Objective: To investigate the potential and early effect of hypertonic saline resuscitation on T-lymphocyte sub- populations in rats with hemorrhagic shock. Methods: A model of rat with severe hemorrhagic shock was es...Objective: To investigate the potential and early effect of hypertonic saline resuscitation on T-lymphocyte sub- populations in rats with hemorrhagic shock. Methods: A model of rat with severe hemorrhagic shock was established in 18 Sprague-Dawley (SD) rats. The rats were randomly divided into Sham group, HTS group (hypertonic saline resuscitation group) and NS group (normal saline resuscitation group). Each group contained 6 rats. The CD4+ and CD8+ subpopulations of T-lymphocytes in peripheral blood were detected respectively before shock and after resuscitation by double antibody labelling and flow cytometry. Results: In the early stage after hemorrhagic shock, fluid resuscitation and emergency treatment, the CD4+ lymphocytes of peripheral blood in HTS and NS groups markedly increased. Small volume resuscitation with HTS also induced peripheral CD8+ lymphocytes to a certain extent, whereas NS resuscitation showed no effect in this respect. Consequently, compared with Sham and HTS groups, CD4+/CD8+ ratio of peripheral blood in NS group was obviously increased, and showed statistically differences. Conclusion: In this model of rat with severe hemorrhagic shock, small volume resuscitation with HTS is more effective than NS in reducing immunologic disorders and promoting a more balanced profile of T-lymphocyte subpopula- tions regulating network.展开更多
Stem cells(SCs)with their self-renewal and pluripotent differentiation potential,show great promise for therapeutic applications to some refractory diseases such as stroke,Parkinsonism,myocardial infarction,and diabet...Stem cells(SCs)with their self-renewal and pluripotent differentiation potential,show great promise for therapeutic applications to some refractory diseases such as stroke,Parkinsonism,myocardial infarction,and diabetes.Furthermore,as seed cells in tissue engineering,SCs have been applied widely to tissue and organ regeneration.However,previous studies have shown that SCs are heterogeneous and consist of many cell subpopulations.Owing to this heterogeneity of cell states,gene expression is highly diverse between cells even within a single tissue,making precise identification and analysis of biological properties difficult,which hinders their further research and applications.Therefore,a defined understanding of the heterogeneity is a key to research of SCs.Traditional ensemble-based sequencing approaches,such as microarrays,reflect an average of expression levels across a large population,which overlook unique biological behaviors of individual cells,conceal cell-to-cell variations,and cannot understand the heterogeneity of SCs radically.The development of high throughput single cell RNA sequencing(scRNA-seq)has provided a new research tool in biology,ranging from identification of novel cell types and exploration of cell markers to the analysis of gene expression and predicating developmental trajectories.scRNA-seq has profoundly changed our understanding of a series of biological phenomena.Currently,it has been used in research of SCs in many fields,particularly for the research of heterogeneity and cell subpopulations in early embryonic development.In this review,we focus on the scRNA-seq technique and its applications to research of SCs.展开更多
Diabetes mellitus(DM),an increasingly prevalent chronic metabolic disease,is characterised by prolonged hyperglycaemia,which leads to long-term health consequences.Although much effort has been put into understanding ...Diabetes mellitus(DM),an increasingly prevalent chronic metabolic disease,is characterised by prolonged hyperglycaemia,which leads to long-term health consequences.Although much effort has been put into understanding the pathogenesis of diabetic wounds,the underlying mechanisms remain unclear.The advent of single-cell RNA sequencing(scRNAseq)has revolutionised biological research by enabling the identification of novel cell types,the discovery of cellular markers,the analysis of gene expression patterns and the prediction of develop-mental trajectories.This powerful tool allows for an in-depth exploration of pathogenesis at the cellular and molecular levels.In this editorial,we focus on progenitor-based repair strategies for diabetic wound healing as revealed by scRNAseq and highlight the biological behaviour of various healing-related cells and the alteration of signalling pathways in the process of diabetic wound healing.ScRNAseq could not only deepen our understanding of the complex biology of diabetic wounds but also identify and validate new targets for inter-vention,offering hope for improved patient outcomes in the management of this challenging complication of DM.展开更多
Marginal zone(MZ)B cells,which are composed of heterogeneous subpopulations,are participate in the rapid response to antigens.Lee et al.showed that MZ B cells can be divided into two distinct subpopulations based on C...Marginal zone(MZ)B cells,which are composed of heterogeneous subpopulations,are participate in the rapid response to antigens.Lee et al.showed that MZ B cells can be divided into two distinct subpopulations based on CD80 expression.These two subpopulations of MZ B cells exhibit differential autoreactivity,radiosensitivity,and functional capacities.展开更多
Carcinogenic process has been proposed to relay on the capacity to induce local tissue damage and proliferative repair. Liver has a great regeneration capacity and currently, most studies point towards the dominant ro...Carcinogenic process has been proposed to relay on the capacity to induce local tissue damage and proliferative repair. Liver has a great regeneration capacity and currently, most studies point towards the dominant role of hepatocytes in regeneration at all levels of liver damage. The most frequent liver cancer is hepatocellular carcinoma(HCC). Historical findings originally led to the idea that the cell of origin of HCC might be a progenitor cell. However, current linage tracing studies put the progenitor hypothesis of HCC origin into question. In agreement with their dominant role in liver regeneration, mature hepatocytes are emerging as the cell of origin of HCC, although, the specific hepatocyte subpopulation of origin is yet to be determined. The relationship between the cancer cell of origin(CCO) and cancer-propagating cells, known as hepatic cancer stem cell(HCSC) is unknown. It has been challenging to identify the definitive phenotypic marker of HCSC, probably due to the existence of different cancer stem cells(CSC) subpopulations with different functions within HCC. There is a dynamic interconversion among different CSCs, and between CSC and non-CSCs. Because of that, CSC-state is currently defined as a description of a highly adaptable and dynamic intrinsic property of tumor cells, instead of a static subpopulation of a tumor. Altered conditions could trigger the gain of stemness, some of them include: EMT-MET, epigenetics, microenvironment and selective stimulus such as chemotherapy. This CSC heterogeneity and dynamism makes them out reach from therapeutic protocols directed to a single target. A further avenue of research in this line will be to uncover mechanisms that trigger this interconversion of cell populations within tumors and target it.展开更多
AIM: To compare prevalence rates of non-alcoholic fatty liver disease (NAFLD) between Hispanics of Mexican origin and Hispanics of Dominican and Puerto Rican origin.
