Browsing by Subject "Sepsis"

Now showing 1 - 16 of 16
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    A Proteomic Approach to Elucidate the Changes in Saliva and Serum Proteins of Pigs with Septic and Non-Septic Inflammation
    (MDPI, 2022-06-16) López Martínez, María José; Cerón, José J.; Ortin Bustillo, Alba; Escribano, Damián; Kuleš, Josipa; Beletić, Anđelo; Rubić, Ivana; González Sánchez, Juan Carlos; Mrljak, Vladimir; Martínez Subiela, Silvia; Muñoz Prieto, Alberto; Medicina y Cirugía Animal
    Sepsis is a systemic inflammatory response triggered by an infectious agent and is recognized by the World Health Organization as a global concern, since it is one of the major causes of severe illness in humans and animals. The study of the changes that can occur in saliva and serum in sepsis can contribute to a better understanding of the pathophysiological mechanisms involved in the process and also to discover potential biomarkers that can help in its diagnosis and monitoring. The objective of this study was to characterize the changes that occur in the salivary and serum proteome of pigs with experimentally-induced sepsis. The study included five pigs with sepsis induced by LPS administration and five pigs with non-septic inflammation induced by turpentine for comparative purposes. In saliva, there were eighteen salivary proteins differentially expressed in the sepsis condition and nine in non-septic inflammation. Among these, significant increments in aldolase A and serpin B12 only occurred in the sepsis model. Changes in aldolase A were validated in a larger population of pigs with sepsis due to Streptococcus suis infection. In serum, there were 30 proteins differentially expressed in sepsis group and 26 proteins in the non-septic group, and most of the proteins that changed in both groups were related to non-specific inflammation. In the saliva of the septic animals there were some specific pathways activated, such as the organonitrogen compound metabolic process and lipid transport, whereas, in the serum, one of the main activated pathways was the regulation of protein secretion. Overall, saliva and serum showed different proteome variations in response to septic inflammation and could provide complementary information about the pathophysiological mechanisms occurring in this condition. Additionally, salivary aldolase A could be a potential biomarker of sepsis in pigs that should be confirmed in a larger population
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    Bioinformatics study of the TNFRSF1A mechanism involved in acute liver injury in sepsis through the mTOR signaling pathway
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Chen, Zhidong; Tang, Kankai; Zhang, Hui
    Objectives. This study analyzed potential key genes involved in the mechanism of acute liver injury induced by sepsis through bioinformatics techniques, aiming to provide novel insights for the identification of early-stage sepsis-induced acute liver injury and its diagnosis. Methods. Gene chip data sets containing samples from acute liver injury induced by sepsis and control groups (GSE22009 and GSE60088) were selected from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) with |log fold change| >1 and p<0.05 were screened with the GEO2R tool, which was also used for the selection of upregulated DEGs in the chips with p<0.05. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, Gene Ontology, and protein-protein interaction (PPI) analyses were then conducted. Results were visualized using R language packages, including volcano plots, Venn diagrams, and boxplots. The intersection of candidate genes with relevant genes in the Comparative Toxicogenomics Database (CTD) was performed, and the clinical significance of these genes was explored through a literature review. A rat model of acute liver injury was developed by inducing sepsis with the cecum ligation and puncture method. Real-time PCR was performed to determine the gene expression in rat liver tissues. Results. A total of 646 upregulated DEGs were determined in GSE22009 and 146 in GSE60088. A Venn diagram was used to find the intersection of the upregulated DEGs between the two data sets, and 67 DEGs associated with sepsis-mediated acute liver damage were obtained. Enrichment analysis from the KEGG pathway showed that DEG upregulation was primarily associated with various pathways: TNF, NF-κB, IL-17, ferroptosis, mTOR, and JAK-STAT signaling pathways. DEGs resulted in three clusters and 15 candidate genes, as revealed by the PPI network and module analyses. Intersection with sepsis-induced acute liver injury-related genes in the CTD resulted in the identification of three significant differentially co-expressed genes: CXCL1, ICAM1, and TNFRSF1A. Sepsis-induced liver tissue indicated the overexpression of CXCL1, ICAM1, and TNFRSF1A mRNA, as compared with the control group (p<0.05). Conclusion. The key genes identified and related signaling pathways provided insights into the molecular mechanisms of sepsis-induced acute liver injury. In vivo studies revealed the overexpression of CXCL1, ICAM1, and TNFRSF1A mRNA in sepsis-mediated injured liver tissues, providing a theoretical basis for early diagnosis and targeted treatment research
