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Article ; Online: Update on the diagnosis of tuberculosis.

Kontsevaya, Irina / Cabibbe, Andrea Maurizio / Cirillo, Daniela Maria / DiNardo, Andrew R / Frahm, Nicole / Gillespie, Stephen H / Holtzman, David / Meiwes, Lennard / Petruccioli, Elisa / Reimann, Maja / Ruhwald, Morten / Sabiiti, Wilber / Saluzzo, Francesca / Tagliani, Elisa / Goletti, Delia

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases

2023

Abstract: Background: Tuberculosis (TB) remains a global public health threat, and the development of rapid and precise diagnostic tools is the key to enabling the early start of treatment, monitoring response to treatment, and preventing the spread of the ... ...

Abstract	Background: Tuberculosis (TB) remains a global public health threat, and the development of rapid and precise diagnostic tools is the key to enabling the early start of treatment, monitoring response to treatment, and preventing the spread of the disease. Objectives: An overview of recent progress in host- and pathogen-based TB diagnostics. Sources: We conducted a PubMed search of recent relevant articles and guidelines on TB screening and diagnosis. Content: An overview of currently used methods and perspectives in the following areas of TB diagnostics is provided: immune-based diagnostics, X-ray, clinical symptoms and scores, cough detection, culture of Mycobacterium tuberculosis and identifying its resistance profile using phenotypic and genotypic methods, including next-generation sequencing, sputum- and non-sputum-based molecular diagnosis of TB and monitoring of response to treatment. Implications: A brief overview of the most relevant advances and changes in international guidelines regarding screening and diagnosing TB is provided in this review. It aims at reviewing all relevant areas of diagnostics, including both pathogen- and host-based methods.
Language	English
Publishing date	2023-07-23
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1328418-6
ISSN	1469-0691 ; 1470-9465 ; 1198-743X
ISSN (online)	1469-0691
ISSN	1470-9465 ; 1198-743X
DOI	10.1016/j.cmi.2023.07.014
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Zs.MO 284: Show issues

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Article: Alternative biomarkers of tuberculosis infection in patients with immune-mediated inflammatory diseases.

Petruccioli, Elisa / Petrone, Linda / Najafi-Fard, Saeid / Navarra, Assunta / Vanini, Valentina / Cuzzi, Gilda / Cantini, Fabrizio / Gualano, Gina / Palmieri, Fabrizio / Goletti, Delia

Frontiers in medicine

2023 Volume 10, Page(s) 1271632

Abstract: Introduction: IFN-γ release assays (IGRAs) are one of the referral tests for diagnosing tuberculosis infection (TBI). To improve IGRAs accuracy, several markers have been investigated. Patients with immune-mediated inflammatory diseases (IMID), taking ... ...

Abstract	Introduction: IFN-γ release assays (IGRAs) are one of the referral tests for diagnosing tuberculosis infection (TBI). To improve IGRAs accuracy, several markers have been investigated. Patients with immune-mediated inflammatory diseases (IMID), taking biological drugs, have a higher risk to progress to TB-disease compared to the general population. In several guidelines, annual TBI screening is recommended for patients undergoing biological therapy. Aim of this study was to investigate, within the QuantiFERON-TB-Plus (QFT-Plus) platform, if beside IFN-γ, alternative biomarkers help to diagnose TBI-IMID patients. Methods: We enrolled 146 subjects: 46 with TB disease, 20 HD, 35 with TBI and 45 with TBI and IMID. Thirteen IMID subjects with a QFT-Plus negative result were diagnosed as TBI based on radiological evidence of TBI. We evaluated the IP-10 level in response to TB1 and TB2 peptides of QFT-Plus assay and we compared these results with the standardized assay based on IFN-γ. Multiplex immune assay was performed on plasma from TB1 and TB2 tubes and results were analyzed by a gradient boosting machine (GBM) as learning technique. Results: TBI-IMID showed a significant decreased IP-10 level in response to TB1 and TB2 stimulation compared to TBI-NO IMID ( Discussion: To develop alternative strategies for TBI immune-diagnosis, future studies are needed to evaluate the memory response of TBI defined by radiological tools. These results may help in tuberculosis management of patients taking lifelong immune-suppressive drugs.
Language	English
Publishing date	2023-11-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2023.1271632
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Article ; Online: The ubiquitin ligase TRIM32 promotes the autophagic response to Mycobacterium tuberculosis infection in macrophages.

