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  1. Article: Latent Tuberculosis Patients Have an Increased Frequency of IFN-γ-Producing CD5+ B Cells, Which Respond Efficiently to Mycobacterial Proteins.

    Flores-Gonzalez, Julio / Ramón-Luing, Lucero A / Romero-Tendilla, Jesus / Urbán-Solano, Alexia / Cruz-Lagunas, Alfredo / Chavez-Galan, Leslie

    Pathogens (Basel, Switzerland)

    2023  Volume 12, Issue 6

    Abstract: Tuberculosis (TB) remains a public health problem worldwide and is one of the deadliest infectious diseases, only after the current COVID-19 pandemic. Despite significant advances in the TB field, there needs to be more immune response comprehension; for ...

    Abstract Tuberculosis (TB) remains a public health problem worldwide and is one of the deadliest infectious diseases, only after the current COVID-19 pandemic. Despite significant advances in the TB field, there needs to be more immune response comprehension; for instance, the role played by humoral immunity is still controversial. This study aimed to identify the frequency and function of B1 and immature/transitional B cells in patients with active and latent TB (ATB and LTB, respectively). Here we show that LTB patients have an increased frequency of CD5+ B cells and decreased CD10+ B cells. Furthermore, LTB patients stimulated with mycobacteria's antigens increase the frequency of IFN-γ-producing B cells, whereas cells from ATB do not respond. Moreover, under the mycobacterial protein stimulus, LTB promotes a pro-inflammatory environment characterized by a high level of IFN-γ but also can produce IL-10. Regarding the ATB group, they cannot produce IFN-γ, and mycobacterial lipids and proteins stimulate only the IL-10 production. Finally, our data showed that in ATB, but not in LTB, B cell subsets correlate with clinical and laboratory parameters, suggesting that these CD5+ and CD10+ B cell subpopulations have the potential to be biomarkers to differentiate between LTB and ATB. In conclusion, LTB has increased CD5+ B cells, and these cells can maintain a rich microenvironment of IFN-γ, IL-10, and IL-4. In contrast, ATB only maintains an anti-inflammatory environment when stimulated with mycobacterial proteins or lipids.
    Language English
    Publishing date 2023-06-09
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2695572-6
    ISSN 2076-0817
    ISSN 2076-0817
    DOI 10.3390/pathogens12060818
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Valganciclovir modulates the tumor necrosis factor axis molecules expression and CD4+ T-cell subsets in disseminated Kaposi Sarcoma patients.

    Ramon-Luing, Lucero A / Flores-Gonzalez, Julio / Angel García-Rojas, Luis / Islas-Muñoz, Beda / Volkow-Fernández, Patricia / Chavez-Galan, Leslie

    Clinical and experimental immunology

    2023  Volume 215, Issue 2, Page(s) 190–201

    Abstract: Valganciclovir (VGC) was used in a randomized clinical trial in patients with disseminated Kaposi Sarcoma/human immunodeficiency virus (DKS/HIV) as add-on therapy to evaluate the proinflammatory axis tumor necrosis factor (TNF) and its receptors (TNFRs) ... ...

