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1.
Heliyon ; 10(8): e28979, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38628737

RESUMO

The field production profile over the yearly horizon is planned for a balance between economy, security, and sustainability of energy. An optimal drilling schedule is required to achieve the planned production profile with minimized drilling frequency and summation. In this study, we treat each possible production process of each well as a dependent time series and the basic unit. Then we ensemble all of them into a tensor. Based on formulated tensor calculation and Lasso regularization, a linear mathematical optimization model for well drilling schedule was developed. The model is aimed at minimizing production profile error while optimizing drilling frequency and summation. Although the model proposed in this work requires more memory consumption to be solved using a computer, it is assured as a linear model and could be numerically globally solved in a stable and efficient way using gradient descent, avoiding complex nonlinear programming problems. Main input data and parameters involved in the model are analyzed in detail to understand the effects of different production parameters on the drilling schedule and production profile. The proposed model in this work can evaluate the manual drilling schedule and automatically generate an optimized drilling schedule for the gas field, significantly reducing development plan formulation time.

2.
BMC Pulm Med ; 23(1): 87, 2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36927574

RESUMO

BACKGROUND: Massive hemoptysis is a life-threatening condition that requires immediate treatment. This study aimed to retrospectively analyze the outcome of bronchial artery embolization (BAE) for massive hemoptysis, as well as potential factors that may contribute to the recurrence of hemoptysis after BAE. METHODS: A total of 105 patients with massive hemoptysis treated with BAE were analyzed. RESULTS: The immediate control rate of bleeding was 84.8% (67/79); however, during the 36-month follow-up, 45.3% (29 out of 64) of the patients had recurrent hemoptysis after BAE. Comorbidities, pituitary hormone treatment, the angiographic appearance of artery dilation and hypertrophy, and the materials used for BAE were significantly correlated with the success rate of the BAE, while lack of pituitary hormone treatment and existence of arterio-arterial or arteriovenous fistula were risk factors for the recurrence of hemoptysis after BAE. Only a small proportion of patients (9/105, 8.6%) had mild complications after BAE treatment. CONCLUSION: Findings suggest that BAE continues to be an effective treatment for massive hemoptysis in emergency settings. Moreover, the treatment of underlying pulmonary diseases and comorbidities is important to increase BAE's success rate of BAE and decrease the risk of recurrent hemoptysis after BAE.


Assuntos
Embolização Terapêutica , Hemoptise , Humanos , Hemoptise/etiologia , Hemoptise/terapia , Estudos Retrospectivos , Artérias Brônquicas , Recidiva , Fatores de Risco , Embolização Terapêutica/efeitos adversos , Resultado do Tratamento
3.
Phytomedicine ; 104: 154284, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35777121

RESUMO

BACKGROUND: Lonicera rupicola Hook.f.et Thoms (LRH) is used as a customary medicinal herb in Tibetans. And LRH flavonoids have excellent anti-inflammatory and antioxidant pharmacological activities. However, the specific effects of LRH and its mechanism remain unknown, and there is a deficiency of systematic research, leading to the waste of LRH as a medicinal resource. PURPOSE: In this study, in an attempt to rationalize the development and utilization of Tibetan herbal resources, the therapeutic efficacy and the underlying molecular mechanisms of LRH flavonoids on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) were investigated, establishing the favorable basis for the pharmacodynamic material basis of LRH and providing a scientific basis for the discovery of new drugs for the treatment of UC. METHODS: Firstly, ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was used for identification and detection of the flavonoid components of LRH. Meanwhile, their potential targets, biological functions and signaling pathways were predicted with the assistance of network pharmacology analysis. Subsequently, pharmacological efficacy of LRH were evaluated by body weight loss, colon length, disease activity index (DAI), histology observation and the expression levels of inflammatory mediators, messenger RNA (mRNA) and tight junction proteins. Moreover, in the present investigation, we also profiled the gut microbiome via high-throughput sequencing of the V3-V4 region of 16S ribosomal DNA (rDNA) for bacterial community composition and diversity by Illumina MiSeq platforms. Finally, the key regulatory proteins in the PI3K/AKT pathways were measured to investigate their underlying molecular mechanisms. RESULTS: A total of 37 LRH flavonoid components were identified and detected by UPLC-MS/MS, and 12 potential active components were obtained after screening. 137 of their common targets with UC were further predicted. GO and KEGG pathway enrichment analysis and molecular docking experiments demonstrated that LRH flavonoids could interfere with UC through "multi-component-multi-target-multi-pathway". In the animal experiments, LRH flavonoids could significantly attenuate UC as demonstrated by reducing the body weight loss and DAI, restoring colon length, decreasing oxidative stress, and improving the intestinal epithelial cell barrier. The mRNA and proteins expression levels of inflammatory mediators were returned to dynamic balance following LRH flavonoids treatment. 16S rDNA sequence analysis indicated that LRH flavonoids promoted the recovery of gut microbiome. And the PI3K/AKT pathway was significantly suppressed by LRH flavonoids. CONCLUSIONS: LRH flavonoids exhibited multifaceted protective effects against DSS-induced UC in mice through mitigating colon inflammation and oxidative stress, restoring epithelial barrier function, and improving the gut microenvironment potentially through modulation of the PI3K/AKT pathway. This finding demonstrated that LRH flavonoids possessed great potential for becoming an excellent drug for the treatment of UC.


