantitative analysis showed that when compared with those of normal controls,the Fas and sFas mRNA levels were markedly increased in GD thyroid tissues(P<0.01),whereas in GD thyrocytes only the sFas mRNA levels was significantly elevated(P<0.01). ConclusionGene expression of Fas,sFas and Fas L showed abnormality in both thyroid tissues and thyrocytes from GD. The increased production of sFas might be involved in the hyperplasia of thyroid gland.

Investigation on etretin effects on expression of Fas/FasL ligand and apoptosis in cultured human keratinocytes

Objective:To further illuminate a possibme mechanism of Fas/FasL in the treatment of psoriasis, the expression of it and apoptosis of KC were investigated. Methods: With cell culture,immunocytochemistry, the expression of Fas/FasL protein after the treatment with etretin was observed in cultured human normal keratinocytes. Then, the state of apoptosis in cultured keratinocyte after stimulation with etretin was detected with FACS(Fluorescence Activited Cell Sortor). Results:① There was no expression of Fas/FasL protein in the cultured normal human KC. ②After the treatment with etretin, the strongest expression of FasL protein appeared after 16h,so did Fas after 40h.③ The higher the concentration of etretin,the stronger the expression of Fas/FasL protien.Under the same condition,the expression of Fas is stronger than that of FasL.④ Keratinocytes' apoptosis occurred after stimulation with etretin. Conclusion: Fas/FasL system wasn't involved in apoptosis in cultured normol human keratinocytes.But during limited period, the apoptosis of KC could be induced by (etretin),thus it can antagonize benign proliferate of keratinocytes.Our data showed up-regulation of the expression of Fas/FasL and apoptosis in cultured human keratinocytes stimulated by etretin, and its function may be involved in the therapeutic machanism of psoriasis.

C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 pathway as a therapeutic target and regulatory mechanism for spinal cord injury

Spinal cord injury involves non-reversible damage to the central nervous system that is characterized by limited regenerative capacity and secondary inflammatory damage.The expression of the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis exhibits significant differences before and after injury.Recent studies have revealed that the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis is closely associated with secondary inflammatory responses and the recruitment of immune cells following spinal cord injury,suggesting that this axis is a novel target and regulatory control point for treatment.This review comprehensively examines the therapeutic strategies targeting the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis,along with the regenerative and repair mechanisms linking the axis to spinal cord injury.Additionally,we summarize the upstream and downstream inflammatory signaling pathways associated with spinal cord injury and the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis.This review primarily elaborates on therapeutic strategies that target the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the latest progress of research on antagonistic drugs,along with the approaches used to exploit new therapeutic targets within the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the development of targeted drugs.Nevertheless,there are presently no clinical studies relating to spinal cord injury that are focusing on the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis.This review aims to provide new ideas and therapeutic strategies for the future treatment of spinal cord injury.