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1.
Int J Mol Sci ; 24(7)2023 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-37047220

RESUMO

As the primary site for the biotransformation of drugs, the liver is the most focused on organ type in pharmaceutical research. However, despite being widely used in pharmaceutical research, animal models have inherent species differences, while two-dimensional (2D) liver cell monocultures or co-cultures and three-dimensional (3D) liver cell monoculture in vitro liver models do not sufficiently represent the complexity of the human liver's structure and function, making the evaluation results from these tools less reliable. Therefore, there is a pressing need to develop more representative in vitro liver models for pharmaceutical research. Fortunately, an exciting new development in recent years has been the emergence of 3D liver cell co-culture models. These models hold great promise as in vitro pharmaceutical research tools, because they can reproduce liver structure and function more practically. This review begins by explaining the structure and main cell composition of the liver, before introducing the potential advantages of 3D cell co-culture liver models for pharmaceutical research. We also discuss the main sources of hepatocytes and the 3D cell co-culture methods used in constructing these models. In addition, we explore the applications of 3D cell co-culture liver models with different functional states and suggest prospects for their further development.


Assuntos
Pesquisa Farmacêutica , Animais , Humanos , Técnicas de Cocultura , Fígado , Hepatócitos/metabolismo , Técnicas de Cultura de Células/métodos
2.
J Clin Pharm Ther ; 44(1): 23-38, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30229971

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Sodium cantharidinate has been widely used in lung cancer treatment in China. To investigate whether sodium cantharidinate improves clinical effectiveness in non-small-cell lung cancer, we systematically re-evaluated all related studies. METHODS: All studies of cantharidinate for non-small-cell lung cancers (NSCLC) were selected from the MEDLINE, EMBASE, Web of Science (ISI), China National Knowledge Infrastructure Database (CNKI), Chinese Scientific Journals Full-Text Database (VIP), Wanfang, China Biological Medicine Database (CBM), Cochrane Central Register of Controlled Trials (CENTRAL), Chinese clinical trial registry (Chi-CTR), WHO International Clinical Trials Registry Platform (WHO-ICTRP) and US-clinical trials databases (established to September 2017). Their quality was evaluated using the Cochrane evaluation handbook of randomized controlled trials (RCTs) (5.1.0). The data were extracted following PICO principles and synthesized through meta-analysis. RESULTS AND DISCUSSION: We included 38 trials involving 2845 patients, but most trials had an unclear risk of bias. Sodium cantharidinate could increase the objective response rate (ORR) (1.52, (1.40-1.66]), disease control rate (DCR) (1.20, [1.16-1.25]) and quality of life (QOL) (1.76, [1.56-1.98]), but not the 1-year overall survival (OS) rate (1.16, [0.91-1.47]) and the 2-year OS rate (1.21, [0.51-2.91]). Subgroup analysis revealed that sodium cantharidinate and vitamin B6 at 0.5, 0.4 or 0.3 mg, and cantharidinate at 0.5 mg could all increase the ORR and DCR. Cantharidinate therapy had a lower risk of neutropenia (0.58, [0.50-0.67]), thrombocytopenia (0.57, [0.45-0.72]), gastrointestinal reaction (0.65, [0.52-0.82]) and nausea/vomiting (0.56, [0.41-0.76]) than that of chemotherapy alone. Sensitivity analysis showed that the results had good robustness. WHAT IS NEW AND CONCLUSION: Current evidence reveals that sodium cantharidinate can improve tumour responses and QOL with a lower risk of haematotoxicity and gastrointestinal toxicity than chemotherapy alone in NSCLC. However, the evidence does not indicate that it can improve long-term survival rates.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cantaridina/administração & dosagem , Cantaridina/análogos & derivados , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida , Resultado do Tratamento
3.
Mol Neurobiol ; 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38801630

