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1.
J Korean Med Sci ; 39(34): e278, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39228188

RESUMEN

This report presents the latest statistics on the stroke population in South Korea, sourced from the Clinical Research Collaborations for Stroke in Korea-National Institute for Health (CRCS-K-NIH), a comprehensive, nationwide, multicenter stroke registry. The Korean cohort, unlike western populations, shows a male-to-female ratio of 1.5, attributed to lower risk factors in Korean women. The average ages for men and women are 67 and 73 years, respectively. Hypertension is the most common risk factor (67%), consistent with global trends, but there is a higher prevalence of diabetes (35%) and smoking (21%). The prevalence of atrial fibrillation (19%) is lower than in western populations, suggesting effective prevention strategies in the general population. A high incidence of large artery atherosclerosis (38%) is observed, likely due to prevalent intracranial arterial disease in East Asians and advanced imaging techniques. There has been a decrease in intravenous thrombolysis rates, from 12% in 2017-2019 to 10% in 2021, with no improvements in door-to-needle and door-to-puncture times, worsened by the coronavirus disease 2019 pandemic. While the use of aspirin plus clopidogrel for non-cardioembolic stroke and direct oral anticoagulants for atrial fibrillation is well-established, the application of direct oral anticoagulants for non-atrial fibrillation cardioembolic strokes in the acute phase requires further research. The incidence of early neurological deterioration (13%) and the cumulative incidence of recurrent stroke at 3 months (3%) align with global figures. Favorable outcomes at 3 months (63%) are comparable internationally, yet the lack of improvement in dependency at 3 months highlights the need for advancements in acute stroke care.


Asunto(s)
Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Sistema de Registros , Humanos , República de Corea/epidemiología , Femenino , Ataque Isquémico Transitorio/epidemiología , Accidente Cerebrovascular Isquémico/epidemiología , Masculino , Anciano , Factores de Riesgo , COVID-19/epidemiología , Fibrilación Atrial/epidemiología , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Persona de Mediana Edad , Anticoagulantes/uso terapéutico , Incidencia , Accidente Cerebrovascular/epidemiología , Anciano de 80 o más Años , SARS-CoV-2 , Hipertensión/epidemiología , Hipertensión/complicaciones , Prevalencia
2.
Int Immunopharmacol ; 140: 112825, 2024 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-39079347

RESUMEN

BACKGROUND: Exosomes derived from endometrial regenerative cells (ERC-Exos) can inherit the immunomodulatory function from ERCs, however, whether ERC-Exos exhibit such effect on inflammatory bowel diseases with mucosal immune dysregulation has not been explored. Insulin-like growth factor-Ⅱ (IGF2) is considered to possess the potential to induce an anti-inflammatory phenotype in immune cells. In this study, the contribution of IGF2 in mediating the protective efficacy of ERC-Exos on colitis was investigated. METHODS: Lentiviral transfection was employed to obtain IGF2-specific knockout ERC-Exos (IGF2-/--ERC-Exos). Experimental colitis mice induced by dextran sulfate sodium (DSS) were divided into the phosphate-buffered saline (untreated), ERC-Exos-treated and IGF2-/--ERC-Exos-treated groups. Colonic histopathological analysis and intestinal barrier function were explored. The infiltration of CD4+ T cells and dendritic cells (DCs) were analyzed by immunofluorescence staining and flow cytometry. The maturation and function of bone marrow-derived dendritic cells (BMDCs) in different exosome administrations were evaluated by flow cytometry, ELISA and the coculture system, respectively. RESULTS: Compared with the untreated group, ERC-Exos treatment significantly attenuated DSS-induced weight loss, bloody stools, shortened colon length, pathological damage, as well as repaired the weakened intestinal mucosal barrier, including promoting the goblet cells retention, restoring the intestinal barrier integrity and enhancing the expression of tight junction proteins, while the protective effect of exosomes was impaired with the knockout of IGF2 in ERC-Exos. Additionally, IGF2-expressing ERC-Exos decreased the proportions of Th1 and Th17, increased the proportions of Treg, as well as attenuated DC infiltration and maturation in mesenteric lymph nodes and lamina propria of the colitis mice. ERC-Exos were also observed to be phagocytosed by BMDCs and IGF2 is responsible for the modulating effect of ERC-Exos on BMDCs in vitro. CONCLUSIONS: Exosomes derived from ERCs can exert a therapeutic effect on experimental colitis with remarkable alleviation of the intestinal barrier damage and the abnormal mucosal immune responses. We emphasized that IGF2 plays a critical role for ERC-Exos mediated immunomodulatory function and protection against colitis.


