Given the extremely high inter-patient heterogeneity of acute myeloid leukemia(AML),the identification of biomarkers for prognostic assessment and therapeutic guidance is critical.Cell surface markers(CSMs)have been s...Given the extremely high inter-patient heterogeneity of acute myeloid leukemia(AML),the identification of biomarkers for prognostic assessment and therapeutic guidance is critical.Cell surface markers(CSMs)have been shown to play an important role in AML leukemogenesis and progression.In the current study,we evaluated the prognostic potential of all human CSMs in 130 AML patients from The Cancer Genome Atlas(TCGA)based on differential gene expression analysis and univariable Cox proportional hazards regression analysis.By using multi-model analysis,including Adaptive LASSO regression,LASSO regression,and Elastic Net,we constructed a 9-CSMs prognostic model for risk stratification of the AML patients.The predictive value of the 9-CSMs risk score was further validated at the transcriptome and proteome levels.Multivariable Cox regression analysis showed that the risk score was an independent prognostic factor for the AML patients.The AML patients with high 9-CSMs risk scores had a shorter overall and event-free survival time than those with low scores.Notably,single-cell RNA-sequencing analysis indicated that patients with high 9-CSMs risk scores exhibited chemotherapy resistance.Furthermore,PI3K inhibitors were identified as potential treatments for these high-risk patients.In conclusion,we constructed a 9-CSMs prognostic model that served as an independent prognostic factor for the survival of AML patients and held the potential for guiding drug therapy.展开更多
Mesenchymal stem cell （MSC）-mediated therapy has been shown to be clinically effective in regenerating tissue defects. For improved regenerative therapy, it is critical to isolate homogenous populations of MSCs with...Mesenchymal stem cell （MSC）-mediated therapy has been shown to be clinically effective in regenerating tissue defects. For improved regenerative therapy, it is critical to isolate homogenous populations of MSCs with high capacity to differentiate into appropriate tissues. The utilization of stem cell surface antigens provides a means to identify MSCs from various tissues. However, few surface markers that consistently isolate highly regenerative MSCs have been validated, making it challenging for routine clinical applications and making it all the more imperative to identify reliable surface markers. In this study, we used three surface marker combinations： CD51/CD140a, CD271, and STRO-1/CD146 for the isolation of homogenous populations of dental mesenchymal stem cells （DMSCs） from heterogeneous periodontal ligament cells （PDLCs）. Fluorescence-activated cell sorting analysis revealed that 24% of PDLCs were CD51＋/CD140a＋, 0.8% were CD271＋, and 2.4% were STRO-1＋/CD146＋. Sorted cell populations were further assessed for their multipotent properties by inducing osteogenic and chondrogenic differentiation. All three subsets of isolated DMSCs exhibited differentiation capacity into osteogenic and chondrogenic lineages but with varying degrees. CD271＋ DMSCs demonstrated the greatest osteogenic potential with strong induction of osteogenic markers such as DLX5, RUNX2, and BGLAP. Our study provides evidence that surface marker combinations used in this study are sufficient markers for the isolation of DMSCs from PDLCs. These results provide important insight into using specific surface markers for identifying homogenous populations of DMSCs for their improved utilization in regenerative medicine.展开更多
OBJECTIVE We aimed identification of cell surface molecules, which might serve as diagnostic biomarkers or useful targets for therapies, in breast cancer. METHODS We developed unique DNA microarray coupled with spheri...OBJECTIVE We aimed identification of cell surface molecules, which might serve as diagnostic biomarkers or useful targets for therapies, in breast cancer. METHODS We developed unique DNA microarray coupled with spherical self-organizing map （sSOM） analysis to characterize cells and tissues by the cell surface markers. In the microarray 1,797 probes for human genes coding membrane bound proteins were spotted. With this microarray the gene expression profiles of eight breast carcinoma cell lines were compared to identify the genes that were commonly expressed in breast carcinomas but not in normal cells. RESULTS The gene expression profiles of sSOM from the eight breast carcinoma cell lines were successfully distinguished from that of normal breast tissue derived cells suggesting the presence of genes of interest, sSOMon the data extensively filtered revealed several candidate genes, of which expression was significant in carcinoma cells but low in normal cells. Finally, TM9SF2 was nominated through validations of PCR procedures together with CD24 and ErbB3, which are known breast carcinoma markers. TMgSF2 expression was further confirmed by immunological staining. Interestingly, TMgSF2 was found to be expressed in all the cell lines evaluated while CD24 and ErbB3 were not in all of the carcinoma cells, supporting their relationship in sSOM. Although physiological significance of TMgSF2 is unknown yet, siRNA treatment significantly inhibited the growth of MDA- MB-231 cells. CONCLUSION We propose TM9SF2 as a novel and useful diagnostic marker as well as a potential molecular target specific to breast carcinoma cells covering wide range of breast cancer.展开更多