Romagnoli, Alessandra / Di Rienzo, Martina / Petruccioli, Elisa / Fusco, Carmela / Palucci, Ivana / Micale, Lucia / Mazza, Tommaso / Delogu, Giovanni / Merla, Giuseppe / Goletti, Delia / Piacentini, Mauro / Fimia, Gian Maria

Cell death & disease

2023 Volume 14, Issue 8, Page(s) 505

Abstract: Mycobacterium tuberculosis (Mtb) is known to evade host immune responses and persist in macrophages for long periods. A mechanism that the host uses to combat Mtb is xenophagy, a selective form of autophagy that targets intracellular pathogens for ... ...

Abstract	Mycobacterium tuberculosis (Mtb) is known to evade host immune responses and persist in macrophages for long periods. A mechanism that the host uses to combat Mtb is xenophagy, a selective form of autophagy that targets intracellular pathogens for degradation. Ubiquitination of Mtb or Mtb-containing compartments is a key event to recruit the autophagy machinery and mediate the bacterial delivery to the lysosome. This event relies on the coordinated and complementary activity of different ubiquitin ligases, including PARKIN, SMURF1, and TRIM16. Because each of these factors is responsible for the ubiquitination of a subset of the Mtb population, it is likely that additional ubiquitin ligases are employed by macrophages to trigger a full xenophagic response during Mtb infection. In this study, we investigated the role TRIM proteins whose expression is modulated in response to Mtb or BCG infection of primary macrophages. These TRIMs were ectopically expressed in THP1 macrophage cell line to assess their impact on Mtb replication. This screening identified TRIM32 as a novel player involved in the intracellular response to Mtb infection, which promotes autophagy-mediated Mtb degradation. The role of TRIM32 in xenophagy was further confirmed by silencing TRIM32 expression in THP1 cells, which causes increased intracellular growth of Mtb associated to impaired Mtb ubiquitination, reduced recruitment of the autophagy proteins NDP52/CALCOCO2 and BECLIN 1/BECN1 to Mtb and autophagosome formation. Overall, these findings suggest that TRIM32 plays an important role in the host response to Mtb infection through the induction of autophagy, representing a promising target for host-directed tuberculosis therapies.
MeSH term(s)	Humans ; Ubiquitin/metabolism ; Macrophages/metabolism ; Tuberculosis/genetics ; Autophagy/physiology ; Mycobacterium tuberculosis ; Tripartite Motif Proteins/genetics ; Tripartite Motif Proteins/metabolism ; Ubiquitin-Protein Ligases/genetics ; Ubiquitin-Protein Ligases/metabolism ; Transcription Factors/metabolism
Chemical Substances	Ubiquitin ; TRIM16 protein, human (EC 2.3.2.27) ; Tripartite Motif Proteins ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; TRIM32 protein, human (EC 2.3.2.27) ; Transcription Factors ; SMURF1 protein, human (EC 2.3.2.26)
Language	English
Publishing date	2023-08-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2541626-1
ISSN	2041-4889 ; 2041-4889
ISSN (online)	2041-4889
ISSN	2041-4889
DOI	10.1038/s41419-023-06026-1
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Article ; Online: In Vitro Models for Studying Entry, Tissue Tropism, and Therapeutic Approaches of Highly Pathogenic Coronaviruses.

Najafi Fard, Saeid / Petrone, Linda / Petruccioli, Elisa / Alonzi, Tonino / Matusali, Giulia / Colavita, Francesca / Castilletti, Concetta / Capobianchi, Maria Rosaria / Goletti, Delia

BioMed research international

2021 Volume 2021, Page(s) 8856018

Abstract: Coronaviruses (CoVs) are enveloped nonsegmented positive-sense RNA viruses belonging to the family Coronaviridae that contain the largest genome among RNA viruses. Their genome encodes 4 major structural proteins, and among them, the Spike (S) protein ... ...