Asunto(s)
Colitis , Sulfato de Dextran , Endometrio , Exosomas , Factor II del Crecimiento Similar a la Insulina , Animales , Femenino , Humanos , Ratones , Células Cultivadas , Colitis/inducido químicamente , Colitis/inmunología , Colitis/terapia , Colon/patología , Colon/inmunología , Células Dendríticas/inmunología , Modelos Animales de Enfermedad , Endometrio/inmunología , Endometrio/patología , Exosomas/metabolismo , Exosomas/trasplante , Factor II del Crecimiento Similar a la Insulina/genética , Factor II del Crecimiento Similar a la Insulina/metabolismo , Mucosa Intestinal/inmunología , Mucosa Intestinal/patología , Mucosa Intestinal/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Regeneración
3.
Zhongguo Zhong Yao Za Zhi ; 49(11): 2953-2964, 2024 Jun.
Artículo en Chino | MEDLINE | ID: mdl-39041155

RESUMEN

A sensitive and efficient ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS) approach was established. Based on the self-developed information library, the chemical components from Euodiae Fructus were systematically characterized and identified. The chromatographic separation conditions(e. g., stationary phase,mobile phase, column temperature, and elution gradient) and MS detection conditions(nozzle voltage, capillary voltage, fragmentor,and collision energy) were optimized. Ultimately, an HSS T3 column(2. 1 mm×100 mm, 1. 8 µm) maintained at 35 ℃ was used,and 0. 1% formic acid water-acetonitrile at the flow rate of 0. 4 m L·min~(-1) was used as the mobile phase. Electrospray ionization was adopted to collect the positive and negative ion mass spectrometry data in Auto MS/MS mode. According to the reference compound comparison, fragment ion information interpretation, literature, and retrieval in the self-developed information library, 92 compounds were characterized or derived from the decoction of Euodiae Fructus, including 33 alkaloids, 23 flavonoids, 12 terpenoids, 12phenylpropanoids, and 12 others. Among them, 17 compounds were identified by comparison with the reference compounds, and 11compounds were unreported from Euodiae Fructus. This study realizes the rapid characterization and identification of multi-class chemical components in the decoction of Euodiae Fructus and provides a reference for the studies regarding its effective substances and quality control.


Asunto(s)
Medicamentos Herbarios Chinos , Evodia , Frutas , Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/análisis , Frutas/química , Evodia/química , Espectrometría de Masas/métodos , Espectrometría de Masas en Tándem/métodos , Estructura Molecular , Espectrometría de Masa por Ionización de Electrospray/métodos
4.
Diabetol Metab Syndr ; 16(1): 169, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39026361

RESUMEN

BACKGROUND: The interplay between atrial fibrillation (AF) and obesity on mortality in critically ill patients warrants detailed exploration, given their individual impacts on patient prognosis. This study aimed to assess the associations between AF, obesity, and 1-year mortality in a critically ill population. METHODS: Utilizing data from the Medical Information Mart for Intensive Care (MIMIC)-IV database, we conducted a retrospective analysis of adult patients admitted to the intensive care unit. The primary endpoint was 1-year mortality, analyzed through Cox regression with hazard ratio (HR) and Kaplan-Meier survival methods. RESULTS: The study included 25,654 patients (median age 67.0 years, 40.6% female), with 39.0% having AF and 36.1% being obese. Multivariate COX regression analysis revealed that AF was associated with a 14.7% increase in the risk of 1-year mortality (p < 0.001), while obesity was linked to a 13.9% reduction in mortality risk (p < 0.001). The protective effect of obesity on mortality was similar in patients with (HR = 0.85) and without AF (HR = 0.86). AF led to a slightly higher risk of mortality in patients without obesity (HR = 1.16) compared to those with obesity (HR = 1.13). Kaplan-Meier survival curves highlighted that non-obese patients with AF had the lowest survival rate, whereas the highest survival was observed in obese patients without AF. CONCLUSIONS: AF significantly increased 1-year mortality risk in critically ill patients, whereas obesity was associated with a decreased mortality risk. The most adverse survival outcomes were identified in non-obese patients with AF.