Assuntos
Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Lonicera , Animais , Cromatografia Líquida , Colite/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Colo/patologia , DNA Ribossômico/metabolismo , DNA Ribossômico/farmacologia , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Mediadores da Inflamação/metabolismo , Lonicera/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/metabolismo , Espectrometria de Massas em Tandem , Redução de Peso
4.
Macromol Biosci ; 22(1): e2100302, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34679241

RESUMO

Wound healing process is usually accompanied by infection and the wound dressing loaded with antibiotics is usually used to treat skin wound. However, the intensive use of antibiotics may lead to development of resistance and the antibiotic resistance has become a major global problem. Finding new wound dressing with sustained antibacterial property to overcome the problem of resistance is one of clinical challenge. In this work, phenolic acids in Spenceria ramalana Trimen and sliver nanoparticle incorporated thermoplastic polyurethane nanofibrous membrane (TPU/AgNPs/TPA) are fabricated via electrospinning. The TPU/AgNPs/TPA membrane exhibits excellent physicochemical properties with uniform morphology, good mechanical capacity, and appropriate hydrophilia providing suitable environment for wound healing. Moreover, the TPU/AgNPs/TPA membrane shows mild antioxidant property and exhibits continuous antibacterial activity against Staphylococcus aureus and Escherichia coli especially against drug-resistant E. coli. The antibacterial efficiency is as high as 99% lasting for 36 h. Furthermore, the TPU/AgNPs/TPA membrane used as wound dressing can accelerate wound healing through downregulating TNF-α and IL-1ß and upregulating vascular endothelial growth factor and epidermal growth factor. Therefore, the TPU/AgNPs/TPA membrane presented in this work with good antibacterial activity is an excellent wound dressing and has great potential in wound healing applications to overcome the problem of resistance.


Assuntos
Escherichia coli , Poliuretanos , Antibacterianos/química , Antibacterianos/farmacologia , Bandagens , Poliuretanos/química , Poliuretanos/farmacologia , Fator A de Crescimento do Endotélio Vascular , Cicatrização
5.
ACS Appl Mater Interfaces ; 13(51): 61098-61106, 2021 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-34908396

RESUMO

La0.8Sr0.2Mn0.5Co0.5O3 (LSMC) perovskite anchored with RuOx (LSMC-Ru) is fabricated as a new bifunctional electrocatalyst, with low dosage (2.43 wt %) and high utilization of noble metal Ru. The LSMC-Ru exhibits outstanding bifunctional activity with a low potential gap of 0.72 V between the oxygen evolution reaction (OER) potential at 10 mA cm-2 and the oxygen reduction reaction (ORR) half-wave potential. The strong electronic interaction between RuOx and LSMC is confirmed by both experiments and theoretical calculations. Consequently, the electron-rich Mn centers promote ORR, while the electron-deficient Ru centers facilitate OER. A Zn-air battery using the LSMC-Ru air electrode delivers a peak power density of 159 mW cm-2 and a low charge-discharge potential gap of 0.58 V at 2 mA cm-2. The high round-trip energy efficiency of 60.6% is retained after 300 cycles. This strategy of anchoring a low dosage noble metal catalyst to perovskite can be extended to other systems of noble metal-non-noble metal composite electrocatalysts to achieve both competitive performance and low cost.

6.
Drug Deliv ; 28(1): 2594-2602, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34866536

RESUMO

It is urgently needed to develop novel adjuvants for improving the safety and efficacy of vaccines. Metal-organic frameworks (MOFs), with high surface area, play an important role in drug delivery. With perfect biocompatibility and green preparation process, the γ-cyclodextrin metal-organic framework (γ-CD-MOF) fabricated with cyclodextrin and potassium suitable for antigen delivery. In this study, we modified γ-CD-MOF with span-85 to fabricate the SP-γ-CD-MOF as animal vaccine adjuvants. The ovalbumin (OVA) as the model antigen was encapsulated into particles to investigate the immune response. SP-γ-CD-MOF displayed excellent biocompatibility in vitro and in vivo. After immunization, SP-γ-CD-MOF loaded with OVA could induce high antigen-specific IgG titers and cytokine secretion. Meanwhile, SP-γ-CD-MOF also significantly improved the proliferation of spleen cells and activated and matured the bone marrow dendritic cells (BMDCs). The study showed the potential of SP-γ-CD-MOF in vaccine adjuvants and provided a novel idea for the development of vaccine adjuvants.