RESUMO

The pathophysiological regulatory mechanisms in postoperative neurocognitive disorders (PNCDs) are intricately complex. Currently, the pathogenesis of PNCDs has not been fully elucidated. The mechanism involved may include a variety of factors, such as neuroinflammation, oxidative stress, and neuroendocrine dysregulation. Research into the gut microbiota-induced regulations on brain functions is increasingly becoming a focal point of exploration. Emerging evidence has shown that intestinal bacteria may play an essential role in maintaining the homeostasis of various physiological systems and regulating disease occurrence. Recent studies have confirmed the association of the gut-brain axis with central nervous system diseases. However, the regulatory effects of this axis in the pathogenesis of PNCDs remain unclear. Therefore, this paper intends to review the bidirectional signaling and mechanism of the gut-brain axis in PNCDs, summarize the latest research progress, and discuss the possible mechanism of intestinal bacteria affecting nervous system diseases. This review is aimed at providing a scientific reference for predicting the clinical risk of PNCD patients and identifying early diagnostic markers and prevention targets.

4.
World J Gastroenterol ; 30(40): 4393-4398, 2024 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-39494094

RESUMO

Liver diseases pose a significant threat to human health. Although effective therapeutic agents exist for some liver diseases, there remains a critical need for advancements in research to address the gaps in treatment options and improve patient outcomes. This article reviews the assessment of Elafibranor's effects on liver fibrosis and intestinal barrier function in a mouse model of alcoholic liver disease (ALD), as reported by Koizumi et al in the World Journal of Gastroenterology. We summarize the impact and mechanisms of Elafibranor on ALD, metabolic-associated fatty liver disease, and cholestatic liver disease based on current research. We also explore its potential as a dual agonist of PPARα/δ, which is undergoing Phase III clinical trials for metabolic-associated steatohepatitis. Our goal is to stimulate further investigation into Elafibranor's use for preventing and treating these liver diseases and to provide insights for its clinical application.


Assuntos
Butiratos , Modelos Animais de Doenças , Hepatopatias Alcoólicas , Humanos , Animais , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/tratamento farmacológico , Butiratos/uso terapêutico , Butiratos/metabolismo , Camundongos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Colestase/tratamento farmacológico , Colestase/metabolismo , PPAR alfa/agonistas , PPAR alfa/metabolismo , PPAR delta/agonistas , PPAR delta/metabolismo , Resultado do Tratamento , Fígado Gorduroso/tratamento farmacológico , Fígado Gorduroso/metabolismo , Fígado Gorduroso/etiologia , Propionatos , Chalconas
5.
Artigo em Inglês | MEDLINE | ID: mdl-39152884

RESUMO

The efficacy and safety of combining H1 antihistamines (AHs) for treating urticaria are currently unclear. This scoping review aims to provide a comprehensive overview of the evidence regarding the efficacy and safety of H1 AH combinations in the management of urticaria up to May 2023. The search encompassed databases such as PubMed, Web of Science, the Cochrane Central Register of Controlled Trials, and the China Biological Medicine Database. The inclusion criteria comprised randomised controlled trials (RCTs), non-randomised trials (NRTs), case reports, and case series focusing on urticaria treatment. Initially screening 12,887 studies, this review ultimately selected 109 studies involving 11,435 patients. These studies documented 43 different combination treatments across 11 types of urticaria. In comparison to monotherapy, combination therapy exhibited superior efficacy in 94 studies that reported treatment efficacy. Regarding adverse drug reactions (ADRs), 67 studies disclosed ADR incidences, with combination therapy showing lower ADR rates in 32 studies. Additionally, 7 studies reported similar ADR rates between combination therapy and monotherapy with AHs. Common ADRs included symptoms such as drowsiness, nausea, fatigue, dry mouth, dizziness, and headache, while less frequent side effects encompassed hypotension, otitis media, polyuria, rhinorrhoea, abnormal liver function, and rash. ADR rates ranged from 0% to 21% in the treatment group, and from 0.5% to 75% in the control group. Importantly, patients generally tolerated these ADRs well, with symptoms resolving upon discontinuation of treatment. The study's findings suggest that combining AHs leads to enhanced efficacy and reduced safety risks compared to monotherapy in the context of urticaria treatment. These results advocate for considering combination therapy as a viable option in clinical practice, especially for chronic urticaria cases. Nonetheless, caution is advised, and close monitoring for potential ADRs is crucial during treatment.