5.
J Extracell Vesicles ; 13(7): e12489, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39016198

RESUMEN

Recently, extracellular vesicles (EVs) have been developed as therapeutic targets for various diseases. Biodistribution is crucial for EVs intended for therapeutic purposes because it can determine the degree of on- and off-target effects. This study aimed to explore techniques to evaluate the biodistribution of unmodified EVs. We devised a novel quantitative polymerase chain reaction (qPCR)-based assay to detect unmodified EVs by targeting mitochondrial deoxyribonucleic acid (mtDNA), a constituent of EVs. We focused on specific mtDNA regions that exhibited homologous variations distinct from their rodent mtDNA counterparts to establish this analytical approach. Herein, we successfully designed primers and probes targeting human and rodent mtDNA sequences and developed a highly specific and sensitive qPCR method. Furthermore, the quantification range of EVs isolated from various cells differed based on the manufacturer and cell source. IRDye 800CW-labelled Expi293F EV mimetics were administered to the animals via the tail vein to compare the imaging test and mtDNA-qPCR results. The results obtained from imaging tests and mtDNA-qPCR to investigate EV biodistribution patterns revealed differences. The results revealed that our newly developed method effectively determined the biodistribution of unmodified EVs with high sensitivity and reproducibility.


Asunto(s)
ADN Mitocondrial , Vesículas Extracelulares , Vesículas Extracelulares/metabolismo , Animales , ADN Mitocondrial/metabolismo , Humanos , Distribución Tisular , Ratones , Ratas , Mitocondrias/metabolismo
6.
Diabetes Metab Syndr ; 18(6): 103067, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38955095

RESUMEN

BACKGROUND: Semaglutide, a glucagon-like peptide-1 receptor agonist, is reported to have cardiac benefits, but its effects on preventing atrial fibrillation (AF) remain inconclusive. This study aimed to investigate whether semaglutide can prevent AF occurrence in patients with type 2 diabetes mellitus (T2DM), obesity, or overweight. METHODS: We searched MEDLINE, EMBASE, the Cochrane CENTRAL database, and clinicaltrials.gov from inception to December 29, 2023. Randomized controlled trials of semaglutide in patients with T2DM, obesity, or overweight were included. The primary outcome was AF occurrence. Relative risks (RRs) with 95 % confidence intervals (CIs) were calculated for the overall population and subgroups. RESULTS: Twenty-one trials comprising 25957 patients were included. In the overall pooled analysis, semaglutide decreased AF occurrence compared to control drugs (RR 0.70, 95 % CI 0.52-0.95). This result was consistent in trials using other antihyperglycemic medications as controls (RR 0.43, 95 % CI 0.21-0.89), but not in placebo-controlled trials (RR 0.77, 95 % CI 0.56-1.07). The outcome was favorable for patients with T2DM (RR 0.71, 95 % CI 0.52-0.97), but not for patients with overweight or obesity (RR 0.56, 95 % CI 0.18-1.73). Results varied by type of semaglutide, with oral semaglutide showing an RR of 0.49 (95 % CI 0.25-0.97) and subcutaneous semaglutide showing an RR of 0.77 (95 % CI 0.55-1.07). CONCLUSION: Semaglutide was associated with a reduced risk of AF occurrence in the overall analysis. Favorable outcomes were observed in subsets using other antihyperglycemic medications as controls, in patients with T2DM, and with oral semaglutide.


Asunto(s)
Fibrilación Atrial , Diabetes Mellitus Tipo 2 , Péptidos Similares al Glucagón , Humanos , Péptidos Similares al Glucagón/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/prevención & control , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Sobrepeso/complicaciones
7.
Acta bioeth ; 30(1)jun. 2024.
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1556627

RESUMEN

Objective: To evaluate the implementation effect of serious illness medical insurance in Guang Xi Zhuang Autonomous Region of western China. Study design: Through the collection of 2017-2021 Guang Xi serious illness medical insurance specific policy making such as fund usage, serious illness compensation, medical expenses data, and data analysis of a serious illness medical insurance effect. Method: Literature research, Policy text analysis, quantitative data collection method, using Excel and SPSS 19.0 data descriptive statistical analysis and comparative analysis. Results: Serious illness medical insurance has had some effect, e.g., from 2017 to 2021, the utilization rate of serious illness medical insurance fund in Guang Xi was 109.49% and 103.87% respectively, the fund balance rate was -9.45% and -8.54% respectively, and the accumulated balance was -2.3871 million CNY and -70.7955 million CNY. Conclusion: The serious illness medical insurance has reduced the burden of large medical expenses of patients to a certain extent, but the fund is under too much pressure, and there is a payment deficit. The coverage and security of serious illness medical insurance need to be expanded and strengthened, and the cooperation mechanism with commercial insurance institutions should be gradually explored to improve the serious illness medical insurance.


