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BACKGROUND: Benign prostatic hyperplasia (BPH) is a common condition, yet it is challenging for the average BPH patient to find credible and accurate information about BPH. Our goal is to evaluate and compare the accuracy and reproducibility of large language models (LLMs), including ChatGPT-3.5, ChatGPT-4, and the New Bing Chat in responding to a BPH frequently asked questions (FAQs) questionnaire. METHODS: A total of 45 questions related to BPH were categorized into basic and professional knowledge. Three LLM-ChatGPT-3.5, ChatGPT-4, and New Bing Chat-were utilized to generate responses to these questions. Responses were graded as comprehensive, correct but inadequate, mixed with incorrect/outdated data, or completely incorrect. Reproducibility was assessed by generating two responses for each question. All responses were reviewed and judged by experienced urologists. RESULTS: All three LLMs exhibited high accuracy in generating responses to questions, with accuracy rates ranging from 86.7% to 100%. However, there was no statistically significant difference in response accuracy among the three (p > 0.017 for all comparisons). Additionally, the accuracy of the LLMs' responses to the basic knowledge questions was roughly equivalent to that of the specialized knowledge questions, showing a difference of less than 3.5% (GPT-3.5: 90% vs. 86.7%; GPT-4: 96.7% vs. 95.6%; New Bing: 96.7% vs. 93.3%). Furthermore, all three LLMs demonstrated high reproducibility, with rates ranging from 93.3% to 97.8%. CONCLUSIONS: ChatGPT-3.5, ChatGPT-4, and New Bing Chat offer accurate and reproducible responses to BPH-related questions, establishing them as valuable resources for enhancing health literacy and supporting BPH patients in conjunction with healthcare professionals.
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Hiperplasia Prostática , Humanos , Hiperplasia Prostática/diagnóstico , Masculino , Reprodutibilidade dos Testes , Inquéritos e Questionários , Idioma , Educação de Pacientes como Assunto/métodosRESUMO
Atherosclerosis is a major cause of death and disability in cardiovascular disease. Atherosclerosis associated with lipid accumulation and chronic inflammation leads to plaques formation in arterial walls and luminal stenosis in carotid arteries. Current approaches such as surgery or treatment with statins encounter big challenges in curing atherosclerosis plaque. The infiltration of proinflammatory M1 macrophages plays an essential role in the occurrence and development of atherosclerosis plaque. A recent study shows that TRIM24, an E3 ubiquitin ligase of a Trim family protein, acts as a valve to inhibit the polarization of anti-inflammatory M2 macrophages, and elimination of TRIM24 opens an avenue to achieve the M2 polarization. Proteolysis-targeting chimera (PROTAC) technology has emerged as a novel tool for the selective degradation of targeting proteins. But the low bioavailability and cell specificity of PROTAC reagents hinder their applications in treating atherosclerosis plaque. In this study we constructed a type of bioinspired PROTAC by coating the PROTAC degrader (dTRIM24)-loaded PLGA nanoparticles with M2 macrophage membrane (MELT) for atherosclerosis treatment. MELT was characterized by morphology, size, and stability. MELT displayed enhanced specificity to M1 macrophages as well as acidic-responsive release of dTRIM24. After intravenous administration, MELT showed significantly improved accumulation in atherosclerotic plaque of high fat and high cholesterol diet-fed atherosclerotic (ApoE-/-) mice through binding to M1 macrophages and inducing effective and precise TRIM24 degradation, thus resulting in the polarization of M2 macrophages, which led to great reduction of plaque formation. These results suggest that MELT can be considered a potential therapeutic agent for targeting atherosclerotic plaque and alleviating atherosclerosis progression, providing an effective strategy for targeted atherosclerosis therapy.
