Mycobacterium tuberculosis 6-kDa early secretory antigenic target (ESAT-6) is a dominant target antigen for cell-mediated immunity in the early phase of tuberculosis. The fms-like tyrosine kinase 3 ligand (FL) tha...Mycobacterium tuberculosis 6-kDa early secretory antigenic target (ESAT-6) is a dominant target antigen for cell-mediated immunity in the early phase of tuberculosis. The fms-like tyrosine kinase 3 ligand (FL) that induces potent immune response has been used as an adjuvant in vaccine development. In this study, a new recombinant plasmid (plRES-epitope-peptides-FL) encoding three T cell epitopes of ESAT-6 and FL was constructed, and the immunogenicity of the DNA vaccine was assessed in C57BL/6 mice immunized with the plasmid DNA vaccine. Additionally, a strategy of intramuscular injection with the DNA vaccine (prime) and intranasal administration of the epitope peptides (boost) was employed to induce higher immune reaction of the mice. The results showed that mice vaccinated with the recombinant plasmid DNA vaccine and boosted with the peptides not only increased the levels of Thl cytokines (IFN-γ and IL-12), the number of IFN-γ+ T cells and activities of cytotoxic T lymphocytes as well as IgG, but also enhanced protection against Mycobacterium tuberculosis challenge. In conclusion, these data indicate that the novel recombinant plRES-epitope-peptides-FL plasmid is a useful DNA vaccine for pre- venting Mycobacterium tuberculosis infection.展开更多
Correction to:Journal of Biomedical Research https://doi.org/10.7555/JBR.27.20120114,published on 30 September 2013.We apologize for the misused images in Fig.7 in our article published on 30 September 2013.The Fig.7 ...Correction to:Journal of Biomedical Research https://doi.org/10.7555/JBR.27.20120114,published on 30 September 2013.We apologize for the misused images in Fig.7 in our article published on 30 September 2013.The Fig.7 by HE staining and immunohistochemistry were partially misused because of our carelessness.Because we couldn't find the original pictures acquired 11 years ago,thus HE and IHC experiments were repeated by our previously reserved wax blocks.Now,the pictures taken by microscope imaging system in each group were collected and combined,respectively.The correct version of Fig.展开更多
Pilot-scale test was carried out to evaluate the performance of a combined ultrafiltration (UF)-nanofiltration (NF) membrane process for the treatment of raw water from Huangpu River, Shanghai, in China. Results showe...Pilot-scale test was carried out to evaluate the performance of a combined ultrafiltration (UF)-nanofiltration (NF) membrane process for the treatment of raw water from Huangpu River, Shanghai, in China. Results showed that UF could significantly remove turbidity, iron and manganese, and also could retain a part of high molecular weight (MW) organic compounds. Subsequently, NF could further reject low MW organics and inorganic salts, and ensured the treated water to reach the Standards for Drinking Water Quality in China. It seemed that 90 L/m2·h was an appropriate permeate flux for UF system when the raw water was directly filtered by UF membrane, the addition of coagulant (alum or ferric chloride) was not preferable to mitigate the fouling of the UF membrane. After near 120 days operation, the permeate flux of NF could be main-tained at 24-25 L/m2·h steadily, and no chemical clean was required.展开更多
The failure of a massive influx of tumor-infiltrating T lymphocytes to eradicate tumor cells in the tumor microenvironment is mainly due to the dysfunction of T cells hyporesponsive to tumors.T-cell exhaustion and sen...The failure of a massive influx of tumor-infiltrating T lymphocytes to eradicate tumor cells in the tumor microenvironment is mainly due to the dysfunction of T cells hyporesponsive to tumors.T-cell exhaustion and senescence induced by malignant tumors are two important dysfunctional states that coexist in cancer patients,hindering effective antitumor immunity and immunotherapy and sustaining the suppressive tumor microenvironment.Although exhausted and senescent T cells share a similar dysfunctional role in antitumor immunity,they are distinctly different in terms of generation,development,and metabolic and molecular regulation during tumor progression.Here,we discuss the unique phenotypic and functional characteristics of these two types of dysfunctional T cells and their roles in tumor development and progression.In addition,we further discuss the potential molecular and metabolic signaling pathways responsible for the control of T-cell exhaustion and senescence in the suppressive tumor microenvironment.Understanding these critical and fundamental features should facilitate rethinking the unresponsiveness to current immunotherapies in clinical patients and lead to further development of novel and effective strategies that target different types of dysfunctional T cells to enhance cancer immunotherapy.展开更多
Cellular energy metabolism not only promotes tumor cell growth and metastasis but also directs immune cell survival,proliferation and the ability to perform specific and functional immune responses within the tumor mi...Cellular energy metabolism not only promotes tumor cell growth and metastasis but also directs immune cell survival,proliferation and the ability to perform specific and functional immune responses within the tumor microenvironment.A better understanding of the molecular regulation of metabolism in different cell components in the tumor-suppressive microenvironment is critical for the development of effective strategies for human cancer treatments.Toll-like receptors(TLRs)have recently been recognized as critical factors involved in tumor pathogenesis,regulating both tumor cells and tumor-infiltrating innate and adaptive immune cells.However,little is known about the molecular crosstalk between TLR signaling and tumor or/and immune cell metabolism,although there is abundant expression of TLRs in these cells.In this review,we explore the functional role of TLR signaling in reprogramming cell metabolism in the tumor microenvironment.In particular,we discuss how malignant tumors regulate metabolism to support their growth and survival,summarize more recently identified metabolic profiles of different immune cell subsets and TLR-mediated regulation of cellular metabolism in both tumor and immune cells,and further explore potential strategies targeting cell metabolism for TLR-based cancer therapy.An improved understanding of these issues should open new avenues for the development of novel strategies via TLR-mediated metabolic reprogramming of the tumor microenvironment for cancer immunotherapy.展开更多
基金supported by the Natural Scientific Fund (09KJA310002DG216D50162011NJMU263 and 11JC005) of China
文摘Mycobacterium tuberculosis 6-kDa early secretory antigenic target (ESAT-6) is a dominant target antigen for cell-mediated immunity in the early phase of tuberculosis. The fms-like tyrosine kinase 3 ligand (FL) that induces potent immune response has been used as an adjuvant in vaccine development. In this study, a new recombinant plasmid (plRES-epitope-peptides-FL) encoding three T cell epitopes of ESAT-6 and FL was constructed, and the immunogenicity of the DNA vaccine was assessed in C57BL/6 mice immunized with the plasmid DNA vaccine. Additionally, a strategy of intramuscular injection with the DNA vaccine (prime) and intranasal administration of the epitope peptides (boost) was employed to induce higher immune reaction of the mice. The results showed that mice vaccinated with the recombinant plasmid DNA vaccine and boosted with the peptides not only increased the levels of Thl cytokines (IFN-γ and IL-12), the number of IFN-γ+ T cells and activities of cytotoxic T lymphocytes as well as IgG, but also enhanced protection against Mycobacterium tuberculosis challenge. In conclusion, these data indicate that the novel recombinant plRES-epitope-peptides-FL plasmid is a useful DNA vaccine for pre- venting Mycobacterium tuberculosis infection.