6.
Exp Ther Med ; 27(5): 217, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38590569

RESUMO

Total saikosaponins (TSS) form a group of chemically and biologically active components that can be extracted from Bupleurum, with reported antidepressive, anti-inflammatory, antiviral, antiendotoxin, antitumor, anti-pulmonary fibrosis and anti-gastric ulcer effects. Bupleurum or TSS is frequently utilized in clinical practice alongside other medications (such as entecavir, lamivudine, compound paracetamol and amantadine hydrochloride capsules), leading to an increased risk of drug-drug interactions. The cytochrome P450 (CYP) family serves a critical role in the metabolism of numerous essential drugs (such as tamoxifen, ibuprofen and phenytoin), where the majority of drug interactions involve CYP-mediated metabolism. It is therefore essential to understand the effects of key components of Bupleurum on CYPs when administering combination therapies containing TSS or Bupleurum. The present study aimed to investigate the effects of TSS on the mRNA and protein expression of CYP3A4 and CYP1A2 in HepaRG cells. The effects of TSS on the survival of HepaRG cells was investigated using the Cell Counting Kit-8 (CCK-8) method. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot (WB) analysis were used to assess the effects of different concentrations of TSS (0, 5, 10 and 15 µg/ml) on CYP3A4 and CYP1A2 mRNA and protein expression in HepaRG cells. Based on the CCK-8 assay results, it was observed that the cell viability remained above 80% when treated with 1, 5, 10 and 15 µg/ml TSS. Although there was a statistically significant reduced cell viability at TSS concentrations of 10 and 15 µg/ml compared with the control group, the findings indicated that TSS did not exhibit notable cytotoxic effects at these concentrations. Furthermore, RT-qPCR results revealed that compared with those in the control group, TSS at concentrations of 10 and 15 µg/ml reduced CYP3A4 mRNA expression but increased CYP1A2 mRNA expression in HepaRG cells at concentrations of 15 µg/ml. WB analysis found that TSS at concentrations of 10 and 15 µg/ml downregulated CYP3A4 protein expression in HepaRG cells while increasing CYP1A2 protein expression at concentrations of 15 µg/ml. Results in the present study suggest that TSS can inhibit CYP3A4 mRNA and protein expression, but exerts opposite effects on their CYP1A2 counterparts. These findings suggest that it is necessary to consider drug interactions between clinical preparations containing TSS or Bupleurum and drugs metabolized by CYP3A4 and CYP1A2 to avoid potential adverse drug reactions in clinical practice.

7.
World J Clin Cases ; 12(19): 3671-3675, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38994317

RESUMO

This editorial provides insights from a case report by Sun et al published in the World Journal of Clinical Cases. The case report focuses on a case where a multilocular thymic cyst (MTC) was misdiagnosed as a thymic tumor, resulting in an unnecessary surgical procedure. Both MTCs and thymic tumors are rare conditions that heavily rely on radiological imaging for accurate diagnosis. However, the similarity in their imaging presentations can lead to misinterpretation, resulting in unnecessary surgical procedures. Due to the ongoing lack of comprehensive knowledge about MTCs and thymic tumors, we offer a summary of diagnostic techniques documented in recent literature and examine potential causes of misdiagnosis. When computer tomography (CT) values surpass 20 Hounsfield units and display comparable morphology, there is a risk of misdiagnosing MTCs as thymic tumors. Employing various differential diagnostic methods like biopsy, molecular biology, multi-slice CT, CT functional imaging, positron emission tomography/CT molecular functional imaging, magnetic resonance imaging and radiomics, proves advantageous in reducing clinical misdiagnosis. A deeper understanding of these conditions requires increased attention and exploration by healthcare providers. Moreover, the continued advancement and utilization of various diagnostic methods are expected to enhance precise diagnoses, provide appropriate treatment options, and improve the quality of life for patients with thymic tumors and MTCs in the future.