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Aterosclerose , Placa Aterosclerótica , Quimera de Direcionamento de Proteólise , Animais , Camundongos , Anti-Inflamatórios/uso terapêutico , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Inflamação/tratamento farmacológico , Macrófagos , Camundongos Endogâmicos C57BL , Placa Aterosclerótica/tratamento farmacológico , Placa Aterosclerótica/metabolismo , Quimera de Direcionamento de Proteólise/farmacologia , Quimera de Direcionamento de Proteólise/uso terapêutico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacologia , Nanopartículas/uso terapêuticoRESUMO
BACKGROUND: The Citrus reticulata 'Chachi' pericarp (CRCP) is one cultivar of Citri Reticulatae Pericarpium (Chenpi), which is widely applied in medicine and food. To determine the potential value of CRCP harvested at different stages and subjected to different drying processes, the dynamic changes in the bioactive components were profiled and evaluated in this study. RESULTS: The contents of all non-volatile components, i.e. synephrine, limonin, phenolic acids and flavonoids, decreased with delayed harvest time. The volatiles thujene, α-pinene, ß-pinene, d-citronellol, d-citronellal, decanal, linalool, geraniol, l-cis-carveol, terpinen-4-ol, α-terpineol, carvacrol, perillaldehyde, methyl 2-(methylamino)benzoate and d-limonene were considered the characteristic components for distinguishing CRCP harvested at different stages. Phenolic acids, synephrine and limonin were stable at different drying temperatures; however, high-temperature drying at 60 °C induced a significant transformation in the flavonoids (especially polymethoxyflavones) and volatile substances in CRCP. CONCLUSIONS: The results suggested that most of the bioactive components declined with the growth of Citrus reticulata 'Chachi'. And it is believed that the fresh peel should be naturally sun-dried or dried at low temperature (30 or 45 °C) rather than at high temperature (60 °C) to prevent excessive loss of nutrients. © 2020 Society of Chemical Industry.
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Citrus/química , Manipulação de Alimentos/métodos , Frutas/crescimento & desenvolvimento , Extratos Vegetais/química , Monoterpenos Acíclicos/análise , Monoterpenos Bicíclicos/análise , Citrus/crescimento & desenvolvimento , Monoterpenos Cicloexânicos/análise , Flavonoides/análise , Frutas/química , TemperaturaRESUMO
BACKGROUNDS: Surgical resection and adjunct chemotherapy or radio-therapy has been applied for the therapy of superficial malignant tumor in clinics. Whereas, there are still some problems limit its clinical use, such as severe pains and side effect. Thus, it is urgent need to develop effective, minimally invasive and low toxicity therapy stagey for superficial malignant tumor. Topical drug administration such as microneedle patches shows the advantages of reduced systemic toxicity and nimble application and, as a result, a great potential to treat superficial tumors. METHODS: In this study, microneedle (MN) patches were fabricated to deliver photosensitizer IR820 and chemotherapy agent cisplatin (CDDP) for synergistic chemo-photodynamic therapy against breast cancer. RESULTS: The MN could be completely inserted into the skin and the compounds carrying tips could be embedded within the target issue for locoregional cancer treatment. The photodynamic therapeutic effects can be precisely controlled and switched on and off on demand simply by adjusting laser. The used base material vinylpyrrolidone-vinyl acetate copolymer (PVPVA) is soluble in both ethanol and water, facilitating the load of both water-soluble and water-insoluble drugs. CONCLUSIONS: Thus, the developed MN patch offers an effective, user-friendly, controllable and low-toxicity option for patients requiring long-term and repeated cancer treatments.
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Neoplasias da Mama/tratamento farmacológico , Cisplatino/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Verde de Indocianina/farmacologia , Fotoquimioterapia/métodos , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Liberação Controlada de Fármacos , Tratamento Farmacológico , Feminino , Humanos , Verde de Indocianina/análogos & derivados , Camundongos Endogâmicos BALB C , Fármacos Fotossensibilizantes/administração & dosagem , Povidona/análogos & derivadosRESUMO
Citrus reticulata semen, a traditional Chinese medicinal material, has desirable medicinal and dietary properties. In this study, a method combining ultra high performance liquid chromatography with Q Exactive Orbitrap tandem mass spectrometry was established and validated for the identification and analysis of the chemical components of C. reticulata semen for the first time. The evaluation of different retention times and fragmentation characteristics, as well as comparative analysis with the literature, resulted in the identification of 35 chemical constituents, including 21 flavonoids and 14 other compounds. The 21 flavonoids derived from C. reticulata semen were reported for the first time. Seven of the chemical components of C. reticulata semen were quantitatively analyzed using the developed method under the optimal conditions. The results showed that the content of limonin, hesperidin, nobiletin, synephrine, tangeretin, 3,5,6,7,8,3',4'-heptamethoxyflavone and 5-hydroxide-6,7,8,3',4'-pentamethoxyflavone in C. reticulata semen was 11.1666, 0.0404, 0.0092, 0.0255, 0.0087, 0.0010, and 0.0008 mg/g, respectively. This study demonstrated that the ultra high performance liquid chromatography Q Exactive Orbitrap mass spectrometry based method can be used to rapidly and reliably analyze the chemical constituents of C. reticulata semen. These results provide a scientific basis for further studies of C. reticulata semen.
