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BACKGROUND: The aim of the present study was to investigate the therapeutic effects of p75 tumor necrosis factor receptor monoclonal antibody D8F2 on a traumatic arthritis model in rats, and to explore the underlying mechanism. METHODS: Forty male Sprague Dawley rats were randomly divided into five groups: (A) sham operation control group, (B) traumatic arthritis model group, (C) low-dose D8F2 group (1 mg/kg), (D) medium-dose D8F2 group (3 mg/kg), and (E) high-dose D8F2 group (10 mg/kg). Joint fluid samples were collected at 72 h after surgery, and enzyme-linked immunosorbent assay was performed to measure the following inflammatory factors: tumor necrosis factor α (TNF-α) and interleukin 1ß. One week after the surgery, rats were killed, and immunohistochemical staining was applied to detect the matrix metalloproteinase (MMP1 and MMP3) expression in the synovium. In cultured synovial fibroblast experiments, the D8F2-induced ubiquitination of TNF receptor-associated factor 2 (TRAF2) was examined by immunoprecipitation, and nuclear translocation of p65 nuclear factor-κB (p65NF-κB) mediated by TNF-α and D8F2 was analyzed by western blotting. RESULTS: In the traumatic arthritis model group, the inflammatory factors and MMPs were significantly increased relative to the sham operation control group (P < 0.05), whereas D8F2 could downregulate these factors in a dose-dependent manner (P < 0.05). The results from in vitro studies indicated that D8F2 can induce TRAF2 ubiquitination and inhibit the nuclear translocation of p65NF-κB mediated by TNF-α. CONCLUSIONS: p75 Tumor necrosis factor receptor monoclonal antibody has a therapeutic effect on traumatic arthritis, which may occur via the downregulation of inflammatory factors and MMPs at the transcription level because of TRAF2 degradation and inhibited activation of NF-κB.
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Anticuerpos Monoclonales/uso terapéutico , Artritis/tratamiento farmacológico , Articulaciones/lesiones , Receptores Tipo II del Factor de Necrosis Tumoral/antagonistas & inhibidores , Animales , Citocinas/análisis , Modelos Animales de Enfermedad , Masculino , Metaloproteinasa 1 de la Matriz/análisis , FN-kappa B/antagonistas & inhibidores , Ratas , Ratas Sprague-Dawley , Receptores Tipo II del Factor de Necrosis Tumoral/fisiología , Factor 2 Asociado a Receptor de TNF/metabolismoRESUMEN
Tin-lead (Sn-Pb) perovskite solar cells (PSCs) have gained interest as candidates for the bottom cell of all-perovskite tandem solar cells due to their broad absorption of the solar spectrum. A notable challenge arises from the prevalent use of the hole transport layer, PEDOT:PSS, known for its inherently high doping level. This high doping level can lead to interfacial recombination, imposing a significant limitation on efficiency. Herein, NaOH is used to dedope PEDOT:PSS, with the aim of enhancing the efficiency of Sn-Pb PSCs. Secondary ion mass spectrometer profiles indicate that sodium ions diffuse into the perovskite layer, improving its crystallinity and enlarging its grains. Comprehensive evaluations, including photoluminescence and nanosecond transient absorption spectroscopy, confirm that dedoping significantly reduces interfacial recombination, resulting in an open-circuit voltage as high as 0.90 V. Additionally, dedoping PEDOT:PSS leads to increased shunt resistance and high fill factor up to 0.81. As a result of these improvements, the power conversion efficiency is enhanced from 19.7% to 22.6%. Utilizing NaOH to dedope PEDOT:PSS also transitions its nature from acidic to basic, enhancing stability and exhibiting less than a 7% power conversion efficiency loss after 1176 h of storage in N2 atmosphere.