Assuntos
Adjuvantes de Vacinas/farmacologia , Estruturas Metalorgânicas/química , Ovalbumina/farmacologia , gama-Ciclodextrinas/química , Adjuvantes de Vacinas/administração & dosagem , Animais , Animais não Endogâmicos , Células da Medula Óssea/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Química Farmacêutica , Citocinas/efeitos dos fármacos , Feminino , Hemólise/efeitos dos fármacos , Imunoglobulina G/efeitos dos fármacos , Camundongos , Ovalbumina/administração & dosagem , Células RAW 264.7 , Distribuição Aleatória , Baço/efeitos dos fármacos
7.
ACS Biomater Sci Eng ; 7(8): 3898-3907, 2021 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-34279078

RESUMO

Skin wounds are usually accompanied by bacterial infections and inflammations, leading to delayed wound healing, which remain a great challenge in clinical treatment. Therefore, it is of great significance to develop wound dressings that inhibit bacterial infections to accelerate wound healing. Herein, we reported the fabrication of inclusion complex (a ß-cyclodextrin covalent organic framework loaded with enrofloxacin and flunixin meglumine)-incorporated electrospun thermoplastic polyurethane fibers (named ENR-FM-COF-TPU) via electrospinning. The obtained ENR-FM-COF-TPU fibrous membrane exhibited excellent physicochemical and biological properties such as uniform and stable morphology, proper hydrophobicity, good water uptake capacity, and admirable biocompatibility, which showed perfect behavior as a wound dressing. In addition, the ENR-FM-COF-TPU membrane achieved a sustained drug release of enrofloxacin and flunixin meglumine and displayed powerful antibacterial activity against Staphylococcus aureus and Escherichia coli with 99% inhibitory efficiency for 50 h. More importantly, the wound healing therapy effect was investigated using a full-thickness skin defect model of mice. It suggested that the ENR-FM-COF-TPU membrane could significantly accelerate and enhance wound healing through downregulating inflammatory cytokines (IL-1ß and TNF-α) and increasing the expression of growth factors (VEGF and EGF). Due to its excellent properties, the ENR-FM-COF-TPU membrane may have promising potential in wound healing applications.


Assuntos
Ciclodextrinas , Estruturas Metalorgânicas , Animais , Antibacterianos/farmacologia , Bandagens , Camundongos , Cicatrização
8.
Front Psychiatry ; 12: 648755, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093269

RESUMO

Background: Medical students are affected by high levels of general anxiety disorder. However, few studies have specifically focused on the applicability of universal anxiety screening tools in this sample. This study was aimed to evaluate the psychometric property of the 7-item Generalized Anxiety Disorder Scale (GAD-7) among Chinese medical university students. Methods: A questionnaire survey was conducted among 1,021 medical postgraduates from six polyclinic hospitals. Internal consistency and convergent validity of the GAD-7 were evaluated. Factor analyses were used to test the construct validity of the scale. An item response theory (IRT) framework was used to estimate the parameters of each item. Multi-group confirmatory analyses and differential item function analyses were used to evaluate the measurement equivalence of the GAD-7 across age, gender, educational status, and residence. Results: Cronbach's α coefficient was 0.93 and the intraclass correlation coefficients ranged from 0.71 to 0.87. The GAD-7 summed score was significantly correlated with measures of depression symptoms, perceived stress, sleep disorders, and life satisfaction. Parallel analysis and confirmatory factor analysis supported the one-factor structure of the GAD-7. Seven items showed appropriate discrimination and difficulty parameters. The GAD-7 showed good measurement equivalence across demographic characteristics. The total test information of the scale was 22.85, but the test information within the range of mild symptoms was relatively low. Conclusions: The GAD-7 has good reliability, validity, and measurement invariance among Chinese medical postgraduate students, but its measurement precision for mild anxiety symptoms is insufficient.