This study was designed to analyze the sperm kinematic and morphometric subpopulations in the different fractions of the ejaculate in normozoospermic men. Ejaculates from eight normozoospermic men were collected by ma...This study was designed to analyze the sperm kinematic and morphometric subpopulations in the different fractions of the ejaculate in normozoospermic men. Ejaculates from eight normozoospermic men were collected by masturbation in three fractions after 3-5 days of sexual abstinence. Analyses of sperm motility by computer-assisted sperm analysis （CASA-Mot）, and of sperm morphometry by computer-assisted sperm morphometry analysis （CASA-Morph） using fluorescence were performed. Clustering and discriminant procedures were performed to identify sperm subpopulations in the kinematic and morphometric data obtained. Clustering procedures resulted in the classification of spermatozoa into three kinematic subpopulations （slow with low ALH [35.6% of all motile spermatozoa], with circular trajectories [32.0%], and rapid with high ALH [32.4%]）, and three morphometric subpopulations （large-round [33.9% of all spermatozoa], elongated [32.0%], and small [34.10%]）. The distribution of kinematic sperm subpopulations was different among ejaculate fractions （P 〈 0.001）, with higher percentages of spermatozoa exhibiting slow movements with low ALH in the second and third portions, and with a more homogeneous distribution of kinematic sperm subpopulations in the first portion. The distribution of morphometric sperm subpopulations was also different among ejaculate fractions （P〈 0.001）, with more elongated spermatozoa in the first, and of small spermatozoa in the third, portion. It is concluded that important variations in the distribution of kinematic and morphometric sperm subpopulations exist between ejaculate fractions, with possible functional implications.展开更多
2,4-dinitrophenol （DNP）, an organic compound which frequently used in industry, is considered to have high toxicity. This study aimed to investigate the early changes of lymphocyte subpopulations in patients with oc...2,4-dinitrophenol （DNP）, an organic compound which frequently used in industry, is considered to have high toxicity. This study aimed to investigate the early changes of lymphocyte subpopulations in patients with occupational 2,4-DNP poisoning. Totally 9 patients with acute occupational 2,4-DNP poisoning and 30 healthy volunteers as control were enrolled. The patients received immediately comprehensive supportive treatments, including large-dose glucocorticoid and repeated hemoperfusion （HP）. The ratio of CD4＋/CD8＋ T cells were significantly higher in patients upon admission compared to healthy controls （P 〈 0.01）; however, counts of total lymphocytes, CD3＋, CD3＋CD4＋, CD3＋CD8＋, B （CD19＋）, and natural killer （NK） cells （CD16＋CD56＋） were significantly reduced （all P 〈 0.001）. The NK cell count was negatively correlated with initial plasma 2,4-DNP concentration （r = -0.750, P = 0.026）. Thus, acute occupational 2,4-DNP poisoning was accompanied by immediate complex immune cell reactions, especially NK cells might play important role in severe 2,4-DNP poisoning.展开更多
Hand osteoarthritis is a common heterogeneous joint disorder with unclear molecular mechanisms and no disease-modifying drugs.In this study,we performed single-cell RNA sequencing analysis to compare the cellular comp...Hand osteoarthritis is a common heterogeneous joint disorder with unclear molecular mechanisms and no disease-modifying drugs.In this study,we performed single-cell RNA sequencing analysis to compare the cellular composition and subpopulationspecific gene expression between cartilage with macroscopically confirmed osteoarthritis(n=5)and cartilage without osteoarthritis(n=5)from the interphalangeal joints of five donors.Of 105142 cells,we identified 13 subpopulations,including a novel subpopulation with inflammation-modulating potential annotated as inflammatory chondrocytes.Fibrocartilage chondrocytes exhibited extensive alteration of gene expression patterns in osteoarthritic cartilage compared with nonosteoarthritic cartilage.Both inflammatory chondrocytes and fibrocartilage chondrocytes showed a trend toward increased numbers in osteoarthritic cartilage.In these two subpopulations from osteoarthritic cartilage,the ferroptosis pathway was enriched,and expression of iron overload-related genes,e.g.,FTH1,was elevated.To verify these findings,we conducted a Mendelian randomization study using UK Biobank and a population-based cross-sectional study using data collected from Xiangya Osteoarthritis Study.Genetic predisposition toward higher expression of FTH1 mRNA significantly increased the risk of hand osteoarthritis(odds ratio=1.07,95%confidence interval:1.02–1.11)among participants(n=332668)in UK Biobank.High levels of serum ferritin(encoded by FTH1),a biomarker of body iron overload,were significantly associated with a high prevalence of hand osteoarthritis among participants(n=1241)of Xiangya Osteoarthritis Study(P-for-trend=0.037).In conclusion,our findings indicate that inflammatory and fibrocartilage chondrocytes are key subpopulations and that ferroptosis may be a key pathway in hand osteoarthritis,providing new insights into the pathophysiology and potential therapeutic targets of hand osteoarthritis.展开更多