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    Caracterización de la mortalidad a corto y largo plazo en pacientes con sepsis
    (Universidad de Murcia, 2025-06-26) Martínez Martínez, Mónica; Bernal Morell, Enrique; Escuela Internacional de Doctorado; Escuela Internacional de Doctorado
    INTRODUCCIÓN: La sepsis es una patología infecciosa de incidencia creciente y un problema importante de salud pública, con una elevada mortalidad que tiende a disminuir, lo que ha aumentado el número de pacientes sépticos que sobreviven. Estos supervivientes se enfrentan a secuelas propias de enfermedades críticas con una menor calidad de vida en un futuro inmediato. Además, cada vez hay más conciencia de que existen consecuencias a largo plazo que aumentan la morbimortalidad. La identificación de factores clínicos y biomarcadores que permitan la implementación de modelos predictivos es clave para mejorar la estratificación del riesgo y el desarrollo de estrategias dirigidas a los supervivientes a la sepsis con la intención de mejorar los resultados clínicos en esta población vulnerable. OBJETIVO: Evaluar la mortalidad a corto (30 días) y largo plazo (2 y 5 años) en pacientes con sepsis y sus factores asociados. MATERIAL Y MÉTODOS: Estudio observacional prospectivo en el que se incluyeron consecutivamente a todos los pacientes procedentes del Servicio de urgencias del Hospital General Universitario Reina Sofía de Murcia con sepsis, según los criterios de la campaña para sobrevivir a la sepsis de 2012, durante un periodo de 6 meses. Se recogieron marcadores inflamatorios, datos clínicos de comorbilidad, gravedad y mortalidad y se realizó un seguimiento vía informática a cinco años desde el ingreso. Para el análisis de los datos se ha utilizado el IBM SPSS Statistics ® versión 22.0 para Windows® y para la realización del árbol de decisión se ha utilizado el lenguaje de programación mediante Python a través de Google Colab. RESULTADOS: Se incluyeron 290 pacientes con comorbilidad (87,2%) y factores predisponentes (66,9%). Ciento noventa y siete tenían una puntuación SOFA ≥ 2. El 10% falleció en los 30 días desde el ingreso y el 55% en los primeros 5 años. El 46,9% de los supervivientes sufrió infecciones recurrentes en los próximos dos años y reingresaron el 51,8%. La sepsis se asoció de forma significativa e independiente con la mortalidad tanto aguda como tardía a los dos años aún ajustando el análisis con las comorbilidades. No se relacionó de forma independiente con la mortalidad a los cinco años. La demencia y el tener una neoplasia o un ulcus péptico se asociaron a mayor mortalidad aguda junto al desarrollo de shock o disfunción respiratoria durante el evento. En los pacientes que sobreviven a la sepsis, la demencia y el antecedente de insuficiencia cardíaca crónica se asocian a mayor mortalidad a los dos años, al igual que el uso de corticoides durante el evento, tratamiento que se asoció también a una mayor mortalidad aguda. En cuanto a los biomarcadores analizados, el proBNP fue el único predictor de mortalidad tanto precoz como tardía en pacientes con sepsis con una precisión que aumenta al hacer el análisis combinado con otros factores relacionados con una mayor mortalidad como la demencia o el uso de corticoides, entre otros. El Árbol de Decisión basado en inteligencia artificial implementado proporcionó una precisión global de 0,71, con un mejor desempeño en la identificación de casos de mortalidad. La sepsis por sí misma no se relacionó con un aumento del riesgo de reinfecciones ni reingresos durante los dos años siguientes al evento, siendo las comorbilidades las que alcanzaron significación estadística, sobre todo, el padecer diabetes mellitus. CONCLUSIONES: Los pacientes con sepsis presentan un riesgo elevado de mortalidad a corto y largo plazo, independientemente de sus comorbilidades, así como una alta tasa de reingresos y reinfecciones. El uso de corticoides durante el ingreso se asocia con mayor mortalidad, mientras que el proBNP es un marcador predictivo útil, especialmente en combinación con otros factores de riesgo.