    Abstract Valganciclovir (VGC) was used in a randomized clinical trial in patients with disseminated Kaposi Sarcoma/human immunodeficiency virus (DKS/HIV) as add-on therapy to evaluate the proinflammatory axis tumor necrosis factor (TNF) and its receptors (TNFRs) in T cells. Two treatment schedules were used: an experimental regime (ER) and a conventional treatment (CT). Mononuclear cells from patients with DKS/HIV were obtained at baseline (W0), 4 (W4), and 12 weeks (W12). Ten DKS/HIV patients received CT (antiretroviral therapy [cART]) and 10 ER (valganciclovir [VGC] initially, plus cART at the fourth week). HIV+ without KS and HIV- patient groups were included as controls. Correlation between T-cell subsets and HHV-8 viral load (VL) and a multivariate linear regression was performed. Data showed that DKS/HIV patients have an increased frequency of CD8+ T cells, which display a high density of CD8 expression. The ER scheme increases naïve and central memory CD4+ T cells at W4 and W12 of follow-up and induces a balanced distribution of activated CD4+ T-cell subsets. Moreover, ER decreases solTNFR2 since W4 and CT decreased the transmembrane forms of TNF axis molecules. Although CT induces a positive correlation between HHV-8 VL and TNFRs, the use of ER positively correlates with TNF and TNFRs levels through follow-up and a moderate correlation with HHV-8 VL and TNF soluble levels. In conclusion, VGC, as an add-on therapy in DKS/HIV patients, gradually modulates the activation of CD4+ T-cell subsets and the TNF/TNFRs axis, suggesting a better regulation of the inflammatory status.
    MeSH term(s) Humans ; Sarcoma, Kaposi/drug therapy ; Sarcoma, Kaposi/metabolism ; HIV Infections/metabolism ; Valganciclovir/metabolism ; Valganciclovir/therapeutic use ; CD4-Positive T-Lymphocytes/metabolism ; T-Lymphocyte Subsets ; CD8-Positive T-Lymphocytes/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Viral Load ; Sulfonamides
    Chemical Substances Valganciclovir (GCU97FKN3R) ; W 12 (35517-12-5) ; Tumor Necrosis Factor-alpha ; Sulfonamides
    Language English
    Publishing date 2023-12-15
    Publishing country England
    Document type Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218531-3
    ISSN 1365-2249 ; 0009-9104 ; 0964-2536
    ISSN (online) 1365-2249
    ISSN 0009-9104 ; 0964-2536
    DOI 10.1093/cei/uxad115
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: The presence of cytotoxic CD4 and exhausted-like CD8+ T-cells is a signature of active tuberculosis.

    Flores-Gonzalez, Julio / Ramón-Luing, Lucero A / Falfán-Valencia, Ramcés / Batista, Cesar V F / Soto-Alvarez, Silverio / Huerta-Nuñez, Lidia / Chávez-Galán, Leslie

    Biochimica et biophysica acta. Molecular basis of disease

    2024  , Page(s) 167219

    Abstract: Chronic infections induce CD4+ T-cells with cytotoxic functions (CD4 CTLs); at present, it is still unknown whether latent tuberculosis (LTB) and active tuberculosis (ATB) induce CD4 CTLs. Plasma and cells from four patient groups-uninfected contact (UC), ...

    Abstract Chronic infections induce CD4+ T-cells with cytotoxic functions (CD4 CTLs); at present, it is still unknown whether latent tuberculosis (LTB) and active tuberculosis (ATB) induce CD4 CTLs. Plasma and cells from four patient groups-uninfected contact (UC), LTB, and ATB (divided as sensitive [DS-TB]- or resistant [DR-TB]-drug)-were evaluated by flow cytometry, q-PCR, and proteomics. The data showed that ATB patients had an increased frequency of CD4+ T-cells and a decreased frequency of CD8+ T-cells. The latter displays an exhausted-like profile characterized by CD39, CD279, and TIM-3 expression. ATB had a high frequency of CD4 + perforin+ cells, suggesting a CD4 CTL profile. The expression (at the transcriptional level) of granzyme A, granzyme B, granulysin, and perforin, as well as the genes T-bet (Tbx21) and NKG2D (Klrk1), in enriched CD4+ T-cells, confirmed the cytotoxic signature of CD4+ T-cells during ATB (which was stronger in DS-TB than in DR-TB). Moreover, proteomic analysis revealed the presence of HSP70 (in DS-TB) and annexin A5 (in DR-TB), which are molecules that have been associated with favoring the CD4 CTL profile. Finally, we found that lipids from Mycobacterium tuberculosis increased the presence of CD4 CTLs in DR-TB patients. Our data suggest that ATB is characterized by exhausted-like CD8+ T-cells, which, together with a specific microenvironment, favor the presence of CD4 CTLs.
    Language English
    Publishing date 2024-05-09
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 60-7
    ISSN 1879-260X ; 1879-2596 ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    ISSN (online) 1879-260X ; 1879-2596 ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
    ISSN 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    DOI 10.1016/j.bbadis.2024.167219
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Flow Cytometry: From Experimental Design to Its Application in the Diagnosis and Monitoring of Respiratory Diseases.

