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Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.
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Objective To investigate the effect of exosomes derived from Echinococcus multilocularis on macrophage polarization after treatment for different durations and concentrations. Methods A total of 60 BALB/c mice were used for modeling, among which 4 mice were selected to observe the growth of abdominal lesions on 7.0T MRI. The mice for modeling were dissected, and the protoscoleces was taken from the abdominal lesion and cultured in vitro ; ultracentrifugation was used to extract the exosomes from the supernatant, and transmission electron microscopy and Western blotting were used for the characterization of exosomes. The macrophages without exosome treatment were established as control group, and the macrophages co-cultured with different concentrations of exosomes derived from Echinococcus multilocularis were established as experimental group (10 μg/mL group and 50 μg/mL group) and were cultured for 48 and 72 hours. The morphological changes of macrophages were observed under a microscope, and flow cytometry and ELISA were used to observe polarization state. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results The results of 7.0T MRI showed the formation of diffuse lesions with different sizes in the abdominal cavity of mice, and the exosomes derived from Echinococcus multilocularis were approximately 100 nm in diameter and were cup-shaped or saucer-shaped, with the positive expression of the surface markers CD9, TSG101, and CD63. After co-culture, most of the cells in the experimental group were elongated with an irregular and polygonal shape. Flow cytometry showed that after 48 hours of co-culture, the positive rates of CD16/32, CD206, and CD369 in the control group were 99.53%±0.06%, 90.27%±0.21%, and 2.40%±0.20%, respectively; compared with the control group, except that the 10 μg/mL exosome group had a significant reduction in the positive rate of CD369 (0.80%±0.00%) ( P < 0.05), all the other groups had a significant increase in the positive rates of CD16/32, CD206, and CD369 (all P < 0.000 1); after 72 hours of co-culture, the positive rates of CD16/32, CD206, and CD369 in the control group were 99.67%±0.06%, 85.47%±0.55%, and 6.60%±0.20%, respectively, and compared with the control group, the experimental group had significant increases in the positive rates of CD16/32, CD206, and CD369 (all P < 0.05). ELISA showed that after 48 hours of co-culture, the levels of IL-6 and TNFα in the control group were 58.53±15.52 pg/mL and 320.70±5.30 pg/mL, respectively, and when the exosome concentration was 50 μg/mL, the level of IL-6 in the experimental group was 98.81±15.55 pg/mL, which was higher than that in the control group ( P < 0.05); after 72 hours of co-culture, the levels of IL-6 and TNFα in the control group were 76.22±9.68 pg/mL and 323.90±87.37 pg/mL, respectively, and when the exosome concentration was 10 μg/mL, the level of TNFα was 164.20±14.17 pg/mL, which was significantly lower than that in the control group ( P < 0.05); when the exosome concentration was 50 μg/mL, the level of IL-6 was 99.52±8.35 pg/mL, which was significantly higher than that in the control group ( P < 0.05). Conclusion Exosomes derived from Echinococcus multilocularis can regulate macrophage polarization and induce M2-like polarization of macrophages after co-culture at a concentration of 10 μg /mL for 72 hours, and further studies are needed to clarify the specific method.
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Objective:To explore the application effect of small private online course (SPOC) teaching mode in clinical practice teaching of thoracic surgery.Methods:A total of 56 undergraduate students who were internships from May to July 2018 were selected as subjects. They were randomly divided into experimental group and control group. SPOC teaching mode and traditional teaching mode were respectively adopted in the practice teaching, and the teaching effect was evaluated by questionnaires and written examinations. SPSS 22.0 was used for statistical analysis, ttest for independent-sample test, and chi-square test for counting data. There were significant differences when P<0.05. Results:The questionnaire showed that the six teaching effect evaluation indicators of the experimental group were higher than those of the control group ( P<0.01). In terms of written test assessment, the average score of the experimental group was significantly higher than that of the control group, with significant differences ( P<0.05). Conclusion:The SPOC teaching mode can improve the teaching effect of clinical practice in thoracic surgery and improve students' self-learning ability.