8.
World J Clin Cases ; 12(5): 875-879, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38414600

RESUMO

The global spread of severe acute respiratory syndrome coronavirus 2 has resulted in a significant number of individuals developing pulmonary fibrosis (PF), an irreversible lung injury. This condition can manifest within a short interval following the onset of pneumonia symptoms, sometimes even within a few days. While lung transplantation is a potentially lifesaving procedure, its limited availability, high costs, intricate surgeries, and risk of immunological rejection present significant drawbacks. The optimal timing of medication administration for coronavirus disease 2019 (COVID-19)-induced PF remains controversial. Despite this, it is crucial to explore pharmacotherapy interventions, involving early and preventative treatment as well as pharmacotherapy options for advanced-stage PF. Additionally, studies have demonstrated disparities in anti-fibrotic treatment based on race and gender factors. Genetic mutations may also impact therapeutic efficacy. Enhancing research efforts on pharmacotherapy interventions, while considering relevant pharmacological factors and optimizing the timing and dosage of medication administration, will lead to enhanced, personalized, and fair treatment for individuals impacted by COVID-19-related PF. These measures are crucial in lessening the burden of the disease on healthcare systems and improving patients' quality of life.

9.
Patient Prefer Adherence ; 17: 547-555, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36896269

RESUMO

Objective: To investigate the effect of psychological contract of outpatients with hospital pharmacists on medication adherence, providing reference for improving the management of patients' medication adherence from the perspective of pharmacist-patient relationship and psychological contract. Methods: The 8 patients who received medication dispensing service at the outpatient pharmacies at the First Affiliated Hospital of Zunyi Medical University and the Second Affiliated Hospital of Zunyi Medical University were selected for face-to-face in-depth interviews through a purposive sampling method. In order to get more potential information and adjust flexibly according to the actual situation of the interview, the interviews were set as semi-structured, and the interview content was analyzed by using Colaizzi's seven-step method of phenomenological analysis and NVivo11.0 software. Results: The following four themes about effects of patients' psychological contract with hospital pharmacists on medication adherence were extracted: from the perspective of patients, the relationship between pharmacists and patients is generally harmonious; pharmacists can basically fulfil their responsibilities; patients' medication adherence needs to be improved; the status of patients' psychological contract with hospital pharmacists may affect medication adherence. Conclusion: The psychological contract of outpatients with hospital pharmacists has a positive effect on their medication adherence. Effective management on medication adherence should involve the management on patients' psychological contract with hospital pharmacists.

10.
Proc Natl Acad Sci U S A ; 106(13): 5105-10, 2009 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-19289834

RESUMO

How do you design a peptide building block to make 2-dimentional nanowebs and 3-dimensional fibrous mats? This question has not been addressed with peptide self-assembling nanomaterials. This article describes a designed 9-residue peptide, N-Pro-Ser-Phe-Cys-Phe-Lys-Phe-Glu-Pro-C, which creates a strong fishnet-like nanostructure depending on the peptide concentrations and mechanical disruptions. This peptide is intramolecularly amphiphilic because of a single pair of ionic residues, Lys and Glu, at one end and nonionic residues, Phe, Cys, and Phe, at the other end. Circular dichroism and Fourier transform infrared spectroscopy analysis demonstrated that this peptide adopts stable beta-turn and beta-sheet structures and self-assembles into hierarchically arranged supramolecular aggregates in a concentration-dependent fashion, demonstrated by atomic force microscopy and electron microscopy. At high concentrations, the peptide dominantly self-assembled into globular aggregates that were extensively connected with each other to form "beads-on-a-thread" type nanofibers. These long nanofibers were extensively branched and overlapped to form a self-healing peptide hydrogel consisting of >99% water. This peptide can encapsulate the hydrophobic model drug pyrene and slowly release pyrene from coated microcrystals to liposomes. It can effectively stop animal bleeding within 30 s. We proposed a plausible model to interpret the intramolecular amphiphilic self-assembly process and suggest its importance for the future development of new biomaterials for drug delivery and regenerative medicine.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Nanoestruturas/química , Peptídeos/química , Animais , Feminino , Hemorragia/tratamento farmacológico , Lipossomos , Nanoestruturas/uso terapêutico , Peptídeos/uso terapêutico , Estrutura Secundária de Proteína , Pirenos/administração & dosagem , Ratos , Ratos Sprague-Dawley , Tensoativos
11.
Polymers (Basel) ; 14(22)2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36433033

