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1.
BMC Health Serv Res ; 23(1): 455, 2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37158912

RESUMO

BACKGROUND: Long waiting time in hospital leads to patient's low satisfaction. In addition to reducing the actual waiting time (AWT), we can also improve satisfaction by adjusting the expected waiting time (EWT). Then how much can the EWT be adjusted to attribute a higher satisfaction? METHODS: This study was conducted though experimental with hypothetical scenarios. A total of 303 patients who were treated by the same doctor from August 2021 to April 2022 voluntarily participated in this study. The patients were randomly divided into six groups: a control group (n = 52) and five experimental groups (n = 245). In the control group, the patients were asked their satisfaction degree regarding a communicated EWT (T0) and AWT (Ta) under a hypothetical situation. In the experimental groups, in addition to the same T0 and Ta as the control group, the patients were also asked about their satisfaction degree with the extended communicated EWT (T1). Patients in five experimental groups were given T1 values with 70, 80, 90, 100, and 110 min respectively. Patients in both control and experiment groups were asked to indicate their initial EWT, after given unfavorable information (UI) in a hypothetical situation, the experiment groups were asked to indicate their extended EWT. Each participant only participated in filling out one hypothetical scenario. 297 valid hypothetical scenarios were obtained from the 303 hypothetical scenarios given. RESULTS: The experimental groups had significant differences between the initial indicated EWT and extended indicated EWT under the effect of UI (20 [10, 30] vs. 30 [10, 50], Z = -4.086, P < 0.001). There was no significant difference in gender, age, education level and hospital visit history (χ2 = 3.198, P = 0.270; χ2 = 2.177, P = 0.903; χ2 = 3.988, P = 0.678; χ2 = 3.979, P = 0.264) in extended indicated EWT. As for patient's satisfaction, compared with the control group, significant differences were found when T1 = 80 min (χ2 = 13.511, P = 0.004), T1 = 90 min (χ2 = 12.207, P = 0.007) and T1 = 100 min (χ2 = 12.941, P = 0.005). When T1 = 90 min, which is equal to the Ta, 69.4% (34/49) of the patients felt "very satisfied", this proportion is not only significantly higher than that of the control group (34/ 49 vs. 19/52, χ2 = 10.916, P = 0.001), but also the highest among all groups. When T1 = 100 min (10 min longer than Ta), 62.5% (30/48) of the patients felt "very satisfied", it is significantly higher than that of the control group (30/ 48 vs. 19/52, χ2 = 6.732, P = 0.009). When T1 = 80 min (10 min shorter than Ta), 64.8% (35/54) of the patients felt "satisfied", it is significantly higher than that of the control group (35/ 54 vs. 17/52, χ2 = 10.938, P = 0.001). However, no significant difference was found when T1 = 70 min (χ2 = 7.747, P = 0.052) and T1 = 110 min (χ2 = 4.382, P = 0.223). CONCLUSIONS: Providing UI prompts can extend the EWT. When the extended EWT is closer to the AWT, the patient's satisfaction level can be improved higher. Therefore, medical institutions can adjust the EWT of patient's through UI release according to the AWT of hospitals to improve patient's satisfaction.


Assuntos
Satisfação do Paciente , Listas de Espera , Humanos , Grupos Controle , Escolaridade , Satisfação Pessoal
2.
Zhongguo Zhong Yao Za Zhi ; 48(17): 4598-4609, 2023 Sep.
Artigo em Zh | MEDLINE | ID: mdl-37802799

RESUMO

Alkaloids are important active ingredients occurring in many traditional Chinese medicines, and alkaloid glycosides are one of their existence forms. The introduction of saccharide units improves the water solubility of alkaloid glycosides thus presenting better biological activity.Because of the low content in plants, alkaloid glycosides have been not comprehensively studied. In this study, ultrahigh performance liquid chromatography-quadrupole time of flight-tandem mass spectrometry(UPLC-QTOF-MS/MS) was employed to identify and analyze the alkaloid glycosides in Coptis chinensis, Phellodendron chinense, Menispermum dauricum, Sinomenium acutum, Tinospora sagittata and Stephania tetrandra. The results showed that except Tinospora sagittata, the other five herbal medicines contained alkaloid glycosides. Furthermore, the alkaloid glycosides in each herbal medicine were identified based on UV absorption spectra, quasimolecular ion peaks in MS, fragment ions information in the MS/MS, and previous literature reports. A total of 42 alkaloid glycosides were identified. More alkaloid glycosides were identified in C. chinensis and Menispermum dauricum, and eleven in C. chinensis were potential new compounds. Furthermore, the alkaloid glycosides in the water extract of C. chinensis were coarsely se-parated by macroporous adsorption resin, purified by column chromatography with D151 cation exchange resin, ODS and MCI, combined with semi-preparative high performance liquid chromatography. Two new alkaloid glycosides were obtained, and their structures were identified by mass spectrometry and NMR data as(S)-7-hydroxy-1-(p-hydroxybenzyl)-2,2-N,N-dimethyl-1,2,3,4-tetrahydroisoquinoline-6-O-ß-D-glucopyranoside and(S)-N-methyltetrahydropalmatubine-9-O-ß-D-glucopyranoside, respectively. This study is of great significance for enriching the information about the chemical composition and the in-depth development of C. chinensis. Meanwhile, it can provide a reference for rapid identification and isolation of alkaloid glycosides from other Chinese herbal medicines.