    Flores-Gonzalez, Julio / Cancino-Díaz, Juan Carlos / Chavez-Galan, Leslie

    International journal of molecular sciences

    2020  Volume 21, Issue 22

    Abstract: Recent advances in the field of flow cytometry (FCM) have highlighted the importance of incorporating it as a basic analysis tool in laboratories. FCM not only allows the identification of cell subpopulations by detecting the expression of molecules in ... ...

    Abstract Recent advances in the field of flow cytometry (FCM) have highlighted the importance of incorporating it as a basic analysis tool in laboratories. FCM not only allows the identification of cell subpopulations by detecting the expression of molecules in the cell membrane or cytoplasm, but it can also quantify and identify soluble molecules. The proper functioning of the FCM requires six fundamental systems, from those related to the transport of events to the systems dedicated to the analysis of information. In this review, we have identified the main considerations that every FCM user must know for an optimal antibody panel design, the quality systems that must govern the FCM protocols to guarantee reproducible results in research or clinical laboratories. Finally, we have introduced the current evidence that highlights the relevance of FCM in the investigation and clinical diagnosis of respiratory diseases, establishing important advances in the basic and clinical study of diseases as old as Tuberculosis along with the recent proposals for the monitoring and classification of patients infected with the new SARS-CoV2 virus.
    MeSH term(s) Flow Cytometry/methods ; Humans ; Respiratory Tract Diseases/diagnosis
    Language English
    Publishing date 2020-11-22
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms21228830
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Telomere Shortening and Its Association with Cell Dysfunction in Lung Diseases.

    Ruiz, Andy / Flores-Gonzalez, Julio / Buendia-Roldan, Ivette / Chavez-Galan, Leslie

    International journal of molecular sciences

    2021  Volume 23, Issue 1

    Abstract: Telomeres are localized at the end of chromosomes to provide genome stability; however, the telomere length tends to be shortened with each cell division inducing a progressive telomere shortening (TS). In addition to age, other factors, such as exposure ...

    Abstract Telomeres are localized at the end of chromosomes to provide genome stability; however, the telomere length tends to be shortened with each cell division inducing a progressive telomere shortening (TS). In addition to age, other factors, such as exposure to pollutants, diet, stress, and disruptions in the shelterin protein complex or genes associated with telomerase induce TS. This phenomenon favors cellular senescence and genotoxic stress, which increases the risk of the development and progression of lung diseases such as idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, SARS-CoV-2 infection, and lung cancer. In an infectious environment, immune cells that exhibit TS are associated with severe lymphopenia and death, whereas in a noninfectious context, naïve T cells that exhibit TS are related to cancer progression and enhanced inflammatory processes. In this review, we discuss how TS modifies the function of the immune system cells, making them inefficient in maintaining homeostasis in the lung. Finally, we discuss the advances in drug and gene therapy for lung diseases where TS could be used as a target for future treatments.
    MeSH term(s) Animals ; COVID-19/genetics ; COVID-19/immunology ; Cellular Senescence/genetics ; Genetic Therapy/methods ; Humans ; Immunotherapy/methods ; Lung Diseases/drug therapy ; Lung Diseases/genetics ; Lung Diseases/immunology ; Telomere Shortening/immunology
    Language English
    Publishing date 2021-12-31
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms23010425
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  6. Article ; Online: Tuberculosis en tiempos de COVID-19

    Alexia Urbán-Solano / Yerany Aguilar-Durán / Julio Flores-Gonzalez / Leslie Chavéz-Galán

    Ciencia Ergo Sum, Vol 29, Iss

    cambios y oportunidades

    2022  Volume 4

    Abstract: Se discute cómo el proyecto End TB, que planteaba erradicar la tuberculosis para 2030, se ha visto afectado por atender patologías emergentes; en consecuencia, su tasa de infección y mortalidad incrementó en 2021. Aunque la atención de la comunidad ... ...