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    CD14 release induced by P2X7 receptor restrict inflammation and increases survival during sepsis
    (eLife Sciences Publications, 2020-11-26) Alarcón-Vila, Cristina; Baroja-Mazo, Alberto; Torre-Minguela, Carlos de; Martínez, Carlos M.; Martínez-García, Juan J.; Martínez-Banaclocha, Helios; Gracia-Palenciano, Carlos; Pelegrín Vivancos, Pablo; Bioquímica y Biología Molecular B e Inmunología
    P2X7 receptor activation induces the release of different cellular proteins, such as CD14, a glycosylphosphatidylinositol (GPI)-anchored protein to the plasma membrane important for LPS signaling via TLR4. Circulating CD14 has been found at elevated levels in sepsis, but the exact mechanism of CD14 release in sepsis has not been established. Here we show for first time that P2X7 receptor induces the release of CD14 in extracellular vesicles, resulting in a net reduction in macrophage plasma membrane CD14 that functionally affects LPS, but not monophosphoryl lipid A, pro-inflammatory cytokine production. Also, we found that during a murine model of sepsis, P2X7 receptor activity is important for maintaining elevated levels of CD14 in biological fluids and a decrease in its activity results in higher bacterial load and exacerbated organ damage, ultimately leading to premature deaths. Our data reveal that P2X7 is a key receptor for helping to clear sepsis because it maintains elevated concentrations of circulating CD14 during infection.
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    Downregulation of miR-527 alleviates sepsisinduced acute kidney injury via targeting Beclin1
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Xu, Ke; Mo, Xiaojun; Wang, Yijun; Zeng, Zhenhua; Xu, Ziqiang; Yue, Dongyou; Li, Guicheng; Li, Tao; Liu, Junhong; Yuan, Jiemin
    Background. Sepsis-induced acute kidney injury (AKI) is known to result from the inflammatory responses. MiRNAs participate in the development of sepsis-induced AKI. Nevertheless, the function of miR527 in sepsis-induced AKI remains unclear. Methods. Cell viability was evaluated by CCK8 assay, and TUNEL staining was applied to assess cell apoptosis. Pro-inflammatory cytokine (TNF-α, IL-6 and IL-1β) levels were evaluated by ELISA. Meanwhile, the relation among miR-527 and Beclin1 was detected by dual luciferase report assay. Western blot and RT-qPCR were used to examine the protein and mRNA levels, respectively. Furthermore, an in vivo model was constructed to assess the function of miR-527 in sepsisinduced AKI. Results. MiR-527 downregulation significantly alleviated the symptoms of sepsis-induced AKI in mice. MiR-527 level in HK-2 cells was significantly upregulated by LPS, and downregulation of miR-527 notably reversed LPS-induced inhibition of HK-2 cell viability by inhibiting apoptosis. In addition, LPS greatly increased TNF-α, IL-6 and IL-1β levels in supernatant of HK-2 cells, while miR-527 inhibitor partially restored this phenomenon. Meanwhile, Beclin1 was found to be the downstream mRNA of miR-527, and miR-527 inhibitor notably upregulated the level of LC3. MiR-527 downregulation reversed LPS-induced HK-2 cell injury through suppression of TGF-β pathway. Conclusion. Downregulation of miR-527 alleviated sepsis-induced AKI via targeting Beclin1. Thus, miR527 might act as a vital mediator in sepsis-induced AK
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    Enhanced IL-10 inhibits proliferation and promotes apoptosis of HUVECs through STAT3 signaling pathway in sepsis