Assuntos
Alcaloides , Antineoplásicos , Coptis , Medicamentos de Ervas Chinesas , Plantas Medicinais , Glicosídeos/química , Medicina Tradicional Chinesa , Espectrometria de Massas em Tandem/métodos , Coptis chinensis , Medicamentos de Ervas Chinesas/química , Alcaloides/análise , Extratos Vegetais/química , Plantas Medicinais/química , Água , Cromatografia Líquida de Alta Pressão/métodos , Coptis/química
3.
Zhongguo Zhong Yao Za Zhi ; 48(19): 5235-5243, 2023 Oct.
Artigo em Zh | MEDLINE | ID: mdl-38114112

RESUMO

The aim of this study is to investigate the effects of Gynostemma pentaphyllum dried with two different methods(air drying and heating) on inflammation in acute lung injury(ALI) mice in vivo and in vitro. Lipopolysaccharide(LPS) was sprayed into the airway of wild type C57BL/6J male mice to establish the model, and the drug was injected into the tail vein 24 h after modeling. Lung function, lung tissue wet/dry weight(W/D) ratio, the total protein concentration, interleukin 6(IL-6), IL-1ß, and tumor necrosis factor-α(TNF-α) in the bronchoalveolar lavage fluid(BALF), and pathological changes of the lung tissue were used to evaluate the effects of different gypenosides on ALI mice. The results showed that total gypenosides(YGGPs) and the gypenosides substituted with one or two glycosyl(GPs_(1-2)) in the air-dried sample improved the lung function, significantly lowered the levels of IL-1ß and TNF-α in BALF, and alleviated the lung inflammation of ALI mice. Moreover, GPs_(1-2) had a more significant effect on inhibiting NO release in RAW264.7 cells. This study showed that different drying methods affected the anti-inflammatory activity of G. pentaphyllum, and the rare saponins in the air-dried sample without heating had better anti-inflammatory activity.


Assuntos
Gynostemma , Fator de Necrose Tumoral alfa , Masculino , Camundongos , Animais , Fator de Necrose Tumoral alfa/metabolismo , Camundongos Endogâmicos C57BL , Pulmão , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/metabolismo , Interleucina-6/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Lipopolissacarídeos/farmacologia
4.
Glycobiology ; 32(2): 101-109, 2022 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-34939084

RESUMO

O-GlcNAcylation is a post-translational modification that links metabolism with signal transduction. High O-GlcNAcylation appears to be a general characteristic of cancer cells. It promotes the invasion, metastasis, proliferation and survival of tumor cells, and alters many metabolic pathways. Glycogen metabolism increases in a wide variety of tumors, suggesting that it is an important aspect of cancer pathophysiology. Herein we focused on the O-GlcNAcylation of liver glycogen phosphorylase (PYGL)-an important catabolism enzyme in the glycogen metabolism pathway. PYGL expressed in both HEK 293T and HCT116 was modified by O-GlcNAc. And both PYGL O-GlcNAcylation and phosphorylation of Ser15 (pSer15) were decreased under glucose and insulin, whereas increased under glucagon and Na2S2O4 (hypoxia) conditions. Then, we identified the major O-GlcNAcylation site to be Ser430, and demonstrated that pSer15 and Ser430 O-GlcNAcylation were mutually reinforced. Lastly, we found that Ser430 O-GlcNAcylation was fundamental for PYGL activity. Thus, O-GlcNAcylation of PYGL positively regulated pSer15 and therefore its enzymatic activity. Our results provided another molecular insight into the intricate post-translational regulation network of PYGL.