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Citrus/química , Flavonas/análise , Flavonoides/análise , Limoninas/análise , Sinefrina/análise , Cromatografia Líquida de Alta Pressão , Estrutura Molecular , Espectrometria de Massas em TandemRESUMO
To systematically identify the lipophilic constituents of Citri Reticulatae Pericarpium from different cultivars, supercritical CO2 fluid extraction and ultra-high-performance liquid chromatography-Q Exactive Orbitrap tandem mass spectrometry were integrated for the component analysis of 18 batches of Citri Reticulatae Pericarpium from 12 cultivars for the first time. A total of 57 components from the supercritical CO2 fluid extracts were demonstrably or tentatively identified by the obtained parent peaks, fragment peaks, and retention times. In total, two flavonoids, six organic acids, nine coumarins, three aldehydes, seven esters, three terpenes, one limonoid, and five other compounds were detected for the first time; notably, coumarin components have not yet been reported in Citri Reticulatae Pericarpium. Furthermore, the extract constituents differed between cultivars. In particular, organic acids were more abundant in Citrus reticulata "Chachi" than in other cultivars, and pterostilbene was exclusively found in Citrus reticulata "Yichangju". The results showed that a greater variety of compounds in Citri Reticulatae Pericarpium could be extracted by supercritical CO2 fluid extraction and detected by ultra-high-performance liquid chromatography-Q Exactive Orbitrap tandem mass spectrometry. This study provides a more scientific basis for further analysis of the pharmacological activity and quality of Citri Reticulatae Pericarpium components from different cultivars.
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Dióxido de Carbono/química , Cromatografia com Fluido Supercrítico , Citrus/química , Aldeídos/análise , Cromatografia Líquida de Alta Pressão , Cumarínicos/análise , Ésteres/análise , Flavonoides/análise , Interações Hidrofóbicas e Hidrofílicas , Limoninas/análise , Espectrometria de Massas em Tandem , Terpenos/análiseRESUMO
A lactoferrin-containing PEGylated liposome system (Lf-PLS) was developed and tested in vitro as a hepatoma-targeting drug delivery system. PEGylated liposomes (PLS) were successfully prepared using the thin film hydration method with peglipid post insertion. Lf was covalently conjugated onto the carboxyl terminal of DSPE-PEG2000-COOH on liposomes. Coumarin-6 was used to trace Lf-PLS with fluorescence. The cellular uptake of this system was carried out in asialoglycoprotein receptor (ASGPR) positive HepG2 cells via confocal microscopy and flow cytometry. The Lf-PLS liposome was observed as spherical or oval vesicles with the particle size around 130 nm, zeta potential about -30 mV and encapsulation efficiency more than 80%. The confocal microscopy images and flow cytometry data demonstrated that Lf-PLS resulted in significantly higher cell association by ASGPR positive HepG2 cells compared to PLS. The association between Lf-PLS and cells were dependent on the concentration, time and temperature, which was inhibited by pre-incubation with excessive free Lf. The results suggest that Lf-PLS has a good targeting effect on HepG2 cells in vitro. The targeting mechanism may be related to the specific binding of Lf and ASGPR on HepG2 cells, which guides Lf-PLS to the cell surface to induce an active endocytosis process. All these results demonstrated that Lf-PLS might be a potential drug delivery system in targeting hepatocellular carcinoma, which deserves more research on its targeting ability, antitumor efficiency, and metabolism in vivo for treatment of hepatomacellular carcinoma.
