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1.
Eur J Immunol ; 51(8): 2027-2039, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33974710

RESUMEN

Immune deficiency is one of the hallmarks of HIV infection and a major cause of adverse outcomes in people living with HIV (PLWH). Long-lived memory CD8+ T cells (LLMCs) are essential executors of long-term protective immunity; however, the generation and maintenance of LLMCs during chronic HIV infection are not well understood. In the present study, we analyzed circulating LLMCs in healthy controls (HCs) and PLWH with different disease statuses, including treatment naïve patients (TNs), complete responders (CRs), and immunological nonresponders (INRs). We found that both TNs and INRs showed severely compromised LLMCs compared with HCs and CRs, respectively. The decrease of LLMCs in TNs correlated positively with the reduction of their precursors, namely memory precursor effector T cells (MPECs), which might be associated with elevated pro-inflammatory cytokines. Strikingly, INRs showed an accumulation of MPECs, which exhibited diminished responsiveness to interleukin 7 (IL-7), thereby indicating abrogated differentiation into LLMCs. Moreover, in vitro studies showed that treatment with dexamethasone could improve the IL7-phosphorylated (p)-signal transducer and activator of transcription (STAT5) response by upregulating the expression of the interleukin 7 receptor (IL-7Rα) on MPECs in INRs. These findings provide insights that will encourage the development of novel therapeutics to improve immune function in PLWH.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Infecciones por VIH/inmunología , Memoria Inmunológica/inmunología , Interleucina-7/inmunología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad
2.
BMC Plant Biol ; 19(1): 361, 2019 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-31419941

RESUMEN

BACKGROUND: The transfer of chloroplast DNA into nuclear genome is a common process in plants. These transfers form nuclear integrants of plastid DNAs (NUPTs), which are thought to be driving forces in genome evolution, including sex chromosome evolution. In this study, NUPTs in the genome of a dioecious plant Asparagus officinalis L. were systematically analyzed, in order to investigate the characteristics of NUPTs in the nuclear genome and the relationship between NUPTs and sex chromosome evolution in this species. RESULTS: A total of 3155 NUPT insertions were detected, and they represented approximated 0.06% of the nuclear genome. About 45% of the NUPTs were organized in clusters. These clusters were derived from various evolutionary events. The Y chromosome contained the highest number and largest proportion of NUPTs, suggesting more accumulation of NUPTs on sex chromosomes. NUPTs were distributed widely in all of the chromosomes, and some regions preferred these insertions. The highest density of NUPTs was found in a 47 kb region in the Y chromosome; more than 75% of this region was occupied by NUPTs. Further cytogenetic and sequence alignment analysis revealed that this region was likely the centromeric region of the sex chromosomes. On the other hand, the male-specific region of the Y chromosome (MSY) and the adjacent regions did not have NUPT insertions. CONCLUSIONS: These results indicated that NUPTs were involved in shaping the genome of A. officinalis through complicated process. NUPTs may play important roles in the centromere shaping of the sex chromosomes of A. officinalis, but were not implicated in MSY formation.


Asunto(s)
Asparagus/genética , Núcleo Celular/genética , Cromosomas de las Plantas/genética , ADN de Cloroplastos/genética , Genoma de Planta/genética , Evolución Biológica , Evolución Molecular
3.
BMC Plant Biol ; 17(1): 143, 2017 08 22.
Artículo en Inglés | MEDLINE | ID: mdl-28830346