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Xie, Zuohua; Lin, Bing; Jia, Xinju; Su, Ting; Wei, Ying; Tang, Jiping; Yang, Chengzhi; Cui, Chuanbao; Liu, Jinxiang
    Aims. The present study aims to determine the expression of interleukin (IL)-10 in peripheral blood of patients with sepsis, and investigate its effects on the biological function of vascular endothelial cells. Methods. Thirty-six sepsis patients and 20 healthy subjects were included. Peripheral blood was collected from all subjects. ELISA was used to determine IL-10 content in serum. A ratio of IL-10+ T cells was determined by flow cytometry. CCK-8 assay was used to investigate proliferation. Cell cycle and apoptosis were analyzed by flow cytometry. Western blotting was used to examine the expression of phosphorylated STAT3 protein. Results. The content of IL-10 and the ratio of IL-10+ T cells were enhanced in pa-tients with sepsis. Serum from patients with sepsis inhibited the proliferation of HU-VECs, and addition of IL-10 antibody reversed this effect. IL-10 in the serum from patients with sepsis promoted the apoptosis of HUVECs. IL-10 inhibited the proliferation and promoted the apoptosis of HUVECs by enhancing the phosphorylation of STAT3. Conclusions. The present study demonstrates that the content of IL-10 and the ratio of IL-10+ T cells in peripheral blood of patients with sepsis are up-regulated, and this inhibits HUVEC proliferation and promotes HUVEC apoptosis through STAT3 sig-naling pathway. The results in this study provide a new experimental basis for further understanding the molecular mechanism of sepsis-induced vascular injury.
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    Histochemical and ultrastructural study of skeletal muscle in patients with sepsis and multiple organ failure syndrome (MOFS)
    (F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 1998) Díaz, N. L.; Finol, H. J.; Torres, S. H.; Zambrano, C. I.; Adjounian, H.
    Muscle biopsies for histochemical and ultrastuctural analysis were obtained from seven critically ill patients admitted to the Intensive Care Unit of the "Domingo Luciani" Hospital, Caracas, Venezuela. The sample included two patients with sepsis of abdominal origin, and five that presented sepsis/MOFS, with renal, hepatic, and respiratory disturbances and muscular weakness. Sections were examined for myosin adenosine triphosphatase (ATPase) after pre-incubation with both acid buffer (pH 4.37 and 4.6) and alkaline buffer (pH 10.3), for reduced nicotinamide dinucleotide diaphorase (NADHd), and for a-glycerophosphate dehydrogenase (a-GPDH). Sections were stained with hematoxilin and eosin to look for pathological changes and examined with a transmission electron microscope. Skeletal muscle of patients in early stage of sepsis showed a normal aspect with light microscopy, but at the ultrastructural level some of the fibres showed atrophy and some capillaries looked altered . Patients with sepsis/MOFS exhibited an evident muscle disorder with oedema. infiltrate, atrophy and segmental necrosis. All fibre types showed decrease in diameter; specially fibre types IIA and lIB . Intramuscular capillaries were thickened and occluded , indexes of capillarity were slightly reduced, and fibre oxidative activity was decreased. At ultrastructural level fibres showed severe atrophy, contractile system disorganization and segmental necrosis. Capillaries were also altered and the mononuclear cell infiltrate was abundant and represented by macrophages. lymphocytes and mastocytes.