文摘Correction to:Journal of Biomedical Research https://doi.org/10.7555/JBR.27.20120114,published on 30 September 2013.We apologize for the misused images in Fig.7 in our article published on 30 September 2013.The Fig.7 by HE staining and immunohistochemistry were partially misused because of our carelessness.Because we couldn't find the original pictures acquired 11 years ago,thus HE and IHC experiments were repeated by our previously reserved wax blocks.Now,the pictures taken by microscope imaging system in each group were collected and combined,respectively.The correct version of Fig.
文摘Pilot-scale test was carried out to evaluate the performance of a combined ultrafiltration (UF)-nanofiltration (NF) membrane process for the treatment of raw water from Huangpu River, Shanghai, in China. Results showed that UF could significantly remove turbidity, iron and manganese, and also could retain a part of high molecular weight (MW) organic compounds. Subsequently, NF could further reject low MW organics and inorganic salts, and ensured the treated water to reach the Standards for Drinking Water Quality in China. It seemed that 90 L/m2·h was an appropriate permeate flux for UF system when the raw water was directly filtered by UF membrane, the addition of coagulant (alum or ferric chloride) was not preferable to mitigate the fouling of the UF membrane. After near 120 days operation, the permeate flux of NF could be main-tained at 24-25 L/m2·h steadily, and no chemical clean was required.
基金This work was partially funded by grants from the American Cancer Society(RSG-10-160-01-LIB,to G.P.)Melanoma Research Alliance(to G.P.),and NIH(AI097852,AI094478,and CA184379 to G.P.).
文摘The failure of a massive influx of tumor-infiltrating T lymphocytes to eradicate tumor cells in the tumor microenvironment is mainly due to the dysfunction of T cells hyporesponsive to tumors.T-cell exhaustion and senescence induced by malignant tumors are two important dysfunctional states that coexist in cancer patients,hindering effective antitumor immunity and immunotherapy and sustaining the suppressive tumor microenvironment.Although exhausted and senescent T cells share a similar dysfunctional role in antitumor immunity,they are distinctly different in terms of generation,development,and metabolic and molecular regulation during tumor progression.Here,we discuss the unique phenotypic and functional characteristics of these two types of dysfunctional T cells and their roles in tumor development and progression.In addition,we further discuss the potential molecular and metabolic signaling pathways responsible for the control of T-cell exhaustion and senescence in the suppressive tumor microenvironment.Understanding these critical and fundamental features should facilitate rethinking the unresponsiveness to current immunotherapies in clinical patients and lead to further development of novel and effective strategies that target different types of dysfunctional T cells to enhance cancer immunotherapy.
基金supported by grants from the American Cancer Society(RSG-10-160-01-LIB,to GP)Melanoma Research Alliance(to GP)and the NIH(AI097852,AI094478 and CA184379 to GP).
文摘Cellular energy metabolism not only promotes tumor cell growth and metastasis but also directs immune cell survival,proliferation and the ability to perform specific and functional immune responses within the tumor microenvironment.A better understanding of the molecular regulation of metabolism in different cell components in the tumor-suppressive microenvironment is critical for the development of effective strategies for human cancer treatments.Toll-like receptors(TLRs)have recently been recognized as critical factors involved in tumor pathogenesis,regulating both tumor cells and tumor-infiltrating innate and adaptive immune cells.However,little is known about the molecular crosstalk between TLR signaling and tumor or/and immune cell metabolism,although there is abundant expression of TLRs in these cells.In this review,we explore the functional role of TLR signaling in reprogramming cell metabolism in the tumor microenvironment.In particular,we discuss how malignant tumors regulate metabolism to support their growth and survival,summarize more recently identified metabolic profiles of different immune cell subsets and TLR-mediated regulation of cellular metabolism in both tumor and immune cells,and further explore potential strategies targeting cell metabolism for TLR-based cancer therapy.An improved understanding of these issues should open new avenues for the development of novel strategies via TLR-mediated metabolic reprogramming of the tumor microenvironment for cancer immunotherapy.