RESUMEN

BACKGROUND: Garden asparagus (Asparagus officinalis) is a highly valuable vegetable crop of commercial and nutritional interest. It is also commonly used to investigate the mechanisms of sex determination and differentiation in plants. However, the sex expression mechanisms in asparagus remain poorly understood. RESULTS: De novo transcriptome sequencing via Illumina paired-end sequencing revealed more than 26 billion bases of high-quality sequence data from male and female asparagus flower buds. A total of 72,626 unigenes with an average length of 979 bp were assembled. In comparative transcriptome analysis, 4876 differentially expressed genes (DEGs) were identified in the possible sex-determining stage of female and male/supermale flower buds. Of these DEGs, 433, including 285 male/supermale-biased and 149 female-biased genes, were annotated as flower related. Of the male/supermale-biased flower-related genes, 102 were probably involved in anther development. In addition, 43 DEGs implicated in hormone response and biosynthesis putatively associated with sex expression and reproduction were discovered. Moreover, 128 transcription factor (TF)-related genes belonging to various families were found to be differentially expressed, and this finding implied the essential roles of TF in sex determination or differentiation in asparagus. Correlation analysis indicated that miRNA-DEG pairs were also implicated in asparagus sexual development. CONCLUSIONS: Our study identified a large number of DEGs involved in the sex expression and reproduction of asparagus, including known genes participating in plant reproduction, plant hormone signaling, TF encoding, and genes with unclear functions. We also found that miRNAs might be involved in the sex differentiation process. Our study could provide a valuable basis for further investigations on the regulatory networks of sex determination and differentiation in asparagus and facilitate further genetic and genomic studies on this dioecious species.


Asunto(s)
Asparagus/crecimiento & desarrollo , Asparagus/genética , Regulación de la Expresión Génica de las Plantas , Expresión Génica , Flores/genética , Flores/crecimiento & desarrollo , Perfilación de la Expresión Génica , MicroARNs/genética , MicroARNs/metabolismo
4.
Yi Chuan ; 39(12): 1168-1177, 2017 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-29258987

RESUMEN

Classical forward genetic analysis relies on construction of complicated progeny populations and development of many molecular markers for linkage analysis in genetic mapping, which is both time- and cost-consuming. The recently developed MutMap is a new forward genetic approach based on high-throughput next-generation sequencing technologies. It is more efficient and affordable than traditional methods. Moreover, new extended methods based on MutMap have been developed: MutMap+, which is based on self-crossing; MutMap-Gap, which is used to recognize the causative variations occurring in genome gap regions; QTL-seq, a method similar to MutMap for mapping quantitative trait loci. These methods are free from constructing complicated mapping population, genetic hybridization and linkage information. They have greatly accelerated the identification of genetic elements associated with interested phenotypic variation. Here, we review the basic principles of MutMap, and discuss their future applications in next generation sequencing-based forward genetic mapping and crop improvement.


Asunto(s)
Mapeo Cromosómico/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Mutación , Secuenciación Completa del Genoma , Animales , Humanos , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo
5.
Planta ; 243(5): 1083-95, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26919983

RESUMEN

MAIN CONCLUSION: The present review discusses the roles of repetitive sequences played in plant sex chromosome evolution, and highlights epigenetic modification as potential mechanism of repetitive sequences involved in sex chromosome evolution. Sex determination in plants is mostly based on sex chromosomes. Classic theory proposes that sex chromosomes evolve from a specific pair of autosomes with emergence of a sex-determining gene(s). Subsequently, the newly formed sex chromosomes stop recombination in a small region around the sex-determining locus, and over time, the non-recombining region expands to almost all parts of the sex chromosomes. Accumulation of repetitive sequences, mostly transposable elements and tandem repeats, is a conspicuous feature of the non-recombining region of the Y chromosome, even in primitive one. Repetitive sequences may play multiple roles in sex chromosome evolution, such as triggering heterochromatization and causing recombination suppression, leading to structural and morphological differentiation of sex chromosomes, and promoting Y chromosome degeneration and X chromosome dosage compensation. In this article, we review the current status of this field, and based on preliminary evidence, we posit that repetitive sequences are involved in sex chromosome evolution probably via epigenetic modification, such as DNA and histone methylation, with small interfering RNAs as the mediator.