RESUMEN
OBJECTIVE: To investigate the effects of and mechanisms underlying the activation of the p75 tumor necrosis factor receptor (p75TNFR) signaling pathway in inflammatory responses in mice with traumatic brain injury. METHODS: We first generated hybridomas that produced antibodies specific for p75TNFR, by inoculating BALB/c mice with antigenic peptides derived from mouse p75TNFR, which is critical to the binding of tumor necrosis factor-alpha (TNF-α) and p75TNFR. The isotype, epitope, titer, specificity, and affinity constant of monoclonal antibodies (mAbs) were determined using commercial kits and enzyme-linked immunosorbent assay. We then screened the agonist antibody via L929 cytotoxicity assay. The levels of inflammatory factors were detected in C57BL/6 mice with traumatic brain injury and then the mice were injected with either saline (control) or p75TNFR agonist mAb. Furthermore, we investigated the effects of p75TNFR agonist mAb on p38MAPK and nuclear factor-κB signals. RESULTS: Seven mAbs against p75TNFR were generated. Among them, the mAb D8F2 could markedly enhance the cytotoxicity of TNF-α on L929 cells. In a traumatic brain injury model, D8F2 could inhibit the levels of inflammatory factors and downregulate RNA transcription of these factors by suppressing the activation of p38 mitogen-activated protein kinase and nuclear factor-κB. CONCLUSION: The mAb D8F2 could inhibit posttraumatic inflammatory responses effectively. In this study, we developed an agonist anti-mouse p75TNFR mAb, which may be used in the future to devise new strategies for the clinical treatment of inflammation after trauma.
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Anticuerpos Monoclonales/uso terapéutico , Lesiones Encefálicas/complicaciones , Encefalitis/etiología , Encefalitis/prevención & control , Receptores Tipo II del Factor de Necrosis Tumoral/antagonistas & inhibidores , Transducción de Señal/fisiología , Animales , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/farmacología , Lesiones Encefálicas/metabolismo , Modelos Animales de Enfermedad , Encefalitis/metabolismo , Femenino , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Receptores Tipo II del Factor de Necrosis Tumoral/inmunología , Transducción de Señal/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
BACKGROUND: Organ dysfunction or multiple organ dysfunction syndrome caused by developing immunological dysfunction and subsequent sepsis or the systemic inflammatory response syndrome after trauma is the leading cause of death in trauma patient. It is believed that mitogen-activated protein kinase) (p38MAPK) is one of the most important kinases in inflammatory signaling. In this study, the change of p38 MAPK signaling pathway in trauma patient with different severity and its clinical significance in trauma inflammation were investigated. METHODS: One hundred fifty major trauma patients were included in the study and divided into three groups according to injury severity score (ISS). All data required to calculate ISS and determine organ function were registered on admission and during the ICU-stay. Peripheral blood samples were collected from trauma patients 6 h, 1 d, 3 d, 5 d, and 7 d after injury. RQ-PCR and Western blot was used to examine the changes in gene expression, protein expression, and activation level of leukocyte p38 MAPK. Plasma IL-6 and TNFalpha were assayed by ELISA. RESULTS: Organ dysfunction in 33 trauma patients developed and eight deaths occurred after 24 h in ICU. The causes of death included severe ARDS, MODS, and irreversible brain injury. Incidence of organ dysfunction was related to the increase of injury severity (P < 0.01). Compared with healthy control, the gene expression of p38 MAPK in trauma patients increased significantly 6 h after injury (P < 0.05), and reached a maximum in 1 d (P < 0.01). The expression maintained a high level for 7 d (P < 0.05). One day after injury, significant elevation was observed in protein expression and activation level of p38 MAPK (P < 0.05), as well as the plasma TNFalpha and IL-6 level (P < 0.01). Further investigation found that the gene expression, protein expression, and activation levels of p38 MAPK increased with higher ISS (P < 0.05), and the elevation of plasma TNFalpha and IL-6 level was associated with the increase of activated p38 MAPK and ISS (P < 0.05). CONCLUSION: p38 MAPK signal pathway was activated in trauma patients. The severity of trauma had highly positive correlation with the expression and activation of p38 MAPK, as well as the elevation of plasma TNFalpha and IL-6 expression. These findings indicate that p38 MAPK signaling pathway plays an important role in the pathological mechanism of trauma.