Regardless of its anatomical site,adipose tissue shares a common energy-storage role but exhibits distinctive properties.Exploring the cellular and molecular heterogeneity of white adipose tissue(WAT)is crucial for co...Regardless of its anatomical site,adipose tissue shares a common energy-storage role but exhibits distinctive properties.Exploring the cellular and molecular heterogeneity of white adipose tissue(WAT)is crucial for comprehending its function and properties.However,existing single-nucleus RNA sequencing(snRNA-seq)studies of adipose tissue heterogeneity have examined only one or two depots.In this study,we employed snRNA-seq to test five representative depots including inguinal,epididymal,mesenteric,perirenal,and pericardial adipose tissues in mice under physiological conditions.By analyzing the contents of main cell catego-ries and gene profiles of various depots,we identified their distinctive physiological properties.Immune cells and fibro-adipogenic progenitor cells(FAPs)showed dramatic differences among WAT depots,while adipocytes seemed to be conserved.The heightened presence of regulatory macrophages and B cells in pericardial adipose tissues implied their potential contribution to the preservation of coronary vascular function.Moreover,the selective aggregation of pericytes within mesenteric adipose tissue was likely associated with the maintenance of intestinal barrier homeostasis.Using a combination of RNA sequencing and snRNA-seq analysis,the major subpopulations of FAPs derived from these depots determined the site characteristics of FAPs to a certain extent.Our work estab-lishes a systematic and reliable foundation for investigating the heterogeneity of WAT depots and elucidating the unique roles these depots play in coordinating the function of adjacent organs.展开更多
采用酸性α-醋酸萘酯酶(ANAE)染色法和碱性磷酸酶——抗碱性磷酸酶(APAAP)酶联免疫染色法测定未妊娠、妊娠前期(<100 d)、妊娠中期(100～200 d)和妊娠后期(>200 d)的黑白花奶牛各10头的外周血T淋巴细胞总数和 T 淋巴细胞亚群的变...采用酸性α-醋酸萘酯酶(ANAE)染色法和碱性磷酸酶——抗碱性磷酸酶(APAAP)酶联免疫染色法测定未妊娠、妊娠前期(<100 d)、妊娠中期(100～200 d)和妊娠后期(>200 d)的黑白花奶牛各10头的外周血T淋巴细胞总数和 T 淋巴细胞亚群的变化.结果表明:未孕与不同妊娠阶段母牛 T 外周血淋巴细胞总数、CD_3亚群和 CD_4:CD_8比值差异显著(P<0.05),而不同妊娠期之间则差异不显著(P>0.05).这表明妊娠母牛的细胞免疫功能是下降的,这种情况可能是通过降低 T 淋巴细胞和 CD_4:CD_8比值来实现的,有利于胚胎的植入和发育.展开更多
Objective： To explore the effects of dentritic cells on the peripheral blood lymphocyte subpopulations of metastatic breast cancer patients treated with chemotherapy. Methods： The current study involved 44 metastati...Objective： To explore the effects of dentritic cells on the peripheral blood lymphocyte subpopulations of metastatic breast cancer patients treated with chemotherapy. Methods： The current study involved 44 metastatic breast cancer patients treated with docetaxel-based chemotherapy. Among them, 25 cases were treated with dendritic cells derived from CD34＋ hematopoietic stem cells enriched autologous peripheral mononuclear cells after chemotherapy, and 19 cases received chemotherapy alone. Peripheral blood samples were collected from each patient before and after treatment, and lymphocyte subpopulations including CD3＋, CD3＋/CD4＋, CD3＋/CD8＋, CD3-/CD16＋56＋, CD3＋/CD16＋56＋, CD4＋/CD25＋, CD8＋/CD28-, CD8＋/CD28＋, CD4/CD8, DC1, DC2 and DC1/DC2 were analysed by a 3-color flow cytometric analysis. Results： The two treatment groups were well matched with regard to demographic and baseline disease characteristics. Comparing the changes of lymphocyte subpopulations between the two groups, it showed that the difference of the change of CD8＋/CD28-lymphocyte had statistic significance. The percentage of CD8＋/CD28-lymphocyte was lower in the chemotherapy＋DC group, but higher in the chemotherapy-alone group. Conclusion： As CD8＋/CD28-lymphocyte represent a kind of suppressive T lymphocyte, we conclude that dentritic cell therapy can relieve immunosuppression to some extent.展开更多
The regulation of acupuncture on the immunological function has been studied inlaboratory and clinic. The results showed that stimulating the biological active point (or acupoint)with electroacupuncture could inhibit ...The regulation of acupuncture on the immunological function has been studied inlaboratory and clinic. The results showed that stimulating the biological active point (or acupoint)with electroacupuncture could inhibit the growth of tumor in experimental rats and prolongate the life-span of rats bearing tumor; and that electro-acupuncture had a good effect on the immunoregulatingsubpopulations of lymphocyte of patients with cancer.展开更多