Asunto(s)
Cromosomas de las Plantas , Epigénesis Genética , Plantas/genética , Secuencias Repetitivas de Ácidos Nucleicos , Evolución Biológica , ADN de Plantas/genética , Recombinación Genética
6.
J Plant Res ; 129(5): 979-987, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27294968

RESUMEN

∆(8)-sphingolipid desaturase catalyzes the C8 desaturation of a long chain base, which is the characteristic structure of various complex sphingolipids. The genes of 20 ∆(8)-sphingolipid desaturases from 12 plants were identified and functionally detected by using Saccharomyces cerevisiae system to elucidate the relationship between the biochemical function and evolution of this enzyme. Results showed that the 20 genes all can encode a functional ∆(8)-sphingolipid desaturase, which catalyzes different ratios of two products, namely, 8(Z) and 8(E)-C18-phytosphingenine. The coded enzymes could be divided into two groups on the basis of biochemical functions: ∆(8)-sphingolipid desaturase with a preference for an E-isomer product and ∆(8)-sphingolipid desaturase with a preference for a Z-isomer product. The conversion rate of the latter was generally lower than that of the former. Phylogenetic analysis revealed that the 20 desaturases could also be clustered into two groups, and this grouping is consistent with that of the biochemical functions. Thus, the biochemical function of ∆(8)-sphingolipid desaturase is correlated with its evolution. The two groups of ∆(8)-sphingolipid desaturases could arise from distinct ancestors in higher plants. However, they might have initially evolved from ∆(8)-sphingolipid desaturases in lower organisms, such as yeasts, which can produce E-isomer products only. Furthermore, almost all of the transgenic yeasts harboring ∆(8)-sphingolipid desaturase genes exhibit an improvement in aluminum tolerance. Our study provided new insights into the biochemical function and evolution of ∆(8)-sphingolipid desaturases in plants.


Asunto(s)
Evolución Molecular , Genes de Plantas , Oxidorreductasas/genética , Plantas/enzimología , Plantas/genética , Aluminio/toxicidad , Cromatografía Líquida de Alta Presión , Clonación Molecular , Oxidorreductasas/metabolismo , Filogenia , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/genética , Transformación Genética/efectos de los fármacos
7.
Hepatol Int ; 18(4): 1122-1134, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38829576

RESUMEN

BACKGROUND: The role of neutrophils in hepatitis B virus (HBV) infection has been a subject of debate due to their involvement in antiviral responses and immune regulation. This study aimed to elucidate the neutrophil characteristics in patients with chronic hepatitis B (CHB). METHODS: Through flow cytometry and ribonucleic acid-sequencing analysis, the phenotypes and counts of neutrophils were analyzed in patients with CHB. Moreover, the effects of HBeAg on neutrophils and the corresponding pattern recognition receptors were identified. Simultaneously, the cross-talk between neutrophils and natural killer (NK) cells was investigated. RESULTS: Neutrophils were activated in patients with CHB, characterized by higher expression levels of programmed death-ligand 1 (PD-L1), cluster of differentiation 86, and interleukin-8, and lower levels of CXC motif chemokine receptor (CXCR) 1 and CXCR2. Hepatitis B e antigen (HBeAg) partially induces neutrophil activation through the Toll-like receptor 2 (TLR2). A consistent upregulation of the TLR2 and HBeAg expression was observed in patients with CHB. Notably, the genes encoding molecules pivotal for NK-cell function upon NK receptor engagement enriched in neutrophils after HBeAg activation. The HBeAg-activated neutrophils demonstrated the ability to decrease the production of interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) in NK cells, while the PD-1 and PD-L1 pathways partially mediated the immunosuppression. CONCLUSIONS: The immunosuppression of neutrophils induced by HBeAg suggests a novel pathogenic mechanism contributing to immune tolerance in patients with CHB.


Asunto(s)
Antígenos e de la Hepatitis B , Hepatitis B Crónica , Células Asesinas Naturales , Activación Neutrófila , Neutrófilos , Humanos , Hepatitis B Crónica/inmunología , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Antígenos e de la Hepatitis B/inmunología , Antígenos e de la Hepatitis B/sangre , Masculino , Femenino , Adulto , Neutrófilos/inmunología , Neutrófilos/metabolismo , Persona de Mediana Edad , Antígeno B7-H1/metabolismo , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/genética , Receptor Toll-Like 2/genética , Receptor Toll-Like 2/metabolismo , Interferón gamma/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
8.
Hepatol Commun ; 7(6)2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-37204414