Background: The pathophysiology of the inflammatory process reveals intricate signaling which includes the IL-1β, IL-6, and TNFα pathways that could serve as drug targets. Aim: This study determined the effect of th...Background: The pathophysiology of the inflammatory process reveals intricate signaling which includes the IL-1β, IL-6, and TNFα pathways that could serve as drug targets. Aim: This study determined the effect of the aqueous extract of Gongronema latifolium (AEGL) leaves on the expression of IFNγ, IL-10, CD3, and CD56 in rabbits. Materials and Methods: ELISA tests were performed to determine the effect of the AEGL on the expression of a pro-inflammatory cytokine (IFNγ), an anti-inflammatory cytokine (IL-10), and CD3 and CD56 cell surface markers in rabbits. Twenty cross-bred male rabbits with an average weight range of 1.0 - 1.5 kg were selected. The rabbits were separated into four groups of four rabbits each treated as follows: Grp1 is the untreated control;Grp2 is the treated control;and Grp3, Grp4, and Grp5 were treated with 200, 400, and 600 mg/kg of AEGL respectively for 28 days. Results: The AEGL showed its greatest inhibitory effect in Group 4 on IL-10 (118.5 pg/ml), and IFNγ (332 pg/ml) on days 14 and 21 respectively. AEGL also showed the highest inhibition of CD3 expression on days 14 and 21 (0 pg/ml) in Group 3;and CD56 expression on day 21 (630.5 pg/ml) in Group 4. Conclusion: AEGL showed exhibited strong T cell mediated anti- inflammatory, and immunomodulatory activity in test rabbits within the 28-day period which can be confirmed by cell based assays. Specifically at 400 mg/kg, AEGL exhibited the greatest anti-inflammatory activity which is suggestive of its maximum effective dose.展开更多
Liver cancer stem cells(LCSCs),a small subpopulation that constitutes liver cancer heterogeneity,play a vital role in cancer initiation,invasion,recurrence,metastasis,and resistance to chemo-radiotherapy.It is believe...Liver cancer stem cells(LCSCs),a small subpopulation that constitutes liver cancer heterogeneity,play a vital role in cancer initiation,invasion,recurrence,metastasis,and resistance to chemo-radiotherapy.It is believed that therapies targeting LCSCs can improve the efficacy of conventional chemotherapy and radiotherapy by completely eliminating tumors while preventing recurrence.Therefore,during last decades,numerous surface markers for LCSCs have been identified and characterized in many subtypes of liver cancer,especially in hepatocellular carcinoma(HCC).These well-recognized surface markers significantly promote the therapeutic efficacy that identifies,targets and destroys LCSCs.Meanwhile,there have been intensive studies that aim to investigate the molecular mechanism of how stemness contributes to liver cancer relapse,recurrence and resistance.However,liver cancer stemness seems to be regulated by a hierarchical organization and crosstalk of a wide variety of signaling pathways.Using individual or few LCSC surface markers may not be able to completely reveal the intrinsic stemness hierarchy.From an integrated perspective,understanding of recent advances in LCSC surface markers remains important and urgent.In this review,we concentrate on demonstrating the indispensable roles of LCSC surface markers in identification and characterization of multiple cancer stages including initiation,invasion,metastasis,resistance and highlighting the cutting-edge therapeutic strategies against cancer stem cells in HCC.展开更多
Mesenchymal stem cells （MSCs） are a promising tool in regenerative medicine due to their capacity to differentiate into multiple lineages. In addition to MSCs isolated from bone marrow （BMSCs）, adult MSCs are isol...Mesenchymal stem cells （MSCs） are a promising tool in regenerative medicine due to their capacity to differentiate into multiple lineages. In addition to MSCs isolated from bone marrow （BMSCs）, adult MSCs are isolated from craniofacial tissues including dental pulp tissues （DPs） using various stem cell surface markers. However, there has been a lack of consensus on a set of surface makers that are reproducibly effective at isolating putative multipotent dental mesenchymal stem cel^s （~M^Cs）. II1 ~his stucly, we used clif^et（~nt combinations of surface markers （CD51/CD140a, CD271, and STRO-1/CD146） to isolate homogeneous populations of DMSCs from heterogeneous dental pulp cells （DPCs） obtained from DP and compared their capacity to undergo multilineage differentiation. Fluorescence-activated cell sorting revealed that 27.3% of DPCs were CD51＋/CD140a＋, 10.6% were CD271＋, and 0.3% were STRO-1＋/CD146＋. Under odontogenic conditions, all three subsets of isolated DMSCs exhibited differentiation capacity into odontogenic lineages. Among these isolated subsets of DMSCs, CD271＋ DMSCs demonstrated the greatest odontogenic potential. While all three combinations of surface markers in this study successfully isolated DMSCs from DPCs, the single CD271 marker presents the most effective stem cell surface marker for identification of DMSCs with high odontogenic potential. Isolated CD271＋ DMSCs could potentially be utilized for future clinical applications in dentistry and regenerative medicine.展开更多
Embryonic stem （ES） cells are potent resources for cell therapy,and monoclonal antibodies （mAbs） against native cell surface markers of ES cells could be useful tools for therapeutic applications.Here,we report th...Embryonic stem （ES） cells are potent resources for cell therapy,and monoclonal antibodies （mAbs） against native cell surface markers of ES cells could be useful tools for therapeutic applications.Here,we report the development of a feasible approach,which could be used in mass production,for experimentally producing rabbit mAbs against native cell surface antigens on the cell surface.Two of the 14 mAbs,which were selected at random,could be bound to the cell surface antigens of mES cells.The immunocytochemistry （ICC） and Western blot results showed that mAb 39 recognises conformational epitopes.The target antigen of mAb 39 was then successfully purified using an improved immunoprecipitation approach in which mAb was bounded to intact mES cells before the cells were lysed.The LC-LTQ mass spectrum analysis showed that the target antigen of mAb 39 was Glut3.This result was further confirmed by Western blot using commercially available antibodies against Glut3.Further experiments showed that mAb 39 exhibited an antiproliferative effect on mES cells.We also found that Glut3 was differentially expressed among the mES cell population as detected by flow cytometry.展开更多