A computational analysis of genome-scale transcriptomic data collected on -1,700 tissue samples of three cancer types： breast carcinoma, colon adenocarcinoma and lung adenocarcinoma, revealed that each tissue consist...A computational analysis of genome-scale transcriptomic data collected on -1,700 tissue samples of three cancer types： breast carcinoma, colon adenocarcinoma and lung adenocarcinoma, revealed that each tissue consists of （at least） two major subpopulations of cancer cells with different capabilities to handle fluctuating Oz levels. The two populations have distinct genomic and transcriptomic characteristics, one accelerating its proliferation under hypoxic conditions and the other proliferating faster with higher O2 levels, referred to as the hypoxia and the reoxygenation subpopulations, respectively. The proportions of the two subpopulations within a cancer tissue change as the average 02 level changes. They both contribute to cancer development but in a complementary manner. The hypoxia subpopulation tends to have higher proliferation rates than the reoxygenation one as well as higher apoptosis rates; and it is largely responsible for the acidic environment that enables tissue invasion and provides protection against attacks from T-cells. In comparison, the reoxygenation subpopulation generates new extracellular matrices in support of further growth of the tumor and strengthens cell-cell adhesion to provide scaffolds to keep all the cells connected. This subpopulation also serves as the major source of growth factors for tissue growth. These data and observations strongly suggest that these two major subpopulations within each tumor work together in a conjugative relationship to allow the tumor to overcome stresses associated with the constantly changing Oz level due to repeated growth and angiogenesis. The analysis results not only reveal new insights about the population dynamics within a tumor but also have implications to our understanding of possible causes of different cancer phenotypes such as diffused versus more tightly connected tumor tissues.展开更多
This study was designed to characterize morphometric sperm subpopulations in normozoospermic men by using different statistical methods and examining their suitability to classify correctly different sperm nuclear mor...This study was designed to characterize morphometric sperm subpopulations in normozoospermic men by using different statistical methods and examining their suitability to classify correctly different sperm nuclear morphologies present in human ejaculates. Ejaculates from 21 normozoospermic men were collected for the study. After semen collection and analysis, samples were prepared for morphometric determination. At least 200 spermatozoa per sample were assessed for sperm morphometry by computer-assisted sperm morphometry analysis （CASA-Morph） using fluorescence. Clustering and discriminant procedures were performed to identify sperm subpopulations from the morphometric data obtained. Clustering procedures resulted in the classification of spermatozoa into three morphometric subpopulations （large-round 30.4%, small-round 46.6%, and large-elongated 22.9%）. In the second analysis, using discriminant methods, the classification was made independently of size and shape. Three morphological categories according to nuclear size （small 〈10.90 μm^2, intermediate 10.91-13.07 μm^2, and large 〉13.07 μm^2） and four categories were defined on 400 canonical cells （100 × 4） from 10 men according to sperm nuclear shape （oval, pyriform, round, and elongated）. Thereafter, the resulting classification functions were used to categorize 4200 spermatozoa from 21 men. Differences in the class distribution were observed among men from both clustering and discriminant procedures. It was concluded that the combination of CASA-Morph fluorescence-based technology with multivariate cluster or discriminant analyses provides new information on the description of different morphometric sperm subpopulations in normal individuals, and that important variations in the distribution of morphometric sperm subpopulations may exist between men, with possible functional implications.展开更多
Sperm quality is evaluated for the calculation of sperm dosage in artificial reproductive programs. The most common parameter used is motility, but morphology has a higher potential as a predictor of genetic quality. ...Sperm quality is evaluated for the calculation of sperm dosage in artificial reproductive programs. The most common parameter used is motility, but morphology has a higher potential as a predictor of genetic quality. Morphometry calculations from CASA-Morph technology improve morphological evaluation and allow mathematical approaches to the problem. Semen from 28 Holstein bulls was collected by artificial vagina, and several ejaculates were studied. After general evaluation, samples were diluted, packaged in 0.25 ml straws, and stored in liquid nitrogen. Two straws per sample were thawed, and slides were processed and stained with Diff-Quik. Samples were analyzed by a CASA-Morph system for eight morphometric parameters. In addition to the ＂classical＂ statistical approach, based on variance analysis （revealing differences between animals, ejaculates, and straws）, principal component （PC） analysis showed that the variables were grouped into PC1, related to size, and PC2 to shape. Subpopulation structure analysis showed four groups, namely, big, small, short, and narrow from their dominant characteristics, representing 31.0%, 27.3%, 24.1%, and 17.7% of the total population, respectively. The distributions varied between animals and ejaculates, but between straws, there were no differences in only four animals. This modern approach of considering an ejaculate sperm population as divided into subpopulations reflecting quantifiable parameters generated by CASA-Morph systems technology opens a new view on sperm function. This is the first study applying this approach to evaluate different ejaculates and straws from the same individual. More work must be done to improve seminal dose calculations in assisted reproductive programs.展开更多