Objetivo: evaluar el efecto de la implementación de seguros médicos para enfermedades graves en la Región Autónoma Guang Xi Zhuang, al oeste de China. Diseño del estudio: a través de la recopilación de pólizas de seguro médico específicas para enfermedades graves de la región de Guang Xi entre 2017-2021, como por ejemplo: uso de fondos, compensación por enfermedades graves, datos de gastos médicos y análisis de datos del efecto de seguros médicos para enfermedades graves. Método: investigación de literatura, análisis de textos de políticas públicas, metodología de recolección de datos cuantitativos utilizando Excel y SPSS 19.0, análisis estadístico descriptivo de datos y análisis comparativo. Resultados: el seguro médico para enfermedades graves ha demostrado tener efectos, tales como: entre 2017 y 2021, la tasa de utilización de fondos de seguros médicos para enfermedades graves en Guang Xi fue de 109,49 % y 103,87 % respectivamente, las tasas de saldo del fondo fue de -9,45 % y -8,54 % respectivamente y el saldo acumulado fue de -2,3871 millones de CNY y -70,7955 millones de CNY. Conclusión: El seguro médico para enfermedades graves ha reducido en cierta medida la carga de los grandes gastos médicos de los pacientes, pero al existir un déficit de pagos está bajo demasiada presión. Por ello, es necesario ampliar y fortalecer la cobertura y seguridad del seguro médico para enfermedades graves, y explorar gradualmente mecanismos de cooperación con instituciones de seguros comerciales.


Objetivo: Avaliar o efeito da implementação de seguro médico para doenças graves na Região Autônoma de Guang Xi Zhuang da China Ocidental. Desenho do Estudo: Através da coleta de políticas específicas de seguro médico para doenças graves de Guang Xi 2017-2021, uso de fundos, compensação por doenças graves, dados de despesas médicas e análise de dados de um efeito de seguro médico para doenças graves. Método: Pesquisa na literatura, análise do texto da política, método de coleta de dados quantitativos usando Excel e SPSS 19.0, análise estatística descritiva de dados e análise comparativa. Resultados: Seguro médico de doenças graves teve um certo efeito. Em 2017 e 2021, a taxa de utilização do fundo de seguro médico para doenças graves em Guang Xi foi 109,49% e 103,87% respectivamente, a taxa de saldo do fundo foi -9,45% e -8,54% respectivamente e o saldo acumulado foi -2,3871 milhões de yuans e -70,7955 milhões de yuans. Conclusão: O seguro médico para doenças graves reduziu o ônus de grandes despesas médicas dos pacientes até certo ponto mas o fundo está sob demasiada pressão e há um déficit de pagamentos. A cobertura e segurança do seguro médico de doenças graves necessitam ser expandidas e fortalecidas, e o mecanismo de cooperação com instituições de seguros comerciais deve ser gradualmente explorado para melhorar o seguro médico para doenças graves.

9.
J Cardiovasc Electrophysiol ; 35(7): 1440-1449, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38757370

RESUMEN

INTRODUCTION: The accuracy of surface ECG algorithms for predicting the origin of outflow tract ventricular arrhythmias (OT-VAs) might be questioned. Intracardiac electrograms recorded at anatomic landmarks could provide new predictive insights. We aim to evaluate the efficacy of a novel criterion utilizing the activation pattern of the coronary sinus (CS) in localizing OT-VAs, including VAs originating from the right ventricular outflow tract (RVOT), endocardial left ventricular outflow tract (Endo-LVOT), and epicardial left ventricular outflow tract (Epi-LVOT). METHODS: We measured the ventricular activation time of the mitral annulus (MA) from the onset of the earliest QRS complex of VAs to the initial deflection over the isoelectric line at local signals, namely the QRS-MA interval. The activation at 3 and 12 o'clock of the MA was recorded as the QRS-MA3 and QRS-MA12 intervals, respectively. Their predictive values were compared to previous ECG algorithms. RESULTS: A total of 68 patients with OT-VAs were enrolled (51 for development and 17 for validation). From early to late, the ventricular activation sequences at MA12 were as follows: Epi-LVOT, Endo-LVOT, and RVOT. In LBBB morphology OT-VAs, the QRS-MA12 interval was significantly earlier for LVOT origins than RVOT origins. In the combined cohort of development and validation cohort, a cut-off value of ≤10 ms predicted the LVOT origin with a sensitivity of 100% and specificity of 78%. The QRS-MA12 interval ≤ -24 ms additionally predicted epicardial LVOT sites of origin. CONCLUSIONS: The QRS-MA interval could accurately differentiate the OT-VAs localization.


