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Aberrant RSPO1 expression is implicated in tumor progression across various cancers and correlates with anti-cancer immune cell characteristics. However, the specific role of R-spondin 1 (RSPO1) in lung adenocarcinoma (LUAD) remains unclear. In this study, we utilized data from The Cancer Genome Atlas (TCGA) to assess RSPO1 expression across 33 tumor types. Kaplan-Meier (K-M) analysis revealed the prognostic significance of RSPO1 in various cancers. Using statistical software R, we examined RSPO1's associations with immune cell infiltration, methylation, mutation, and competing endogenous RNA (ceRNA) networks. Exploration via the Tumor Immune Single Cell Hub (TISCH) database uncovered RSPO1's link to the tumor microenvironment (TME) and identified potential small molecule drug targets. We further investigated RSPO1's impact on LUAD cell proliferation, metastasis, and the Wnt pathway in vitro. Our findings highlight RSPO1's role in cancer progression and suggest its potential as both a prognostic marker and therapeutic target in LUAD, implicating the modulation of the Wnt pathway.
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Objective To determine which method of Positive End-expiratory Pressure (PEEP) titration is more useful, and to establish an evidence base for the clinical impact of Electrical Impedance Tomography (EIT) based individual PEEP setting which appears to be a promising method to optimize PEEP in Acute Respiratory Distress Syndrome (ARDS) patients. Design A systematic review and meta-analysis. Setting 4 databases (PUBMED, EMBASE, Web Of Science, and the Cochrane Library) from 1980 to December 2020 were performed. Participants Randomized clinical trials patients with ARDS. Main variables PaO2/FiO2-ratio and respiratory system compliance. Intervension The quality of the studies was assessed with the Cochrane risk and bias tool. Results 8 trials, including a total of 222 participants, were eligible for analysis. Meta-analysis demonstrates a significantly EIT-based individual PEEP setting for patients receiving higher PaO2/FiO2 ratio as compared to other PEEP titration strategies [5 trials, 202 patients, SMD 0.636, (95% CI 0.364−0.908)]. EIT-drived PEEP titration strategy did not significantly increase respiratory system compliance when compared to other peep titration strategies, [7 trials, 202 patients, SMD −0.085, (95% CI −0.342 to 0.172)]. Conclusions The benefits of PEEP titration with EIT on clinical outcomes of ARDS in placebo-controlled trials probably result from the visible regional ventilation of EIT. These findings offer clinicians and stakeholders a comprehensive assessment and high-quality evidence for the safety and efficacy of the EIT-based individual PEEP setting as a superior option for patients who undergo ARDS (AU)
Objetivo Para determinar qué método de valoración de la presión espirfinal positiva (PEEP) es más útil, y para establecer una base de evidencia para el impacto clínico de la tomode impedeléctrica (EIT) basada en el ajuste individual de PEEP que parece ser un método prometedor para optimizar la PEEP en pacientes con síndrome de dificultad respiraguda (ARDS). Diseño Una revisión sistemática y metanálisis. Ámbito Se realizaron 4 bases de datos (PUBMED, EMBASE, Web Of Science y Cochrane Library) de 1980 a diciembre de 2020. Participantes Ensayos clínicos aleatorizados de pacientes con SDRA. Variables principals PaO2/FiO2 ratio y compatibilidad respiratoria. Intervención La calidad de los estudios se evaluó con la Cochrane risk and bias tool. Resultados Ocho ensayos, incluyendo un total de 222 participantes, fueron elegibles para el análisis. El análisis de ≥ eta demuestra una configuración individual significativamente basada en MEITPpara pacientes que reciben una mayor proporción EE2/P PiO2en comparación con otras estrategias de titulación FOPEEP SMD CI. La estrategia de titulación de PEEP derivada del tie no aumentó significativamente el cumplimiento del sistema respiren comparación con otras estrategias de titulación de PEEP, [7 ensayos, 202 pacientes, DME -0,085, (IC del 95%: −0,342−0,172)]. Conclusiones Los beneficios de la valoración de la PEEP con EIT en los resultados clínicos de SDRA en ensayos controlados con placebo probablemente sean el resultado de la ventilación regional visible del EIT. Estos hallazgos ofrecen a los médicos y a las partes interesadas una evaluación integral y evidencia de alta calidad para la seguridad y eficacia de la configuración individual de PEEP basada en EIT como una opción superior para los pacientes que se someten a SDRA (AU)