Assuntos
N-Acetilglucosaminiltransferases , Neoplasias , Acetilglucosamina/metabolismo , Glucose/metabolismo , Glicogênio/metabolismo , Humanos , N-Acetilglucosaminiltransferases/genética , Fosforilação , Processamento de Proteína Pós-Traducional
5.
Muscle Nerve ; 66(4): 438-446, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35799473

RESUMO

INTRODUCTION/AIMS: Hereditary transthyretin-mediated amyloidosis with polyneuropathy (hATTR-PN) progressively affects patients' functionality and compromises health-related quality of life (HRQL). The aim of this study was to quantify the projected long-term treatment effects of inotersen vs placebo on HRQL measures. METHODS: The inotersen phase 2/3 randomized, double-blind, placebo-controlled trial NEURO-TTR (NCT01737398, 65 weeks) and its subsequent open-label extension (OLE; NCT02175004, 104 weeks) included 172 (112 inotersen and 60 placebo) patients. Placebo double-blind period and overall inotersen-inotersen (double-blind/OLE) treatment period (170 weeks) data were used to extrapolate the long-term placebo-placebo effect using mixed-effects models with repeated measures. Changes from baseline in the Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) and 36-Item Short Form Health Survey version 2 (SF-36v2) in hATTR-PN were estimated. Differences in changes were compared between the inotersen-inotersen and extrapolated placebo-placebo arms. RESULTS: Inotersen-inotersen patients maintained their HRQL with an observed change ranging from 10.3% improvement (Norfolk QoL-DN item "Pain kept you awake at night") to 11.6% deterioration (SF-36v2 Activities of Daily Living subdomain). The extrapolated placebo-placebo results suggest greater deterioration over time compared with inotersen-inotersen treatment on Norfolk QoL-DN total score (23.6; 95% confidence interval [CI], 8.9-38.3; P < .01), Activities of Daily Living (4.6; 95% CI, 2.0-7.3; P < .001), and "Pain kept you awake at night" (1.2; 95% CI, 0.4-1.9; P < .01). Similarly, greater deterioration was expected for the SF-36v2 Physical Component Summary (8.0; 95% CI, 3.2-12.8, P < .01), Bodily Pain (7.8; 95% CI, 2.0-13.5; P < .01), and Physical Functioning (10.6; 95% CI, 5.5-15.6; P < .0001). DISCUSSION: Long-term (>3 years) inotersen treatment was associated with slowing and, in some domains, halting of deterioration in key HRQL outcome measures, particularly physical functioning and pain.


Assuntos
Neuropatias Amiloides Familiares , Neuropatias Diabéticas , Polineuropatias , Atividades Cotidianas , Neuropatias Amiloides Familiares/complicações , Neuropatias Amiloides Familiares/tratamento farmacológico , Neuropatias Diabéticas/complicações , Humanos , Oligonucleotídeos , Dor/complicações , Polineuropatias/complicações , Polineuropatias/tratamento farmacológico , Pré-Albumina/uso terapêutico , Qualidade de Vida
6.
Zhongguo Zhong Yao Za Zhi ; 47(4): 967-971, 2022 Feb.
Artigo em Zh | MEDLINE | ID: mdl-35285196

RESUMO

A new polyketide, coptaspin A(1), along with two known compounds 4-acetyl-3,4-dihydro-6,8-dihydroxy-3-methoxy-5-methylisocoumarin(2), and cytochalasin Z_(12)(3), was isolated from the endophytic fungi Aspergillus sp. ZJ-58, which was isolated from the genuine medicinal plant Coptis chinensis in Chongqing after solid-state fermentation on rice and silica gel, MCI, and HPLC-based separation. Their structures were elucidated by MS, NMR, IR, UV, and ECD. The newly isolated compound 1 showed moderate inhibitory activities against LPS-induced NO production in RAW264.7 macrophages with the IC_(50) value of 58.7 µmol·L~(-1), suggesting its potential anti-inflammatory activity.


Assuntos
Plantas Medicinais , Policetídeos , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Aspergillus/química , Coptis chinensis , Policetídeos/farmacologia
7.
Zhongguo Zhong Yao Za Zhi ; 47(8): 2165-2169, 2022 Apr.
Artigo em Zh | MEDLINE | ID: mdl-35531732

RESUMO

Two new polyketides, lasobutone A(1) and lasobutone B(2), along with three known compounds, guignardianone C(3), guignardic acid(4), and 4-hydroxy-17R-methylincisterol(5), were isolated from the endophytic fungi Xylaria sp. by silica gel, MCI, and preparative HPLC, which was separated from the Chinese medicinal material Coptis chinensis and cultivated through solid fermentation with rice. Their structures were elucidated on the basis of spectroscopic methods, such as MS, NMR, IR, UV, and ECD. Compounds 2 and 4 showed inhibitory activities against the nitric oxide(NO) production in the LPS-induced macrophage RAW264.7 with IC_(50) values of 58.7 and 42.5 µmol·L~(-1) respectively, while compound 5 exhibited cytotoxic activities against HT-29 with IC_(50) value of 14.3 µmol·L~(-1).