    Abstract Se discute cómo el proyecto End TB, que planteaba erradicar la tuberculosis para 2030, se ha visto afectado por atender patologías emergentes; en consecuencia, su tasa de infección y mortalidad incrementó en 2021. Aunque la atención de la comunidad científica está centrada en COVID-19, no debe olvidarse a la tuberculosis. Ambas patologías muestran importantes similitudes, las cuales permiten sugerir que la inversión en la investigación conjunta puede aprovecharse para el desarrollo de nuevas estrategias diagnósticas y terapéuticas. Analizar la tuberculosis, enfermedad infecciosa que es un problema de salud pública, en el contexto de la pandemia por COVID-19 ayuda a evidenciar las carencias de los sistemas de salud en el mundo.
    Keywords tuberculosis ; enfermedades infecciosas ; covid ; 19 ; epidemiología ; Science ; Q ; Social Sciences ; H
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Universidad Autonoma del Estado de Mexico
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Telomere Shortening and Its Association with Cell Dysfunction in Lung Diseases

    Andy Ruiz / Julio Flores-Gonzalez / Ivette Buendia-Roldan / Leslie Chavez-Galan

    International Journal of Molecular Sciences, Vol 23, Iss 425, p

    2022  Volume 425

    Abstract: Telomeres are localized at the end of chromosomes to provide genome stability; however, the telomere length tends to be shortened with each cell division inducing a progressive telomere shortening (TS). In addition to age, other factors, such as exposure ...

    Abstract Telomeres are localized at the end of chromosomes to provide genome stability; however, the telomere length tends to be shortened with each cell division inducing a progressive telomere shortening (TS). In addition to age, other factors, such as exposure to pollutants, diet, stress, and disruptions in the shelterin protein complex or genes associated with telomerase induce TS. This phenomenon favors cellular senescence and genotoxic stress, which increases the risk of the development and progression of lung diseases such as idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, SARS-CoV-2 infection, and lung cancer. In an infectious environment, immune cells that exhibit TS are associated with severe lymphopenia and death, whereas in a noninfectious context, naïve T cells that exhibit TS are related to cancer progression and enhanced inflammatory processes. In this review, we discuss how TS modifies the function of the immune system cells, making them inefficient in maintaining homeostasis in the lung. Finally, we discuss the advances in drug and gene therapy for lung diseases where TS could be used as a target for future treatments.
    Keywords telomere shortening ; lung diseases ; immune system ; treatments ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2022-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Latent Tuberculosis Patients Have an Increased Frequency of IFN-γ-Producing CD5+ B Cells, Which Respond Efficiently to Mycobacterial Proteins

    Julio Flores-Gonzalez / Lucero A. Ramón-Luing / Jesus Romero-Tendilla / Alexia Urbán-Solano / Alfredo Cruz-Lagunas / Leslie Chavez-Galan

    Pathogens, Vol 12, Iss 818, p

    2023  Volume 818

    Abstract: Tuberculosis (TB) remains a public health problem worldwide and is one of the deadliest infectious diseases, only after the current COVID-19 pandemic. Despite significant advances in the TB field, there needs to be more immune response comprehension; for ...