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Aim To figure out whether Lonicera mac-ranthoides could induce hemolysis. Methods In vitro, macroscopic observation and spectrophotometry were used to observe whether the solutions of extracts from Lonicera macranthoides, MacranthoidinB and Dipsa-cosideB could induce hemolysis in 2% red cell suspen-sion of New Zealand white rabbits. And the three test-ed materials were prepared in concentration gradient of 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100 mg· L - 1; and in vivo, mice were respectively treated with MacranthoidinB (0. 110 g·kg - 1 , 0. 055 g·kg - 1 ), DipsacosideB(0. 020 g·kg - 1 , 0. 010 g·kg - 1 ), ex-tracts (2. 275 g·kg - 1 , 1. 137 g·kg - 1 , crude drugs) once per day for 7 days, and all of the tested doses de-pended on the clinical doses. Then, RBC, RET and MCHC before and after administration were tested. Re-sults The hemolytic ratio in each treated group was below 5% in vitro. And in vivo, the three materials did not induce hemolysis and had no significant influence on RBC,RET and MCHC(P > 0. 05). Conclusions Extracts from flower bud of Lonicera macranthoides, MacranthoidinB and DipsacosideB, have not caused hemolysis in vivo and in vitro in this research.
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Objective To investigate the influences of HLA mismatching on renal function in the kidney transplant patients re-ceiving pairs of allograft from the same donor.Methods 171 pairs of renal transplant patients receiving the kidneys from the same donors were investigated.They were admitted in our hospital before 2008.Their human leukocyte antigens (HLA)were typed with the commercial polymerase chain reaction (PCR)-sequence-specific primers (SSP)HLA typing kit (One Lambda,Inc.,USA;and GTI Diagnostics,USA).The serum creatinine (SCr)and blood urea nitrogen(BUN)were measured in the clinical laboratory of our hospital.Results Among 171 pairs of renal transplant patients,there were 162 recipients with HLA mismatch≤4,in which the re-nal function was remained stable in 107 recipients and lost or decreased in 55 patients.There were 180 recipients with HLA mis-match >4,in which the renal function was stayed normal in 84 recipients and lost or decreased in 96 patients.The difference in in-fluencing the renal function between the HLA mismatch≤4 and HLA mismatch>4 had statistical significance (χ2 =12.22,P <0.05).Conclusion Excellent HLA typing match has important significance for renal long term survival.
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<p><b>BACKGROUND</b>Advances in transplantation immunology show that the balance between dendritic cells (DCs) and their subsets can maintain stable immune status in the induction of tolerance after transplantation. The aim of this study was to investigate if DCs and DC subpopulations in recipient peripheral blood are effective diagnostic indicators of acute rejection following kidney transplantation.</p><p><b>METHODS</b>Immunofluorescent flow cytometry was used to classify white blood cells (WBCs), the levels of mononuclear cells and DCs (including the dominant subpopulations, plasmacytoid DC (pDC) and myeloid DC (mDC)) in peripheral blood at 0, 1, 7, and 28 days and 1 year after kidney transplantation in 33 patients. In addition, the blood levels of interleukin-10 (IL-10) and IL-12 were monitored before and after surgery. Fifteen healthy volunteers served as normal controls. Patients were undertaking hemodialysis owing to uremia before surgery.</p><p><b>RESULTS</b>The total number of DCs, pDC, and mDC in peripheral blood and the pDC/mDC ratio were significantly lower in patients than controls (P < 0.05). Peripheral DCs suddenly decreased at the end of day 1, then gradually increased through day 28 but remained below normal levels. After 1 year, levels were higher than before surgery but lower than normal. The mDC levels were higher in patients with acute rejection before and 1 day after surgery (P < 0.005). There was no significant difference in IL-10 and IL-12 levels between patients with and without acute rejection.</p><p><b>CONCLUSION</b>The changes in DCs and DC subpopulations during the acute rejection period may serve as effective markers and referral indices for monitoring the immune state, and predicting rejection and reasonably adjusting immunosuppressants.</p>