Assuntos
Antineoplásicos , Policetídeos , Coptis chinensis , Endófitos/química , Fungos , Policetídeos/química
8.
Zhongguo Zhong Yao Za Zhi ; 47(5): 1286-1292, 2022 Mar.
Artigo em Zh | MEDLINE | ID: mdl-35343156

RESUMO

This study discovered that the resolution of 3,5-O-dicaffeoylquinic acid(isochlorogenic acid A) in the content determination method of Chrysanthemi Flos in Chinese Pharmacopoeia(ChP)(2020 edition) was poor, which affected accurate quantification. We tested the method in ChP with chromatographic columns of seven brands to clarify the problems in the existing method, optimized the chromatographic conditions by adjusting the mobile phase composition and elution ratio and replacing the chromatographic column packing, and carried out the reproducibility assay for the new method. The two methods were compared for the content determination results of Chrysanthemi Flos prepared from six different varieties. As evaluated by the resolution based on different chromatographic columns of seven brands, the existing method failed to separate isochlorogenic acid A and isochlorogenic acid D well. The peaks of the two components were not completely separated on three chromatographic columns, and isochlorogenic acid A and isochlorogenic acid D generated a co-effluent peak in the other four columns. Isochlorogenic acid A and isochlorogenic acid D could be completely separated under the optimized chromatographic conditions. The difference in the peak areas of isochlorogenic acid A+isochlorogenic acid D obtained by the optimized method and the method in ChP was not significant, with deviation less than 3.0%, which further proved that the result measured by the method in ChP was the co-effluent of isochlorogenic acid A and isochlorogenic acid D. The optimized method can ensure the accurate quantification of isochlorogenic acid A. The existing content determination method of Chrysanthemi Flos has the problem of poor resolution. It is recommended to revise the chromatographic conditions for the content determination method of Chrysanthemi Flos to improve the resolution of isochlorogenic acid A and ensure its accurate quantification.


Assuntos
Medicamentos de Ervas Chinesas , China , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Flores/química , Reprodutibilidade dos Testes
9.
Zhongguo Zhong Yao Za Zhi ; 47(18): 5022-5031, 2022 Sep.
Artigo em Zh | MEDLINE | ID: mdl-36164912

RESUMO

The saponins in different parts of Gynostemma pentaphyllum were analyzed via UPLC-Q-TOF-MS~E. A total of 46 saponins were identified, and the underground part had 26 saponins more than the aboveground part, most of which were trisaccharide saponins. The rat model of hyperlipidemia was established with high-fat diet. This study explored the lipid-lowering activity of total saponins in the underground part of G. pentaphyllum, so as to provide a theoretical basis for the comprehensive utilization of the underground part of G. pentaphyllum. A total of 99 healthy SD rats were randomly assigned into a blank group, a model group, a positive drug group, an aboveground total saponins group, and low-, medium-, and high-dose underground total saponins groups. Except the blank group, the other groups were fed with high-fat diet for 6 weeks. Then, the blood was collected from the orbital cavity to determine whether the modeling was successful according to the serum levels of total cholesterol(TC) and triglyceride(TG). After intragastric administration of the corresponding agents for 30 continuous days, the physical state of the rats were observed, and the body weight and liver specific gravity were measured. Furthermore, the levels of TC, TG, low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), alanine transaminase(ALT), aspartate transaminase(AST), bilirubin, and total bile acids in serum, as well as the levels of superoxide dismutase(SOD), malondialdehyde(MDA), peroxidase proliferator-activated receptor(PPAR-γ) in the liver tissue, were determined. The pathological changes of liver was observed via HE staining. The results showed that the aboveground total saponins and medium-and high-dose underground total saponins can treat hepatocyte steatosis, lower TC, TG, LDL-C, ALT, AST, total bilirubin, MDA, and PPAR-γ levels, and increase HDL-C and SOD levels in the model rats. The effect tended to be more obvious with the increase in dosage. Therefore, the total saponins in the underground part of G. pentaphyllum have good pharmacological effect of reducing blood lipid, which provides a theoretical basis for the comprehensive utilization of the underground part of G. pentaphyllum.