文摘Objective: To investigate the potential and early effect of hypertonic saline resuscitation on T-lymphocyte sub- populations in rats with hemorrhagic shock. Methods: A model of rat with severe hemorrhagic shock was established in 18 Sprague-Dawley (SD) rats. The rats were randomly divided into Sham group, HTS group (hypertonic saline resuscitation group) and NS group (normal saline resuscitation group). Each group contained 6 rats. The CD4+ and CD8+ subpopulations of T-lymphocytes in peripheral blood were detected respectively before shock and after resuscitation by double antibody labelling and flow cytometry. Results: In the early stage after hemorrhagic shock, fluid resuscitation and emergency treatment, the CD4+ lymphocytes of peripheral blood in HTS and NS groups markedly increased. Small volume resuscitation with HTS also induced peripheral CD8+ lymphocytes to a certain extent, whereas NS resuscitation showed no effect in this respect. Consequently, compared with Sham and HTS groups, CD4+/CD8+ ratio of peripheral blood in NS group was obviously increased, and showed statistically differences. Conclusion: In this model of rat with severe hemorrhagic shock, small volume resuscitation with HTS is more effective than NS in reducing immunologic disorders and promoting a more balanced profile of T-lymphocyte subpopula- tions regulating network.
基金Supported by the National Natural Science Foundation of China,No.81670951
文摘Stem cells(SCs)with their self-renewal and pluripotent differentiation potential,show great promise for therapeutic applications to some refractory diseases such as stroke,Parkinsonism,myocardial infarction,and diabetes.Furthermore,as seed cells in tissue engineering,SCs have been applied widely to tissue and organ regeneration.However,previous studies have shown that SCs are heterogeneous and consist of many cell subpopulations.Owing to this heterogeneity of cell states,gene expression is highly diverse between cells even within a single tissue,making precise identification and analysis of biological properties difficult,which hinders their further research and applications.Therefore,a defined understanding of the heterogeneity is a key to research of SCs.Traditional ensemble-based sequencing approaches,such as microarrays,reflect an average of expression levels across a large population,which overlook unique biological behaviors of individual cells,conceal cell-to-cell variations,and cannot understand the heterogeneity of SCs radically.The development of high throughput single cell RNA sequencing(scRNA-seq)has provided a new research tool in biology,ranging from identification of novel cell types and exploration of cell markers to the analysis of gene expression and predicating developmental trajectories.scRNA-seq has profoundly changed our understanding of a series of biological phenomena.Currently,it has been used in research of SCs in many fields,particularly for the research of heterogeneity and cell subpopulations in early embryonic development.In this review,we focus on the scRNA-seq technique and its applications to research of SCs.
基金Supported by Shenzhen Science and Technology Program,No.GJHZ20210705142543019Guangdong Basic and Applied Basic Research Foundation,No.2023A1515220074.
文摘Diabetes mellitus(DM),an increasingly prevalent chronic metabolic disease,is characterised by prolonged hyperglycaemia,which leads to long-term health consequences.Although much effort has been put into understanding the pathogenesis of diabetic wounds,the underlying mechanisms remain unclear.The advent of single-cell RNA sequencing(scRNAseq)has revolutionised biological research by enabling the identification of novel cell types,the discovery of cellular markers,the analysis of gene expression patterns and the prediction of develop-mental trajectories.This powerful tool allows for an in-depth exploration of pathogenesis at the cellular and molecular levels.In this editorial,we focus on progenitor-based repair strategies for diabetic wound healing as revealed by scRNAseq and highlight the biological behaviour of various healing-related cells and the alteration of signalling pathways in the process of diabetic wound healing.ScRNAseq could not only deepen our understanding of the complex biology of diabetic wounds but also identify and validate new targets for inter-vention,offering hope for improved patient outcomes in the management of this challenging complication of DM.
文摘Marginal zone(MZ)B cells,which are composed of heterogeneous subpopulations,are participate in the rapid response to antigens.Lee et al.showed that MZ B cells can be divided into two distinct subpopulations based on CD80 expression.These two subpopulations of MZ B cells exhibit differential autoreactivity,radiosensitivity,and functional capacities.