Abstract	Coronaviruses (CoVs) are enveloped nonsegmented positive-sense RNA viruses belonging to the family Coronaviridae that contain the largest genome among RNA viruses. Their genome encodes 4 major structural proteins, and among them, the Spike (S) protein plays a crucial role in determining the viral tropism. It mediates viral attachment to the host cell, fusion to the membranes, and cell entry using cellular proteases as activators. Several in vitro models have been developed to study the CoVs entry, pathogenesis, and possible therapeutic approaches. This article is aimed at summarizing the current knowledge about the use of relevant methodologies and cell lines permissive for CoV life cycle studies. The synthesis of this information can be useful for setting up specific experimental procedures. We also discuss different strategies for inhibiting the binding of the S protein to the cell receptors and the fusion process which may offer opportunities for therapeutic intervention.
MeSH term(s)	Antiviral Agents/chemistry ; Antiviral Agents/pharmacology ; COVID-19 ; Cells, Cultured ; Coronaviridae/drug effects ; Coronaviridae/metabolism ; Coronaviridae/pathogenicity ; Coronaviridae/physiology ; Coronaviridae Infections ; Humans ; Models, Biological ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus/chemistry ; Spike Glycoprotein, Coronavirus/metabolism ; Viral Tropism ; Virus Internalization
Chemical Substances	Antiviral Agents ; Spike Glycoprotein, Coronavirus
Language	English
Publishing date	2021-06-21
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2698540-8
ISSN	2314-6141 ; 2314-6133
ISSN (online)	2314-6141
ISSN	2314-6133
DOI	10.1155/2021/8856018
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Article ; Online: QuantiFERON TB Gold Plus for the diagnosis of tuberculosis: a systematic review and meta-analysis.

Sotgiu, Giovanni / Saderi, Laura / Petruccioli, Elisa / Aliberti, Stefano / Piana, Andrea / Petrone, Linda / Goletti, Delia

The Journal of infection

2019 Volume 79, Issue 5, Page(s) 444–453

Abstract: Estimated 2017 tuberculosis (TB) incidence is 10 million and mainly depends on the reservoir of individuals with latent TB infection (LTBI). Quantiferon: Objectives: To perform a systematic review and meta-analysis to assess the diagnostic accuracy ... ...

Abstract	Estimated 2017 tuberculosis (TB) incidence is 10 million and mainly depends on the reservoir of individuals with latent TB infection (LTBI). Quantiferon Objectives: To perform a systematic review and meta-analysis to assess the diagnostic accuracy for TB of QFT-Plus compared to QFT-GIT. Methods: PubMed and Scopus were used to detect records related to predefined strings from 2015 to 2018. Full text articles dealing with the sensitivity and/or specificity of the QFT-Plus vs. QFT-GIT for active-TB and LTBI detection were analyzed. Scientific quality and risk of bias were assessed using QADAS-2. Results: We selected 15 articles. Studies were mainly observational and cross-sectional, performed in 8 countries. Sample size differed in the TB group (27 to 164) compared to LTBI group (29 to 1031). Pooled sensitivity of QFT-Plus for active-TB was 0.94 (0.91 and 0.95 for TB1 and TB2, respectively), whereas pooled specificity for healthy status was 0.96. Pooled sensitivity and specificity for LTBI was 0.91 and 0.95, respectively. Conclusions: We show that QFT-Plus is more sensitive compared to QFT-GIT for detecting M. tuberculosis infection, mainly due to TB2 responses.
MeSH term(s)	Female ; Humans ; Interferon-gamma Release Tests/methods ; Male ; Mycobacterium tuberculosis/immunology ; Sensitivity and Specificity ; Tuberculosis/diagnosis
Language	English
Publishing date	2019-08-29
Publishing country	England
Document type	Evaluation Study ; Journal Article ; Meta-Analysis ; Systematic Review
ZDB-ID	424417-5
ISSN	1532-2742 ; 0163-4453
ISSN (online)	1532-2742
ISSN	0163-4453
DOI	10.1016/j.jinf.2019.08.018
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Zs.A 1501: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 48: Show issues

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Article ; Online: Optimization of the autophagy measurement in a human cell line and primary cells by flow cytometry.

Alonzi, Tonino / Petruccioli, Elisa / Vanini, Valentina / Fimia, Gian Maria / Goletti, Delia

European journal of histochemistry : EJH

2019 Volume 63, Issue 2

Abstract: The limited availability of rapid and reliable flow cytometry-based assays for ex vivo quantification of autophagy has hampered their clinical applications for studies of diseases pathogenesis or for the implementation of autophagy-targeting therapies. ... ...