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    Measurement of procalcitonin in saliva of pigs: a pilot study
    (BMC, 2022-04-15) López Martínez, María Jose; Escribano, Damián; Martínez Miró, Silvia; Ramis, Guillermo; Manzanilla, Edgar G.; Tecles, Fernando; Martínez Subiela, Silvia; Cerón, Jose J.; Medicina y Cirugía Animal
    Background: Procalcitonin (PCT) is a widely used biomarker of sepsis in human medicine and can have potential applications in the veterinary field. This study aimed to explore whether PCT could be measured in the saliva of pigs and whether its concentration changes in sepsis. Therefore, a specific assay was developed and analytically validated, and changes in PCT concentration were evaluated in two conditions: a) in an experimental model of sepsis produced by the administration of lipopolysaccharide (LPS) to pigs (n = 5), that was compared with a model of non‑septic inflammation induced by turpentine oil (n = 4), and b) in healthy piglets (n = 11) compared to piglets with meningitis (n = 20), a disease that usually involves sepsis and whose treatment often requires large amounts of antibiotics in farms. Results: The assay showed coefficients of variation within the recommended limits and adequate linearity after serial sample dilutions. The method’s detection limit was set at 68 μg/L, and the lower limit of quantification was 414 μg/L. In the LPS experiment, higher concentrations of PCT were found after 24 h in the animals injected with LPS (mean = 5790 μg/L) compared to those treated with turpentine oil (mean = 2127 μg/L, P = 0.045). Also, animals with meningitis had higher concentrations of PCT (mean = 21515 μg/L) than healthy pigs (mean = 6096 μg/L, P value < 0.0001). Conclusions: According to these results, this assay could be potentially used as a tool for the non‑invasive detection of sepsis in pigs, which is currently a topic of high importance due to antibiotic use restriction.
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    Mejora de la calidad de la atención a pacientes con sepsis en el contexto de un servicio de emergencia
    (Universidad de Murcia. Servicio de publicaciones, 2022) Robson Xavier de Souza, Damito; Dantas Torres de Araújo, Isabela; Teixeira Xavier Nobre, Thaiza; da Silva Gama, Zenewton André; Grabois, Victor; Medeiros de Araújo Nunes, Vilani
    Objetivo: Describir el proceso de implementación de una intervención participativa y multifacética para mejorar la atención de la sepsis y sus efectos en la mejora de la calidad de la atención. Materiales y métodos: Se trata de un estudio cuasi-experimental del tipo antes-después realizado en 2017/2018 en el servicio de urgencias de un hospital del noreste de Brasil. La calidad de la atención de 564 pacientes diagnosticados con sepsis, se evaluó utilizando nueve criterios de proceso y un criterio de resultado. La intervención fue participativa y multifacética, con una duración de 10 meses. Resultados: Después de la intervención, el número de incumplimientos disminuyó en un 67% (843 vs 506), y los 10 criterios mejoraron, con una mejora significativa (p <0,05) en ocho de ellos. La letalidad disminuyó en un 10% (p = 0,005). Conclusión: El modelo de intervención presentado fue eficaz para mejorar la calidad de la atención de la sepsis en el servicio de urgencias, con la posibilidad de ampliar su uso en los hospitales brasileños. Palabras clave: Sepsis; Mejoramiento de la Calidad; Servicios Médicos de Urgencia; Gestión de Riesgos; Administración de la Seguridad
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    Neoastilbin ameliorates sepsis-induced liver and kidney injury by blocking the TLR4/NF-κB pathway
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2024) Xu, Ruiming; Wang, Dawei; Shao, Zhengyi; Li, Xiangbo; Cao, Qiumei