文摘Carcinogenic process has been proposed to relay on the capacity to induce local tissue damage and proliferative repair. Liver has a great regeneration capacity and currently, most studies point towards the dominant role of hepatocytes in regeneration at all levels of liver damage. The most frequent liver cancer is hepatocellular carcinoma(HCC). Historical findings originally led to the idea that the cell of origin of HCC might be a progenitor cell. However, current linage tracing studies put the progenitor hypothesis of HCC origin into question. In agreement with their dominant role in liver regeneration, mature hepatocytes are emerging as the cell of origin of HCC, although, the specific hepatocyte subpopulation of origin is yet to be determined. The relationship between the cancer cell of origin(CCO) and cancer-propagating cells, known as hepatic cancer stem cell(HCSC) is unknown. It has been challenging to identify the definitive phenotypic marker of HCSC, probably due to the existence of different cancer stem cells(CSC) subpopulations with different functions within HCC. There is a dynamic interconversion among different CSCs, and between CSC and non-CSCs. Because of that, CSC-state is currently defined as a description of a highly adaptable and dynamic intrinsic property of tumor cells, instead of a static subpopulation of a tumor. Altered conditions could trigger the gain of stemness, some of them include: EMT-MET, epigenetics, microenvironment and selective stimulus such as chemotherapy. This CSC heterogeneity and dynamism makes them out reach from therapeutic protocols directed to a single target. A further avenue of research in this line will be to uncover mechanisms that trigger this interconversion of cell populations within tumors and target it.
基金Supported by National Heart,Lung,and Blood Institute at the National Institutes of Health grants R01 HL071739 and by contracts N01-HC-95159 through N01-HC-95165 and N01 HC 95169
文摘AIM: To compare prevalence rates of non-alcoholic fatty liver disease (NAFLD) between Hispanics of Mexican origin and Hispanics of Dominican and Puerto Rican origin.
文摘This study was designed to analyze the sperm kinematic and morphometric subpopulations in the different fractions of the ejaculate in normozoospermic men. Ejaculates from eight normozoospermic men were collected by masturbation in three fractions after 3-5 days of sexual abstinence. Analyses of sperm motility by computer-assisted sperm analysis （CASA-Mot）, and of sperm morphometry by computer-assisted sperm morphometry analysis （CASA-Morph） using fluorescence were performed. Clustering and discriminant procedures were performed to identify sperm subpopulations in the kinematic and morphometric data obtained. Clustering procedures resulted in the classification of spermatozoa into three kinematic subpopulations （slow with low ALH [35.6% of all motile spermatozoa], with circular trajectories [32.0%], and rapid with high ALH [32.4%]）, and three morphometric subpopulations （large-round [33.9% of all spermatozoa], elongated [32.0%], and small [34.10%]）. The distribution of kinematic sperm subpopulations was different among ejaculate fractions （P 〈 0.001）, with higher percentages of spermatozoa exhibiting slow movements with low ALH in the second and third portions, and with a more homogeneous distribution of kinematic sperm subpopulations in the first portion. The distribution of morphometric sperm subpopulations was also different among ejaculate fractions （P〈 0.001）, with more elongated spermatozoa in the first, and of small spermatozoa in the third, portion. It is concluded that important variations in the distribution of kinematic and morphometric sperm subpopulations exist between ejaculate fractions, with possible functional implications.
基金supported by the grants from the Foundation of Science and Technology Department of Zhejiang Province for Beneficial Technology Research of Social Development(2011C23013)
文摘2,4-dinitrophenol （DNP）, an organic compound which frequently used in industry, is considered to have high toxicity. This study aimed to investigate the early changes of lymphocyte subpopulations in patients with occupational 2,4-DNP poisoning. Totally 9 patients with acute occupational 2,4-DNP poisoning and 30 healthy volunteers as control were enrolled. The patients received immediately comprehensive supportive treatments, including large-dose glucocorticoid and repeated hemoperfusion （HP）. The ratio of CD4＋/CD8＋ T cells were significantly higher in patients upon admission compared to healthy controls （P 〈 0.01）; however, counts of total lymphocytes, CD3＋, CD3＋CD4＋, CD3＋CD8＋, B （CD19＋）, and natural killer （NK） cells （CD16＋CD56＋） were significantly reduced （all P 〈 0.001）. The NK cell count was negatively correlated with initial plasma 2,4-DNP concentration （r = -0.750, P = 0.026）. Thus, acute occupational 2,4-DNP poisoning was accompanied by immediate complex immune cell reactions, especially NK cells might play important role in severe 2,4-DNP poisoning.