Abstract	The limited availability of rapid and reliable flow cytometry-based assays for ex vivo quantification of autophagy has hampered their clinical applications for studies of diseases pathogenesis or for the implementation of autophagy-targeting therapies. To this aim, we modified and improved the protocol of a commercial kit developed for quantifying the microtubule-associated protein 1A/1B light chain 3B (LC3), the most reliable marker for autophagosomes currently available. The protocol modifications were set up measuring the autophagic flux in neoplastic (THP-1 cells) and primary cells (peripheral blood mononuclear cells; PBMC) of healthy donors. Moreover, PBMC of active tuberculosis (TB) patients were stimulated with the Mycobacterium tuberculosis purified protein derivatives or infected with live Mycobacterium bovis bacillus Calmette-Guerin (BCG). We found that the baseline median fluorescent intensity (MFI) of THP-1 cells changed depending on the time of sample acquisition to the flow cytometer. To solve this problem, a fixation step was introduced in different stages of the assay's protocol, obtaining more reproducible and sensitive results when a post-LC3 staining fixation was performed, in either THP1 or PBMC. Furthermore, since we found that results are influenced by the type and the dose of the lysosome inhibitor used, the best dose of Chloroquine for LC3 accumulation were set up in either THP-1 cells or PBMC. Finally, applying these experimental settings, we measured the autophagic flux in CD14+ cells from active TB patients' PBMC upon BCG infection. In conclusion, our data indicate that the protocol modifications here described in this work improve the stability and accuracy of a flow cytometry-based assay for the evaluation of autophagy, thus assuring more standardised cell analyses.
MeSH term(s)	Autophagy/drug effects ; Bacterial Proteins/pharmacology ; Chloroquine/pharmacology ; Flow Cytometry/methods ; Fluorescence ; Humans ; Leukocytes, Mononuclear/microbiology ; Microtubule-Associated Proteins/analysis ; Mycobacterium bovis/chemistry ; Staining and Labeling ; THP-1 Cells
Chemical Substances	Bacterial Proteins ; MAP1LC3B protein, human ; Microtubule-Associated Proteins ; Chloroquine (886U3H6UFF)
Language	English
Publishing date	2019-06-26
Publishing country	Italy
Document type	Journal Article
ZDB-ID	1109511-8
ISSN	2038-8306 ; 0391-7258 ; 1121-4201 ; 1121-760X
ISSN (online)	2038-8306
ISSN	0391-7258 ; 1121-4201 ; 1121-760X
DOI	10.4081/ejh.2019.3044
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Article: Evaluation of Cross-Immunity to the Mpox Virus Due to Historic Smallpox Vaccination.

Matusali, Giulia / Petruccioli, Elisa / Cimini, Eleonora / Colavita, Francesca / Bettini, Aurora / Tartaglia, Eleonora / Sbarra, Settimia / Meschi, Silvia / Lapa, Daniele / Francalancia, Massimo / Bordi, Licia / Mazzotta, Valentina / Coen, Sabrina / Mizzoni, Klizia / Beccacece, Alessia / Nicastri, Emanuele / Pierelli, Luca / Antinori, Andrea / Girardi, Enrico /

Vaia, Francesco / Sette, Alessandro / Grifoni, Alba / Goletti, Delia / Puro, Vincenzo / Maggi, Fabrizio

Vaccines

2023 Volume 11, Issue 10

Abstract: When the Mpox virus (MPXV) began spreading globally in 2022, it became critical to evaluate whether residual immunity from smallpox vaccination provided cross-protection. To assess the cross-immune response to MPXV, we collected serum samples ( ...

Abstract	When the Mpox virus (MPXV) began spreading globally in 2022, it became critical to evaluate whether residual immunity from smallpox vaccination provided cross-protection. To assess the cross-immune response to MPXV, we collected serum samples (
Language	English
Publishing date	2023-09-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines11101541
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Article ; Online: In Vitro Models for Studying Entry, Tissue Tropism, and Therapeutic Approaches of Highly Pathogenic Coronaviruses

Saeid Najafi Fard / Linda Petrone / Elisa Petruccioli / Tonino Alonzi / Giulia Matusali / Francesca Colavita / Concetta Castilletti / Maria Rosaria Capobianchi / Delia Goletti

BioMed Research International, Vol

2021 Volume 2021

Abstract	Coronaviruses (CoVs) are enveloped nonsegmented positive-sense RNA viruses belonging to the family Coronaviridae that contain the largest genome among RNA viruses. Their genome encodes 4 major structural proteins, and among them, the Spike (S) protein plays a crucial role in determining the viral tropism. It mediates viral attachment to the host cell, fusion to the membranes, and cell entry using cellular proteases as activators. Several in vitro models have been developed to study the CoVs entry, pathogenesis, and possible therapeutic approaches. This article is aimed at summarizing the current knowledge about the use of relevant methodologies and cell lines permissive for CoV life cycle studies. The synthesis of this information can be useful for setting up specific experimental procedures. We also discuss different strategies for inhibiting the binding of the S protein to the cell receptors and the fusion process which may offer opportunities for therapeutic intervention.
Keywords	Medicine ; R
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
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Article: Tuberculosis Biomarkers: From Diagnosis to Protection.