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Adolescent , Adult , Humans , Middle Aged , Young Adult , Dendritic Cells , Allergy and Immunology , Graft Rejection , Allergy and Immunology , Kidney Transplantation , Myeloid Cells , Allergy and ImmunologyABSTRACT
Objective To study the impact of panel reactive antibody (PRA)on the long-term prognosis of transplant renal function after renal transplantation.Methods The objects of this study were 224 patients,who underwent renal transplantation,received PRA test about 2 weeks after operation and followed up in Affiliated Beijing Friendship Hospital of Capital Medical University from January 1 994 to December 2004.According to the PRA test results,the patients were divided into two groups:negative group (n =1 95)and positive group (n =29).PRA of patients in negative group were tested again in 2007.Serum creatinine (Scr) of patients in both groups were tested recently (from October 201 3 to April 201 4)to know about the renal function.The rates of long-term normal transplant renal function between PRA positive patients (including PRA re-test positive patients)and PRA negative patients were compared.Results In 29 cases of positive group, the re-test result in April 201 4 showed that 1 8 cases were observed with loss (n =1 7)or decline (n =1 )of renal function,and 1 1 cases were observed with normal renal function.In 1 95 cases of negative group,a total of 1 53 cases were re-tested with PRA negative in 2007,1 48 cases were re-tested with normal renal function in April 201 4,and 5 cases were observed with decline or loss of renal function.A total of 42 cases were re-tested with PRA positive in 2007 and the transplant renal function was observed decline or loss by varying degrees.There were a total of 71 cases with PRA positive before 2004 and when re-tested in 2007,and 1 1 cases were re-tested with normal renal function in April 201 4.The rate of long-term normal transplant renal function was 1 5.5%.There were 1 53 cases with PRA negative and 1 48 cases were re-tested with normal renal function in April 201 4.The rate of long-term normal transplant renal function was 96.7%.Significant difference was observed in the rates of long-term normal transplant renal function between PRA positive patients and PRA negative patients (P <0.005).Conclusions PRA after renal transplantation has obvious impacts on the long-term prognosis of transplant renal function.
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Objective To study the relation between donor-recipient human leukocyte antigen (HLA)mismatching and combined malignant tumors after renal transplantation. Methods Clinical data of 1 021 patients who received renal transplantation from 1993 to 2009 in Department of Urology of Beijing Friendship Hospital of Affiliated Capital University of Medical Sciences over 5 years and had complete HLA typing were analyzed. In the 1 021 patients after renal transplantation,928 cases were non-tumor patients and 93 cases were malignant tumor patients. The mismatching data of 3 locus (HLA-A,B and DR)with a total of 6 antigens of the donors and recipients were collected. The relation between donor-recipient HLA mismatching number and postoperative combined malignant tumors was analyzed. And that between genders was also analyzed. Results Malignant tumors occurred in 9.11% (93/1 021)of the patients. The malignant tumor incidences of patients with HLA mismatch of 0-1,2,3,4,5 and 6 antigens were 14%,13%,14%,6%, 3% and 4%respectively. Patients with HLA over half-matched (0-3 antigens mismatch)had higher incidence of malignant tumors compared with that in patients with HLA less than half matched (4-6 antigens mismatch) (14% vs. 5%;χ2 =24.11,P<0.005). In the malignant tumor patients of0-3 antigens mismatch,12 cases were males and 54 cases were females. In the patients of 4-6 antigens mismatch,12 cases were males and 15 cases were females. The proportion of female patients of 0-3 antigens mismatch was higher than that of male patients (χ2 =5.60,P<0.025). Conclusions For the renal transplant patients,especially female patients, the lower the HLA mismatching number is,the higher the malignant tumor incidence is.