Adipose-derived mesenchymal stem cells （ADSCs） can be largely and easily obtained from a wide range of sources. Moreover, they have self-renewal ability, multi-differentiation potential, and an important role in imm...Adipose-derived mesenchymal stem cells （ADSCs） can be largely and easily obtained from a wide range of sources. Moreover, they have self-renewal ability, multi-differentiation potential, and an important role in immune regulation. They can secrete a variety of cytokines to regulate the in vivo micro-environment. Therefore, ADSCs are the ideal seed ceils for stem ceils application. This paper reviews the location, isolation, surface markers, proliferation, differentiation and other biological characteristics of ADSCs, as well as their secretory function and relative researches. ADSCs are expected to become excellent seed cells for cell therapy and tissue engineering through in-depth studies.展开更多
Mesenchymal stem cells(MSCs)are multipotent stromal cells with great potential for clinical applications.However,little is known about their cell heterogeneity at a single-cell resolution,which severely impedes the de...Mesenchymal stem cells(MSCs)are multipotent stromal cells with great potential for clinical applications.However,little is known about their cell heterogeneity at a single-cell resolution,which severely impedes the development of MSC therapy.In this review,we focus on advances in the identification of novel surface markers and functional subpopulations of MSCs made by single-cell RNA sequencing and discuss their participation in the pathophysiology of stem cells and related diseases.The challenges and future directions of single-cell RNA sequencing in MSCs are also addressed in this review.展开更多
Objective To assess the relationship between murine recurrent spontaneous abortion and lymphocyte infiltration at the fetomaternal interface Materials&Methods Hysterolaparotomy was performed on d13.5 of murine ges...Objective To assess the relationship between murine recurrent spontaneous abortion and lymphocyte infiltration at the fetomaternal interface Materials&Methods Hysterolaparotomy was performed on d13.5 of murine gestation,and resorption rate of embryos was calculated in two different mating combinations of abortion model CBA/J×DBA/2 and of the fertile control CBA/J×BALB/c,respectively.CD69 was used as an activation marker on NK cell surface,while DX5 was used as a common marker of NK cell in this study.The proportions of CD 69^(+)cells in isolated lymphocytes,and CD 69^(+)DX 5^(+)cells in DX5^(+)subpopulation at the fetomaternal interface were determined by two-color flow cytometry.It was further evaluated whether there was linear correlation between these cell proportions and resorption rate of embryos.Results Resorption rate of embryos were 36.0%and 7.2%(P<0.01)in CBA/J×DBA/2 and CBA/J×BALB/c(genotypes are all of H-2^(k)×H-2^(d)),respectively.In CBA/J×DBA/2 mice,no linear correlation was observed between the proportion of CD69^(+)cells in lymphocytes(x)and resorption rate(y)(r=0.4054).However,it appeared that the proportion of CD69^(+)DX 5^(+)cells/DX5^(+)cells(x)was strongly linear correlated with the resorption rate of embryos(y)(r=0.8156,y=-0.3958+2.1237x)in this model.Conclusion Infiltration of CD 69^(+)DX5^(+)cells at the fetomaternal interface may be associated with recurrent embryo-resorption in CBA/J×DBA/2 mice.展开更多
The aim of this study was to evaluate the relationship between the embryo resorption rate （RR） and the status of local immunity at the feto-maternal interface in pregnant NOD/SCID mice. RR was calculated in NOD/SCID...The aim of this study was to evaluate the relationship between the embryo resorption rate （RR） and the status of local immunity at the feto-maternal interface in pregnant NOD/SCID mice. RR was calculated in NOD/SCID x NOD/SCID mice and compared with non-immunodeficiency BALB/c × BALB/c mice on day 13.5 of gestation. Intraeellular detection of cytokine expression was performed with four-color flow cytometry to identify the functional subsets of lymphocytes in NOD/SCID mice before being bred or during pregnancy. No statistically supported difference in RRs was observed between NOD/SCID × NOD/SCID and control BALB/c × BALB/c mice. Accordingly, although multiple immunodeficits were confirmed in NOD/SCID mice, the percentages of several functional cell subsets were spontaneously altered during pregnancy, and this may be correlated with the roughly normal pregnancy outcomes observed in these mice. The spontaneous alteration of cell percentages at the feto-maternal interfaee in NOD/SCID mice may be of benefit to the pregnancy outcomes.展开更多
Glioma,the most common primary intracranial tumor,has high morbidity and mortality.The detection of circulating tumor cells(CTCs)is an important part of the liquid biopsy of gliomas.CTCs,carrying the genetic and biolo...Glioma,the most common primary intracranial tumor,has high morbidity and mortality.The detection of circulating tumor cells(CTCs)is an important part of the liquid biopsy of gliomas.CTCs,carrying the genetic and biological information of tumor tissue,provide a new perspective and dimension for the study of tumor metastasis,progression,chemotherapy sensitivity and drug resistance.Cerebrospinal fluid(CSF)circulates through the ventricle and spinal cord cistern,which can better maintain the original information of tumor cells compared with the complicated environments of tissues and plasma.Study on the dynamic changes of CTCs in the CSF of the central nervous system(CNS)is relatively rare.However,the analysis of CTCs in CSF can be used to guide the treatment of gliomas and reveal the patho-physiological and genetic mechanisms of tumor cell metastasis to the CSF.This paper reviews the progress in the research on CTC detection in gliomas.展开更多