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Carcinoma Hepatocelular/patologia , Sistemas de Liberação de Medicamentos , Lactoferrina/farmacologia , Lipossomos , Neoplasias Hepáticas/patologia , Receptor de Asialoglicoproteína/metabolismo , Cumarínicos , Endocitose , Células Hep G2/efeitos dos fármacos , Humanos , Tamanho da Partícula , Fosfatidiletanolaminas , Polietilenoglicóis , TiazóisRESUMO
Limonin is a natural tetracyclic triterpenoid compound in citrus seeds that presents hepatoprotective effects but is often discarded as agricultural waste because of its low content and low solubility. Herein, limonin with high purity (98.11%) from citrus seeds was obtained via purification by high-speed counter-current chromatography (HSCCC) and recrystallization. Limonin-loaded liposomes (Lip-LM) prepared by thin film hydration and high pressure homogenization method to enhance its solubility and hepatoprotective effect on APAP-induced liver injury (AILI). Lip-LM appeared as lipid nanoparticles under a transmission electron microscope, and showed well dispersed nano-scale size (69.04 ± 0.42 nm), high encapsulation efficiency (93.67% ± 2.51%), sustained release, fine stability. Lip-LM also exhibited significantly better hepatoprotective activity on AILI than free limonin in vivo. In summary, Lip-LM might be used as a potential hepatoprotective agent in the form of dietary supplement and provide an effective strategy to improve the potential value of citrus seeds.
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Acetaminofen , Doença Hepática Induzida por Substâncias e Drogas , Citrus , Limoninas , Lipossomos , Substâncias Protetoras , Sementes , Limoninas/isolamento & purificação , Limoninas/farmacologia , Citrus/química , Sementes/química , Animais , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Camundongos , Substâncias Protetoras/farmacologia , Substâncias Protetoras/isolamento & purificação , Masculino , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologiaRESUMO
PURPOSE: The importance of structured radiology reports has been fully recognized, as they facilitate efficient data extraction and promote collaboration among healthcare professionals. Our purpose is to assess the accuracy and reproducibility of ChatGPT, a large language model, in generating structured thyroid ultrasound reports. METHODS: This is a retrospective study that includes 184 nodules in 136 thyroid ultrasound reports from 136 patients. ChatGPT-3.5 and ChatGPT-4.0 were used to structure the reports based on ACR-TIRADS guidelines. Two radiologists evaluated the responses for quality, nodule categorization accuracy, and management recommendations. Each text was submitted twice to assess the consistency of the nodule classification and management recommendations. RESULTS: On 136 ultrasound reports from 136 patients (mean age, 52 years ± 12 [SD]; 61 male), ChatGPT-3.5 generated 202 satisfactory structured reports, while ChatGPT-4.0 only produced 69 satisfactory structured reports (74.3 % vs. 25.4 %, odds ratio (OR) = 8.490, 95 %CI: 5.775-12.481, p < 0.001). ChatGPT-4.0 outperformed ChatGPT-3.5 in categorizing thyroid nodules, with an accuracy of 69.3 % compared to 34.5 % (OR = 4.282, 95 %CI: 3.145-5.831, p < 0.001). ChatGPT-4.0 also provided more comprehensive or correct management recommendations than ChatGPT-3.5 (OR = 1.791, 95 %CI: 1.297-2.473, p < 0.001). Finally, ChatGPT-4.0 exhibits higher consistency in categorizing nodules compared to ChatGPT-3.5 (ICC = 0.732 vs. ICC = 0.429), and both exhibited moderate consistency in management recommendations (ICC = 0.549 vs ICC = 0.575). CONCLUSIONS: Our study demonstrates the potential of ChatGPT in transforming free-text thyroid ultrasound reports into structured formats. ChatGPT-3.5 excels in generating structured reports, while ChatGPT-4.0 shows superior accuracy in nodule categorization and management recommendations.