    Sepsis frequently causes systemic inflammatory response syndrome and multiple organ failure in patients. Neoastilbin (NAS) is a flavonoid that plays vital functions in inflammation. This work aims to investigate the protective effects of NAS against sepsisinduced liver and kidney injury and elucidate its underlying mechanisms. The mouse model was established using cecal ligation puncture (CLP) induction. NAS was given to mice by gavage for 7 consecutive days before surgery. Liver and kidney function, oxidative stress, and inflammatory factors in serum or tissues were examined by ELISA or related kits. The expression of relevant proteins was assessed by Western blot. Hematoxylin and eosin and/or periodic acid-Schiff staining revealed that NAS ameliorated the pathological damage in liver and kidney tissues of CLPinduced mice. NAS improved liver and kidney functions, as evidenced by elevated levels of blood urea nitrogen, Creatinine, ALT, and AST in the serum of septic mice. TUNEL assay and the expression of Bcl-2 and Bax showed that NAS dramatically reduced apoptosis in liver and renal tissues. NAS treatment lowered the levels of myeloperoxidase and malondialdehyde, while elevated the superoxide dismutase content in liver and kidney tissues of CLPinduced mice. The levels of inflammatory cytokines (IL6, TNF-α, and IL-1β) in the serum and both tissues of CLP-injured mice were markedly decreased by NAS. Mechanically, NAS downregulated TLR4 expression and inhibited NF-κB activation, and overexpression of TLR4 reversed the protective effects of NAS against liver and kidney injury. Collectively, NAS attenuated CLP-induced apoptosis, oxidative stress, inflammation, and dysfunction in the liver and kidney by restraining the TLR4/NF-κB pathway.
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    Presence of KIR2DL2/S2, KIR2DL5, and KIR3DL1 molecules in liver transplant recipients with alcoholic cirrhosis could be implicated in death by graft failure
    (MDPI, 2023-03-23) Morales, Raquel; Bolarín, José Miguel; Muro, Manuel; Legaz Pérez, Isabel; Ciencias Sociosanitarias
    Background: The second-most frequent diagnosis among patients receiving liver transplants (LTs) is alcoholic liver disease. The multifactorial pathophysiology of alcoholic liver disease depends on the innate immune system and the inflammatory cascade. According to recent studies on these receptors, killer-cell immunoglobulin-like receptors (KIRs) may be involved in sepsis, liver rejection, and virus relapse. We aimed to investigate the impact of preclinical issues like ascites and encephalopathy and KIR genetic traits on death from sepsis, multiorgan failure (MF), and graft failure (GF) in AC patients undergoing LTs. Methods: We retrospectively reviewed 164 consecutive and deceased Caucasian AC patients who underwent LTs. Pre-transplant complications, cause of death, and patient survival were analyzed. Genomic DNA was taken from peripheral blood, and PCR-SSO was used for genotyping KIR. Results: Compared to GF patients, there was a statistically significant increase in the frequency of KIR2DL2+ (75.8% vs. 51.2%; p = 0.047). Another increase in frequency was also observed in KIR2DS2+ in sepsis compared to the GF group (51.2% vs. 43.7%; p = 0.018). In patients who passed away from MF, a decrease in KIR2DL5+ was observed in AC patients with and without encephalopathy (p = 0.018). The frequency of KIR3DL1+ in the AC patients significantly increased the mortality from sepsis (p = 0.045), which was confirmed by multivariate logistic regression. The frequency of KIR3DL1+ in the AC patients significantly increased the mortality from sepsis (p = 0.012) and was confirmed by multivariate logistic regression. KIR2DS1+ and KIR2DS4+ showed increased mortality due to GF compared to patients without these genes (p = 0.011 and 0.012, respectively). However, this fact was confirmed only for KIR2DS1+ by multivariate logistic Cox regression. Conclusions: The presence of the KIR2DL2/S2+, KIR2DL5+, and KIR3DL1+ genes increases the frequency of death from multiple organ failure or graft failure. Our findings highlight the AC patient’s vulnerability to a LT during hospitalization. Following the transplant and outside of it, we adopt essential preventive measures to create a routine healthcare screening to enhance and modify treatments to increase survival.