Goletti, Delia / Petruccioli, Elisa / Joosten, Simone A / Ottenhoff, Tom H M

Infectious disease reports

2016 Volume 8, Issue 2, Page(s) 6568

Abstract: New approaches to control tuberculosis (TB) worldwide are needed. In particular, new tools for diagnosis and new biomarkers are required to evaluate both pathogen and host key elements of the response to infection. Non-sputum based diagnostic tests, ... ...

Abstract	New approaches to control tuberculosis (TB) worldwide are needed. In particular, new tools for diagnosis and new biomarkers are required to evaluate both pathogen and host key elements of the response to infection. Non-sputum based diagnostic tests, biomarkers predictive of adequate responsiveness to treatment, and biomarkers of risk of developing active TB disease are major goals. Here, we review the current state of the field. Although reports on new candidate biomarkers are numerous, validation and independent confirmation are rare. Efforts are needed to reduce the gap between the exploratory up-stream identification of candidate biomarkers, and the validation of biomarkers against clear clinical endpoints in different populations. This will need a major commitment from both scientists and funding bodies.
Language	English
Publishing date	2016-06-24
Publishing country	Italy
Document type	Journal Article ; Review
ISSN	2036-7430
ISSN	2036-7430
DOI	10.4081/idr.2016.6568
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Article ; Online: Evaluation of the immunomodulatory effects of interleukin-10 on peripheral blood immune cells of COVID-19 patients: Implication for COVID-19 therapy.

Najafi-Fard, Saeid / Petruccioli, Elisa / Farroni, Chiara / Petrone, Linda / Vanini, Valentina / Cuzzi, Gilda / Salmi, Andrea / Altera, Anna Maria Gerarda / Navarra, Assunta / Alonzi, Tonino / Nicastri, Emanuele / Palmieri, Fabrizio / Gualano, Gina / Carlini, Valentina / Noonan, Douglas McClain / Albini, Adriana / Goletti, Delia

Frontiers in immunology

2022 Volume 13, Page(s) 984098

Abstract: ... COV-2 antigens and then treated with IL-10. Plasma was collected and used for ELISA and multiplex ... evaluated by ELISA and a multiplex analysis (Luminex) in "study population B". Importantly, IL-10 did not ...

Abstract	Objective: Several therapies with immune-modulatory functions have been proposed to reduce the overwhelmed inflammation associated with COVID-19. Here we investigated the impact of IL-10 in COVID-19, through the Methods: Two cohorts were evaluated: in "study population A", plasma levels of 27 immune factors were measured by a multiplex (Luminex) assay in 39 hospitalized "COVID-19 patients" and 29 "NO COVID-19 controls" all unvaccinated. In "study population B", 29 COVID-19 patients and 30 NO COVID-19-Vaccinated Controls (NO COVID-19-VCs) were prospectively enrolled for the IL-10 study. Whole-blood was stimulated overnight with SARS-COV-2 antigens and then treated with IL-10. Plasma was collected and used for ELISA and multiplex assay. In parallel, whole-blood was stimulated and used for flow cytometry analysis. Results: Baseline levels of several immune factors, including IL-10, were significantly elevated in COVID-19 patients compared with NO COVID-19 subjects in "study population A". Among them, IL-2, FGF, IFN-γ, and MCP-1 reached their highest levels within the second week of infection and then decreased. To note that, MCP-1 levels remained significantly elevated compared with controls. IL-10, GM-CSF, and IL-6 increased later and showed an increasing trend over time. Moreover, exogenous addition of IL-10 significantly downregulated IFN-γ response and several other immune factors in both COVID-19 patients and NO COVID-19-VCs evaluated by ELISA and a multiplex analysis (Luminex) in "study population B". Importantly, IL-10 did not affect cell survival, but decreased the frequencies of T-cells producing IFN-γ, TNF-α, and IL-2 (p<0.05) and down-modulated HLA-DR expression on CD8 Conclusion: This study provides important insights into immune modulating effects of IL-10 in COVID-19 and may provide valuable information regarding the further
MeSH term(s)	COVID-19 ; Granulocyte-Macrophage Colony-Stimulating Factor ; HLA-DR Antigens/analysis ; Humans ; Interleukin-10 ; Interleukin-2 ; Interleukin-6 ; SARS-CoV-2 ; Tumor Necrosis Factor-alpha
Chemical Substances	HLA-DR Antigens ; Interleukin-2 ; Interleukin-6 ; Tumor Necrosis Factor-alpha ; Interleukin-10 (130068-27-8) ; Granulocyte-Macrophage Colony-Stimulating Factor (83869-56-1)
Language	English
Publishing date	2022-09-06
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.2022.984098
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