Asunto(s)
Potenciales de Acción , Seno Coronario , Electrocardiografía , Frecuencia Cardíaca , Valor Predictivo de las Pruebas , Humanos , Seno Coronario/fisiopatología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Algoritmos , Técnicas Electrofisiológicas Cardíacas , Reproducibilidad de los Resultados , Factores de Tiempo , Taquicardia Ventricular/fisiopatología , Taquicardia Ventricular/diagnóstico , Arritmias Cardíacas/fisiopatología , Arritmias Cardíacas/diagnóstico , Adulto , Diagnóstico Diferencial
10.
Cell Rep Med ; 5(5): 101567, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38744277

RESUMEN

Bispecific T cell engagers (TCEs) show promising clinical efficacy in blood tumors, but their application to solid tumors remains challenging. Here, we show that Fc-fused IL-7 (rhIL-7-hyFc) changes the intratumoral CD8 T cell landscape, enhancing the efficacy of TCE immunotherapy. rhIL-7-hyFc induces a dramatic increase in CD8 tumor-infiltrating lymphocytes (TILs) in various solid tumors, but the majority of these cells are PD-1-negative tumor non-responsive bystander T cells. However, they are non-exhausted and central memory-phenotype CD8 T cells with high T cell receptor (TCR)-recall capacity that can be triggered by tumor antigen-specific TCEs to acquire tumoricidal activity. Single-cell transcriptome analysis reveals that rhIL-7-hyFc-induced bystander CD8 TILs transform into cycling transitional T cells by TCE redirection with decreased memory markers and increased cytotoxic molecules. Notably, TCE treatment has no major effect on tumor-reactive CD8 TILs. Our results suggest that rhIL-7-hyFc treatment promotes the antitumor efficacy of TCE immunotherapy by increasing TCE-sensitive bystander CD8 TILs in solid tumors.


Asunto(s)
Linfocitos T CD8-positivos , Inmunoterapia , Interleucina-7 , Linfocitos Infiltrantes de Tumor , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , Interleucina-7/inmunología , Interleucina-7/metabolismo , Humanos , Animales , Inmunoterapia/métodos , Ratones , Neoplasias/inmunología , Neoplasias/terapia , Línea Celular Tumoral , Receptores de Antígenos de Linfocitos T/inmunología , Receptores de Antígenos de Linfocitos T/metabolismo , Efecto Espectador/inmunología
11.
Eur J Pharmacol ; 976: 176665, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-38797312

RESUMEN

OBJECTIVE: Sepsis is frequently complicated by neuroinflammation. Gibberellic acid (GA3) is recognized for its anti-inflammatory properties. In this study, our objective was to investigate whether GA3 could alleviate Nuclear factor-kappa B (NF-κB) -dependent inflammatory stress in sepsis-induced neuroinflammation. METHODS: C57BL/6 J mice were administered 10 mg/kg lipopolysaccharide (LPS) to induce sepsis. BV2 cells were pre-incubated with GA3 and subjected lipopolysaccharide stimulation to replicate the inflammatory microglia during sepsis. Subsequently, we assessed the release of IL-6, TNF-α, and IL-1ß, along with the expression of Zbtb16, NF-κB, and IκB. To investigate whether any observed anti-inflammatory effects of GA3 were mediated through a Zbtb16-dependent mechanism, Zbtb16 was silenced using siRNA. RESULTS: GA3 improved the survival of sepsis mice and alleviated post-sepsis cognitive impairment. Additionally, GA3 attenuated microglial M1 activation (pro-inflammatory phenotype), inflammation, and neuronal damage in the brain. Moreover, GA3 inhibited the release of TNF-α, IL-6, and IL-1ß in microglia stimulated with LPS. The NF-κB signaling pathway emerged as one of the key molecular pathways associated with the impact of GA3 on LPS-stimulated microglia. Lastly, GA3 upregulated Zbtb16 expression in microglia that had been downregulated by LPS. The inhibitory effects of GA3 on microglial M1 activation were partially reversed through siRNA knockdown of Zbtb16. CONCLUSIONS: Pre-incubation of microglia with GA3 led to the upregulation of the NF-κB regulator, Zbtb16. This process counteracted LPS-induced microglial M1 activation, resulting in an anti-inflammatory effect upon subsequent LPS stimulation.


Asunto(s)
Giberelinas , Lipopolisacáridos , Ratones Endogámicos C57BL , Microglía , FN-kappa B , Sepsis , Animales , Sepsis/complicaciones , Sepsis/tratamiento farmacológico , Sepsis/metabolismo , Ratones , FN-kappa B/metabolismo , Masculino , Microglía/efectos de los fármacos , Microglía/metabolismo , Giberelinas/farmacología , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Transducción de Señal/efectos de los fármacos , Línea Celular , Citocinas/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo
12.
Cytokine ; 179: 156598, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-38583255