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    Purinergic P2X7 receptor expression increases in leukocytes from intra-abdominal septic patients
    (Frontiers Media, 2023-11-29) Martínez Banaclocha, Helios; García Palenciano, Carlos; Martínez Alarcón, Laura; Amores Iniesta, Joaquín; Martín Sánchez, Fátima; Ercole, Giovanni A.; González Lisorge, Ada; Fernánde Pacheco, José; Martínez Gil, Piedad; Padilla Rodríguez, Julio; Baroja Mazo, Alberto; Pelegrín, Pablo; Martínez García, Juan José; Sanidad Animal
    Inflammation is a tightly coordinated response of the host immune system to bacterial and viral infections, triggered by the production of inflammatory cytokines. Sepsis is defined as a systemic inflammatory response followed by immunosuppression of the host and organ dysfunction. This imbalance of the immune response increases the risk of mortality of patients with sepsis, making it a major problem for critical care units worldwide. The P2X7 receptor plays a crucial role in activating the immune system by inducing the activation of peripheral blood mononuclear cells. In this study, we analyzed a cohort of abdominal origin septic patients and found that the expression of the P2X7 receptor in the plasma membrane is elevated in the different subsets of lymphocytes. We observed a direct relationship between the percentage of P2X7-expressing lymphocytes and the early inflammatory response in sepsis. Additionally, in patients whose lymphocytes presented a higher percentage of P2X7 surface expression, the total lymphocytes populations proportionally decreased. Furthermore, we found a correlation between elevated soluble P2X7 receptors in plasma and inflammasome-dependent cytokine IL-18. In summary, our work demonstrates that P2X7 expression is highly induced in lymphocytes during sepsis, and this correlates with IL-18, along with other inflammatory mediators such as IL-6, IL-8, and procalcitonin.
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    Rapamycin mitigates organ damage by autophagy-mediated NLRP3 inflammasome inactivation in sepsis
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Li, Xiaofeng; Zeng, Qingqiu; Yao, Rui; Zhang, Lingyan; Kong, Ying; Shen, Bin
    Autophagy activation can alleviate sepsis-induced organ injuries. Rapamycin (Rap) has emerged as an autophagy regulator in multiple forms of organ injuries. This study aimed to assess whether Rap protects rats from cecal ligation and puncture (CLP)-induced sepsis through autophagy-mediated inactivation of the NLRP3 inflammasome. Rats were allocated to the sham, CLP, Rap (10 mg/kg), or 3-Methyladenine (3-MA) (15 mg/kg) groups. A rat CLP model was established. The survival of rats and lung wet-to-dry weight ratio in each group was assessed. Blood biochemical indexes and oxidative stress-related factors were analyzed with an automatic biochemical analyzer. The bacterial counts of blood and organs were monitored. The degrees of myeloperoxidase of the ileum, inflammation-related indexes, and pathological changes in the tissues were detected by ELISA and hematoxylin-eosin staining. The levels of NLRP3 inflammasome and autophagy-related factors were analyzed by Western blot. Rap increased the survival and SOD activity, and repressed ALT, AST, BUN, SCr, MDA, and inflammation-related marker levels in CLP rats, it also restrained the bacterial counts of blood, lung, liver, and kidney in CLP rats; the effects of 3-MA on CLP rats on the above-mentioned indicators were opposite to those of Rap. Additionally, Rap alleviated the pathological injury of the lung, liver, and kidney, which was the opposite to the effect of 3-MA on CLP rats. Furthermore, Rap mitigated the ASC, Pro-caspase 1, and NLRP3 levels and increased the Beclin-1 levels and the LC3II/LC3I ratio in the organ tissues. Collectively, autophagy activation can mitigate organ damage by suppressing the NLRP3 inflammasome in sepsis rats.
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    Research progress on SIRT1 and sepsis.