Breast cancer metastasis and relapse remain uncontrollable despite significant advancements in early diagnosis and treatment,resulting in increased mortality.Breast cancer is the most frequently diagnosed cancer in wo...Breast cancer metastasis and relapse remain uncontrollable despite significant advancements in early diagnosis and treatment,resulting in increased mortality.Breast cancer is the most frequently diagnosed cancer in women worldwide and has become the leading cause of cancer-related deaths.Cancer stem cells(CSCs)may play significant roles in tumor initiation,maintenance,invasion,relapse,metastasis,and therapy resistance.Although this small,highly heterogeneous,and restricted population of CSCs has been extensively studied,their cellular and molecular physiology remains unclear.Nonetheless,CSCs have increasingly become an attractive therapeutic target for combating advanced,treatment-resistant cancers.This necessitates the development of effective and reliable methods for their isolation and enrichment.This review provides an overview of the key characteristics of breast cancer stem cells(BCSCs)and illustrates their role in therapeutic resistance.Furthermore,it highlights various mechanisms underlying cancer cell adaptability and therapy-induced resistance across different breast cancer subtypes.The commonly used methods for BCSC isolation and identification are also discussed,as they could facilitate a deeper understanding of tumorigenesis,metastasis,resistance,and relapse,consequently contributing to the development of more effective therapeutic strategies for breast cancer.展开更多
Relapse remains the worst life-threatening complications after allogeneic hematopoietic stem cell transplantation(allo-HSCT)in patients with acute myeloid leukemia(AML),whose prognosis has been historically dismal.Giv...Relapse remains the worst life-threatening complications after allogeneic hematopoietic stem cell transplantation(allo-HSCT)in patients with acute myeloid leukemia(AML),whose prognosis has been historically dismal.Given the rapid development of genomics and immunotherapies,the interference strategies for AML recurrence have been changing these years.More and more novel targeting agents that have received the U.S.Food and Drug Administration(FDA)approval for de novo AML treatment have been administrated in the salvage or maintenance therapy of post-HSCT relapse.Targeted strategies that regulate the immune microenvironment of and optimize the graft versus leukemia(GVL)effect of immune cells are gradually improved.Such agents not only have been proven to achieve clinical benefits from a single drug,but if combined with classic therapies,can significantly improve the poor prognosis of AML patients who relapse after allo-HSCT.This review will focus on currently available and promising upcoming agents and also discuss the challenges and limitations of targeted therapies in the allogeneic hematopoietic stem cell transplantation community.展开更多
Erythropoiesis is a process during which multipotential hematopoietic stem cells proliferate, differentiate and eventually form mature erythrocytes. Interestingly, unlike most cell types, an important feature of eryth...Erythropoiesis is a process during which multipotential hematopoietic stem cells proliferate, differentiate and eventually form mature erythrocytes. Interestingly, unlike most cell types, an important feature of erythropoiesis is that following each mitosis the daughter cells are morphologically and functionally different from the parent cell from which they are derived, demonstrating the need to study erythropoiesis in a stage-specific manner. This has been impossible until recently due to lack of methods for isolating erythroid cells at each distinct developmental stage. This review summarizes recent advances in the development of methods for isolating both murine and human erythroid cells and their applications. These methods provide powerful means for studying normal and impaired erythropoiesis associated with hematological disorders.展开更多
Induced pluripotent stem （iPS） cells are a recent development which has brought a promise of great therapeutic values. The previous technique of somatic ceil nuclear transfer （SCNT） has been ineffective in humans....Induced pluripotent stem （iPS） cells are a recent development which has brought a promise of great therapeutic values. The previous technique of somatic ceil nuclear transfer （SCNT） has been ineffective in humans. Recent discoveries show that human fibroblasls can be reprogrammed by a transient over expression of a small number of genes; they can undergo induced pluripotency, iPS were first produced in 2006. By 2008, work was underway to remove the potential oncogenes from their structure. In 2009, protein iPS （piPS） cells were discovered. Surface markers and reporter genes play an important role in stem cell research. Clinical applications include generation of self renewing stem cells, tissue replacement and many more. Stem cell therapy has the ability to dramatically change the treatment of human diseases.展开更多
Cluster of differentiation(CD)antigens are cell surface molecules expressed on leukocytes and other cells associated with the immune system.Antibodies that react with CD antigens are known to be one of the most essent...Cluster of differentiation(CD)antigens are cell surface molecules expressed on leukocytes and other cells associated with the immune system.Antibodies that react with CD antigens are known to be one of the most essential tools for identifying leukocyte subpopulations.T lymphocytes,as an important population of leukocytes,play essential roles in the adaptive immune system.Many of the CD antigens expressed on T lymphocytes are used as surface markers for T lymphocyte classification,including CD3,CD4 and CD8 molecules.In this review,we summarize the recent advances in the identification of CD molecules on T lymphocytes in teleosts,with emphasis on the functions of CD markers in the classification of T lymphocyte subsets.We notice that genes encoding CD3,co-receptors CD4 and CD8 have been cloned in several fish species and antibodies have been developed to study protein expression in morphological and functional contexts.T lymphocytes can be divided into CD4^(+)and CD8^(+)cells discriminated by the expression of CD4 and CD8 molecules in teleost,which are functionally similar to mammalian helper T cells(Th)and cytotoxic T cells(Tc),respectively.Further studies are still needed on the particular characteristics of teleost T cell repertoires and adaptive responses,and results will facilitate the health management and development of vaccines for fish.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.32200590 to K.L.,81972358 to Q.W.,91959113 to Q.W.,and 82372897 to Q.W.)the Natural Science Foundation of Jiangsu Province(Grant No.BK20210530 to K.L.).