RESUMEN

BACKGROUND: Allograft rejection remains a major obstacle to long-term graft survival. Although previous studies have demonstrated that IL-37 exhibited significant immunomodulatory effects in various diseases, research on its role in solid organ transplantation has not been fully elucidated. In this study, the therapeutic effect of recombinant human IL-37 (rhIL-37) was evaluated in a mouse cardiac allotransplantation model. METHODS: The C57BL/6 recipients mouse receiving BALB/c donor hearts were treated with rhIL-37. Graft pathological and immunohistology changes, immune cell populations, and cytokine profiles were analyzed on postoperative day (POD) 7. The proliferative capacities of Th1, Th17, and Treg subpopulations were assessed in vitro. Furthermore, the role of the p-mTOR pathway in rhIL-37-induced CD4+ cell inhibition was also elucidated. RESULTS: Compared to untreated groups, treatment of rhIL-37 achieved long-term cardiac allograft survival and effectively alleviated allograft rejection indicated by markedly reduced infiltration of CD4+ and CD11c+ cells and ameliorated graft pathological changes. rhIL-37 displayed significantly less splenic populations of Th1 and Th17 cells, as well as matured dendritic cells. The percentages of Tregs in splenocytes were significantly increased in the therapy group. Furthermore, rhIL-37 markedly decreased the levels of TNF-α and IFN-γ, but increased the level of IL-10 in the recipients. In addition, rhIL-37 inhibited the expression of p-mTOR in CD4+ cells of splenocytes. In vitro, similar to the in vivo experiments, rhIL-37 caused a decrease in the proportion of Th1 and Th17, as well as an increase in the proportion of Treg and a reduction in p-mTOR expression in CD4+ cells. CONCLUSIONS: We demonstrated that rhIL-37 effectively suppress acute rejection and induce long-term allograft acceptance. The results highlight that IL-37 could be novel and promising candidate for prevention of allograft rejection.


Asunto(s)
Aloinjertos , Rechazo de Injerto , Trasplante de Corazón , Interleucina-1 , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Proteínas Recombinantes , Animales , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Humanos , Ratones , Proteínas Recombinantes/farmacología , Interleucina-1/metabolismo , Supervivencia de Injerto/efectos de los fármacos , Supervivencia de Injerto/inmunología , Células TH1/inmunología , Células TH1/efectos de los fármacos , Células Th17/inmunología , Células Th17/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/efectos de los fármacos , Masculino , Serina-Treonina Quinasas TOR/metabolismo , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/efectos de los fármacos , Transducción de Señal/efectos de los fármacos
13.
Exp Ther Med ; 27(5): 180, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38515645

RESUMEN

The number of artificial total hip revision arthroplasties is increasing yearly in China, and >50% of these cases have acetabular defects. Accurately locating and quantifying the bone defect is one of the current challenges of this surgery. Thus, the objective of the present study was to simulate acetabular implantation with the aid of Mimics 17.0 software (Materialise NV) in patients with loosened acetabular prosthesis, to evaluate the 'ideal acetabular center' and the 'actual acetabular center' to guide the choice of prosthesis and surgical method. From January 2017 to June 2021, the present study included 10 hips from 10 patients [seven men (seven hips) and three women (three hips)]. In all patients, the Mimics software was applied to simulate the dislocation of the femoral prosthesis and acetabular prosthesis implantation before surgery; calculate the height difference between the 'ideal acetabular center' and the 'actual acetabular center' to assess the bone defect; confirm the size of the acetabular prosthesis, abduction angle, anteversion angle and bone coverage of the acetabular cup; and measure the intraoperative bleeding and postoperative follow-up Harris score of the hip joint. After statistical analysis, the present study revealed that digital simulation assistance could improve the accuracy of hip revision acetabular prosthesis implantation, reduce postoperative shortening of the affected limb, especially for surgeons with relatively little experience in hip revision surgery, and greatly reduce the occurrence of complications such as hip dislocation because of poor postoperative prosthesis position.