Assuntos
Gynostemma , Hipolipemiantes , Saponinas , Alanina Transaminase/análise , Animais , Aspartato Aminotransferases/análise , Ácidos e Sais Biliares/sangue , Bilirrubina/sangue , LDL-Colesterol/sangue , Dieta Hiperlipídica/efeitos adversos , Gynostemma/química , Hipolipemiantes/farmacologia , Hipolipemiantes/uso terapêutico , Lipoproteínas HDL/sangue , Fígado/química , Fígado/metabolismo , Malondialdeído/análise , Receptores Ativados por Proliferador de Peroxissomo/análise , Ratos , Ratos Sprague-Dawley , Saponinas/farmacologia , Saponinas/uso terapêutico , Superóxido Dismutase , Triglicerídeos/sangue , Trissacarídeos/farmacologia , Trissacarídeos/uso terapêutico
10.
Zhongguo Zhong Yao Za Zhi ; 47(4): 980-987, 2022 Feb.
Artigo em Zh | MEDLINE | ID: mdl-35285198

RESUMO

The ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS~E) technology was employed to compare the chemical components between the aerial and underground parts of Coptis chinensis samples from different batches. According to the retention time, molecular ion peak, and LC-MS~E fragment information of the reference substances and available literature, we identified a total of 40 components. Thirty-three and 31 compounds were respectively identified in the underground part(taproots) and the aerial part(stems and leaves) of C. chinensis. Among them, 24 compounds, including alkaloids(e.g., berberine and jatrorrhizine) and phenolic acids(e.g., chlorogenic acid, quinic acid, and tanshinol), were common in the two parts. In addition, differential components were also identified, such as magnoline glucoside in the underground part and(±) lariciresionol-4-ß-D-glucopyranoside in the aerial part. The analysis of fragmentation pathways based on spectra of reference substances indicated the differences among samples of different batches. Furthermore, we performed the principal component analysis(PCA) for the peak areas of C. chinensis in different batches. The results showed that the underground part and the aerial part were clearly clustered into two groups, indicating that the chemical components contained in the two parts were different. Furthermore, the results of partial least squares discriminant analysis(PLS-DA) identified 31 differential compounds(VIP value>1) between the underground part and the aerial part, mainly including alkaloids, phenolic acids, lignans, and flavonoids. This study proves that C. chinensis possesses great development potential with multiple available compounds in stems and leaves. Moreover, it sheds light on for the development and utilization of non-medicinal organs of C. chinensis and other Chinese medicinal herbs.


Assuntos
Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão/métodos , Coptis chinensis , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos , Tecnologia
11.
Scand J Immunol ; 93(2): e12992, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33140452

RESUMO

Autophagy is a highly conserved protein degradation pathway that is essential for affecting some autoimmune diseases. Immune thrombocytopenia (ITP) is a common autoimmune disorder, and the complex dysregulation of cellular immunity has been observed; however, the relationship between autophagy-related proteins and immune responses in ITP remains unclear. Using real-time quantitative polymerase chain reaction (RT-PCR), the mRNA expression levels of Beclin-1, SQSTM1/p62 and LC3 were measured in the peripheral blood mononuclear cells (PBMCs) of 20 newly diagnosed patients with active ITP, 16 ITP patients in remission and 21 healthy volunteers. The stained Beclin-1 and SQSTM1/p62 proteins were also observed in the bone marrow of active ITP patients and normal controls by immunofluorescence. SQSTM1/p62 mRNA expression in PBMCs in newly diagnosed patients was significantly decreased. At the same time, Beclin-1 mRNA was increased significantly. During the remission stages, the levels of these autophagy-related proteins were comparable with those observed in healthy controls. Taken together, these results suggest that the aberrant expression of autophagy-related proteins might be involved in the pathogenesis of ITP. Further study of the autophagy pathway may provide a new strategy and direction for the treatment of ITP.


Assuntos
Autofagia/genética , Púrpura Trombocitopênica Idiopática/genética , Trombocitopenia/genética , Adolescente , Adulto , Idoso , Autoimunidade/genética , Proteínas Relacionadas à Autofagia/genética , Proteína Beclina-1/genética , Feminino , Humanos , Leucócitos Mononucleares/fisiologia , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Proteínas de Ligação a RNA/genética , Proteína Sequestossoma-1/genética , Adulto Jovem
12.
Cancer Cell Int ; 21(1): 548, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663331