RESUMO

Large bone defects resulting from trauma, infection and tumors are usually difficult for the body's repair mechanisms to heal spontaneously. Generally, various types of bones and orthopedic implants are adopted to enhance bone repair and regeneration in the clinic. Due to the limitations of traditional treatments, bone defect repair is still a compelling challenge for orthopedic surgeons. In recent years, bone tissue engineering has become a potential option for bone repair and regeneration. Amidst the various scaffolds for bone tissue engineering applications, hydrogels are considered a new type of non-toxic, non-irritating and biocompatible materials, which are widely used in the biomedicine field currently. Some studies have demonstrated that hydrogels can provide a three-dimensional network structure similar to a natural extracellular matrix for tissue regeneration and can be used to transport cells, biofactors, nutrients and drugs. Therefore, hydrogels may have the potential to be multifunctional sustained-release drug carriers in the treatment of bone defects. The recent applications of different types of hydrogels in bone defect repair were briefly reviewed in this paper.

12.
Risk Manag Healthc Policy ; 15: 121-131, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35125897

RESUMO

OBJECTIVE: To investigate the current status of knowledge and behavior about rational drug use in college students in different colleges and universities in a city in southwest China, providing reference for students' education of rational drug use in colleges and universities. METHODS: A questionnaire survey on knowledge and behavior in rational drug use was carried out on the students recruited by occasional sampling method in 6 colleges and universities in Zunyi, China. Statistical analyses on demographic information and answers to questionnaire questions were carried out with SPSS 18.0. RESULTS: A total of 865 valid questionnaires were recovered from 923 questionnaires sent out. Some knowledge and behaviors of the students on drug use were irrational. There was statistically significant difference in some specific questions of the knowledge in rational drug use between medical and non-medical students (P<0.05); the average score of rational drug use behavior of medical students was lower than that of non-medical students (P<0.05); the average score of the rational drug use behavior of female students was lower than that of male (P<0.05); the students' major types had significantly different influence on their behavior in rational drug use (P<0.05). The school-carried pharmacy education can effectively improve students' rational medication; the majority of college students believed that it is necessary to popularize the knowledge of rational drug use on campus; and students' favorite way to acquire knowledge about rational drug use was to attend related lectures or elective courses. CONCLUSION: The knowledge and behavior of rational drug use among college students need to be improved. Professional medical education may exert a positive impact on rational drug use among college students. Thus, it is necessary to popularize the knowledge of rational drug use among college students, especially in non-medical colleges and universities.

13.
Polymers (Basel) ; 14(23)2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36501615

RESUMO

Ion-complementary self-assembling peptides have been studied in many fields for their distinct advantages, mainly due to their self-assembly properties. However, their shortcomings, such as insufficient specific activity and poor mechanical properties, also limited their application. For the better and wider application of these promising biomaterials, ion-complementary self-assembling peptides can be modified with their self-assembly properties not being destroyed to the greatest extent. The modification strategies were reviewed by taking RADA16-I as an example. For insufficient specific activity, RADA16-I can be structurally modified with active motifs derived from the active domain of the extracellular matrix or other related active factors. For weak mechanical properties, materials with strong mechanical properties or that can undergo chemical crosslinking were used to mix with RADA16-I to enhance the mechanical properties of RADA16-I. To improve the performance of RADA16-I as drug carriers, appropriate adjustment of the RADA16-I sequence and/or modification of the RADA16-I-related delivery system with polymer materials or specific molecules can be considered to achieve sustained and controlled release of specific drugs or active factors. The modification strategies reviewed in this paper may provide some references for further basic research and clinical application of ion-complementary self-assembling peptides and their derivatives.

