AIM： To evaluate the safety and clinical efficacy of a new immunotherapy using both α-Gal epitope-pulsed dendritic cells （DCs） and cytokine-induced killer cells. METHODS： Freshly collected hepatocellular carcino...AIM： To evaluate the safety and clinical efficacy of a new immunotherapy using both α-Gal epitope-pulsed dendritic cells （DCs） and cytokine-induced killer cells. METHODS： Freshly collected hepatocellular carcinoma （HCC） tumor tissues were incubated with a mixture of neuraminidase and recombinant αl,3-galactosyltrans- ferase （αI,3GT） to synthesize α-Gal epitopes on car- bohydrate chains of the glycoproteins of tumor mem- branes. The subsequent incubation of the processed membranes in the presence of human natural anti-Gal IgG resulted in the effective phagocytosis to the tumor membrane by DCs. Eighteen patients aged 38-78 years with stage 111 primary HCC were randomly chosen for the study; 9 patients served as controls, and 9 patients were enrolled in the study group.RESULTS： The evaluation demonstrated that the pro- cedure was safe; no serious side effects or autoimmune diseases were observed. The therapy significantly pro- longed the survival of treated patients as compared with the controls （17.1 ± 2.01 mo vs 10.1 ±4.5 mo, P = 0.00121）. After treatment, all patients in the study group had positive delayed hypersensitivity and robust systemic cytotoxicity in response to tumor lysate as measured by interferon-y-expression in peripheral blood mononuclear cells using enzyme-linked immunosorbent spot assay. They also displayed increased numbers of CD8-, CD45RO- and CD56-positive cells in the peripheral blood and decreased α-fetoprotein level in the se- rum. CONCLUSION： This new tumor-specific immunotherapy is safe, effective and has a great potential for the treat- ment of tumors.展开更多
Decellularised extracellular matrix(dECM)biomaterials originating from allogeneic and xenogeneic tissues have been broadly studied in the field of regenerative medicine and have already been used in clinical treatment...Decellularised extracellular matrix(dECM)biomaterials originating from allogeneic and xenogeneic tissues have been broadly studied in the field of regenerative medicine and have already been used in clinical treatments.Allogeneic dECMs are considered more compatible,but they have the drawback of extremely limited human tissue sources.Their availability is also restricted by the health and age of the donors.To investigate the viability of xenogeneic tissues as a substitute for human tissues,we fabricated both porcine decellularised nerve matrix(pDNM)and human decellularised nerve matrix for a comprehensive comparison.Photomicrographs showed that both dECM scaffolds retained the ECM microstructures of native human nerve tissues.Proteomic analysis demonstrated that the protein compositions of both dECMs were also very similar to each other.Their functional ECM contents effectively promoted the proliferation,migration,and maturation of primary human Schwann cells in vitro.However,pDNM contained a few antigens that induced severe host immune responses in humanised mice.Interestingly,after removing theα-galactosidase antigen,the immune responses were highly alleviated and the pre-treated pDNM maintained a human decellularised nerve matrix-like pro-regenerative phenotype.Therefore,we believe that anα-galactosidase-free pDNM may serve as a viable substitute for human decellularised nerve matrix in future clinical applications.展开更多
AIM: To examine the α-Gal gene expression and distribution in the different species/genus and developing phase animal ocular surface tissue.METHODS: α-Gal binding assay were carried out on various animal eye section...AIM: To examine the α-Gal gene expression and distribution in the different species/genus and developing phase animal ocular surface tissue.METHODS: α-Gal binding assay were carried out on various animal eye sections. Photograph, slit-lamp observation on various eye showed normal corneal transparence.RESULTS: A strong α-Gal expression in invertebrates and some vertebrates ocular tissue, but no α-Gal binding in birds, fish and mammal. α-Gal expression change in the development of mice ocular surface tissue (except sclera) and display genus dependency in the different murine ocular surface tissue.CONCLUSION: This study identified specific α-Gal epitopes binding area in the ocular surface of several species and may solve the problem that naive ocular surface may be used as natural α-Gal gene knockout model/high risk immunologic rejection model or ocular surface scaffold material.展开更多
We aimed to explore the prevalence of Fabry disease in Thai patients who were diagnosed with end-stage renal disease（ESRD） of an unknown origin.Venous blood samples were collected from ESRD patients for biochemical ...We aimed to explore the prevalence of Fabry disease in Thai patients who were diagnosed with end-stage renal disease（ESRD） of an unknown origin.Venous blood samples were collected from ESRD patients for biochemical and molecular studies.Alpha-galactosidase A（a-GAL A） screening was performed from dried-blood spots using fluorometry.Molecular confirmation was performed using DNA sequencing of the GLA gene.A total of 142 male and female patients were included in this study.Ten patients（7.04%） exhibited a significant decrease in a-GAL A activity.There were no definitive pathogenic mutations observed in the molecular study.However,four patients revealed a novel nucleotide variant at c.l-10 C〉T,which was identified as a benign variant following screening in the normal population.In conclusion,the a-GAL A assay utilizing dried-blood spots revealed a significant false positive rate.There was no definitive Fabry disease confirmed in Thai patients diagnosed with ESRD of unknown etiology.展开更多