RESUMO

BACKGROUND: Immune thrombocytopenia (ITP) is an autoimmune haemorrhagic disease whose pathogenesis is associated with bone marrow megakaryocyte maturation disorder and destruction of the haematopoietic stem cell microenvironment. METHODS: In this study, we report the qualitative and quantitative profiles of the ITP proteome. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was conducted to elucidate the protein profiles of clinical bone marrow mononuclear cell (BMMC) samples from ITP patients and healthy donors (controls). Gene Ontology (GO) and Kyoto Encyclopaedia Genes and Genome (KEGG) pathway analyses were performed to annotate the differentially expressed proteins. A protein-protein interaction (PPI) network was constructed with the BLAST online database. Target proteins associated with autophagy were quantitatively identified by parallel reaction monitoring (PRM) analysis. RESULTS: Our approaches showed that the differentially expressed autophagy-related proteins, namely, HSPA8, PARK7, YWHAH, ITGB3 and CSF1R, were changed the most. The protein expression of CSF1R in ITP patients was higher than that in controls, while other autophagy-related proteins were expressed at lower levels in ITP patients than in controls. CONCLUSION: Bioinformatics analysis indicated that disruption of the autophagy pathway is a potential pathological mechanism of ITP. These results can provide a new direction for exploring the molecular mechanism of ITP.

13.
Acta Pharmacol Sin ; 42(10): 1714-1722, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33469196

RESUMO

Lung cancer is one of the leading causes of cancer-related death worldwide. Various therapeutic failed in the effective treatment of the lung cancer due to their limited accumulation and exposure in tumors. In order to promote the chemotherapeutics delivery to lung tumor, we introduced chitosan oligosaccharide (CSO) modification on the liposomes. CSO conjugated Pluronic P123 polymers with different CSO grafting amounts, called as CP50 and CP20, were synthesized and used to prepare CSO modified liposomes (CP50-LSs and CP20-LSs). CP50-LSs and CP20-LSs displayed significantly enhanced cellular uptake in A549 cells in vitro as well as superior tumor accumulation in vivo compared with non-CSO modified liposomes (P-LSs). This phenomenon was related to the increased affinity between CSO modified liposomes and tumor cells following massive adsorption of collagen, which was highly expressed in lung tumors. In the A549 tumor-bearing mouse model, intravenous injection of paclitaxel (PTX)-loaded CP50-LSs every 3 days for 21 days resulted in optimal antitumor therapeutic performance with an inhibition rate of 86.4%. These results reveal that CSO modification provides promising applicability for nanomedicine design in the lung cancer treatment.


Assuntos
Antineoplásicos/uso terapêutico , Quitosana/química , Portadores de Fármacos/química , Lipossomos/química , Neoplasias Pulmonares/tratamento farmacológico , Paclitaxel/uso terapêutico , Células A549 , Animais , Antineoplásicos/química , Quitosana/metabolismo , Portadores de Fármacos/metabolismo , Liberação Controlada de Fármacos , Humanos , Lipossomos/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Oligossacarídeos/química , Oligossacarídeos/metabolismo , Paclitaxel/química
14.
Acta Pharmacol Sin ; 42(5): 832-842, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33824461

RESUMO

Nanomedicine has attracted increasing attention and emerged as a safer and more effective modality in cancer treatment than conventional chemotherapy. In particular, the distinction of tumor microenvironment and normal tissues is often used in stimulus-responsive drug delivery systems for controlled release of therapeutic agents at target sites. In this study, we developed mesoporous silica nanoparticles (MSNs) coated with polyacrylic acid (PAA), and pH-sensitive lipid (PSL) for synergistic delivery and dual-pH-responsive sequential release of arsenic trioxide (ATO) and paclitaxel (PTX) (PL-PMSN-PTX/ATO). Tumor-targeting peptide F56 was used to modify MSNs, which conferred a target-specific delivery to cancer and endothelial cells under neoangiogenesis. PAA- and PSL-coated nanoparticles were characterized by TGA, TEM, FT-IR, and DLS. The drug-loaded nanoparticles displayed a dual-pH-responsive (pHe = 6.5, pHendo = 5.0) and sequential drug release profile. PTX within PSL was preferentially released at pH = 6.5, whereas ATO was mainly released at pH = 5.0. Drug-free carriers showed low cytotoxicity toward MCF-7 cells, but ATO and PTX co-delivered nanoparticles displayed a significant synergistic effect against MCF-7 cells, showing greater cell-cycle arrest in treated cells and more activation of apoptosis-related proteins than free drugs. Furthermore, the extracellular release of PTX caused an expansion of the interstitial space, allowing deeper penetration of the nanoparticles into the tumor mass through a tumor priming effect. As a result, FPL-PMSN-PTX/ATO exhibited improved in vivo circulation time, tumor-targeted delivery, and overall therapeutic efficacy.