14.
Biochem Biophys Res Commun ; 705: 149724, 2024 04 23.
Artículo en Inglés | MEDLINE | ID: mdl-38432111

RESUMEN

BACKGROUND: Although there are several studies in the development of various human cancers, the role of exosomes is poorly understood in the progression of gallbladder cancer. This study aims to characterize the metabolic changes occurring in exosomes obtained from patients with gallbladder cancer compared with those from other gallbladder disease groups. METHODS: Biliary exosomes were isolated from healthy donors (n = 3) and from patients with gallbladder cancer (n = 3), gallbladder polyps (n = 4), or cholecystitis (n = 3) using a validated exosome isolation kit. Afterward, we performed miRNA profiling and untargeted metabolomic analysis of the exosomes. The results were validated by integrating the results of the miRNA and metabolomic analyses. RESULTS: The gallbladder cancer group exhibited a significant reduction in the levels of multiple unsaturated phosphatidylethanolamines and phosphatidylcholines compared to the normal group, which resulted in the loss of exosome membrane integrity. Additionally, the gallbladder cancer group demonstrated significant overexpression of miR-181c and palmitic acid, and decreased levels of conjugated deoxycholic acid, all of which are strongly associated with the activation of the PI3K/AKT pathway. CONCLUSIONS: Our findings demonstrate that the contents of exosomes are disease-specific, particularly in gallbladder cancer, and that altered metabolites convey critical information regarding their phenotype. We believe that our metabolomic and miRNA profiling results may provide important insights into the development of gallbladder cancer.


Asunto(s)
Exosomas , Neoplasias de la Vesícula Biliar , MicroARNs , Humanos , Neoplasias de la Vesícula Biliar/genética , Fosfatidilinositol 3-Quinasas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Exosomas/metabolismo
16.
Adv Sci (Weinh) ; 11(23): e2306050, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38544344

RESUMEN

COVID-19 can lead to adverse outcomes in patients with pre-existing diseases. Azvudine has been approved for treating COVID-19 in China, but the real-world data is limited. It is aimed to investigate the efficacy of Azvudine in patients with COVID-19 and pre-existing cardiovascular diseases. Patients with confirmed COVID-19 and pre-existing cardiovascular diseases are retrospectively enrolled. The primary outcome is all-cause death during hospitalization. Overall, 351 patients are included, with a median age of 74 years, and 44% are female. 212 (60.6%) patients are severe cases. Azvudine is used in 106 (30.2%) patients and not in 245 (69.8%). 72 patients died during hospitalization. After multivariate adjustment, patients who received Azvudine a lower risk of all-cause death (hazard ratio: 0.431; 95% confidence interval: 0.252-0.738; p = 0.002) than controls. Azvudine therapy is also associated with lower risks of shock and acute kidney injury. For sensitivity analysis in the propensity score-matched cohort (n = 90 for each group), there is also a significant difference in all-cause death between the two groups (hazard ratio: 0.189; 95% confidence interval: 0.071-0.498; p < 0.001). This study indicated that Azvudine therapy is associated with better outcomes in COVID-19 patients with pre-existing cardiovascular diseases.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , COVID-19 , Enfermedades Cardiovasculares , Humanos , Femenino , Masculino , Anciano , Enfermedades Cardiovasculares/tratamiento farmacológico , Estudios Retrospectivos , COVID-19/complicaciones , COVID-19/mortalidad , Persona de Mediana Edad , China/epidemiología , Antivirales/uso terapéutico , SARS-CoV-2/efectos de los fármacos , Resultado del Tratamiento , Anciano de 80 o más Años , Hospitalización/estadística & datos numéricos
17.
Int Med Case Rep J ; 17: 167-175, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38504721

RESUMEN

Introduction: Pancreatic cancer (PC) is among the deadliest malignancies. Kidney cancer (KC) is a common malignancy globally. Chemo- or radio-therapies are not very effective to control PC or KC, and overdoses often cause severe site reactions to the patients. As a result, novel treatment strategies with high efficacy but without toxic side effects are urgently desired. Secoisolariciresinol diglucoside (SDG) belongs to plant lignans with potential anticancer activities, but clinical evidence is not available in PC or KC treatment. Patient Concerns: We report a rare case of an 83-year-old female patient with pancreatic and kidney occupying lesions that lacked the conditions to receive surgery or chemo- or radiotherapy. Diagnosis: Pancreatic and kidney cancers. Interventions: We gave dietary SDG to the patient as the only therapeutics. Outcomes: SDG effectively halted progression of both PC and KC. All clinical manifestations, including bad insomnia, loss of appetite, stomach symptoms, and skin itching over the whole body, all disappeared. The initial massive macroscopic hematuria became microscopic and infrequent, and other laboratory results also gradually returned to normal. Most of the cancer biomarkers, initially high such as CEA, CA199, CA724, CA125, came down rapidly, among which CA199 changed most radically. This patient has had progression-free survival of one year so far. Conclusion: These results demonstrate the potent inhibitory effects of SDG on PC and KC of this patient and provide promising novel therapeutics for refractory malignant tumors.