Asunto(s)
Humanos , Síndrome Respiratorio Agudo Grave/terapia , Presión de las Vías Aéreas Positiva Contínua/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Tomografía Computarizada por Rayos X/métodos , Impedancia EléctricaRESUMEN
OBJECTIVE: To determine which method of Positive End-expiratory Pressure (PEEP) titration is more useful, and to establish an evidence base for the clinical impact of Electrical Impedance Tomography (EIT) based individual PEEP setting which appears to be a promising method to optimize PEEP in Acute Respiratory Distress Syndrome (ARDS) patients. DESIGN: A systematic review and meta-analysis. SETTING: 4 databases (PUBMED, EMBASE, Web Of Science, and the Cochrane Library) from 1980 to December 2020 were performed. PARTICIPANTS: Randomized clinical trials patients with ARDS. MAIN VARIABLES: PaO2/FiO2-ratio and respiratory system compliance. INTERVENSION: The quality of the studies was assessed with the Cochrane risk and bias tool. RESULTS: 8 trials, including a total of 222 participants, were eligible for analysis. Meta-analysis demonstrates a significantly EIT-based individual PEEP setting for patients receiving higher PaO2/FiO2 ratio as compared to other PEEP titration strategies [5 trials, 202 patients, SMD 0.636, (95% CI 0.364-0.908)]. EIT-drived PEEP titration strategy did not significantly increase respiratory system compliance when compared to other peep titration strategies, [7 trials, 202 patients, SMD -0.085, (95% CI -0.342 to 0.172)]. CONCLUSIONS: The benefits of PEEP titration with EIT on clinical outcomes of ARDS in placebo-controlled trials probably result from the visible regional ventilation of EIT. These findings offer clinicians and stakeholders a comprehensive assessment and high-quality evidence for the safety and efficacy of the EIT-based individual PEEP setting as a superior option for patients who undergo ARDS.
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Síndrome de Dificultad Respiratoria , Tomografía Computarizada por Rayos X , Humanos , Síndrome de Dificultad Respiratoria/terapia , Pulmón , Respiración con Presión Positiva/métodos , Fenómenos Fisiológicos RespiratoriosRESUMEN
Pulmonary arterial hypertension (PAH) is characterized by pulmonary artery smooth muscle cell (PASMC) dysfunction. However, the underlying mechanisms of PASMC dysfunction remain largely unknown. Here, we show that mitochondrial fragmentation contributes to PASMC dysfunction through enhancement of endoplasmic reticulum (ER) stress. PASMC dysfunction accompanied by mitochondrial fragmentation and ER stress was observed in the pulmonary arteries of hypoxia-induced rats with PAH, as well as isolated PASMCs under hypoxia. Treatment with Mdivi-1 inhibited mitochondrial fragmentation and ER stress and improved PASMC function in isolated PASMCs under hypoxia, while Drp1 overexpression increased mitochondrial fragmentation and ER stress, impairing PASMC function in isolated PASMCs under normoxia. However, inhibition of ER stress using ER stress inhibitors showed a negligible effect on mitochondrial morphology but improved PASMC function during hypoxia. Additionally, we found that mitochondrial fragmentation-promoted ER stress was dependent on mitochondrial reactive oxygen species. Furthermore, inhibition of mitochondrial fragmentation using Mdivi-1 attenuated mitochondrial fragmentation and ER stress in hypoxic PASMCs and improved the pulmonary artery smooth muscle function in hypoxic rats. These results suggest that hypoxia induces pulmonary artery smooth muscle dysfunction through mitochondrial fragmentation-mediated ER stress and that mitochondrial morphology is a potential target for treatment of hypoxia-induced pulmonary artery smooth muscle dysfunction.