基金Supported by Hong Kong Wang Kuan Cheng GrantInner Mongolia Stem Cell Grant, No. kjk10jhg
文摘AIM： To evaluate the safety and clinical efficacy of a new immunotherapy using both α-Gal epitope-pulsed dendritic cells （DCs） and cytokine-induced killer cells. METHODS： Freshly collected hepatocellular carcinoma （HCC） tumor tissues were incubated with a mixture of neuraminidase and recombinant αl,3-galactosyltrans- ferase （αI,3GT） to synthesize α-Gal epitopes on car- bohydrate chains of the glycoproteins of tumor mem- branes. The subsequent incubation of the processed membranes in the presence of human natural anti-Gal IgG resulted in the effective phagocytosis to the tumor membrane by DCs. Eighteen patients aged 38-78 years with stage 111 primary HCC were randomly chosen for the study; 9 patients served as controls, and 9 patients were enrolled in the study group.RESULTS： The evaluation demonstrated that the pro- cedure was safe; no serious side effects or autoimmune diseases were observed. The therapy significantly pro- longed the survival of treated patients as compared with the controls （17.1 ± 2.01 mo vs 10.1 ±4.5 mo, P = 0.00121）. After treatment, all patients in the study group had positive delayed hypersensitivity and robust systemic cytotoxicity in response to tumor lysate as measured by interferon-y-expression in peripheral blood mononuclear cells using enzyme-linked immunosorbent spot assay. They also displayed increased numbers of CD8-, CD45RO- and CD56-positive cells in the peripheral blood and decreased α-fetoprotein level in the se- rum. CONCLUSION： This new tumor-specific immunotherapy is safe, effective and has a great potential for the treat- ment of tumors.
基金the National Natural Science Foundation of China(Nos.51903255 and 52073314)The Key Areas Research and Development Program of Guangdong Province(No.2020B1111150003)Science and Technology Program of Guangzhou City(No.201904010364).
文摘Decellularised extracellular matrix(dECM)biomaterials originating from allogeneic and xenogeneic tissues have been broadly studied in the field of regenerative medicine and have already been used in clinical treatments.Allogeneic dECMs are considered more compatible,but they have the drawback of extremely limited human tissue sources.Their availability is also restricted by the health and age of the donors.To investigate the viability of xenogeneic tissues as a substitute for human tissues,we fabricated both porcine decellularised nerve matrix(pDNM)and human decellularised nerve matrix for a comprehensive comparison.Photomicrographs showed that both dECM scaffolds retained the ECM microstructures of native human nerve tissues.Proteomic analysis demonstrated that the protein compositions of both dECMs were also very similar to each other.Their functional ECM contents effectively promoted the proliferation,migration,and maturation of primary human Schwann cells in vitro.However,pDNM contained a few antigens that induced severe host immune responses in humanised mice.Interestingly,after removing theα-galactosidase antigen,the immune responses were highly alleviated and the pre-treated pDNM maintained a human decellularised nerve matrix-like pro-regenerative phenotype.Therefore,we believe that anα-galactosidase-free pDNM may serve as a viable substitute for human decellularised nerve matrix in future clinical applications.
基金National Natural Science Foundation of China (No. 81160118)Natural Science Foundation of Jiangxi Province (No. 20114BAB215029)+3 种基金Technology Foundation of Jiangxi Province (No. 20111BBG70026-2)Health Department Science and Technology Foundation(No.20121026)Education Department Youth Scientific Research Foundation (No. JJJ12158)National High Technology Research of China (863 project) (No. 2006AA02A131)
文摘AIM: To examine the α-Gal gene expression and distribution in the different species/genus and developing phase animal ocular surface tissue.METHODS: α-Gal binding assay were carried out on various animal eye sections. Photograph, slit-lamp observation on various eye showed normal corneal transparence.RESULTS: A strong α-Gal expression in invertebrates and some vertebrates ocular tissue, but no α-Gal binding in birds, fish and mammal. α-Gal expression change in the development of mice ocular surface tissue (except sclera) and display genus dependency in the different murine ocular surface tissue.CONCLUSION: This study identified specific α-Gal epitopes binding area in the ocular surface of several species and may solve the problem that naive ocular surface may be used as natural α-Gal gene knockout model/high risk immunologic rejection model or ocular surface scaffold material.
文摘We aimed to explore the prevalence of Fabry disease in Thai patients who were diagnosed with end-stage renal disease（ESRD） of an unknown origin.Venous blood samples were collected from ESRD patients for biochemical and molecular studies.Alpha-galactosidase A（a-GAL A） screening was performed from dried-blood spots using fluorometry.Molecular confirmation was performed using DNA sequencing of the GLA gene.A total of 142 male and female patients were included in this study.Ten patients（7.04%） exhibited a significant decrease in a-GAL A activity.There were no definitive pathogenic mutations observed in the molecular study.However,four patients revealed a novel nucleotide variant at c.l-10 C〉T,which was identified as a benign variant following screening in the normal population.In conclusion,the a-GAL A assay utilizing dried-blood spots revealed a significant false positive rate.There was no definitive Fabry disease confirmed in Thai patients diagnosed with ESRD of unknown etiology.