文摘Given the extremely high inter-patient heterogeneity of acute myeloid leukemia(AML),the identification of biomarkers for prognostic assessment and therapeutic guidance is critical.Cell surface markers(CSMs)have been shown to play an important role in AML leukemogenesis and progression.In the current study,we evaluated the prognostic potential of all human CSMs in 130 AML patients from The Cancer Genome Atlas(TCGA)based on differential gene expression analysis and univariable Cox proportional hazards regression analysis.By using multi-model analysis,including Adaptive LASSO regression,LASSO regression,and Elastic Net,we constructed a 9-CSMs prognostic model for risk stratification of the AML patients.The predictive value of the 9-CSMs risk score was further validated at the transcriptome and proteome levels.Multivariable Cox regression analysis showed that the risk score was an independent prognostic factor for the AML patients.The AML patients with high 9-CSMs risk scores had a shorter overall and event-free survival time than those with low scores.Notably,single-cell RNA-sequencing analysis indicated that patients with high 9-CSMs risk scores exhibited chemotherapy resistance.Furthermore,PI3K inhibitors were identified as potential treatments for these high-risk patients.In conclusion,we constructed a 9-CSMs prognostic model that served as an independent prognostic factor for the survival of AML patients and held the potential for guiding drug therapy.
基金supported by National Institute of Dental and Craniofacial Research grant T90DE022734
文摘Mesenchymal stem cell （MSC）-mediated therapy has been shown to be clinically effective in regenerating tissue defects. For improved regenerative therapy, it is critical to isolate homogenous populations of MSCs with high capacity to differentiate into appropriate tissues. The utilization of stem cell surface antigens provides a means to identify MSCs from various tissues. However, few surface markers that consistently isolate highly regenerative MSCs have been validated, making it challenging for routine clinical applications and making it all the more imperative to identify reliable surface markers. In this study, we used three surface marker combinations： CD51/CD140a, CD271, and STRO-1/CD146 for the isolation of homogenous populations of dental mesenchymal stem cells （DMSCs） from heterogeneous periodontal ligament cells （PDLCs）. Fluorescence-activated cell sorting analysis revealed that 24% of PDLCs were CD51＋/CD140a＋, 0.8% were CD271＋, and 2.4% were STRO-1＋/CD146＋. Sorted cell populations were further assessed for their multipotent properties by inducing osteogenic and chondrogenic differentiation. All three subsets of isolated DMSCs exhibited differentiation capacity into osteogenic and chondrogenic lineages but with varying degrees. CD271＋ DMSCs demonstrated the greatest osteogenic potential with strong induction of osteogenic markers such as DLX5, RUNX2, and BGLAP. Our study provides evidence that surface marker combinations used in this study are sufficient markers for the isolation of DMSCs from PDLCs. These results provide important insight into using specific surface markers for identifying homogenous populations of DMSCs for their improved utilization in regenerative medicine.
基金supported by the Grantin-Aid for scientific research(B)No.18300164"Screening of carcinoma cell surface markers and its application in molecular targeting with bionanocapsules"Japan Society for the Promotion of Science(JSPS).
文摘OBJECTIVE We aimed identification of cell surface molecules, which might serve as diagnostic biomarkers or useful targets for therapies, in breast cancer. METHODS We developed unique DNA microarray coupled with spherical self-organizing map （sSOM） analysis to characterize cells and tissues by the cell surface markers. In the microarray 1,797 probes for human genes coding membrane bound proteins were spotted. With this microarray the gene expression profiles of eight breast carcinoma cell lines were compared to identify the genes that were commonly expressed in breast carcinomas but not in normal cells. RESULTS The gene expression profiles of sSOM from the eight breast carcinoma cell lines were successfully distinguished from that of normal breast tissue derived cells suggesting the presence of genes of interest, sSOMon the data extensively filtered revealed several candidate genes, of which expression was significant in carcinoma cells but low in normal cells. Finally, TM9SF2 was nominated through validations of PCR procedures together with CD24 and ErbB3, which are known breast carcinoma markers. TMgSF2 expression was further confirmed by immunological staining. Interestingly, TMgSF2 was found to be expressed in all the cell lines evaluated while CD24 and ErbB3 were not in all of the carcinoma cells, supporting their relationship in sSOM. Although physiological significance of TMgSF2 is unknown yet, siRNA treatment significantly inhibited the growth of MDA- MB-231 cells. CONCLUSION We propose TM9SF2 as a novel and useful diagnostic marker as well as a potential molecular target specific to breast carcinoma cells covering wide range of breast cancer.
