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The COVID-19 pandemic significantly impacted the global populace, resulting in a staggering number of deaths across the globe. New approaches and biomarkers to evaluate disease progression are crucial for improving disease management. In this context, serum proteomics has emerged as a promising tool for identifying molecular alterations related to COVID-19. This work carried out a bibliometric evaluation of the current status and trends of studies applying serum proteomics to COVID-19 subjects. The search was performed using Web of Science and Scopus databases, and the results were analyzed in VOSviewer software. The investigation was limited to articles published between January 2020 and February 2023. The analysis found 48 articles, primarily experimental studies. China is the most influential country in this field, followed by the USA. The co-occurrence analysis performed by VOSviewer showed 170 keywords, of which 9 reached the occurrence threshold and were divided into two groups. The most cited words were related to biomarker identification and the use of proteomics for diagnosing and treating COVID-19. The most cited proteins include those classically associated with the immune system (IgG, IgM, interleukins, CXCL, CCL, MCP, CRP) and SAA1, SAA1, ApoA-1, TTR (prealbumin), SerpinA and ITIH4. Other studies have validated the predictive value of these serum markers and have the potential to improve the management of COVID-19 patients. The findings highlighted in this bibliometric study can help the researchers design new projects to enhance our understanding of the complex interplay between SARS-CoV-2 and host immunity.
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Autoantibodies against the M2 subtype of muscarinic acetylcholine receptors with functional activities have been found in the sera of patients with dilated cardiomyopathy (DCM), and the second extracellular loop has been established as the predominant epitope. However, it has been shown that the third intracellular loop is recognized by Chagas disease patients with severe cardiac dysfunction. In this work, BALB/c mice were immunized with plasmids encoding these two epitopes, and a control group received the empty plasmid (pcDNA3 vector). Serum from these DNA-immunized animals had elevated and persistent titres of antibodies against respective antigens. Heart echocardiography indicated diminished left ventricular wall thickness and reduced ejection fraction for both epitope-immunized groups, and ergospirometry tests showed a significant decrease in the exercise time and oxygen consumption. Transfer of serum from these immunized mice into naïve recipients induced the same alterations in cardiac structure and function. Furthermore, electron microscopy analysis of donor-immunized animals revealed several ultrastructural alterations suggestive of autophagy and mitophagy, suggesting novel roles for these autoantibodies. Overall, greater functional and structural impairment was observed in the donor and recipient epitope groups, implicating the third intracellular loop epitope in the pathological effects for the first-time. Therefore, the corresponding peptides could be useful for autoimmune DCM diagnosis and targeted therapy.
Asunto(s)
Autoanticuerpos , Autofagia/inmunología , Cardiomiopatía Dilatada/inmunología , Miocardio/inmunología , Receptor Muscarínico M2/inmunología , Animales , Cardiomiopatía Dilatada/patología , Modelos Animales de Enfermedad , Epítopos/inmunología , Femenino , Vectores Genéticos/administración & dosificación , Vectores Genéticos/genética , Humanos , Ratones , Ratones Endogámicos BALB C , Microscopía Electrónica , Miocardio/patología , Miocardio/ultraestructura , Péptidos/genética , Péptidos/inmunología , Plásmidos/genética , Receptor Muscarínico M2/genéticaRESUMEN
Autoantibodies against the M2 receptors (M2AChR) have been associated with Dilated Cardiomyopathy (DCM). In the heart, P2×7 receptors influence electrical conduction, coronary circulation and response to ischemia. They can also trigger pro-inflammatory responses and the development of neurological, cardiac and renal disorders. Here, P2×7(-/-) mice displayed an increased heart rate and ST segment depression, but similar exercise performance when compared to wild type (WT) animals. After immunization with plasmid containing M2AChR cDNA sequence, WT mice produced anti-M2AChR antibodies, while P2×7(-/-) mice showed an attenuated production. Despite this, WT and P2×7(-/-) showed left ventricle cavity enlargement and decreased exercise tolerance. Transfer of serum from M2AChR WT immunized mice to näive recipients led to an alteration in heart shape. P2×7(-/-) mice displayed a significant increase in the frequency of spleen regulatory T cells population, which is mainly composed by the FoxP3(+)CD25(-) subset. M2AChR WT immunized mice showed an increase in IL-1ß, IFNγ and IL-17 levels in the heart, while P2×7(-/-) group produced lower amounts of IL-1ß and IL-17 and higher amounts of IFNγ. These results pointed to previously unnoticed roles of P2×7 in cardiovascular and immune systems, and underscored the participation of IL-17 and IFNγ in the progress of autoimmune DCM.
Asunto(s)
Cardiomiopatía Dilatada/genética , Interleucina-17/inmunología , Miocardio/inmunología , Receptor Muscarínico M2/genética , Receptores Purinérgicos P2X7/genética , Linfocitos T Reguladores/inmunología , Animales , Autoanticuerpos/biosíntesis , Autoantígenos/genética , Autoantígenos/inmunología , Cardiomiopatía Dilatada/inmunología , Cardiomiopatía Dilatada/patología , Femenino , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/inmunología , Regulación de la Expresión Génica , Frecuencia Cardíaca , Inmunización , Interferón gamma/biosíntesis , Interferón gamma/inmunología , Interleucina-17/biosíntesis , Interleucina-1beta/biosíntesis , Interleucina-1beta/inmunología , Subunidad alfa del Receptor de Interleucina-2/genética , Subunidad alfa del Receptor de Interleucina-2/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Miocardio/patología , Condicionamiento Físico Animal , Plásmidos/administración & dosificación , Receptor Muscarínico M2/inmunología , Receptores Purinérgicos P2X7/deficiencia , Transducción de Señal , Bazo/inmunología , Bazo/patología , Linfocitos T Reguladores/patología , Remodelación VentricularRESUMEN
BACKGROUND: Sepsis is associated with high mortality rates in intensive care units worldwide and represents a systemic inflammatory response to infection. P2X7 is an ionotropic purine receptor with known proinflammatory activity. Here, we investigated the role of the P2X7 receptor in sepsis induced by cecal ligation and puncture (CLP). METHODS: Wild-type (WT) and P2X7KO (P2X7 null) mice were subjected to CLP and their survival was monitored for 7 days. Blood, peritoneal wash and lungs were collected 24 h after CLP and used to measure bacterial load, immune cell infiltration, nitric oxide (NO), cytokine levels, and peritoneal cell death and to assess lung injury. RESULTS: P2X7KO mice showed significantly increased survival 7 days after CLP (30% compared to 60% in WT animals) accompanied by an overall attenuated inflammatory response, with decreased cell recruitment to the peritoneum, no or limited increases in the levels of NO and proinflammatory cytokines (IL-1ß, IL-6, IL-12, IL-17, and IL-4), reduced peritoneal cell apoptosis, and less pronounced lung infiltration and morphological changes. CONCLUSIONS: Our data show the P2X7 receptor is required for the development of the inflammatory response associated with sepsis and support the notion that P2X7 receptor is a valid therapeutic target against inflammatory diseases.