RESUMEN

BACKGROUND: Mucosal-associated invariant T cells (MAITs) are markedly reduced in patients with alcohol-associated liver disease (ALD); however, the potential mechanism underlying MAITs' loss remains elusive. Hence, we aimed to explore what induced MAITs' loss and its clinical significance. METHODS: The characteristics of pyroptotic MAITs were evaluated in a cohort of patients with ALD, including 41 patients with alcohol-associated liver cirrhosis (ALC) and 21 patients with ALC complicated with severe alcoholic hepatitis (ALC + SAH). RESULTS: In patients with ALD, blood MAITs were significantly decreased, hyperactivated, and displayed enhanced cell death through pyroptosis. The frequencies of pyroptotic MAITs increased with disease severity in patients with ALC and patients with ALC + SAH. These frequencies were negatively associated with the frequencies of MAITs and positively correlated with the levels of MAITs' activation, plasma levels of intestinal fatty acid-binding protein (a marker of intestinal enterocyte damage), soluble CD14, lipopolysaccharide-binding protein, and peptidoglycan recognition proteins (surrogate markers of microbial translocation). Pyroptotic MAITs were also found in the liver of patients with ALD. Interestingly, MAITs underwent further activation and pyroptosis in vitro under stimulation by Escherichia coli or direct bilirubin. Notably, blocking IL-18 signaling reduced the activation and frequencies of pyroptotic MAITs. CONCLUSIONS: The loss of MAITs in patients with ALD is, at least in part, due to cell death from pyroptosis and is associated with the severity of ALD. Such increased pyroptosis may be affected by dysregulated inflammatory responses to intestinal microbial translocation or direct bilirubin.


Asunto(s)
Hepatitis Alcohólica , Hepatopatías Alcohólicas , Humanos , Cirrosis Hepática Alcohólica , Biomarcadores , Bilirrubina
9.
Commun Biol ; 6(1): 696, 2023 07 07.
Artículo en Inglés | MEDLINE | ID: mdl-37419968

RESUMEN

CD8 + T cells are essential for long-lasting HIV-1 control and have been harnessed to develop therapeutic and preventive approaches for people living with HIV-1 (PLWH). HIV-1 infection induces marked metabolic alterations. However, it is unclear whether these changes affect the anti-HIV function of CD8 + T cells. Here, we show that PLWH exhibit higher levels of plasma glutamate than healthy controls. In PLWH, glutamate levels positively correlate with HIV-1 reservoir and negatively correlate with the anti-HIV function of CD8 + T cells. Single-cell metabolic modeling reveals glutamate metabolism is surprisingly robust in virtual memory CD8 + T cells (TVM). We further confirmed that glutamate inhibits TVM cells function via the mTORC1 pathway in vitro. Our findings reveal an association between metabolic plasticity and CD8 + T cell-mediated HIV control, suggesting that glutamate metabolism can be exploited as a therapeutic target for the reversion of anti-HIV CD8 + T cell function in PLWH.


Asunto(s)
Infecciones por VIH , VIH-1 , Humanos , Ácido Glutámico , Linfocitos T CD8-positivos , Infecciones por VIH/tratamiento farmacológico , VIH-1/fisiología
10.
Hepatol Int ; 17(5): 1125-1138, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36976426

RESUMEN

BACKGROUND: Restoration of HBV-specific T cell immunity is a promising approach for the functional cure of chronic Hepatitis B (CHB), necessitating the development of valid assays to boost and monitor HBV-specific T cell responses in patients with CHB. METHODS: We analyzed hepatitis B virus (HBV) core- and envelope (env)-specific T cell responses using in vitro expanded peripheral blood mononuclear cells (PBMCs) from patients with CHB exhibiting different immunological phases, including immune tolerance (IT), immune activation (IA), inactive carrier (IC), and HBeAg-negative hepatitis (ENEG). Additionally, we evaluated the effects of metabolic interventions, including mitochondria-targeted antioxidants (MTA), polyphenolic compounds, and ACAT inhibitors (iACAT), on HBV-specific T-cell functionality. RESULTS: We found that HBV core- and env-specific T cell responses were finely coordinated and more profound in IC and ENEG than in the IT and IA stages. HBV env-specific T cells were more dysfunctional but prone to respond to metabolic interventions using MTA, iACAT, and polyphenolic compounds than HBV core-specific T-cells. The responsiveness of HBV env-specific T cells to metabolic interventions can be predicted by the eosinophil (EO) count and the coefficient of variation of red blood cell distribution width (RDW-CV). CONCLUSION: These findings may provide valuable information for metabolically invigorating HBV-specific T-cells to treat CHB.