文摘Background: The pathophysiology of the inflammatory process reveals intricate signaling which includes the IL-1β, IL-6, and TNFα pathways that could serve as drug targets. Aim: This study determined the effect of the aqueous extract of Gongronema latifolium (AEGL) leaves on the expression of IFNγ, IL-10, CD3, and CD56 in rabbits. Materials and Methods: ELISA tests were performed to determine the effect of the AEGL on the expression of a pro-inflammatory cytokine (IFNγ), an anti-inflammatory cytokine (IL-10), and CD3 and CD56 cell surface markers in rabbits. Twenty cross-bred male rabbits with an average weight range of 1.0 - 1.5 kg were selected. The rabbits were separated into four groups of four rabbits each treated as follows: Grp1 is the untreated control;Grp2 is the treated control;and Grp3, Grp4, and Grp5 were treated with 200, 400, and 600 mg/kg of AEGL respectively for 28 days. Results: The AEGL showed its greatest inhibitory effect in Group 4 on IL-10 (118.5 pg/ml), and IFNγ (332 pg/ml) on days 14 and 21 respectively. AEGL also showed the highest inhibition of CD3 expression on days 14 and 21 (0 pg/ml) in Group 3;and CD56 expression on day 21 (630.5 pg/ml) in Group 4. Conclusion: AEGL showed exhibited strong T cell mediated anti- inflammatory, and immunomodulatory activity in test rabbits within the 28-day period which can be confirmed by cell based assays. Specifically at 400 mg/kg, AEGL exhibited the greatest anti-inflammatory activity which is suggestive of its maximum effective dose.
基金This study was supported by a grant of the Basic Research(Discipline Layout)of Shenzhen Science and Technology Project(No.JCYJ20180508153249223).
文摘Liver cancer stem cells(LCSCs),a small subpopulation that constitutes liver cancer heterogeneity,play a vital role in cancer initiation,invasion,recurrence,metastasis,and resistance to chemo-radiotherapy.It is believed that therapies targeting LCSCs can improve the efficacy of conventional chemotherapy and radiotherapy by completely eliminating tumors while preventing recurrence.Therefore,during last decades,numerous surface markers for LCSCs have been identified and characterized in many subtypes of liver cancer,especially in hepatocellular carcinoma(HCC).These well-recognized surface markers significantly promote the therapeutic efficacy that identifies,targets and destroys LCSCs.Meanwhile,there have been intensive studies that aim to investigate the molecular mechanism of how stemness contributes to liver cancer relapse,recurrence and resistance.However,liver cancer stemness seems to be regulated by a hierarchical organization and crosstalk of a wide variety of signaling pathways.Using individual or few LCSC surface markers may not be able to completely reveal the intrinsic stemness hierarchy.From an integrated perspective,understanding of recent advances in LCSC surface markers remains important and urgent.In this review,we concentrate on demonstrating the indispensable roles of LCSC surface markers in identification and characterization of multiple cancer stages including initiation,invasion,metastasis,resistance and highlighting the cutting-edge therapeutic strategies against cancer stem cells in HCC.
基金supported by National Institute of Dental and Craniofacial Research grant T90DE022734
文摘Mesenchymal stem cells （MSCs） are a promising tool in regenerative medicine due to their capacity to differentiate into multiple lineages. In addition to MSCs isolated from bone marrow （BMSCs）, adult MSCs are isolated from craniofacial tissues including dental pulp tissues （DPs） using various stem cell surface markers. However, there has been a lack of consensus on a set of surface makers that are reproducibly effective at isolating putative multipotent dental mesenchymal stem cel^s （~M^Cs）. II1 ~his stucly, we used clif^et（~nt combinations of surface markers （CD51/CD140a, CD271, and STRO-1/CD146） to isolate homogeneous populations of DMSCs from heterogeneous dental pulp cells （DPCs） obtained from DP and compared their capacity to undergo multilineage differentiation. Fluorescence-activated cell sorting revealed that 27.3% of DPCs were CD51＋/CD140a＋, 10.6% were CD271＋, and 0.3% were STRO-1＋/CD146＋. Under odontogenic conditions, all three subsets of isolated DMSCs exhibited differentiation capacity into odontogenic lineages. Among these isolated subsets of DMSCs, CD271＋ DMSCs demonstrated the greatest odontogenic potential. While all three combinations of surface markers in this study successfully isolated DMSCs from DPCs, the single CD271 marker presents the most effective stem cell surface marker for identification of DMSCs with high odontogenic potential. Isolated CD271＋ DMSCs could potentially be utilized for future clinical applications in dentistry and regenerative medicine.
基金supported by the National Key Scientific Research Program of China,the Ministry of Science and Technology of the People’s Republic of China (No 2007947804)
文摘Embryonic stem （ES） cells are potent resources for cell therapy,and monoclonal antibodies （mAbs） against native cell surface markers of ES cells could be useful tools for therapeutic applications.Here,we report the development of a feasible approach,which could be used in mass production,for experimentally producing rabbit mAbs against native cell surface antigens on the cell surface.Two of the 14 mAbs,which were selected at random,could be bound to the cell surface antigens of mES cells.The immunocytochemistry （ICC） and Western blot results showed that mAb 39 recognises conformational epitopes.The target antigen of mAb 39 was then successfully purified using an improved immunoprecipitation approach in which mAb was bounded to intact mES cells before the cells were lysed.The LC-LTQ mass spectrum analysis showed that the target antigen of mAb 39 was Glut3.This result was further confirmed by Western blot using commercially available antibodies against Glut3.Further experiments showed that mAb 39 exhibited an antiproliferative effect on mES cells.We also found that Glut3 was differentially expressed among the mES cell population as detected by flow cytometry.
