Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo , Microbioma Gastrointestinal/fisiologia , Prevotella/fisiologia , Animais , Linhagem Celular Tumoral , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/microbiologia , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Metabolômica , Camundongos , Compostos Organoplatínicos/uso terapêutico , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Huang-Qin Decoction (HQD) is a classic prescription for diarrhea in Chinese medicine treatment. Recent studies have demonstrated that HQD and its modified formulation PHY906 could ameliorate irinotecan (CPT-11) induced gastrointestinal (GI) toxicity and enhance its anticancer therapeutic efficacy. Nevertheless, which constituents in HQD are effective is still unclear so far. The study aims to screen out the key bioactive components combination from HQD that could enhance the anticancer effect of CPT-11. First, the potential bioactive constituents were obtained through system pharmacology strategy. Then the bioactivity of each constituent was investigated synthetically from the aspects of NCM460 cell migration, TNF-α release of THP-1-derived macrophage and MTT assay in HCT116 cell. The contribution of each constituent in HQD was evaluated using the bioactive index Ei, which taken the content and bioactivity into comprehensive consideration. And then, the most contributing constituents were selected out to form a key-component combination. At last, the bioefficacy of the key-component combination was validated in vitro and in vivo. As a result, a key-component combination (HB4) consisting of four compounds baicalin, baicalein, glycyrrhizic acid and wogonin was screened out. In vitro assessment indicated that HB4 could enhance the effect of CPT-11 on inhibiting cell proliferation and inducing apoptosis in HCT116. Furthermore, the in vivo study confirmed that HB4 and HQD have similar pharmacological activity and could both enhance the antitumor effect of CPT-11 in HCT116 xenograft model. Meanwhile, HB4 could also reduce the CPT-11 induced GI toxicity.
Assuntos
Antineoplásicos/farmacologia , Medicamentos de Ervas Chinesas , Irinotecano/farmacologia , Scutellaria baicalensis , Animais , Apoptose , Proliferação de Células , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Células HCT116 , Humanos , Scutellaria baicalensis/química , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Microplastics (MPs, particle size<5 mm), as a new pollutant, have attracted wide attention in recent years. The distributions of MPs in effluent of a sewage treatment plant (STP) were examined. Surface water, sediment, and freshwater organism samples were taken from the STP discharge outlet in the Lijiang River tributary (S1), the confluence of tributaries and main streams in the Lijiang River (S2), and downstream locations in the Lijiang River (S3). The impact of STP discharge effluent on the characteristics and spatial distribution of MPs pollution in freshwater organisms was studied. The results showed that the freshwater organisms had a probability of uptake of MPs by 94.2%. The mean abundance of MPs in S1 (2.7 n·ind-1) was significantly higher than that of S3 (1.9 n·ind-1, P<0.05). The MPs found in S1 and S3 were mainly <0.10 mm, accounting for 46.0% and 30.5%, respectively. The fiber type of MPs was observed in the body of freshwater organisms. Polyethylene terephthalate was the major polymer form in S1 organisms, while polypropylene was the major polymer form in S3. The effluent discharged from the STP led to the accumulation of MPs in freshwater organisms.