Asunto(s)
Hepatitis B Crónica , Linfocitos T , Humanos , Virus de la Hepatitis B , Leucocitos Mononucleares , Antígenos e de la Hepatitis B , Antígenos de Superficie de la Hepatitis B
11.
Hepatol Int ; 16(6): 1398-1411, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36109429

RESUMEN

BACKGROUND AND AIMS: Natural killer (NK) cells are critical innate effectors that respond to viral infections and contribute to immunopathology. Here, we aimed to investigate the role of NK cells in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) and elucidate the underlying mechanism by examining their phenotypic and functional profiles. METHODS: We included patients with HBV-ACLF (n = 37) and chronic hepatitis B (n = 19), and healthy controls (n = 13) in our study. We examined the phenotype and function of different subsets of peripheral NK cells using flow cytometry and RNA-sequencing analysis, and screened liver NK cells using immunohistochemistry. We detected inflammatory cytokines using a Luminex assay. In addition, we analyzed the relationships between these parameters and disease severity. RESULTS: Peripheral NK cells were decreased and characterized by high expression of caspase-3, Ki67, CXCR3, NKG2D, NKp46, CD107a, and GM-CSF, and typified by higher cell migration and immune response by RNA-sequencing analysis in patients with HBV-ACLF than in those with chronic hepatitis B. Accumulations of CXCL-10 and NK cells were found in the liver, and excessive production of CXCL-10 in the peripheral blood contributed to the apoptosis of NK cells in vitro. The decrease in NK cells was associated with the level of HBV DNA and disease severity and had good prognostic performance in predicting the outcome of patients with HBV-ACLF through AUROC analysis. CONCLUSION: NK cells were significantly decreased and showed dysfunction of phenotypic and functional profiles across distinct subsets in the peripheral blood of patients with ACLF. Crosstalk between CXCL-10 and NK cells may mediate the unbalanced distribution of NK cells. Understanding the dysfunction and decrease in NK cells may provide new insights into ACLF pathogenesis.


Asunto(s)
Insuficiencia Hepática Crónica Agudizada , Hepatitis B Crónica , Humanos , Virus de la Hepatitis B/genética , Células Asesinas Naturales , ARN
12.
Front Immunol ; 13: 897569, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35720272

RESUMEN

Recent studies highlighted that CD8+ T cells are necessary for restraining reservoir in HIV-1-infected individuals who undergo antiretroviral therapy (ART), whereas the underlying cellular and molecular mechanisms remain largely unknown. Here, we enrolled 60 virologically suppressed HIV-1-infected individuals, to assess the correlations of the effector molecules and phenotypic subsets of CD8+ T cells with HIV-1 DNA and cell-associated unspliced RNA (CA usRNA). We found that the levels of HIV-1 DNA and usRNA correlated positively with the percentage of CCL4+CCL5- CD8+ central memory cells (TCM) while negatively with CCL4-CCL5+ CD8+ terminally differentiated effector memory cells (TEMRA). Moreover, a virtual memory CD8+ T cell (TVM) subset was enriched in CCL4-CCL5+ TEMRA cells and phenotypically distinctive from CCL4+ TCM subset, supported by single-cell RNA-Seq data. Specifically, TVM cells showed superior cytotoxicity potentially driven by T-bet and RUNX3, while CCL4+ TCM subset displayed a suppressive phenotype dominated by JUNB and CREM. In viral inhibition assays, TVM cells inhibited HIV-1 reactivation more effectively than non-TVM CD8+ T cells, which was dependent on CCL5 secretion. Our study highlights CCL5-secreting TVM cells subset as a potential determinant of HIV-1 reservoir size. This might be helpful to design CD8+ T cell-based therapeutic strategies for cure of the disease.