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Accidentes por Caídas , Accidentes de Tránsito , Sistema de Señalización de MAP Quinasas , Heridas Punzantes/enzimología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Adolescente , Adulto , Anciano , Activación Enzimática , Femenino , Expresión Génica , Humanos , Interleucina-6/sangre , Leucocitos/enzimología , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/etiología , Índice de Severidad de la Enfermedad , Factor de Necrosis Tumoral alfa/sangre , Adulto JovenRESUMEN
OBJECTIVE: To explore the change of serious abdominal traumatic patients' cellular immunity and the effect of Astragalus Injection (AI) on it. METHODS: Sixty-three serious abdominal traumatic patients were randomly assigned into two groups, the conventional group and the treated group, patients in the conventional group were given conventional treatment, while others in the treated group were given conventional treatment as the basis, with AI 20 ml was added into 250 ml of 5% glucose solution given through intravenous dripping, and then on the first day and 14th day, their T cell activated antigens as well as that of 10 healthy subjects were monitored. RESULTS: On the first day, in the conventional group and treated group, the levels of CD(3)(+), CD(4)(+), CD(4)(+)/CD(8)(+), CD(16)(+), CD(69)(+) and CD(3)(+)/homologous leucocytic antigen-DR (HLA-DR(+)) were apparently lower than those in the healthy group (P < 0.05), while the CD(8)(+) was significantly higher than that in the healthy group (P < 0.05), and there was no significant difference between the conventional group and the treated group (P > 0.05); on the 14th days, the levels of CD(3)(+), CD(4)(+), CD(4)(+)/CD(8)(+), CD(16)(+), CD(69)(+) and CD(3)(+)/HLA-DR(+) of the treated group got closed to healthy subject value, and got even higher than those of conventional group (P < 0.05); CD(8)(+) got close to that of healthy subjects, while obviously lower than that of conventional group (P < 0.05). CONCLUSION: After serious abdominal trauma, cellular immunity lowered, auxiliary use of AI was beneficial to the restoration of cellular immunity.
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Traumatismos Abdominales/inmunología , Adyuvantes Inmunológicos/uso terapéutico , Astragalus propinquus , Medicamentos Herbarios Chinos/uso terapéutico , Fitoterapia , Adulto , Antígenos CD/análisis , Antígenos de Diferenciación de Linfocitos T/análisis , Femenino , Humanos , Inmunidad Celular , Lectinas Tipo C , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Receptores de IgG/análisis , Subgrupos de Linfocitos TRESUMEN
Patients with schizophrenia have a higher risk for cardiovascular disease (CVD) than the general population. Research has suggested that autonomic imbalance is a common pathway to increased morbidity and mortality for CVD. Heart rate variability (HRV) analysis is a non-invasive method that assesses autonomic imbalance, and low HRV is correlated with high cardiovascular risk. Olanzapine, a widely used antipsychotic drug, is considered to have good cardiac safety because of not causing significant corrected QT-interval (QTc) prolongation; however, it is still unclear whether olanzapine affects HRV. We recruited 83 patients with schizophrenia who were medication-free for at least 1 month and tested their HRV at the baseline and 4 weeks after treatment with olanzapine. We found that patients who had substantial weight gain (EWG) manifested significantly lower HRV than those who had non-substantial weight gain (NWG) and that HRV decrease was positively correlated to an increase in body mass index (BMI) and weight gain. Our results indicate that olanzapine-induced weight gain may play an important role in its potential cardiovascular risk. Since olanzapine has a very high potential for weight gain compared with other antipsychotics, further research is needed to explore its cardiovascular safety profile, specifically long-term cardiac safety.
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Antipsicóticos/efectos adversos , Benzodiazepinas/efectos adversos , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/fisiopatología , Frecuencia Cardíaca/efectos de los fármacos , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Aumento de Peso/efectos de los fármacos , Adulto , Antipsicóticos/uso terapéutico , Benzodiazepinas/uso terapéutico , Índice de Masa Corporal , Enfermedades Cardiovasculares/epidemiología , China/epidemiología , Femenino , Humanos , Masculino , Olanzapina , Factores de Riesgo , Esquizofrenia/complicaciones , Esquizofrenia/tratamiento farmacológico , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéuticoRESUMEN
BACKGROUND & OBJECTIVE: Immunity, especially cellular immunity, of patients with tumor is related to tumorigenesis. The correlation of changes of T Lymphocyte phenotype to tumor stage and operative pattern of gastric cancer is unclear. This study was to evaluate the perioperative immune state in patients with gastric cancer (GC) of different stage and accepted different operative pattern. METHODS: Six kinds of T lymphocyte phenotype in 33 GC patients were measured by flow cytometry before and after operation, and compared with that of benign disease patients. RESULTS: With progress of cancer stage, CD3, CD4, CD4/CD8, CD16, and CD69 gradually decreased, while CD8 gradually increased (P< 0.05). There was no significant difference of activated T cell CD3+/HLA-DR+ among patients of stage I,II,III. After radical resection, CD8 decreased, while CD3, CD4, CD4/CD8, CD16, CD69, and CD3+/HLA-DR+ increased significantly (P< 0.01). CD3, and CD4 unchanged after palliative operation. CD16, and CD4/CD8 further decreased in patients with unresectable tumor (P< 0.05). CONCLUSIONS: The preoperative immune state of GC patients is negatively related to cancer stage. Tumor removal may improve the cellular immunity of patients.