18.
Anal Bioanal Chem ; 416(7): 1571-1587, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38279012

RESUMEN

Dragon's Blood (DB) serves as a precious Chinese medicine facilitating blood circulation and stasis dispersion. Daemonorops draco (D. draco; Qi-Lin-Jie) and Dracaena cochinchinensis (D. cochinchinenesis; Long-Xue-Jie) are two reputable plant sources for preparing DB. This work was designed to comprehensively characterize and compare the metabolome differences between D. draco and D. cochinchinenesis, by integrating liquid chromatography/mass spectrometry and untargeted metabolomics analysis. Offline two-dimensional liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (2D-LC/IM-QTOF-MS), by utilizing a powerful hybrid scan approach, was elaborated for multicomponent characterization. Configuration of an XBridge Amide column and an HSS T3 column in offline mode exhibited high orthogonality (A0 0.80) in separating the complex components in DB. Particularly, the hybrid high-definition MSE-high definition data-dependent acquisition (HDMSE-HDDDA) in both positive and negative ion modes was applied for data acquisition. Streamlined intelligent data processing facilitated by the UNIFI™ (Waters) bioinformatics platform and searching against an in-house chemical library (recording 223 known compounds) enabled efficient structural elucidation. We could characterize 285 components, including 143 from D. draco and 174 from D. cochinchinensis. Holistic comparison of the metabolomes among 21 batches of DB samples by the untargeted metabolomics workflows unveiled 43 significantly differential components. Separately, four and three components were considered as the marker compounds for identifying D. draco and D. cochinchinenesis, respectively. Conclusively, the chemical composition and metabolomic differences of two DB resources were investigated by a dimension-enhanced analytical approach, with the results being beneficial to quality control and the differentiated clinical application of DB.


Asunto(s)
Quimiometría , Metaboloma , Extractos Vegetales , Espectrometría de Masas , Cromatografía Liquida , Cromatografía Líquida de Alta Presión/métodos
19.
Heliyon ; 10(2): e24302, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38293491

RESUMEN

Traditional Chinese medicine volatile oil has a long history and possesses extensive pharmacological activity. However, volatile oils have characteristics such as strong volatility, poor water solubility, low bioavailability, and poor targeting, which limit their application. The use of volatile oil nano drug delivery systems can effectively improve the drawbacks of volatile oils, enhance their bioavailability and chemical stability, and reduce their volatility and toxicity. This article first introduces the limitations of the components of traditional Chinese medicine volatile oils, discusses the main classifications and latest developments of volatile oil nano formulations, and briefly describes the preparation methods of traditional Chinese medicine volatile oil nano formulations. Secondly, the limitations of nano formulation technology are discussed, along with future challenges and prospects. A deeper understanding of the role of nanotechnology in traditional Chinese medicine volatile oils will contribute to the modernization of volatile oils and broaden their application value.

20.
Huan Jing Ke Xue ; 45(1): 123-130, 2024 Jan 08.
Artículo en Chino | MEDLINE | ID: mdl-38216464

RESUMEN

Based on the actual operating conditions and data monitoring, the carbon emission characteristics of typical processes of a drinking water treatment plant (DWTP) in Tianjin were studied. The total carbon emission intensity measured by CO2-eq was 0.254 kg·m-3, and the proportion of carbon emissions from electricity consumption and reagent consumption was 81.76% and 9.15%, respectively. The key carbon emission sectors of electricity consumption were the water supply pump house, ultrafiltration membrane process, and inlet pump house, which accounted for 50.99%-73.51%, 17.64%-20.70%, and 17.97%-22.40% of the total carbon emission from electricity consumption in the DWTP, respectively. The contribution of sodium hypochlorite to the carbon emission of reagent consumption was 89.12%-90.30%, followed by ferric chloride, PAC, and ammonium sulfate. In the traditional water purification process, the carbon emission intensity of the process unit was in the order of inlet pump house > rapid filter > sedimentation tank. The order in the ultrafiltration membrane advanced treatment process was inlet pump house > ultrafiltration membrane > mechanical coagulation > clarification tank. The carbon emission intensity of the rapid filter process and the ultrafiltration membrane process were 0.070 9 kg·m-3 and 0.109 0 kg·m-3, respectively. The ultrafiltration membrane process could save 23% of the reagent consumption, and its carbon emission of electricity consumption was twice that of the traditional treatment process. The analysis of factors affecting carbon emission in key sectors showed that the raw water quality parameters such as turbidity, pH, ammonia nitrogen, temperature, etc., were significantly correlated with the carbon emission intensity of sodium hypochlorite. There was a significant linear regression relationship between ex-factory water pressure, daily water supply, and carbon emission intensity of the water supply pump house. The control measures of water quality and water pressure can effectively reduce the carbon emissions of the DWTP.


Asunto(s)
Agua Potable , Purificación del Agua , Carbono , Hipoclorito de Sodio , Abastecimiento de Agua , Ultrafiltración
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