Asunto(s)
Infecciones por VIH , Seropositividad para VIH , VIH-1 , Linfocitos T CD8-positivos , Diferenciación Celular , Quimiocina CCL5/farmacología , Infecciones por VIH/tratamiento farmacológico , VIH-1/fisiología , Humanos
13.
Front Immunol ; 12: 670616, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34489929

RESUMEN

Neutrophils are characterized by their heterogeneity. They fight against pathogens and are involved in tissue injury repair and immune system regulation. Neutrophils have an extremely short life span in the peripheral blood and undergo aging after being released from the bone marrow. The over-aggregation of aged neutrophils is associated with phenotypical and functional changes. Here, we aimed to investigate the dynamics of neutrophil aging and its relationship with T cell exhaustion in HIV-1 infection, as they are not well understood. In this study, we enrolled 23 treatment naïve (TN) patients, 23 individuals that had received antiretroviral therapy (ART), and 21 healthy controls (HC). In these cohorts, we measured the degree of neutrophil aging, and its possible correlation with T cell dysfunction. In TN patients, peripheral neutrophils showed a more distinct aging phenotype and were over-activated compared to those in ART-treated patients. The degree of neutrophil aging was positively correlated with HIV-1 RNA viral load and negatively correlated with CD4+ T cell count. Moreover, aged neutrophils had impaired reactive oxygen species (ROS) production after lipopolysaccharide (LPS) stimulation, and were characterized by increased PD-L1 and arginase-1 expression in a time-dependent manner. Aged neutrophils demonstrated an increased inhibition of IFN-γ and TNF-α secretion by CD8+ T cell compared to non-aged neutrophils. The inhibition effect could be partially reversed by blocking PD-L1 and arginase-1 in vitro, and LPS was identified as an important activator of neutrophil aging. These results provide evidence that dampening neutrophil aging may provide a novel approach to recover T cell dysfunction in patients with HIV-1 infection.


Asunto(s)
Envejecimiento/inmunología , Arginasa/metabolismo , Antígeno B7-H1/metabolismo , Infecciones por VIH/inmunología , VIH-1/fisiología , Neutrófilos/inmunología , Linfocitos T/inmunología , Adulto , Terapia Antirretroviral Altamente Activa , Células Cultivadas , Senescencia Celular , Estudios de Cohortes , Femenino , Humanos , Tolerancia Inmunológica , Masculino , Persona de Mediana Edad , Activación Neutrófila
14.
Front Immunol ; 12: 687296, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34177939

RESUMEN

Background: Targeting immune checkpoints for HIV treatment potentially provides a double benefit resulting from the ability to restore viral-specific CD8+ T-cell functions and enhance HIV production from reservoir cells. Despite promising pre-clinical data, PD-1 blockade alone in HIV-1-infected patients with advanced cancer has shown limited benefits in controlling HIV, suggesting the need for additional targets beyond PD-1. CD39 and PD-1 are highly co-expressed on CD8+ T cells in HIV-1 infection. However, the characteristics of CD39 and PD-1 dual-positive CD8+ T-cell subsets in chronic HIV-1 infection remain poorly understood. Methods: This study enrolled 72 HIV-1-infected patients, including 40 treatment naïve and 32 ART patients. A total of 11 healthy individuals were included as controls. Different subsets of CD8+ T cells defined by CD39 and/or PD-1 expression were studied by flow cytometry. The relationships between the frequencies of the different subsets and parameters indicating HIV-1 disease progression were analyzed. Functional (i.e., cytokine secretion, viral inhibition) assays were performed to evaluate the impact of the blockade of adenosine and/or PD-1 signaling on CD8+ T cells. Results: The proportions of PD-1+, CD39+, and PD-1+CD39+ CD8+ T cells were significantly increased in treatment naïve patients but were partially lowered in patients on antiretroviral therapy. In treatment naïve patients, the proportions of PD-1+CD39+ CD8+ T cells were negatively correlated with CD4+ T-cell counts and the CD4/CD8 ratio, and were positively correlated with viral load. CD39+CD8+ T cells expressed high levels of the A2A adenosine receptor and were more sensitive to 2-chloroadenosine-mediated functional inhibition than their CD39- counterparts. In vitro, a combination of blocking CD39/adenosine and PD-1 signaling showed a synergic effect in restoring CD8+ T-cell function, as evidenced by enhanced abilities to secrete functional cytokines and to kill autologous reservoir cells. Conclusion: In patients with chronic HIV-1 infection there are increased frequencies of PD-1+, CD39+, and PD-1+CD39+ CD8+ T cells. In treatment naïve patients, the frequencies of PD-1+CD39+ CD8+ T cells are negatively correlated with CD4+ T-cell counts and the CD4/CD8 ratio and positively correlated with viral load. Combined blockade of CD39/adenosine and PD-1 signaling in vitro may exert a synergistic effect in restoring CD8+ T-cell function in HIV-1-infected patients.