基金supported by the National Natural Science Foundation of China(81930071,82072502)the National Natural Science Foundation Regional Innovation and Development Joint Fund(U21A20352)+5 种基金the National Key Research and Development Project(2022YFC3601900,2022YFC2505500)the Project Program of National Clinical Research Center for Geriatric Disorders(Xiangya Hospital,2021LNJJ06,2022LNJJ07)the Natural Science Foundation of Hunan Province(2022JJ20100)the Key Research and Development Program of Hunan Province(2021SK2017)the Science and Technology Innovation Program of Hunan Province(2022RC3075)the Central South University Innovation-Driven Research Program(2023CXQD031)。
文摘Hand osteoarthritis is a common heterogeneous joint disorder with unclear molecular mechanisms and no disease-modifying drugs.In this study,we performed single-cell RNA sequencing analysis to compare the cellular composition and subpopulationspecific gene expression between cartilage with macroscopically confirmed osteoarthritis(n=5)and cartilage without osteoarthritis(n=5)from the interphalangeal joints of five donors.Of 105142 cells,we identified 13 subpopulations,including a novel subpopulation with inflammation-modulating potential annotated as inflammatory chondrocytes.Fibrocartilage chondrocytes exhibited extensive alteration of gene expression patterns in osteoarthritic cartilage compared with nonosteoarthritic cartilage.Both inflammatory chondrocytes and fibrocartilage chondrocytes showed a trend toward increased numbers in osteoarthritic cartilage.In these two subpopulations from osteoarthritic cartilage,the ferroptosis pathway was enriched,and expression of iron overload-related genes,e.g.,FTH1,was elevated.To verify these findings,we conducted a Mendelian randomization study using UK Biobank and a population-based cross-sectional study using data collected from Xiangya Osteoarthritis Study.Genetic predisposition toward higher expression of FTH1 mRNA significantly increased the risk of hand osteoarthritis(odds ratio=1.07,95%confidence interval:1.02–1.11)among participants(n=332668)in UK Biobank.High levels of serum ferritin(encoded by FTH1),a biomarker of body iron overload,were significantly associated with a high prevalence of hand osteoarthritis among participants(n=1241)of Xiangya Osteoarthritis Study(P-for-trend=0.037).In conclusion,our findings indicate that inflammatory and fibrocartilage chondrocytes are key subpopulations and that ferroptosis may be a key pathway in hand osteoarthritis,providing new insights into the pathophysiology and potential therapeutic targets of hand osteoarthritis.
基金This work was supported by the National Key R&D Program of China(2020YFA0803604)the National Natural Science Foundation of China,Key Program(82130024)for funding.
文摘Regardless of its anatomical site,adipose tissue shares a common energy-storage role but exhibits distinctive properties.Exploring the cellular and molecular heterogeneity of white adipose tissue(WAT)is crucial for comprehending its function and properties.However,existing single-nucleus RNA sequencing(snRNA-seq)studies of adipose tissue heterogeneity have examined only one or two depots.In this study,we employed snRNA-seq to test five representative depots including inguinal,epididymal,mesenteric,perirenal,and pericardial adipose tissues in mice under physiological conditions.By analyzing the contents of main cell catego-ries and gene profiles of various depots,we identified their distinctive physiological properties.Immune cells and fibro-adipogenic progenitor cells(FAPs)showed dramatic differences among WAT depots,while adipocytes seemed to be conserved.The heightened presence of regulatory macrophages and B cells in pericardial adipose tissues implied their potential contribution to the preservation of coronary vascular function.Moreover,the selective aggregation of pericytes within mesenteric adipose tissue was likely associated with the maintenance of intestinal barrier homeostasis.Using a combination of RNA sequencing and snRNA-seq analysis,the major subpopulations of FAPs derived from these depots determined the site characteristics of FAPs to a certain extent.Our work estab-lishes a systematic and reliable foundation for investigating the heterogeneity of WAT depots and elucidating the unique roles these depots play in coordinating the function of adjacent organs.
文摘采用酸性α-醋酸萘酯酶(ANAE)染色法和碱性磷酸酶——抗碱性磷酸酶(APAAP)酶联免疫染色法测定未妊娠、妊娠前期(<100 d)、妊娠中期(100～200 d)和妊娠后期(>200 d)的黑白花奶牛各10头的外周血T淋巴细胞总数和 T 淋巴细胞亚群的变化.结果表明:未孕与不同妊娠阶段母牛 T 外周血淋巴细胞总数、CD_3亚群和 CD_4:CD_8比值差异显著(P<0.05),而不同妊娠期之间则差异不显著(P>0.05).这表明妊娠母牛的细胞免疫功能是下降的,这种情况可能是通过降低 T 淋巴细胞和 CD_4:CD_8比值来实现的,有利于胚胎的植入和发育.
基金supported by a grant from the Beijing Capital Development Foundation for Medical Sciences(No. 2007-2053)
文摘Objective： To explore the effects of dentritic cells on the peripheral blood lymphocyte subpopulations of metastatic breast cancer patients treated with chemotherapy. Methods： The current study involved 44 metastatic breast cancer patients treated with docetaxel-based chemotherapy. Among them, 25 cases were treated with dendritic cells derived from CD34＋ hematopoietic stem cells enriched autologous peripheral mononuclear cells after chemotherapy, and 19 cases received chemotherapy alone. Peripheral blood samples were collected from each patient before and after treatment, and lymphocyte subpopulations including CD3＋, CD3＋/CD4＋, CD3＋/CD8＋, CD3-/CD16＋56＋, CD3＋/CD16＋56＋, CD4＋/CD25＋, CD8＋/CD28-, CD8＋/CD28＋, CD4/CD8, DC1, DC2 and DC1/DC2 were analysed by a 3-color flow cytometric analysis. Results： The two treatment groups were well matched with regard to demographic and baseline disease characteristics. Comparing the changes of lymphocyte subpopulations between the two groups, it showed that the difference of the change of CD8＋/CD28-lymphocyte had statistic significance. The percentage of CD8＋/CD28-lymphocyte was lower in the chemotherapy＋DC group, but higher in the chemotherapy-alone group. Conclusion： As CD8＋/CD28-lymphocyte represent a kind of suppressive T lymphocyte, we conclude that dentritic cell therapy can relieve immunosuppression to some extent.