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Sistemas de Informação em Radiologia , Nódulo da Glândula Tireoide , Ultrassonografia , Humanos , Pessoa de Meia-Idade , Masculino , Feminino , Ultrassonografia/métodos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Reprodutibilidade dos Testes , Estudos Retrospectivos , Processamento de Linguagem Natural , Glândula Tireoide/diagnóstico por imagem , AdultoRESUMO
OBJECTIVES: To assess the capabilities of large language models (LLMs), including Open AI (GPT-4.0) and Microsoft Bing (GPT-4), in generating structured reports, the Breast Imaging Reporting and Data System (BI-RADS) categories, and management recommendations from free-text breast ultrasound reports. MATERIALS AND METHODS: In this retrospective study, 100 free-text breast ultrasound reports from patients who underwent surgery between January and May 2023 were gathered. The capabilities of Open AI (GPT-4.0) and Microsoft Bing (GPT-4) to convert these unstructured reports into structured ultrasound reports were studied. The quality of structured reports, BI-RADS categories, and management recommendations generated by GPT-4.0 and Bing were evaluated by senior radiologists based on the guidelines. RESULTS: Open AI (GPT-4.0) was better than Microsoft Bing (GPT-4) in terms of performance in generating structured reports (88% vs. 55%; p < 0.001), giving correct BI-RADS categories (54% vs. 47%; p = 0.013) and providing reasonable management recommendations (81% vs. 63%; p < 0.001). As the ability to predict benign and malignant characteristics, GPT-4.0 performed significantly better than Bing (AUC, 0.9317 vs. 0.8177; p < 0.001), while both performed significantly inferior to senior radiologists (AUC, 0.9763; both p < 0.001). CONCLUSION: This study highlights the potential of LLMs, specifically Open AI (GPT-4.0), in converting unstructured breast ultrasound reports into structured ones, offering accurate diagnoses and providing reasonable recommendations.
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Ultrassonografia Mamária , Humanos , Feminino , Ultrassonografia Mamária/métodos , Estudos Retrospectivos , Neoplasias da Mama/diagnóstico por imagem , Pessoa de Meia-Idade , Adulto , Mama/diagnóstico por imagem , Idoso , Sistemas de Informação em Radiologia , Inteligência ArtificialRESUMO
Cytokine storms characterized by excessive secretion of circulating cytokines and immune-cell hyperactivation are life-threatening systemic inflammatory syndromes. The new strategy is in great demand to inhibit the cytokine storm. Here, we designed a type of magnetically controlled nanorobots (MAGICIAN) by fusing neutrophil membranes onto Fe3O4 nanoparticles (Fe3O4NPs). In our study, the receptors of neutrophil membranes were successfully coated to the surface of Fe3O4NPs. The associated membrane functions of neutrophils were highly preserved. MAGICIAN could in vitro neutralize the inflammatory cytokines including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and interferon γ (IFN-γ). Interestingly, MAGICIAN could be navigated to the liver sites under magnetic control and accelerated the cytokine clearance by the liver. Administration of MAGICIAN could efficiently relieve the inflammation in the acute lung injury mouse model. In addition, MAGICIAN displayed good biosafety in systemic administration. The present study provides a safe and convenient approach for the clearance of cytokine storms, indicating the potential for clinical application in acute lung injury therapy.
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Lesão Pulmonar Aguda , Síndrome da Liberação de Citocina , Camundongos , Animais , Citocinas , Fator de Necrose Tumoral alfa , Lesão Pulmonar Aguda/tratamento farmacológico , Interferon gamaRESUMO
BACKGROUND: Limited data indicated the performance of large language model (LLM) taking on the role of doctors. We aimed to investigate the potential for ChatGPT-3.5 and New Bing Chat acting as doctors using thyroid nodules as an example. METHODS: A total of 145 patients with thyroid nodules were included for generating questions. Each question was entered into chatbot of ChatGPT-3.5 and New Bing Chat five times and five responses were acquired respectively. These responses were compared with answers given by five junior doctors. Responses from five senior doctors were regarded as gold standard. Accuracy and reproducibility of responses from ChatGPT-3.5 and New Bing Chat were evaluated. RESULTS: The accuracy of ChatGPT-3.5 and New Bing Chat in answering Q2, Q3, Q5 were lower than that of junior doctors (all P < 0.05), while both LLMs were comparable to junior doctors when answering Q4 and Q6. In terms of "high reproducibility and accuracy", ChatGPT-3.5 outperformed New Bing Chat in Q1 and Q5 (P < 0.001 and P = 0.008, respectively), but showed no significant difference in Q2, Q3, Q4, and Q6 (P > 0.05 for all). New Bing Chat generated higher accuracy than ChatGPT-3.5 (72.41% vs 58.62%) (P = 0.003) in decision making of thyroid nodules, and both were less accurate than junior doctors (89.66%, P < 0.001 for both). CONCLUSIONS: The exploration of ChatGPT-3.5 and New Bing Chat in the diagnosis and management of thyroid nodules illustrates that LLMs currently demonstrate the potential for medical applications, but do not yet reach the clinical decision-making capacity of doctors.