Asunto(s)
Adenosina/metabolismo , Fármacos Anti-VIH/farmacología , Apirasa/antagonistas & inhibidores , Linfocitos T CD8-positivos/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Inhibidores de Puntos de Control Inmunológico/farmacología , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Adulto , Apirasa/metabolismo , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Linfocitos T CD8-positivos/virología , Estudios de Casos y Controles , Células Cultivadas , Sinergismo Farmacológico , Quimioterapia Combinada , Femenino , Infecciones por VIH/inmunología , Infecciones por VIH/metabolismo , Infecciones por VIH/virología , VIH-1/inmunología , VIH-1/patogenicidad , Humanos , Masculino , Persona de Mediana Edad , Receptor de Muerte Celular Programada 1/metabolismo , Carga Viral , Adulto Joven
15.
Front Immunol ; 12: 811091, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35069597

RESUMEN

Background: Populations of natural killer cells lacking CD56 expression [CD56neg natural killer (NK) cells] have been demonstrated to expand during human immunodeficiency virus (HIV)-1 infection. However, their phenotypic and functional characteristics have not been systematically analyzed, and their roles during disease progression remain poorly understood. Methods: In this study, 84 donors, namely 34 treatment-naïve HIV-1-infected patients (TNs), 29 HIV-1-infected patients with successful antiretroviral therapy (ARTs), and 21 healthy controls (HCs), were enrolled. The phenotypic and functional characteristics of CD56neg NK cells were analyzed using single-cell RNA-sequencing (scRNA-seq) and flow cytometry. A potential link between the characteristics of CD56neg NK cells and the clinical parameters associated with HIV-1 disease progression was examined. Results: The frequency of the CD56neg NK cell population was significantly increased in TNs, which could be partially rescued by ART. Flow cytometry analyses revealed that CD56neg NK cells were characterized by high expression of CD39, TIGIT, CD95, and Ki67 compared to CD56dim NK cells. In vitro assays revealed reduced IFN-γ and TNF-α secretion, as well as decreased expression of granzyme B and perforin in CD56neg NK cells. In line with the data obtained by flow cytometry, scRNA-seq analysis further demonstrated impaired cytotoxic activities of CD56neg NK cells. Notably, a negative correlation was observed between CD39, CD95, and Ki67 expression levels in CD56neg NK cells and CD4+ T cell counts. Conclusions: The results presented in this study indicate that the CD56neg NK cell population expanded in HIV-1-infected individuals is dysfunctional and closely correlates with HIV-1 disease progression.


Asunto(s)
Antígeno CD56/metabolismo , Infecciones por VIH/inmunología , Infecciones por VIH/metabolismo , Infecciones por VIH/virología , VIH-1/inmunología , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Adulto , Recuento de Linfocito CD4 , Relación CD4-CD8 , Progresión de la Enfermedad , Susceptibilidad a Enfermedades , Femenino , Interacciones Huésped-Patógeno/inmunología , Humanos , Masculino , Persona de Mediana Edad , Carga Viral
16.
Artículo en Inglés | MEDLINE | ID: mdl-27173524