基金Supported by The Fund from the Endangered Species Import and Export Management Office of the People’s Republic of China for the Management and Research of Endangered Wild Animals(201441314404)~~
文摘Adipose-derived mesenchymal stem cells （ADSCs） can be largely and easily obtained from a wide range of sources. Moreover, they have self-renewal ability, multi-differentiation potential, and an important role in immune regulation. They can secrete a variety of cytokines to regulate the in vivo micro-environment. Therefore, ADSCs are the ideal seed ceils for stem ceils application. This paper reviews the location, isolation, surface markers, proliferation, differentiation and other biological characteristics of ADSCs, as well as their secretory function and relative researches. ADSCs are expected to become excellent seed cells for cell therapy and tissue engineering through in-depth studies.
基金National Natural Science Foundation of China,No.81871750 and No.81971518the Fundamental Research Funds for the Central Universities,No.19ykpy01 and No.20ykpy04the Key Laboratory of Basic Research and Clinical Translation of Ankylosing Spondylitis,No.ZDSYS20190902092851024.
文摘Mesenchymal stem cells(MSCs)are multipotent stromal cells with great potential for clinical applications.However,little is known about their cell heterogeneity at a single-cell resolution,which severely impedes the development of MSC therapy.In this review,we focus on advances in the identification of novel surface markers and functional subpopulations of MSCs made by single-cell RNA sequencing and discuss their participation in the pathophysiology of stem cells and related diseases.The challenges and future directions of single-cell RNA sequencing in MSCs are also addressed in this review.
基金Supported by the National Key Fundamental Research Plan("973")Projet(G1999050303)Major Project of Science and Technology Guangzhou Province(A302020204)China
文摘Objective To assess the relationship between murine recurrent spontaneous abortion and lymphocyte infiltration at the fetomaternal interface Materials&Methods Hysterolaparotomy was performed on d13.5 of murine gestation,and resorption rate of embryos was calculated in two different mating combinations of abortion model CBA/J×DBA/2 and of the fertile control CBA/J×BALB/c,respectively.CD69 was used as an activation marker on NK cell surface,while DX5 was used as a common marker of NK cell in this study.The proportions of CD 69^(+)cells in isolated lymphocytes,and CD 69^(+)DX 5^(+)cells in DX5^(+)subpopulation at the fetomaternal interface were determined by two-color flow cytometry.It was further evaluated whether there was linear correlation between these cell proportions and resorption rate of embryos.Results Resorption rate of embryos were 36.0%and 7.2%(P<0.01)in CBA/J×DBA/2 and CBA/J×BALB/c(genotypes are all of H-2^(k)×H-2^(d)),respectively.In CBA/J×DBA/2 mice,no linear correlation was observed between the proportion of CD69^(+)cells in lymphocytes(x)and resorption rate(y)(r=0.4054).However,it appeared that the proportion of CD69^(+)DX 5^(+)cells/DX5^(+)cells(x)was strongly linear correlated with the resorption rate of embryos(y)(r=0.8156,y=-0.3958+2.1237x)in this model.Conclusion Infiltration of CD 69^(+)DX5^(+)cells at the fetomaternal interface may be associated with recurrent embryo-resorption in CBA/J×DBA/2 mice.
文摘The aim of this study was to evaluate the relationship between the embryo resorption rate （RR） and the status of local immunity at the feto-maternal interface in pregnant NOD/SCID mice. RR was calculated in NOD/SCID x NOD/SCID mice and compared with non-immunodeficiency BALB/c × BALB/c mice on day 13.5 of gestation. Intraeellular detection of cytokine expression was performed with four-color flow cytometry to identify the functional subsets of lymphocytes in NOD/SCID mice before being bred or during pregnancy. No statistically supported difference in RRs was observed between NOD/SCID × NOD/SCID and control BALB/c × BALB/c mice. Accordingly, although multiple immunodeficits were confirmed in NOD/SCID mice, the percentages of several functional cell subsets were spontaneously altered during pregnancy, and this may be correlated with the roughly normal pregnancy outcomes observed in these mice. The spontaneous alteration of cell percentages at the feto-maternal interfaee in NOD/SCID mice may be of benefit to the pregnancy outcomes.
文摘Glioma,the most common primary intracranial tumor,has high morbidity and mortality.The detection of circulating tumor cells(CTCs)is an important part of the liquid biopsy of gliomas.CTCs,carrying the genetic and biological information of tumor tissue,provide a new perspective and dimension for the study of tumor metastasis,progression,chemotherapy sensitivity and drug resistance.Cerebrospinal fluid(CSF)circulates through the ventricle and spinal cord cistern,which can better maintain the original information of tumor cells compared with the complicated environments of tissues and plasma.Study on the dynamic changes of CTCs in the CSF of the central nervous system(CNS)is relatively rare.However,the analysis of CTCs in CSF can be used to guide the treatment of gliomas and reveal the patho-physiological and genetic mechanisms of tumor cell metastasis to the CSF.This paper reviews the progress in the research on CTC detection in gliomas.