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Gas chromatograph-mass spectrometer (GC-MS), ultra-high-performance liquid chromatograph-Q-Exactive Orbitrap tandem mass spectrometry (UHPLC-Q-Exactive Orbitrap-MS), and high-performance liquid chromatography-photodiode array detection (HPLC-PDA) were used to qualitatively and quantitatively analyze the chemical component of Citri Reticulatae Pericarpium Viride "Geqingpi" (GQP). First of all, the volatile components of GQP are identified by GC-MS. Totally 56 volatile components were determined, and γ-Terpinene (33.39%) and D-Limonene (22.95%) were the main terpenes. Secondly, UHPLC-Q-Exactive Orbitrap-MS was used for identifying nonvolatile compositions and 42 compositions were identified totally, including 23 flavonoids, nine organic acids, three coumarins, two alkaloids compounds, and five other compounds, among which nine of the determined constituents were detected for the first time in GQP. Thirdly, the content of seven main constituents in GQP was quantitatively analyzed via HPLC-PDA, which were synephrine, hesperidin, limonin, nobiletin, HMF, tangeretin, and 5-HPMF. Further investigation for quantitative analysis of seven bioactive compounds suggested that the concentration of hesperidin in GQP approximately was 16.0% (160.78 ± 0.95 mg·g-1), which was far higher than the standard for identification and quality control of CRPV in Chinese Pharmacopoeia (2020 edition) that "the content of hesperidin shall not be less than 5.0%." The phytochemicals of GQP were elucidated in this study, which might be supporting information for identification between GQP and Citri Reticulatae Pericarpium Viride "Sihuaqingpi" (SHQP) and provided a scientific basis for the further active ingredient for pharmacological research and development prospects of GQP.
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Purpose: APAP-induced liver injury (AILI) is a common cause of acute liver failure (ALF). Nobiletin (NOB) is a potential hepatoprotective agent for the treatment of APAP-induced liver injury. However, the poor solubility and low bioavailability of NOB hinders its application. In this study, a novel self-assembly nano-drug delivery system of nobiletin (solid dispersion of NOB, termed as NOB/SD) was developed based on solid dispersion technology to improve the bioavailability and hepatoprotective ability of NOB for APAP-induced liver injury therapy. Methods: The optimized NOB/SD system was constructed using the amphiphilic copolymers of Soluplus and PVP/VA 64 via hot melt extrusion technology (HME). NOB/SD was characterized by solubility, physical interaction, drug release behavior, and stability. The bioavailability and hepatoprotective effects of NOB/SD were evaluated in vitro and in vivo. Results: NOB/SD maintained NOB in matrix carriers in a stable amorphous state, and self-assembled NOB-loaded nanomicelles in water. Nanostructures based on solid dispersion technology exhibited enhanced solubility, improved release behavior, and promoted cellular uptake and anti-apoptosis in vitro. NOB/SD displayed significantly improved bioavailability in healthy Sprague Dawley (SD) rats in vivo. Furthermore, NOB/SD alleviated the APAP-induced liver injury by improving anti-oxidative stress with reactive oxygen species (ROS) scavenging and nuclear factor erythroid 2-related factor 2 (Nrf2) activation. Conclusion: These results suggested that NOB/SD could be considered as a promising hepatoprotective nano-drug delivery system for attenuating APAP-induced acute liver injury with superior bioavailability and efficient hepatoprotection, which might provide an effective strategy for APAP-induced acute liver injury prevention and treatment.