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Estrés del Retículo Endoplásmico , Hipoxia/complicaciones , Mitocondrias Musculares/patología , Dinámicas Mitocondriales , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/patología , Hipertensión Arterial Pulmonar/etiología , Animales , Hipoxia de la Célula , Células Cultivadas , Modelos Animales de Enfermedad , Dinaminas/genética , Dinaminas/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos , Masculino , Mitocondrias Musculares/efectos de los fármacos , Mitocondrias Musculares/metabolismo , Dinámicas Mitocondriales/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , Hipertensión Arterial Pulmonar/metabolismo , Hipertensión Arterial Pulmonar/patología , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/metabolismo , Arteria Pulmonar/patología , Quinazolinonas/farmacología , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismoRESUMEN
BACKGROUND: Glioma remains the most common cause of brain cancer-related mortality. Glioma accounts for 50-60% of brain cancer. Due to their low toxicity and infrequent side effects, traditional herbs have been increasingly popular. Coptis Chinensis is commonly used in cancer treatment in combination with other Chinese Medicine herbs. However, little is known about its biological functions and mechanisms in glioma cells. METHODS: In this study, the anti-glioma cell effect of Coptis Chinensis was determined using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) method, plate clone test, scratch tests, flow cytometry, western blotting and a glioma xenograft tumor model. RESULTS: The results showed that Coptis Chinensis significantly suppressed glioma cell proliferation, tumor formation, migration and tumor growth, and prolonged the survival time of glioma cell-bearing mice. The flow cytometry result showed that Coptis Chinensis induced cell cycle arrest and apoptosis in glioma cells. Western blotting showed that Coptis Chinensis down-regulated the Signal transducer and activator of transcription 3 (STAT3) phosphorylation levels and reduced the expression of Histone deacetylase 3 (HDAC3) and caspase 3. CONCLUSIONS: Coptis Chinensis can inhibit various aspects of glioma cell functions. This study provides favorable scientific evidence for the potential use of natural products such as Coptis Chinensis in the clinical treatment of patients with glioma.
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Antineoplásicos/farmacología , Coptis , Glioma/metabolismo , Histona Desacetilasas/metabolismo , Extractos Vegetales/farmacología , Factor de Transcripción STAT3/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Regulación hacia Abajo/efectos de los fármacos , Femenino , Histona Desacetilasas/análisis , Humanos , Ratones , Ratones Desnudos , Fosforilación/efectos de los fármacos , Factor de Transcripción STAT3/análisis , Factor de Transcripción STAT3/química , Factor de Transcripción STAT3/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: This study aimed to examine the prevalence of diabetes mellitus and other categories of glucose intolerance (impaired glucose tolerance and impaired fasting glucose) and explore the risk factors in an ethnic minority region, Guangxi Zhuang Autonomous Region, People's Republic of China. METHODS: A population-based study enrolled 53,270 residents older than 5 years in Guangxi, People's Republic of China. The prevalence of diabetes was calculated using the 1999 World Health Organization (WHO) oral glucose tolerance test diagnostic criteria. RESULTS: Among 53,270 individuals, the prevalence of diabetes, impaired glucose tolerance, and impaired fasting glucose was 5.96%, 7.36%, and 2.62%, respectively. Of the 3,173 individuals with diabetes mellitus, 696 (21.94%) were found to have a history of diabetes and 2,477 (78.06%) were newly diagnosed. A lower prevalence was found in Zhuang ethnic minority people compared with the majority of Han people. The prevalence was significantly associated with age, body mass index, waist-to-hip ratio, dyslipidemia, medical history of hypertension, and family history of diabetes. CONCLUSION: Guangxi shows a rapidly rising prevalence of diabetes. Weight control and blood lipid control are important to decrease the rapidly increasing prevalence of diabetes in Guangxi, an ethnic minority region.