基金supported by the Universiti Malaysia Sabah(No.:SDK0440-2018).
文摘Breast cancer metastasis and relapse remain uncontrollable despite significant advancements in early diagnosis and treatment,resulting in increased mortality.Breast cancer is the most frequently diagnosed cancer in women worldwide and has become the leading cause of cancer-related deaths.Cancer stem cells(CSCs)may play significant roles in tumor initiation,maintenance,invasion,relapse,metastasis,and therapy resistance.Although this small,highly heterogeneous,and restricted population of CSCs has been extensively studied,their cellular and molecular physiology remains unclear.Nonetheless,CSCs have increasingly become an attractive therapeutic target for combating advanced,treatment-resistant cancers.This necessitates the development of effective and reliable methods for their isolation and enrichment.This review provides an overview of the key characteristics of breast cancer stem cells(BCSCs)and illustrates their role in therapeutic resistance.Furthermore,it highlights various mechanisms underlying cancer cell adaptability and therapy-induced resistance across different breast cancer subtypes.The commonly used methods for BCSC isolation and identification are also discussed,as they could facilitate a deeper understanding of tumorigenesis,metastasis,resistance,and relapse,consequently contributing to the development of more effective therapeutic strategies for breast cancer.
基金supported by the National Natural Science Foundation of China(Grant No.81302043)the Collaborative Innovation Center of Hematology,China
文摘Relapse remains the worst life-threatening complications after allogeneic hematopoietic stem cell transplantation(allo-HSCT)in patients with acute myeloid leukemia(AML),whose prognosis has been historically dismal.Given the rapid development of genomics and immunotherapies,the interference strategies for AML recurrence have been changing these years.More and more novel targeting agents that have received the U.S.Food and Drug Administration(FDA)approval for de novo AML treatment have been administrated in the salvage or maintenance therapy of post-HSCT relapse.Targeted strategies that regulate the immune microenvironment of and optimize the graft versus leukemia(GVL)effect of immune cells are gradually improved.Such agents not only have been proven to achieve clinical benefits from a single drug,but if combined with classic therapies,can significantly improve the poor prognosis of AML patients who relapse after allo-HSCT.This review will focus on currently available and promising upcoming agents and also discuss the challenges and limitations of targeted therapies in the allogeneic hematopoietic stem cell transplantation community.
基金supported by grants from the National Natural Science Foundation of China(814703628117190581272187)
文摘Erythropoiesis is a process during which multipotential hematopoietic stem cells proliferate, differentiate and eventually form mature erythrocytes. Interestingly, unlike most cell types, an important feature of erythropoiesis is that following each mitosis the daughter cells are morphologically and functionally different from the parent cell from which they are derived, demonstrating the need to study erythropoiesis in a stage-specific manner. This has been impossible until recently due to lack of methods for isolating erythroid cells at each distinct developmental stage. This review summarizes recent advances in the development of methods for isolating both murine and human erythroid cells and their applications. These methods provide powerful means for studying normal and impaired erythropoiesis associated with hematological disorders.
文摘Induced pluripotent stem （iPS） cells are a recent development which has brought a promise of great therapeutic values. The previous technique of somatic ceil nuclear transfer （SCNT） has been ineffective in humans. Recent discoveries show that human fibroblasls can be reprogrammed by a transient over expression of a small number of genes; they can undergo induced pluripotency, iPS were first produced in 2006. By 2008, work was underway to remove the potential oncogenes from their structure. In 2009, protein iPS （piPS） cells were discovered. Surface markers and reporter genes play an important role in stem cell research. Clinical applications include generation of self renewing stem cells, tissue replacement and many more. Stem cell therapy has the ability to dramatically change the treatment of human diseases.
基金supported by the National Key Research and Development Program of China(2018YFD0900503)the National Natural Science Foundation of China(31730101,32173005,31672684,31672685)Shandong Provincial Natural Science Foundation(ZR2020KC025).
文摘Cluster of differentiation(CD)antigens are cell surface molecules expressed on leukocytes and other cells associated with the immune system.Antibodies that react with CD antigens are known to be one of the most essential tools for identifying leukocyte subpopulations.T lymphocytes,as an important population of leukocytes,play essential roles in the adaptive immune system.Many of the CD antigens expressed on T lymphocytes are used as surface markers for T lymphocyte classification,including CD3,CD4 and CD8 molecules.In this review,we summarize the recent advances in the identification of CD molecules on T lymphocytes in teleosts,with emphasis on the functions of CD markers in the classification of T lymphocyte subsets.We notice that genes encoding CD3,co-receptors CD4 and CD8 have been cloned in several fish species and antibodies have been developed to study protein expression in morphological and functional contexts.T lymphocytes can be divided into CD4^(+)and CD8^(+)cells discriminated by the expression of CD4 and CD8 molecules in teleost,which are functionally similar to mammalian helper T cells(Th)and cytotoxic T cells(Tc),respectively.Further studies are still needed on the particular characteristics of teleost T cell repertoires and adaptive responses,and results will facilitate the health management and development of vaccines for fish.
