RESUMO
A solvent-controlled regioselective rearrangement reaction of spiroindane-1,3-diones with a leaving group has been developed. In acetonitrile solvent, the spiroindane-1,3-diones 3 were rearranged to provide tritylone alcohols, while 2-benzoylbenzoate ester derivatives were obtained if the reactions were performed in alcohols.
RESUMO
Ocimum gratissimum (O. gratissimum), a medicinal herb with antifungal and antiviral activities, has been found to prevent liver injury and liver fibrosis and induce apoptosis in hepatocellular carcinoma (HCC) cells. In this study, we evaluated the effect of aqueous extracts of O. gratissimum (OGE) on improving the efficacy of chemotherapeutic drugs in HCC cells. Proteomic identification and functional assays were used to uncover the critical molecules responsible for OGE-induced sensitization mechanisms. The antitumor activity of OGE in combination with a chemotherapeutic drug was evaluated in a mouse orthotopic tumor model, and serum biochemical tests were further utilized to validate liver function. OGE sensitized HCC cells to the chemotherapeutic drug cisplatin. Proteomic analysis and Western blotting validation revealed the sensitization effect of OGE, likely achieved through the inhibition of breast cancer type 1 susceptibility protein (BRCA1). Mechanically, OGE treatment resulted in BRCA1 protein instability and increased proteasomal degradation, thereby synergistically increasing cisplatin-induced DNA damage. Moreover, OGE effectively inhibited cell migration and invasion, modulated epithelial-to-mesenchymal transition (EMT), and impaired stemness properties in HCC cells. The combinatorial use of OGE enhanced the efficacy of cisplatin and potentially restored liver function in a mouse orthotopic tumor model. Our findings may provide an alternate approach to improving chemotherapy efficacy in HCC.
Assuntos
Proteína BRCA1 , Carcinoma Hepatocelular , Cisplatino , Neoplasias Hepáticas , Ocimum , Extratos Vegetais , Cisplatino/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Animais , Humanos , Ocimum/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Camundongos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Proteína BRCA1/metabolismo , Proteína BRCA1/genética , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacosRESUMO
Treatment of advanced hepatocellular carcinoma (HCC) has exhibited a poor overall survival rate of only six to ten months, and the urgency of the development of more effective novel agents is ever present. In this line of research, we aimed to investigate the effects and inhibitive mechanisms of aqueous Ocimum gratissimum leaf extract (OGE), the extract of Ocimum gratissimum, which is commonly used as a therapeutic herb for its numerous pharmacological properties, on malignant HCC cells. Our results showed that OGE decreased the cell viability of HCC SK-Hep1 and HA22T cells in a dose-dependent manner (from 400 to 800 µg/mL), while there is little effect on Chang liver cells. Moreover, cell-cycle analysis shows increased Sub-G1 cell count in SK-Hep1 and HA22T cells which is not observed in Chang liver cells. These findings raise suspicion that the OGE-induced cell death may be mediated through proteins that regulate cell cycle and apoptosis in SK-Hep1 and HA22T cells, and further experimentation revealed that OGE treatment resulted in a dose-dependent decrease in caspase 3 and PARP expressions and in CDK4and p-ERK1/2expressions. Moreover, animal tests also exhibited decreased HCC tumor growth by OGE treatment. We therefore suggest that the inhibition of cell viability and tumor growth induced by OGE may be correlated to the alteration of apoptosis-related proteins.
Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Ocimum/química , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Western Blotting , Carcinoma Hepatocelular/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Citometria de Fluxo , Humanos , Neoplasias Hepáticas/metabolismo , Camundongos , Camundongos Nus , Consumo de OxigênioRESUMO
Interleukin-13(IL-13) might play an important role in driving aggregate bronchitic symptoms pathogenesis. However, none of the studies assessed the interaction between air pollutants exposure and IL-13 gene on the risk of aggregate bronchitic symptoms in non-asthma children. To assess the independent and joint effects of the exposure to air pollution and IL-13 haplotypes on the risk of aggregate bronchitic symptoms, we conducted a cross-sectional study and focused on non-asthma children. The study population consisted of 2944 children. The effect of each air pollutant on the risk of aggregate bronchitic symptoms was estimated as odds ratios per interquartile range (IQR) change. In the multiple logistic regressions, adjusted for confounding factors, the risk of chronic phlegm was associated with PM2.5 exposure (aOR, 1.59; 95% CI, 1.07-2.37 per 12.51µg/m3 change), O3 exposure (aOR, 1.54 95% CI, 1.05-2.27 per 8.28ppb change) and SO2 exposure (aOR, 1.19; 95% CI, 1.02-1.39 per 0.98ppb change). Our study further provides the evidence that gene-environment interactions between IL-13 haplotype and O3 exposure on chronic phlegm (95% CI for interaction, 1.01-1.38). Identifying children who are more sensitive to air pollution helps us to provide them an efficient prevention to avoid aggregate bronchitic symptoms.
Assuntos
Poluição do Ar/efeitos adversos , Broncopatias/epidemiologia , Broncopatias/etiologia , Exposição Ambiental/efeitos adversos , Interação Gene-Ambiente , Haplótipos , Interleucina-13/genética , Poluentes Atmosféricos , Criança , Comorbidade , Suscetibilidade a Doenças , Feminino , Frequência do Gene , Humanos , Desequilíbrio de Ligação , Masculino , Razão de Chances , Polimorfismo de Nucleotídeo Único , Vigilância da População , Prevalência , Medição de Risco , Fatores de Risco , Síndrome , Taiwan/epidemiologiaRESUMO
AIMS: This study aimed to develop a family-centered care survey for Chinese adult intensive care units and to establish the survey's psychometric properties. BACKGROUND: Family-centered care (FCC) is widely recognized as an ideal model of care. Few studies have explored FCC perceptions among family members of adult critical care patients in Asian countries, and no Chinese FCC measurement has been developed. METHODS: An English version of the 3-factor family-centered care survey for adult intensive care units (FCCS-AICU) was translated into Chinese using a modified back translation procedure. Based on the literature review, two additional concepts, information and empowerment, were added to the Chinese FCCS-AICU. The psychometric properties of the Chinese FCCS-AICU were determined with 249 family members from a medical center in Taiwan and were tested for construct and convergent validity, and internal consistency. RESULTS: Both the monolingual and bilingual equivalence tests of the English and Chinese versions of the 3-factor FCCS-AICU were supported. Exploratory factor analysis supported the 5-factor structure of the Chinese FCCS-AICU with a total explained variance of 58.34%. The Chinese FCCS-AICU was correlated with the Chinese Critical Care Family Needs Inventory. Internal consistency, determined by Cronbach's α, for the overall scale was .94. CONCLUSIONS: The Chinese FCCS-AICU is a valid and reliable tool for measuring perceptions of FCC by family members of adult intensive care patients within Chinese-speaking communities.
Assuntos
Enfermagem de Cuidados Críticos/métodos , Família , Assistência ao Paciente/métodos , Adolescente , Adulto , Idoso , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Adulto JovemRESUMO
Chitosan (C), alginate-crosslinked chitosan (CA), and pectin-crosslinked chitosan (CP) were covalently bonded to Ti-6Al-4V surfaces and tested for their biocompatibility. Compared to the clinically treated Ti-6Al-4V surface (Ti64), C, CA, and CP, had higher contact angles and promoted higher cell proliferation, type I collagen deposition, and mineralization after two weeks (all p<0.05). Cells on C, CA, and CP expressed more alkaline phosphatase (ALP) activity compared to those on Ti64 (p<0.05). The swelling ratios and drug release efficacies of CA and CP were significantly higher and lower, respectively, than those of C (both p<0.05). Only cells on CA expressed ALP activity after three weeks of culture. Generally speaking, crosslinking with alginate and pectin changed surface wettability as well as the swelling and drug release properties of the chitosan coatings. Cells on the coatings had higher proliferation, type I collagen deposition, and degree of mineralization compared to those on Ti64.