RESUMEN

Dioecious plants usually harbor 'young' sex chromosomes, providing an opportunity to study the early stages of sex chromosome evolution. Transposable elements (TEs) are mobile DNA elements frequently found in plants and are suggested to play important roles in plant sex chromosome evolution. The genomes of several dioecious plants have been sequenced, offering an opportunity to annotate and mine the TE data. However, comprehensive and unified annotation of TEs in these dioecious plants is still lacking. In this study, we constructed a dioecious plant transposable element database (DPTEdb). DPTEdb is a specific, comprehensive and unified relational database and web interface. We used a combination of de novo, structure-based and homology-based approaches to identify TEs from the genome assemblies of previously published data, as well as our own. The database currently integrates eight dioecious plant species and a total of 31 340 TEs along with classification information. DPTEdb provides user-friendly web interfaces to browse, search and download the TE sequences in the database. Users can also use tools, including BLAST, GetORF, HMMER, Cut sequence and JBrowse, to analyze TE data. Given the role of TEs in plant sex chromosome evolution, the database will contribute to the investigation of TEs in structural, functional and evolutionary dynamics of the genome of dioecious plants. In addition, the database will supplement the research of sex diversification and sex chromosome evolution of dioecious plants.Database URL: http://genedenovoweb.ticp.net:81/DPTEdb/index.php.


Asunto(s)
Elementos Transponibles de ADN/genética , Bases de Datos Genéticas , Genoma de Planta/genética , Plantas/genética , Biología Computacional , Internet , Interfaz Usuario-Computador
17.
Zhongguo Zhen Jiu ; 28(6): 414-6, 2008 Jun.
Artículo en Zh | MEDLINE | ID: mdl-18630538

RESUMEN

OBJECTIVE: To scientifically assess effectiveness and safety of mono-use fu-needle. METHODS: Sixty cases of periarthritis of shoulder were randomly divided into a fu-needle group and a routine acupuncture group. The fu-needle group were treated with fu-needle, and the routine acupuncture group were treated with a needle of 0.38 mm in diameter and 40 mm in length. The articular mobility of the most limited direction, soft tissue pain self-rating score and self-rating score of shoulder tenderness before and after treatment, stabbing times and degree at inserting the needle, scattering and during retention of the needle, and bleeding at withdrawing the needle were compared in the two groups. RESULTS: The fu-needle group was better than the routine acupuncture group in improvement of mobility-related pain, tenderness, and the articular mobility of the most limited direction, indicating that the transient effect in the fu-needle group was better than the routine acupuncture group, and the stabbing times and degree at insertion of the needle were less than the routine acupuncture group. And there was no significant difference between the two groups in stabbing times and degree at scattering and retaining the needle and bleeding times in withdrawing the needle. CONCLUSION: The superficial needling therapy with mono-use fu-needle is more effective and more safe than the routine acupuncture for treatment of periarthritis of shoulder.


Asunto(s)
Terapia por Acupuntura/métodos , Periartritis/terapia , Articulación del Hombro , Dolor de Hombro/terapia , Terapia por Acupuntura/efectos adversos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Rango del Movimiento Articular
18.
Zhongguo Zhen Jiu ; 25(12): 837-40, 2005 Dec.
Artículo en Zh | MEDLINE | ID: mdl-16419702

RESUMEN

OBJECTIVE: To observe changes of plasma peptide YY (PYY) in acupuncture for slimming. METHODS: Thirty-four cases of simple obesity were treated with acupuncture for 3 courses. Body mass index (BMI), and fat percent (F%), and insulin, PYY, blood fat, and blood sugar levels before and after treatment were determined, with 20 normal persons used as controls. RESULTS: The clinical total effective rate was 88.23%. Acupuncture could increase the decreased insulin sensitive index and PYY level (both P < 0.01), with no correlativity between them (P > 0.05). CONCLUSION: Regulation of PYY is possibly one of the mechanisms of acupuncture in slimming, but the relation of PPY with insulin resistance remains to be studied.


Asunto(s)
Obesidad , Péptido YY , Índice de Masa Corporal , Humanos , Insulina/sangre , Resistencia a la Insulina , Obesidad/terapia
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