14.
Exp Ther Med ; 21(6): 588, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33850560

RESUMO

Xiaochaihu decoction is one of the most important traditional Chinese medicines that is widely used with other drugs in clinical practice, and may cause drug-drug interactions. However, there is not sufficient experimental evidence for the effects of Xiaochaihu decoction on cytochrome P450s (CYPs). The aim of the present study was to investigate the effects of Xiaochaihu decoction on the mRNA and protein levels of hepatic CYPs. Eighty normal male Sprague-Dawley (SD) rats were randomly divided into two groups based on body weight and duration of drug administration (3 and 6 days). Each group was further divided into subgroups: Control group (2 ml 5‰ CMC-Na); hepatic enzyme inducer group (50 mg/kg/day rifampicin); and experimental groups (Xiaochaihu decoction: Low dose, 1.7 g/kg/day; medium dose, 3.4 g/kg/day; high dose, 6.8 g/kg/day). The effects of Xiaochaihu decoction on Cyp1a2, Cyp3a1, Cyp2d6, and Cyp1b1 mRNA and protein expression in rats were evaluated using reverse transcription quantitative reverse transcription polymerase chain reaction and western blot analysis. After 3 days, medium dose of Xiaochaihu decoction inhibited the mRNA and protein expression of Cyp1a2, Cyp3a1 and Cyp1b1. In addition, after 6 days, Xiaochaihu decoction induced Cyp3a1 mRNA expression at low and medium doses; Cyp2d6 mRNA expression at low and high doses; and Cyp2d6 protein expression at high doses. Nonetheless, the gene and protein expression of Cyp1b1 was not affected at any dose. The findings of the present study may provide insights into potential drug-drug interactions associated with Xiaochaihu decoction.

15.
Basic Clin Pharmacol Toxicol ; 128(5): 661-668, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33369126

RESUMO

Saikosaponin-d (SSd) is a major bioactive triterpenoid saponin extracted from Bupleurum, which has anti-inflammatory, anticancer, antioxidative and anti-hepatic fibrosis effects. Due to the effects of Bupleurum-related formulations on cytochrome P450 (CYPs) expression still remain unclear, the combination therapies involved formulations containing Bupleurum may sometimes lead to unexpected drug-drug interactions in clinical practice. These interactions can limit the clinical applications of related formulations. In this study, we tried to explore the effects of SSd on CYP3A4 mRNA, protein expression and the enzyme activity in HepaRG cells by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR), Western blot (WB) and HPLC method, respectively. The interaction between SSd and CYP3A4 was analysed by molecular docking. HepaRG cells were cultured with different concentrations of SSd (0.5, 1, 5 and 10 µmol/L) for 72 hours. It is revealed that SSd can inhibit CYP3A4 mRNA and its protein expression, and also the enzyme activity. Molecular docking study demonstrated that SSd can bind to several key active sites of amino acid residues of CYP3A4 protein with hydrogen bonds and hydrophobic interactions. Thus, drug-drug interactions resulted by SSd inhibiting CYP3A4 need attention when formulations containing SSd or Bupleurum are co-administrated with drugs metabolized by CYP3A4.