Assuntos
Antineoplásicos/uso terapêutico , Trióxido de Arsênio/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Portadores de Fármacos/química , Nanopartículas/química , Paclitaxel/uso terapêutico , Resinas Acrílicas/química , Resinas Acrílicas/farmacocinética , Resinas Acrílicas/toxicidade , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Apoptose/efeitos dos fármacos , Trióxido de Arsênio/farmacocinética , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Cetrimônio/química , Cetrimônio/toxicidade , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Feminino , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Células MCF-7 , Camundongos Endogâmicos ICR , Nanopartículas/toxicidade , Oligopeptídeos/química , Oligopeptídeos/farmacocinética , Oligopeptídeos/toxicidade , Paclitaxel/química , Paclitaxel/farmacocinética , Porosidade , Dióxido de Silício/química , Dióxido de Silício/farmacocinética , Dióxido de Silício/toxicidade , Ensaios Antitumorais Modelo de Xenoenxerto
15.
J Thromb Thrombolysis ; 51(4): 905-914, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33047245

RESUMO

To investigate differences in the expression of plasma proteins in immune thrombocytopenia (ITP) and normal control groups, bone marrow samples were collected from 20 active ITP patients and 20 healthy controls. Quantitative proteomics analysis based on mass spectrometry was used to measure the protein levels and understand the protein networks. We found differentially expressed proteins in ITP patients and healthy controls. Parallel reaction monitoring (PRM), a targeted proteome quantification technique, was used to quantitatively confirm the identified target proteins and verify the proteomics data. In this study, a total of 829 proteins were identified, and the fold-change cut-off was set at 1.5 (patients vs controls); a total of 26 proteins were upregulated, and 69 proteins were downregulated. The bioinformatics analysis indicated that some differentially expressed proteins were associated with apoptosis. KEGG enrichment analysis showed that the apoptosis-related proteins were closely related to the PI3K-Akt signalling pathway. PRM demonstrated that apoptosis-related proteins were significantly decreased in ITP patients, which further confirmed the important effect of apoptosis on ITP pathogenesis. We hypothesised that apoptosis may be closely related to ITP pathogenesis through the PI3K-Akt signalling pathway.


Assuntos
Púrpura Trombocitopênica Idiopática , Trombocitopenia , Humanos , Apoptose , Proteínas de Choque Térmico HSC70 , Integrina beta3 , Peroxirredoxina VI , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt
16.
Zhongguo Zhong Yao Za Zhi ; 46(19): 5005-5014, 2021 Oct.
Artigo em Zh | MEDLINE | ID: mdl-34738395

RESUMO

Based on the textual research on literature, the key information of Wenjing Decoction were tested and identified, and 15 batches of lyophilized powder samples of Wenjing Decoction were prepared. The specific components, including paeoniflorin, glycyrrhizin, ginsenosides(Rg_1, Re and Rb_1), glycyrrhizic acid, and paeonol, were used as indexes to establish the HPLC method for quantitative evaluation, and the content ranges and transfer rates of these components were determined. The results showed that the contents of paeoniflorin, glycyrrhizin, ginsenosides Rg_1 + Re, ginsenoside Rb_1, glycyrrhizic acid, and paeonol in the 15 batches of samples were 0.62%-0.86%, 0.25%-0.76%, 0.14%-0.30%, 0.07%-0.21%, 0.63%-1.16%, and 0.09%-0.25%, respectively, and their transfer rates from the decoction pieces to the reference materials were 14.99%-19.42%, 28.11%-40.93%, 25.92%-61.88%, 25.03%-64.06%, 23.43%-35.53%, and 5.34%-10.44%, respectively. The consistency of the transfer rates between batches indicated that the preparation process was stable. It is suggested that the contents of paeoniflorin, glycyrrhizin, ginsenosides Rg_1 + Re, ginsenoside Rb_1, glycyrrhizic acid, and paeonol in Wenjing Decoction should not be less than 0.52%, 0.35%, 0.15%, 0.10%, 0.63%, and 0.12%, respectively. In this study, we determined the contents and analyzed the quantity transfer process of the index components in Wenjing Decoction, which can provide a basis for the follow-up development of Wenjing Decoction and the quality control of related preparations.