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Objective To study the correlation between transplanted kidney dysfunction and oc-currence of the panel reactive antibody ( PRA, also referred as anti-HLA antibody ) and anti-Major-Histo-compatibility-Complex class Ⅰrelated chain A (MICA) antibody.Methods The tests for detecting PRA and anti-MICA antibody were performed on 679 renal transplant patients from December , 2009 to June, 2010 who received transplantation before 2008 in Beijing Friendship Hospital .Enzyme-Linked Immunosor-bent Assay ( ELISA) was used to detect anti-HLA antibody using LAT-1240 ( OneLambda Inc .) .MICA Ab-Scan Kit was adopted to detect anti-MICA antibody .Continuous observation of graft function was conducted . Results 108 out of 679 patients showed anti-HLA antibody and/or anti-MICA antibody positive results . Among them, 81 patients were positive only for anti-HLA antibody, 18 patients were positive only for anti-MICA antibody and other 9 patients showed anti-HLA and anti-MICA antibodies double positive .Among all of the kidney transplant patients with a failed or decreased renal function , 71 patients were positive for anti-HLA antibody;16 patients were positive for anti-MICA antibody;and other 9 patients were positive for both anti-HLA and anti-MICA antibodies .The results demonstrated that anti-HLA and anti-MICA antibodies af-fected the renal functions in patient with renal transplantation (χ2 =353.92, P <0.001).Conclusion Anti-HLA and MICA antibodies showed significant positive correlations with chronic allograft failure in the patients with renal transplantation .
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BACKGROUND:Human bone marrow cells-derived extracellular matrix can promote proliferation of human periodontal ligament stem cells and maintain stem cellproperties. OBJECTIVE:To preliminarily investigate the effect of human bone marrow cells-derived extracellular matrix on the proliferation of human periodontal ligament stem cells. METHODS:Human periodontal ligament stem cells and bone marrow cells were separately derived from human periodontal tissue and jaw bone marrow, and human bone marrow cells-derived extracellular matrix was prepared. Human periodontal ligament stem cells were cultured and purified using limited dilution cloning method, and transmission electron microscope was used for ultrastructure observation. Human periodontal ligament stem cells at passage 2 were cultured with human bone marrow cells-derived extracellular matrix and normal culture medium (control group). The cellcounting kit-8 and flow cytometry were used to determine the proliferation potential of human periodontal ligament stem cells cultured on human bone marrow cells-derived extracellular matrix. RESULTS AND CONCLUSION:Compared with the control group, human periodontal ligament stem cells cultured on human bone marrow cells-derived extracellular matrix had a superior capacity of proliferation (P<0.05), and the cells met their morphological and biological characteristics, and grew in good conditions. Human bone marrow cells-derived extracellular matrix is a promising matrix for large-scale expanding human periodontal ligament stem cells for future use in stem cel-based therapy.
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BACKGROUND:Extracellular matrix can simulate microenvironment and make the stem cells proliferate maintaining the characteristics of stem cells wel in vitro. OBJECTIVE:To prepare the extracellular matrix from human bone marrow cells and to analyze its microstructure and composition preliminarily. METHODS:Human bone marrow cells of passage 4 were cultured for 14 days, and the induction medium was used during the last 8 days. After decellularization, cells were removed to prepare human bone marrow cells-derived extracellular matrix. The surface morphology of human bone marrow cells-derived extracellular matrix was observed by inverted microscope and scanning electron microscope. Changes of col agen I and biglycan before and after decellularization were observed by immunofluorescence staining. Human periodontal ligament stem cells were seeded onto human bone marrow cells-derived extracellular matrix, fibronectin coated 6-wel plate and normal culture plate to compare the influence of different matrix on cellmorphology and adhesion. RESULTS AND CONCLUSION:We obtained intact human bone marrow cells-derived extracellular matrix by chemical combined with physical decellularization. The structure and amount of col agen I and biglycan had not been compromised dramatical y after decellularization. Human periodontal ligament stem cells growing on the human bone marrow cells-derived extracellular matrix developed in accordance with the orbit of the extracellular matrix, differing from the original cellmorphology. There were more human periodontal ligament stem cells adhering to the extracellular matrix during the same time. These findings indicate that effective decellularization can produce intact the extracellular matrix membrane without destroying its microstructure. Extracellular matrix protein is not compromised due to decellularization. The extracellular matrix affects cellmorphology and promotes celladhesion. We can use the extracellular matrix model to simulate stem cellmicroenvironment and thereafter, acquire a large number of adult stem cells with high quality in vitro.