Assuntos
Bupleurum/química , Inibidores do Citocromo P-450 CYP3A/farmacologia , Citocromo P-450 CYP3A/metabolismo , Ácido Oleanólico/análogos & derivados , Saponinas/farmacologia , Linhagem Celular Tumoral , Interações Medicamentosas , Humanos , Ligantes , Simulação de Acoplamento Molecular , Ácido Oleanólico/farmacologia
16.
Drug Deliv ; 28(1): 1810-1821, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34470553

RESUMO

Lung cancer is a major cause of cancer-related deaths worldwide. Stimulus-sensitive hydrogels, which can be formed by responding to stimuli in the cancer microenvironment, have been widely studied as controlled-release carriers for hydrophobic anticancer drugs. In this study, self-assembling peptide RADA16-I was used to encapsulate the hydrophobic drug emodin (EM) under magnetic stirring to form a colloidal suspension, and the colloidal suspension (RADA16-I-EM) was introduced into environments with physiological pH/ionic strength to form hydrogels in situ. The results showed that RADA16-I had good cell compatibility and the RADA16-I-EM in situ hydrogels can obviously reduce the toxicity of EM to normal cells. In addition, compared with free EM (in water suspensions without peptide) at equivalent concentrations, RADA16-I-EM in situ hydrogels significantly reduced the survival fraction of LLC lung cancer cells, while increased the uptake of EM by the cells, and it also induced apoptosis and cell cycle arrest in the G2/M phase more significantly and reduced the migration, invasion, and clone abilities of the cells in vitro. The RADA16-I-EM in situ hydrogels also showed better cancer growth inhibition effects in cancer models (mice bearing LLC cells xenograft cancer), which induced cell apoptosis in the cancer tissue and reduced the toxic side effects of EM on normal tissues and organs in vivo compared with the free EM. It was revealed that RADA16-I can be exploited as a promising carrier for hydrophobic anticancer drugs and has the potential to improve the administration of anticancer drugs to treat cancer effectively with enhanced chemotherapy.


Assuntos
Antineoplásicos/farmacologia , Emodina/farmacologia , Hidrogéis/química , Peptídeos/química , Animais , Antineoplásicos/administração & dosagem , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada , Relação Dose-Resposta a Droga , Emodina/administração & dosagem , Concentração de Íons de Hidrogênio , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Suspensões , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Int J Nanomedicine ; 16: 47-60, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33442249

RESUMO

PURPOSE: To study the in vitro and in vivo antitumor effects of the colloidal suspension-in situ hydrogel of emodin (EM) constructed with the self-assembling peptide RADA16-I and systematically evaluate the feasibility of the delivery system. METHODS: The MTT and colony-formation assays were used to determine the viability of normal cells NCTC 1469 and tumor cells Hepa1-6. The uptake of EM in the RADA16-I-EM in situ hydrogel by tumor cells was analyzed by laser confocal microscope and flow cytometry. Flow cytometry was used to detect the cell apoptosis and cell cycle distribution. Transwell assay was used to detect the migration and invasion of tumor cells. The antitumor efficacy of the RADA16-I-EM in situ hydrogel and its toxic effects was further assessed in vivo on Hepa1-6 tumor-bearing C57 mice. RESULTS: The results showed that the RADA16-I-EM in situ hydrogels could obviously reduce the toxicity of EM to normal cells and the survival of tumor cells. The uptake of EM by the cells from the hydrogels was obviously increased and could significantly induce apoptosis and arrest cell cycle in the G2/M phase, and reduce the migration, invasion and clone-formation ability of the cells. The RADA16-I-EM in situ hydrogel could also effectively inhibit the tumor growth and obviously decrease the toxic effects of EM on normal tissues in vivo. CONCLUSION: Our results demonstrated that RADA16-I has the potential to be a carrier for the hydrophobic drug EM and can effectively improve the delivery of hydrophobic antitumor drugs with enhanced antitumor effects and reduced toxic effects of the drugs on normal cells and tissues.