    Abstract Tuberculosis (TB) remains a public health problem worldwide and is one of the deadliest infectious diseases, only after the current COVID-19 pandemic. Despite significant advances in the TB field, there needs to be more immune response comprehension; for instance, the role played by humoral immunity is still controversial. This study aimed to identify the frequency and function of B1 and immature/transitional B cells in patients with active and latent TB (ATB and LTB, respectively). Here we show that LTB patients have an increased frequency of CD5+ B cells and decreased CD10+ B cells. Furthermore, LTB patients stimulated with mycobacteria’s antigens increase the frequency of IFN-γ-producing B cells, whereas cells from ATB do not respond. Moreover, under the mycobacterial protein stimulus, LTB promotes a pro-inflammatory environment characterized by a high level of IFN-γ but also can produce IL-10. Regarding the ATB group, they cannot produce IFN-γ, and mycobacterial lipids and proteins stimulate only the IL-10 production. Finally, our data showed that in ATB, but not in LTB, B cell subsets correlate with clinical and laboratory parameters, suggesting that these CD5+ and CD10+ B cell subpopulations have the potential to be biomarkers to differentiate between LTB and ATB. In conclusion, LTB has increased CD5+ B cells, and these cells can maintain a rich microenvironment of IFN-γ, IL-10, and IL-4. In contrast, ATB only maintains an anti-inflammatory environment when stimulated with mycobacterial proteins or lipids.
    Keywords B cells ; latent tuberculosis (LTB) ; IFN-γ-producing ; CD5+ B cells ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Leiomyoma With Cystic Degeneration in a Pregnancy: Percutaneous Drainage as an Alternative to Myomectomy.

    Delgado, Raquel García / Rodríguez, Raquel García / Flores, Juan Sánchez / González, Julio Pérez / Cárdenes, Ismael Ortega / González, Lourdes Hernández / Martínez, Alicia Martín

    Journal of minimally invasive gynecology

    2024  Volume 31, Issue 4, Page(s) 263–264

    MeSH term(s) Pregnancy ; Female ; Humans ; Uterine Myomectomy ; Leiomyoma/surgery ; Uterine Neoplasms/surgery
    Language English
    Publishing date 2024-01-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2186934-0
    ISSN 1553-4669 ; 1553-4650
    ISSN (online) 1553-4669
    ISSN 1553-4650
    DOI 10.1016/j.jmig.2024.01.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Active tuberculosis patients have high systemic IgG levels and B-cell fingerprinting, characterized by a reduced capacity to produce IFN-γ or IL-10 as a response to

    Flores-Gonzalez, Julio / Urbán-Solano, Alexia / Ramón-Luing, Lucero A / Cancino-Diaz, Juan Carlos / Contreras-Rodriguez, Araceli / Curiel-Quesada, Everardo / Hernández-Pando, Rogelio / Chavez-Galan, Leslie

    Frontiers in immunology

    2023  Volume 14, Page(s) 1263458

    Abstract: Introduction: Tuberculosis (TB) is a bacterial infection caused by : Methods: In this study, we evaluated the distribution of the circulating B cell subsets in patients with active and latent TB (ATB and LTB, respectively) and how they respond to ... ...

    Abstract Introduction: Tuberculosis (TB) is a bacterial infection caused by
    Methods: In this study, we evaluated the distribution of the circulating B cell subsets in patients with active and latent TB (ATB and LTB, respectively) and how they respond to stimuli of protein or lipid from
    Results: Here, we show that ATB patients show an immune fingerprinting. However, patients with drug-sensitive- (DS-TB) or drug-resistant- (DR-TB) TB have altered frequencies of circulating B cells. DS-TB and DR-TB display a unique profile characterized by high systemic levels of IFN-γ, IL-10, IgG, IgG/IgM ratio, and total B cells. Moreover, B cells from DR-TB are less efficient in producing IL-10, and both DS-TB and DR-TB produce less IFN-γ in response to
    Conclusion: These results provide new insights into the population dynamics of the cellular immune response by B cells against
    MeSH term(s) Humans ; Interleukin-10 ; Tuberculosis ; Latent Tuberculosis ; Mycobacterium tuberculosis ; Interferon-gamma/metabolism ; Immunoglobulin G
    Chemical Substances Interleukin-10 (130068-27-8) ; Interferon-gamma (82115-62-6) ; Immunoglobulin G
    Language English
    Publishing date 2023-10-26
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1263458
    Database MEDical Literature Analysis and Retrieval System OnLINE

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