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Doença Hepática Crônica Induzida por Substâncias e Drogas , Ratos , Animais , Ratos Sprague-Dawley , Sistemas de Liberação de Fármacos por Nanopartículas , PolivinilRESUMO
Ultra-high-performance liquid chromatography-Q-Exactive Orbitrap-mass spectrometry (MS) and gas chromatography (GC)-MS were performed for the qualitative and quantitative analyses of Citri Sarcodactylis Fructus (CSF) from different origins. The contents of eight major CSF components, namely 5,7-dimethoxycoumarin, scopoletin, hesperidin, tangeretin, nobiletin, limonin, nomilin, and stachydrine, were quantitatively analyzed. Clustering analysis and principal component analysis (PCA) were, respectively, performed to classify and compare the 10 CSF batches. One hundred and two volatile components were identified accordingly by comparing retention times, reference standards, parent peaks, fragment peaks, and findings from relevant literature. Moreover, high content of 5,7-dimethoxycoumarin and stachydrine was detected in all the CSFs, especially in CSF-Zhe. Therefore, the high content component coumarin "5,7-dimethoxycoumarin" was suggested to be quality analysis component rather than hesperidin. Additionally, characteristic compounds were found to distinguish different CSFs. This work was a comprehensive study about the components of various CSF. It distinguished the basic differences in the compositions of CSF from different origins. Eventually, it provided experimental and systematic bases for the quality control analysis of CSF, which has potential application in the further research.
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The pericarp of Citrus reticulata "Chachi" (CRCP) is used as nutritional food and traditional medicine in China, usually harvested at three periods, namely, immature (CRCP-G1), semi-mature (CRCP-G2), and fully mature (CRCP-G3). Traditionally, if the CRCP is stored for a longer period, then the quality will be better. In this study, the dynamic variation of phytochemical and volatile compounds was profiled in the same batches of CRCP during 2 years of storage. Results illustrated that most of the phytochemical compounds showed a decreasing trend during storage, that is, total flavonoids, total phenolic acids, hesperidin, 3,5,6,7,8,3',4'-heptamethoxyflavone, 5-hydroxy-6,7,8,3',4'-pentamethoxyflavone, synephrine, and limonin. The ferulic acid increased significantly, whereas no significant changes were observed in the total polymethoxyflavones, nobiletin, and tangeretin after 2 years of storage. In addition, we found that the extraction yield of volatile oil decreased significantly in CRCP-G1 during storage, and the herb odors were enhanced with the increase of phenols and esters. No significant difference in the extraction yield of volatile oil of CRCP-G2 and CRCP-G3 was found after 2 years of storage, but the citrus-like notes were increased with the promoted generation of alkenes. In particular, the multivariate statistical analysis indicated that 7 volatiles showed a higher level after 1 year of storage, whereas 11 volatiles decreased and 4 volatiles increased after 2 years of storage, respectively. This study could show the early aging mechanism of CRCP harvested at different periods and provide a scientific guidance in the storage of CRCP. PRACTICAL APPLICATION: This study indicated a comprehensive method for rapid analysis of phytochemical and volatile compounds in pericarp of Citrus reticulata ''Chachi'' (Rutaceae) (CRCP) harvested at different periods during 2 years of storage. The results obtained from this study would be valuable for revealing the early aging mechanism and sustainable storage of CRCP.