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Objective To study the influence on allograft function of HLA antibody in patients who received pairs of allograft from the same donor.Methods In Beijing Friendship Hospital.HLA antibodies were tested from October,2008 to April 2009 in patients.Recently (October,2013-February,2014),renal functions(serum creatinine/urea nitrogen)were studied in 226 patients who received transplant from 113 donors.LATM10x5,One Lambdas used for Panel reactive antibody screen-ing.Results 41 pairs of renal for male,21 pairs of renal for female and 51 pairs of renal for both male and female.PRA posi-tive in 26 patients (only 4 pairs of renal for patients were positive),11 recipients (HLA II antibody positive in only 1 pair of renal for patients)and 36 recipients (only 5 patients produced antibody)in 226 patients,HLA antibody positive in 73 pa-tients,in which renal function lost or decreased in 64 patients.HLA antibody negative in 153 recipients,in which renal func-tion lost or decreased in 4 patients.There was significant difference between the two group (χ2=160.70,P<0.001).Con-clusion HLA antibody is a important factor influence renal function and long term survival.
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This paper presents a unified view of interestingness measures for interesting pattern discovery. Specifically, we first provide three necessary conditions for interestingness measures being used for association pattern discovery. Then, we reveal one desirable property for interestingness measures: the support-ascending conditional antimonotone property (SA-CAMP). Along this line, we prove that the measures possessing SA-CAMP are suitable for pattern discovery if the itemset-traversal structure is defined by a support-ascending set enumeration tree. In addition, we provide a thorough study on the family of the generalized mean (GM) measure and show their appealing properties, which are exploited for developing the GMiner algorithm for finding interesting association patterns. Finally, experimental results show that GMiner can efficiently identify interesting patterns based on SA-CAMP of the GM measure, even at an extremely low level of support.
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Objective To analyze the dynamic changes of dendritic ceils (DCs) and their subsets plasmacytoid DC (pDC) and myeliod DC (mDC) in peripheral blood of renal transplantation patients,and to confer the relationship between DCs subsets and graft rejection.Methods White blood cells (WBC) and mononuclear cells (PBMNCs) in peripheral blood of 28 renal transplantation recipients (test group) were measured before operation and at 1st,7th,28th day after operation.The number of DCs and subsets,and pDC/mDC were detected by using flow cytometry,and IL-10 and IL-12 levels were determined by using ELISA before and after operation.Ten volunteers (control group) served as controls.Results The levels of DCs,pDC and mDC before operation in test group were lower than in control group (P＜0.05),but there was no statistically significant difference in pDC/mDC ratio between two groups (P＞0.05).The number of DCs in test group was significantly decreased on the first day after operation up to the lowest level,then slowly increased,and recovered 73.7 ％ at 28th day after operation.The number of mDC and pDC was also decreased after operation,but mDC recovered faster than pDC (P＜0.05).On the day 7th after operation,the number of mDC in the recipients with graft rejection was higher than in those without graft rejection in test group (P＜0.01 ).There was no significant difference before and after operation in the levels of IL-10 and IL-12 in test group.Conclusion The number of DCs and subsets are related to the recipients' immune state,and their abnormality displays unstable immune state of recipients.The number of DCs and subsets can be used as an assistance index to diagnose graft rejection.
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Objective To investigate the HLA antibody incidence and type renal recipients with different age, and to study the echaracteristics in different age patients, for clinical reference to forecast renal rejection in different age patients. Methods With serum dated from January 2006 to June 2008, patients were classified into three groups: young group, with age below 35 years; middle age group, with age from 36 to 50 years; and old group, with age above 50 years. Penel reactive antibody (PRA) were detected using ELISA. Results Pretransplant HLA antibody incidences in the young, middle age, old group were 18.18%, 23.00% and 6.19%, respectively. In young group, HLA antibody incidences were 5.59% and 8.51% in male and female respectively. In middle age group, they were 21.30% and 25.38% in male and female respectively. In old group, they were 11.36% and 25.00% respectively. HLA Ⅰ and HLA Ⅰ + Ⅱ antibodies were mainly found in all the three groups in pretansplant. Conclusion HLA Ⅰ and HLA Ⅰ + Ⅱ antibodies were mainly found in pretransplant. Antibody incidence was higher in patients who had more than once renal transplant than that in transfusion and pregnancy female. Antibody incidence is higher in female than that in male.