Assuntos
Medicamentos de Ervas Chinesas , Cromatografia Líquida de Alta Pressão , Ácido Glicirrízico , Pós , Controle de Qualidade
17.
Zhongguo Zhong Yao Za Zhi ; 46(12): 2923-2930, 2021 Jun.
Artigo em Zh | MEDLINE | ID: mdl-34467682

RESUMO

The present study determined the quantitative markers of total proanthocyanidins in the purification of the industrial waste Choerospondias axillaris pericarp based on the comparison results of high-performance liquid chromatography(HPLC) and mass spectrometry(MS) and optimized the purification process with two stable procyanidins as markers. The adsorption and desorption of five different macroporous adsorption resins, the static adsorption kinetics curve of NKA-Ⅱ resin, the maximum sample load, and the gradient elution were investigated. The UPLC-Q-TOF-MS/MS was employed for qualitative analysis of the newly-prepared total proanthocyanidins of C. axillaris pericarp. As revealed by the results, NKA-Ⅱ resin displayed strong adsorption and desorption toward total proanthocyanidins. The sample solution(50 mg·mL~(-1)) was prepared from 70% ethanol crude extract of C. axillaris pericarp dissolved in water and 7-fold BV of the sample solution was loaded, followed by static adsorption for 12 h. After 8-fold BV of distilled water and 6-fold BV of 10% ethanol were employed to remove impurities, the solution was eluted with 8-fold BV of 50% ethanol, concentrated, and dried under reduced pressure, and purified total proanthocyanidin powder was therefore obtained. Measured by vanillin-hydrochloric acid method, the purity and transfer rate of total proanthocyanidins were 47.67% and 59.92%, respectively, indicating the feasibi-lity of the optimized process. UPLC-Q-TOF-MS/MS qualitative analysis identified 16 procyanidins in C. axillaris total proanthocyanidins. The optimized purification process is simple in operation and accurate in component identification, and it can be applied to the process investigation of a class of components that are difficult to be separated and purified. It can also provide technical support and research ideas for the comprehensive utilization of industrial waste.


Assuntos
Anacardiaceae , Proantocianidinas , Adsorção , Cromatografia Líquida de Alta Pressão , Extratos Vegetais , Proantocianidinas/análise , Resinas Sintéticas , Espectrometria de Massas em Tandem
18.
Zhongguo Zhong Yao Za Zhi ; 46(6): 1339-1344, 2021 Mar.
Artigo em Zh | MEDLINE | ID: mdl-33787130

RESUMO

Chrysanthemum is widely used as a type of edible flower and also considered as the important materials of many beverages in China. Due to the occurrence of diseases and pests, and the lack of regulations for species, frequency, dose of pesticides in Chrysanthemum, pesticides have become one of the main pollutants in Chrysanthemum. The pesticide residues in Chrysanthemum were detected frequently and worth noting. This paper focused on the types of pesticides, pesticide residue detection techniques, and risk assessment methods for Chrysanthemums on the basis of relevant literatures. The pesticide residues of traditional Chinese medicine are mainly organochlorines, organophosphorus and pyrethroids, and the detection techniques include gas chromatography(GC), liquid chromatography(LC) or both combined with mass spectrometry(MS). With the increasing use of traditional Chinese medicine, Chrysanthemum is widely circulated in the market. Therefore, it is important to understand the current situation of pesticide residues in different varieties of Chrysanthemum, so as to provide theoretical reference for the control of quality and safety of Chrysanthemum and the formulation of the maximum residue limit.


Assuntos
Chrysanthemum , Resíduos de Praguicidas , China , Cromatografia Líquida , Chrysanthemum/genética , Cromatografia Gasosa-Espectrometria de Massas , Resíduos de Praguicidas/análise
19.
Zhongguo Zhong Yao Za Zhi ; 46(2): 391-397, 2021 Jan.
Artigo em Zh | MEDLINE | ID: mdl-33645127

RESUMO

This paper aims to solve the problems of complicated-unstable test solution preparation process and insufficient extraction of the active ingredient astragaloside Ⅳ in the legal method for the determination of astragaloside Ⅳ in Astragali Radix. The continuous single-factor analysis of seven main factors affecting the content of astragaloside Ⅳ was carried out by HPLC-ELSD, and then the pre-paration method of test solution was optimized. This optimized method exhibited excellent performance in precision, repeatability and stability. The average recovery rate of astragaloside Ⅳ was 99.65% with RSD 2.2%. Astragaloside Ⅳ showed a good linearity between the logarithm of peak area and the logarithm of injection quantity in the range of 0.46-9.1 µg(r=0.999 6). The contents of astragaloside Ⅳ in 29 batches of Astragali Radix were determined by the new and the legal methods. The results showed that the average content of astragaloside Ⅳ in these Astragali Radix samples determined by the former method was 1.458 times than that of the latter one, indicating the new method was simple, reliable and more adequate to extract target compound. According to the results, it is suggested to improve the content standard of astragaloside Ⅳ in Astragali Radix in the new edition of Chinese Pharmacopeia.


Assuntos
Astrágalo , Medicamentos de Ervas Chinesas , Saponinas , Triterpenos , Cromatografia Líquida de Alta Pressão , Triterpenos/análise
20.
Acta Pharmacol Sin ; 41(9): 1261, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32081943

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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