文摘The regulation of acupuncture on the immunological function has been studied inlaboratory and clinic. The results showed that stimulating the biological active point (or acupoint)with electroacupuncture could inhibit the growth of tumor in experimental rats and prolongate the life-span of rats bearing tumor; and that electro-acupuncture had a good effect on the immunoregulatingsubpopulations of lymphocyte of patients with cancer.
文摘A computational analysis of genome-scale transcriptomic data collected on -1,700 tissue samples of three cancer types： breast carcinoma, colon adenocarcinoma and lung adenocarcinoma, revealed that each tissue consists of （at least） two major subpopulations of cancer cells with different capabilities to handle fluctuating Oz levels. The two populations have distinct genomic and transcriptomic characteristics, one accelerating its proliferation under hypoxic conditions and the other proliferating faster with higher O2 levels, referred to as the hypoxia and the reoxygenation subpopulations, respectively. The proportions of the two subpopulations within a cancer tissue change as the average 02 level changes. They both contribute to cancer development but in a complementary manner. The hypoxia subpopulation tends to have higher proliferation rates than the reoxygenation one as well as higher apoptosis rates; and it is largely responsible for the acidic environment that enables tissue invasion and provides protection against attacks from T-cells. In comparison, the reoxygenation subpopulation generates new extracellular matrices in support of further growth of the tumor and strengthens cell-cell adhesion to provide scaffolds to keep all the cells connected. This subpopulation also serves as the major source of growth factors for tissue growth. These data and observations strongly suggest that these two major subpopulations within each tumor work together in a conjugative relationship to allow the tumor to overcome stresses associated with the constantly changing Oz level due to repeated growth and angiogenesis. The analysis results not only reveal new insights about the population dynamics within a tumor but also have implications to our understanding of possible causes of different cancer phenotypes such as diffused versus more tightly connected tumor tissues.
文摘This study was designed to characterize morphometric sperm subpopulations in normozoospermic men by using different statistical methods and examining their suitability to classify correctly different sperm nuclear morphologies present in human ejaculates. Ejaculates from 21 normozoospermic men were collected for the study. After semen collection and analysis, samples were prepared for morphometric determination. At least 200 spermatozoa per sample were assessed for sperm morphometry by computer-assisted sperm morphometry analysis （CASA-Morph） using fluorescence. Clustering and discriminant procedures were performed to identify sperm subpopulations from the morphometric data obtained. Clustering procedures resulted in the classification of spermatozoa into three morphometric subpopulations （large-round 30.4%, small-round 46.6%, and large-elongated 22.9%）. In the second analysis, using discriminant methods, the classification was made independently of size and shape. Three morphological categories according to nuclear size （small 〈10.90 μm^2, intermediate 10.91-13.07 μm^2, and large 〉13.07 μm^2） and four categories were defined on 400 canonical cells （100 × 4） from 10 men according to sperm nuclear shape （oval, pyriform, round, and elongated）. Thereafter, the resulting classification functions were used to categorize 4200 spermatozoa from 21 men. Differences in the class distribution were observed among men from both clustering and discriminant procedures. It was concluded that the combination of CASA-Morph fluorescence-based technology with multivariate cluster or discriminant analyses provides new information on the description of different morphometric sperm subpopulations in normal individuals, and that important variations in the distribution of morphometric sperm subpopulations may exist between men, with possible functional implications.
文摘Sperm quality is evaluated for the calculation of sperm dosage in artificial reproductive programs. The most common parameter used is motility, but morphology has a higher potential as a predictor of genetic quality. Morphometry calculations from CASA-Morph technology improve morphological evaluation and allow mathematical approaches to the problem. Semen from 28 Holstein bulls was collected by artificial vagina, and several ejaculates were studied. After general evaluation, samples were diluted, packaged in 0.25 ml straws, and stored in liquid nitrogen. Two straws per sample were thawed, and slides were processed and stained with Diff-Quik. Samples were analyzed by a CASA-Morph system for eight morphometric parameters. In addition to the ＂classical＂ statistical approach, based on variance analysis （revealing differences between animals, ejaculates, and straws）, principal component （PC） analysis showed that the variables were grouped into PC1, related to size, and PC2 to shape. Subpopulation structure analysis showed four groups, namely, big, small, short, and narrow from their dominant characteristics, representing 31.0%, 27.3%, 24.1%, and 17.7% of the total population, respectively. The distributions varied between animals and ejaculates, but between straws, there were no differences in only four animals. This modern approach of considering an ejaculate sperm population as divided into subpopulations reflecting quantifiable parameters generated by CASA-Morph systems technology opens a new view on sperm function. This is the first study applying this approach to evaluate different ejaculates and straws from the same individual. More work must be done to improve seminal dose calculations in assisted reproductive programs.