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Citrus , Óleos Voláteis , Rutaceae , Flavonoides , Compostos FitoquímicosRESUMO
In vitro percutaneous delivery of hepatitis B vaccines was investigated in order to assess the penetration of vaccine under passive diffusion and iontophoresis conditions. The study was carried out using Franz vertical diffusion cell through the hairless abdominal skin of Sprague-Dawley (SD) rats. Enzyme-linked immunosorbent assay (ELISA) was used to determine the cumulative amount of permeation and the retention amount of drug in skin. Passive diffusion alone resulted in less skin permeation and retention of hepatitis B vaccines, only (2.1 +/- 0.1) ng x cm(-2) and (2.3 +/- 0.1) ng x cm(-2) after 24 h when the initial concentration of vaccine in the donor compartment was 23 microg x mL(-1) and 46 microg x mL(-1), respectively. After removing the stratum corneum, the permeation and retention amount of hepatitis B vaccines increased to (383.7 +/- 86.2) ng x cm(-2) and (16.8 +/- 4.6) ng x cm(-2), respectively, 171.6-folds and 2.1-folds more than that from its intact skin with the drug loaded at 46 microg x mL(-1). Iontophoresis induced a significant increase of cumulative and retention amount of hepatitis B vaccines through the skin (P < 0.05). Application of iontophoresis significantly enhanced the permeation of hepatitis B vaccines (P < 0.05) by 2.7-folds and 6.6-folds for the intact skin, and by 1.6-folds and 1.8-folds for the tape-stripped skin with initial drug loading of 23 microg x mL(-1) and 46 microg x mL(-1), respectively. Iontophoresis also significantly increased the amount of drug retained in the skin. After applying iontophoresis for 6 h, the amount of skin retention was nearly the same as passive diffusion for 24 h both from intact skin [(16.8 +/- 4.6) ng x cm(-2) vs (13.3 +/- 5.4) ng x cm(-2)] (P > 0.05) and tape-stripped skin [(36.7 +/- 14.1) ng x cm(-2) vs (26.8 +/- 11.2) ng x cm(-2)] (P > 0.05). Overall, these findings revealed that the transportation efficiency of bioactive substance like hepatitis B vaccines may be improved by iontophoresis, which can be potentially used in the field of transcutaneous immunization.
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Vacinas contra Hepatite B/farmacocinética , Iontoforese/métodos , Absorção Cutânea , Administração Cutânea , Animais , Difusão , Ensaio de Imunoadsorção Enzimática , Vacinas contra Hepatite B/administração & dosagem , Técnicas In Vitro , Masculino , Ratos , Ratos Sprague-Dawley , Pele/metabolismoRESUMO
Indocyanine green (ICG), a near-infrared (NIR) fluorescent dye approved by the Food and Drug Administration (FDA), has been extensively used as a photoacoustic (PA) probe for PA imaging. However, its practical application is limited by poor photostability in water, rapid body clearance, and non-specificity. Herein, we fabricated a novel biomimetic nanoprobe by coating ICG-loaded mesoporous silica nanoparticles with the cancer cell membrane (namely, CMI) for PA imaging. This probe exhibited good dispersion, large loading efficiency, good biocompatibility, and homologous targeting ability to Hela cells in vitro. Furthermore, the in vivo and ex vivo PA imaging on Hela tumor-bearing nude mice demonstrated that CMI could accumulate in tumor tissue and display a superior PA imaging efficacy compared with free ICG. All these results demonstrated that CMI might be a promising contrast agent for PA imaging of cervical carcinoma.
RESUMO
Citri Reticulatae Pericarpium, the desiccative mature peel of Citrus reticulata Blanco or its cultivated varieties, is a national geographical indicated product that has the concomitant function of both medicine and foodstuff. The primary source of Citri Reticulatae Pericarpium is Citrus reticulata "Chachi," called "Guang chenpi," while it differs in variety, propagation, grafting rootstock, and tree age, and the hereditary stability of its biological information between intraspecific plants is worthy of our attention. Homologous analysis result of 4 DNA barcodings in the ribosome or the chloroplast showed that the homology of them (ITS2, rbcl, matK, and psbA-trnH) of 22 samples was 100.00%, 99.97%, 99.99%, and 99.81%, respectively, which indicated that 4 DNA barcodes maintained a high degree of genetic stability in Citrus reticulata "Chachi." Also, ITS2 was considered to identify Citrus reticulata "Chachi" from other varieties because it presented not only low variability within a certain taxon but also a high level of interspecies variability. Simultaneously, variant site detection of Citrus reticulata "Chachi" was analyzed by comparing with the reference Citrus reticulata genome, and 2652697 SNP sites and 533906 InDel sites were detected from whole-genome resequencing data of 22 samples, providing the data resources and theoretical foundation for the future study about the relevant molecular makers of "Guang chenpi."
RESUMO
[This corrects the article DOI: 10.1021/acsomega.9b03123.].