Assuntos
Antineoplásicos/farmacologia , Emodina/farmacologia , Hidrogéis/química , Peptídeos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Endocitose/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Teste de Materiais , Camundongos Endogâmicos C57BL , Invasividade Neoplásica , Coelhos , Suspensões , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Drug Deliv ; 27(1): 460-468, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32166987

RESUMO

The in situ hydrogel drug delivery system is a hot research topic in recent years. Combining both properties of hydrogel and solution, in situ hydrogels can provide many advantages for drug delivery application, including easy application, high local drug concentration, prolonged drug retention time, reduced drug dose in vivo, good biocompatibility and improved patient compliance, thus has potential in tumor treatment. In this paper, the related literature reports in recent years were reviewed to summarize and discuss the research progress and development prospects in the application of in situ hydrogels in tumor treatment.


Assuntos
Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/farmacocinética , Humanos , Hidrogéis , Adesão à Medicação
19.
J Multidiscip Healthc ; 13: 1433-1442, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33173305

RESUMO

OBJECTIVE: To set up a psychological contract scale for hospital pharmacists to strengthen the management of pharmacists and improve the occupational health of pharmacists. METHODS: A psychological contract scale for hospital pharmacists with structured questionnaires was designed according to the professional characteristics of hospital pharmacists and validated through the investigation of pharmacists in 77 public medical institutions in Zunyi, China, which were included through stratified random sampling. Kaiser-Meyer-Olkin (KMO) Measure of Sampling Adequacy and Bartlett's Test of Sphericity were used to assess the suitability of the sample for factor analysis. Validity of the dimensions was investigated with exploratory factor analysis. The principal component analysis and varimax rotation methods were used to identify the factor structure. The internal consistency was assessed by the Cronbach's alpha coefficient. RESULTS: The psychological contract scale for hospital pharmacists was composed of pharmacists' perceptions regarding the hospital, pharmacists themselves, and government/society responsibility. The KMO values of the three perceptions were 0.957, 0.930 and 0.917, respectively, all greater than 0.6. The significance probability of the Bartlett spherical test was 0.000, indicating good structural validity. The Cronbach's alpha coefficient and half coefficient of the responsibilities in three sub-scales were all greater than 0.6, indicating good internal reliability of the scale. The average scores of the pharmacist responsibility, the hospital responsibility and the government/society responsibility in the pharmacists' perception were 5.42±0.637, 4.64±1.069 and 4.49±1.134, respectively. In the pharmacists' perception, their own responsibility has been better fulfilled than those of hospitals and government/society. CONCLUSION: The psychological contract scale for hospital pharmacists can be a useful tool to evaluate the psychological contract of hospital pharmacists for research and occupational health assessments and management in the area of hospital pharmacy.

20.
Patient Prefer Adherence ; 14: 1027-1036, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606619

RESUMO

PURPOSE: Poor medication adherence can negatively affect health outcomes of patients with asthma from medication and significantly increase the healthcare costs. Management of adherence to inhalers remains a challenging topic in the long-term management of patients with asthma. We aim to evaluate the role of asthma control test (ACT) in the management of adherence to inhalers in outpatients with asthma. PATIENTS AND METHODS: Six hundred twenty-seven outpatients with asthma admitted to the clinic of respiratory medicine in a tertiary hospital in northwestern China during 2016 to 2019 were randomly divided into observation group (n= 315) and control (n= 312) and received standard inhalant therapy for 6 months and lung function test before and after treatment. The patients in the observation group took ACT questionnaires at the end of each month, while the patients in control only took an ACT at the end of the last month. The 'Test of Adherence to Inhalers' (TAI) questionnaire was used to evaluate the patients' adherence to inhalant therapy. RESULTS: All patients completed the study. The ACT scores in the observation group showed a gradual increase month by month. The TAI results indicated that adherence to inhalers of patients in the observation group was significantly better than that in control and the patients' non-adherence pattern in the observation group, with significantly lower erratic non-adherence, was also different from that in control. After 6 months of treatment, the lung function indexes and their relative improvement and the ACT scores in the observation group were significantly better or higher than those in control. CONCLUSION: The once-monthly self-reported ACT can effectively improve the adherence to inhalers of outpatients with asthma mainly by addressing erratic non-adherence and improve the treatment effects, and thus deserves widespread use in the treatment adherence management in patients with asthma.

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