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Objective To analyze the sensitized factors in urinemia patients who waiting for renal transplantation.Methods 2429 patients with urinemia from April 2002 to December 2008 were subjected to the detection of panel reactive antibody, and classified into 5 groups according to their clinical data:(A) no history disease group (n = 1097) who never experienced transfusion, pregnancy and transplantation; (B) Transfusion group (n = 361) who received transfusion more than 200 ml; (C) Pregnancy group (n = 481) who experienced pregnancy; (D) Transfusion+ pregnancy group (n= 294) who experienced both pregnancy and transfusion; (E) Re-transplantation group (n = 196) who experienced failed transplantation before, and waited for the second renal transplantation.Results All the males in group A were negative for PRA, and females were weakly positive for HLA Ⅱ antibody.The incidence of PRA production in group B was 15.24 % (55/361).Thirty-nine patients were positive for PRA in group C with the incidence being 8.11 % (39/481).The PRA positive rate in groups D and E was 30.61 % (90/294) and 70.92 % (139/196) respectively.PRA intensity was more than 60 % in 72 patients in group E.Conclusion Transfusion and pregnancy caused lower incidence of PRA positive rate.The incidence was much higher in transfusion + pregnancy patients than that in patients with transfusion or pregnancy alone.Graft caused the higher incidence of PRA than by transfusion and pregnancy.
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BACKGROUND: It is confirmed that panel reactive antibody (PRA) and its immune level is closely related to rejection activation, renal survival rate and the realization of the renal function. Study addressing the relation PRA level and acute rejection has great clinical significance for forecasting acute rejection and improving the renal survival rate.OBJECTIVE: To analyze the relation of PRA and acute rejection prior to and after transplantation by detecting PRA level combined with patient rejection.DESIGN, TIME AND SETTING: Retrospectively case analysis was performed at the Affiliated Beijing Friendship Hospital of Capital University of Medical Sciences from September 1998 to May 2005.PARTICIPANTS: A total of 633 patients receiving renal transplantation were collected, including 348 males and 285 females, aged 16-67 years.METHODS: Company Lymphocyte Tray produced by One Lambda and Biotest were used for this study, serum PRA level was detected prior to and within 2 months after transplantation.MAIN OUTCOME MEASURES: Pre- and post-transplant PRA level and clinical rejection.RESULTS: Totally 591 patients were PRA negative in pre-transplant assay, and 164 patients were positive, 10.32% (61/591) patients occurred acute rejection; 42 patients were PRA positive in pre-transplant assay, and 71.42% (30/42) patients occurred acute rejection. The difference between PRA negative or positive and acute rejection had significance (P < 0.001). 427 patients were PRA negative in both pre- and post- transplant assay, 5.6% (24/427) patients occurred acute rejection. 164 patients were PRA negative in pre-transplant assay, but positive in post-transplant, 42.7% (70/164) patients occurred acute rejection. The comparison of PRA negative pre-transplant and PRA positive post-transplant combined with acute rejection had difference (P < 0.001). The correlation coefficient of pre-transplant PRA and acute rejection was 0.612, which was 0.658 between post-transplant PRA and acute rejection, there was obvious association when P=0.01.CONCLUSION: PRA plays an important role in forecasting renal rejection. The acute rejection probability is higher in patients with positive PRA; in other hand, the probability is lower in patients with negative PRA.
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Tumor suppressor CYLD is a deubiquitination enzyme that could regulate NF-?B and JNK signal pathways by deubiquitinating TRAFs,NEMO,Bcl-3 and p53,and in turn regulating the cell cycle and apoptosis.Loss or deficiency of CYLD would lead to the development of skin tumor,including multiple familial trichoepithelioma(MFT),familial cylindromatosis(FC),Brooke-Spiegler syndrome(BSS).Cancers like uterine cervix,kidney,and colon and hepatocellular carcinoma are related to the down-regulation of CYLD.