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2019) Li, Lincheng; Liu, Mingchuan; Cao, Mengyuan; Bai, Xiaozhi
    SIRT1, a member of the sirtuin family, belongs to the NAD + -dependent class III histone deacetylase. SIRT1 can regulate gene expression by catalyzing non-histone and histone lysine residues deacetylation. SIRT1 also plays important roles in glucose and lipid metabolism, cell aging, tumorigenesis and inflammation. Recent studies indicate that SIRT1 can inhibit the inflammatory responses via regulating several inflammatory signaling pathways. It is closely related to the occurrence and development of sepsis and other inflammatory diseases. Research has been done on relevant signaling pathways of SIRT1 as well as its target genes during inflammation. SIRT1 is a hot spot in uncontrolled inflammatory response research. This article focuses on the role of SIRT1 in inflammation, especially its targets and involved signaling pathways in sepsis, and tries to provide more convincing evidence for the clinical treatment of sepsis and other inflammatory diseases.
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    Role of acupuncture in improving the outcome of sepsis-induced lung injury
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Li, Peng; Li, Fangfang; Chen, Si; Ma, Qiulei; Wang, Jie; Ma, Bingquan; Xu, Jin
    Objective. The purpose of this study was to investigate the effect of serum exosomes of mice after acupuncture (acu-exo) on acute lung injury (ALI) in sepsis in vitro and in vivo. Methods. Serum exosomes (acu-exo) of normal mice were prepared after acupuncture. Lipopolysaccharide (LPS) was used to establish the model of ALI in vivo and in vitro. Immunohistochemistry, western blot, and immunofluorescence were used to evaluate the mechanism of acu-exo on ALI. P2X7 knockout mice and P2X7 siRNA were used to verify the mechanism. Results. Compared with normal mice, serum exosomes were significantly increased in normal mice after acupuncture. The results showed that P2X7 was increased in the lung of septic mice as compared with the WT group. It was also found that the increase in NLRP3 and NF-κB was accompanied by the activation of P2X7. Increased P2X7 led to activation of the P2X7 receptor causing mitochondrial dysfunctions in lung tissue of septic mice. Knockout of P2X7 or silenced P2X7 markedly decreased NLRP3 and NF-κB and led to mitochondrial function recovery in lung tissue of sepsis. At the same time, acu-exo significantly restored the above changes in the lung tissue of septic mice. Conclusions. Inhibition of P2X7 led to mito-chondrial function recovery of lung tissue by inhibiting NLRP3 and NF-κB. At the same time, acu-exo could improve ALI by decreasing NLRP3 and NF-κB activation
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    Validación de checklist para evaluación de la capacitación con simulación clínica de la atención al paciente séptico
    (Murcia: Servicio de publicaciones de la Universidad de Murcia, 2019) Lino, Rafael Luis Bressani; Oliveira, Suelen Alves; Silva, Kellyn Patrícia da; Machado, Regimar Carla
    Objetivo:Construir y validar el contenido de un checklist para evaluación de la capacitación de profesionales del área de la salud en la atención al paciente séptico con simulación clínica.Método:Estudio de validación metodológica de instrumento, con delineamiento estructural en dos etapas: construcción del instrumento y validación de contenido del checklistutilizando la técnica Delphi en dos rondas.Resultados:La validación de contenido fue compuesta por diez ítems y cuarenta y tres subítems analizados por los evaluadores. A través del Índice de Validez de Contenido, se identificaron cuatro ítems con fuerte evidencia de validación, Índice de Validez de Contenido ≥ 0,8. En la segunda ronda Delphi presentó un porcentaje de concordancia superior al 80% para todas las variables pertinentes al instrumento. Se reestructuró el checklist según recomendaciones de los evaluadores, manteniendo los diez ítems, pero con reducción para veintiséis subítems, que en la segunda ronda Delphi presentó un porcentaje de concordancia superior al 80% para todas las variables pertinentes al instrumento.Conclusión:Método fue eficaz para validar el contenido de un checklist que evaluará la capacitación de profesionales de la salud en la atención al paciente séptico, pormedio de simulación clínica.