RESUMEN
OBJECTIVE: Postoperative delirium (POD) is a common, but severe complication in elderly patients undergoing surgery for colorectal cancer, but the prevalence and potential risk factors for POD were not well established. Therefore, a meta-analysis was preformed to clarify the prevalence and risk factors of POD in patients undergoing surgery for colorectal cancer. METHODS: PubMed, Embase, and the Cochrane Library were systematically searched on August 2019. Studies were included if they reported the prevalence and risk factors of POD in patients undergoing colorectal cancer surgery. The guidelines for critically appraising studies of prevalence or incidence of a health problem were used to assess the quality of included studies. Pooled odds ratios (ORs) for individual risk factors were estimated using the Mantel-Haenszel methods in random effect model. Sensitive analyses based on different inclusion criteria were conducted to explore whether the current meta-analysis was enough credible and robust. RESULTS: Seventeen studies totaling 4472 patients undergoing colorectal cancer surgery were included. The pooled prevalence of POD is 14% (95% CI = 12-17%). Twelve significant risk factors were identified in pooled analysis including older age (OR = 1.10), sex (OR = 1.87), history of psychiatric disease (OR = 6.47), comorbidities (OR = 2.17), prognostic nutritional index (OR = 1.12), physical status (OR = 1.27), American Society of Anesthesiologists Score (ASA Scores) (OR = 1.65), history of alcohol abuse (OR = 2.23), postoperative pain management (OR = 1.91), perioperative blood transfusion (OR = 2.37), cognitive status (OR = 1.91), and lower serum level of albumin (OR = 0.58). CONCLUSIONS: POD is a frequent complication in patients undergoing surgery with colorectal cancer. Several risk factors including history of psychiatric disease, transfusion, comorbidities, male gender, and old age were significant predictors for POD.
Asunto(s)
Neoplasias Colorrectales/cirugía , Delirio/epidemiología , Complicaciones Posoperatorias/epidemiología , Factores de Edad , Alcoholismo/complicaciones , Transfusión Sanguínea , Neoplasias Colorrectales/complicaciones , Comorbilidad , Delirio/etiología , Delirio/prevención & control , Estado de Salud , Humanos , Trastornos Mentales/complicaciones , Estado Nutricional , Complicaciones Posoperatorias/prevención & control , Prevalencia , Factores de Riesgo , Albúmina Sérica/análisis , Factores SexualesRESUMEN
Extracellular matrix (ECM) deposition following reactive oxygen species (ROS) overproduction has a key role in diabetic nephropathy (DN), thus, antioxidant therapy is considered as a promising strategy for treating DN. Here, we investigated the therapeutic effects of AB38b, a novel synthetic α, ß-unsaturated ketone compound, on the oxidative stress (OS) and ECM accumulation in type 2 diabetes mice, and tried to clarify the mechanisms underlying the effects in high glucose (HG, 30 mM)-treated mouse glomerular mesangial cells (GMCs). Type 2 diabetes model was established in mice with high-fat diet feeding combined with streptozocin intraperitoneal administration. The diabetic mice were then treated with AB38b (10, 20, 40 mg· kg-1· d-1, ig) or a positive control drug resveratrol (40 mg· kg-1· d-1, ig) for 8 weeks. We showed that administration of AB38b or resveratrol prevented the increases in malondialdehyde level, lactate dehydrogenase release, and laminin and type IV collagen deposition in the diabetic kidney. Simultaneously, AB38b or resveratrol markedly lowered the level of Keap1, accompanied by evident activation of Nrf2 signaling in the diabetic kidney. The underlying mechanisms of antioxidant effect of AB38b were explored in HG-treated mouse GMCs. AB38b (2.5-10 µM) or resveratrol (10 µM) significantly alleviated OS and ECM accumulation in HG-treated GMCs. Furthermore, AB38b or resveratrol treatment effectively activated Nrf2 signaling by inhibiting Keap1 expression without affecting the interaction between Keap1 and Nrf2. Besides, AB38b treatment effectively suppressed the ubiquitination of Nrf2. Taken together, this study demonstrates that AB38b ameliorates experimental DN through antioxidation and modulation of Keap1/Nrf2 signaling pathway.
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Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Nefropatías Diabéticas/tratamiento farmacológico , Proteína 1 Asociada A ECH Tipo Kelch/antagonistas & inhibidores , Cetonas/farmacología , Morfolinas/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Resveratrol/farmacología , Animales , Células Cultivadas , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Matriz Extracelular/efectos de los fármacos , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Cetonas/química , Masculino , Ratones , Ratones Endogámicos C57BL , Estructura Molecular , Morfolinas/química , Estrés Oxidativo/efectos de los fármacos , Resveratrol/química , Transducción de Señal/efectos de los fármacos , Relación Estructura-ActividadRESUMEN
Herein, a series of lasiokaurin derivatives were designed and synthesized. All the derivatives together with lasiokaurin and oridonin were tested for their antimicrobial and antiproliferative activity. Compound 16 showed the most promising antimicrobial activity with MICs of 2.0 and 1.0 µg/mL against Gram-Positive bacteria S. aureus and B. subtilis, respectively. All the synthetic lasiokaurin derivatives showed better antiproliferative activity than parent compound lasiokaurin 1. Compound 10 exhibited the strongest cytotoxicity with IC50 values of 0.47 and 0.20 µM against MGC-803 and CaEs-17 cells, accordingly. Moreover, it was shown to have potent antitumor activity in vivo in a murine model of MGC-803 gastric cancer. Preliminary SARs were also concluded based on obtained data. The apoptosis-inducing effects of 10 were further investigated using CaEs-17 cells. The results showed that lasiokaurin derivative 10 could induce apoptosis via mitochondria related pathway and arrest CaEs-17 cell cycle at S phase. Compound 10 could also affect apoptosis-related proteins that was up-regulation of CDK2 and down-regulation of ATM and cyclin A1.
Asunto(s)
Antiinfecciosos/farmacología , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Diterpenos/farmacología , Animales , Antiinfecciosos/síntesis química , Antiinfecciosos/química , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Diterpenos/síntesis química , Diterpenos/química , Diterpenos de Tipo Kaurano/farmacología , Regulación hacia Abajo/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Concentración 50 Inhibidora , Ratones , Ratones Endogámicos BALB C , Pruebas de Sensibilidad Microbiana , Puntos de Control de la Fase S del Ciclo Celular/efectos de los fármacos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Calixarene-based compounds are highly effective therapeutic agents against cancer. This study aims to prepare a series of calix [n]arene (n = 4, 6, 8) polyhydroxyamine derivatives (3a-3m) and to study their potential antitumor activities. The single crystal structure of calixs[4]arene derivative 3a was determined through X-ray diffraction. We assessed the ability of the prepared calix [n]arene polyhydroxyamine derivatives to induce cytotoxicity in six cancer cell lines by performing cancer cell growth inhibition assays. Results demonstrated that compounds 3a-3d achieved IC50 values ranging from 1.6 µM to 11.3 µM. Among the different compounds, 3a and 3b exerted the strongest cytotoxic effect in inhibiting the growth of SKOV3 cells. In relation to the underlying mechanisms of cytotoxic effects, cell cycle analysis revealed that the exposure of SKOV3 cells to 3a induced cell cycle arrest in the G0/G1 phase, suggesting a reduction in DNA synthesis. Immunofluorescent staining indicated that the protein expression levels of caspase-3 and p53 in cells significantly increased, whereas that of Bcl-2 was effectively suppressed. Meanwhile, no significant changes in Bax were observed in SKOV3 cells. These results highlight that calixarene 3a can be further studied as a potential anticancer agent.