9.
Drug Deliv ; 28(1): 372-379, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33517801

RESUMO

We presented an antibiotic-loaded γ-cyclodextrin metal-organic framework that delivered antibiotics suitable for the treatment of bacterial infections. The γ-cyclodextrin metal-organic framework was developed using γ-cyclodextrin and potassium ion via the ultrasonic method. The antibiotic (florfenicol and enrofloxacin) was primarily encapsulated into the pore structures of γ-CD-MOF, which allowed the sustained release of antibiotics over an extended period of time in vitro and in vivo. Notably, antibiotics-loaded γ-CD-MOF showed much superior activity against bacteria than free antibiotics (lower MIC value) and displayed better long-lasting activity (longer antibacterial time). The antibiotics-loaded γ-CD-MOF showed nontoxic and perfect biocompatibility to mammalian cells and tissues both in vitro and in vivo. These materials thus represent a novel drug-delivery device suitable for antibiotic therapy. This research is of great significance for reducing the generation of bacterial resistance and providing new ideas for the application of γ-CD-MOF.


Assuntos
Ciclodextrinas/farmacologia , Preparações de Ação Retardada/farmacologia , Enrofloxacina/farmacologia , Estruturas Metalorgânicas/farmacologia , Tianfenicol/análogos & derivados , Animais , Disponibilidade Biológica , Linhagem Celular , Sistemas de Liberação de Medicamentos/métodos , Feminino , Camundongos , Coelhos , Solubilidade/efeitos dos fármacos , Tianfenicol/farmacologia , gama-Ciclodextrinas/farmacologia
10.
J Ethnopharmacol ; 267: 113475, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33068653

RESUMO

HEADINGS ETHNOPHARMACOLOGICAL RELEVANCE: Coronary heart disease (CHD) usually refers to myocardial ischemia or myocardial necrosis caused by coronary artery stenosis. GeGen and DanShen (GD) are popular Chinese herbs for the treatment of angina pectoris and myocardial infarction (MI). This sentence needs to be a separate paragraph. AIM OF THE STUDY: This study was to investigate the role of GD extract in promoting ischemic myocardial angiogenesis, and to explore its signaling mechanism, so as to provide a more reliable scientific basis for the clinical treatment of ischemic cardiovascular disease. MATERIALS AND METHODS: GD extract was initially analyzed by HPLC-Q-TOF MS. In vitro, migration assay and tube formation assay were subsequently used to detect the angiogenesis activity of GD extract in human umbilical vein endothelial cells (HUVECs). Following the in vitro study, an MI rat model was established by ligating the left anterior descending coronary artery (LAD), immediately followed by a 4-week daily GD extract treatment by intragastric administration. After the animal sacrifice, hematoxylin-eosin (HE) staining was conducted to observe the pathological changes of the infarct margin. Besides, the MI area was measured by 2,3,5-triphenyltetrazoliumchloride (TTC) staining. The microvascular density (MVD) was also quantified through CD31 immunohistochemistry. Moreover, the levels of VEGF, TXB2 and 6-keto-PGF1α in serum were detected by enzyme-linked immunosorbent assay. The expression of VEGFR2 and ERK were detected by immunohistochemistry as well. RESULTS: In vitro study, GD extract was found to induce significant angiogenesis in HUVECs. In vivo, smaller infarct size was found in treatment groups than that of the model group, and the protein expression of VEGFR2 as well as ERK in the marginal zone of MI in treatment groups were significantly increased. The morphological changes of myocardium were observed with a significant growth in the number of new blood vessels. Regarding the effect of GD extract, the serum levels of CK, LDH and TXB2 were consequently reduced, whereas the levels of VEGF, 6-keto-PGF1α were significantly increased. CONCLUSIONS: Based on the findings of this study, GD extract had a protective effect against MI in rats. The possible mechanism is to promote angiogenesis by regulating the VEGF/VEGFR2 signaling pathway after MI occurrence.


Assuntos
Indutores da Angiogênese/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Infarto do Miocárdio/tratamento farmacológico , Miocárdio/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Animais , Células Cultivadas , Modelos Animais de Doenças , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Masculino , Densidade Microvascular/efeitos dos fármacos , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miocárdio/patologia , Ratos Sprague-Dawley , Transdução de Sinais
11.
J Ethnopharmacol ; 263: 113131, 2020 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-32730879

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Wine-processed Radix scutellariae (RS) is the processed product of RS, which is the dried root of Scutellaria baicalensis Georgi. It is recorded in Chinese traditional formula that wine-processed RS has the effect of anti-migraine, while the effect has not been confirmed and the possible mechanism remains unclear. AIM OF THE STUDY: To verify the anti-migraine effect of wine-processed RS in nitroglycerin (NTG)-induced rats and explore the correlation between compounds dissolution and the pore structure based on fractal theory. MATERIALS AND METHODS: In the validation of pharmacodynamics, the effects of wine-processed RS on migraines were firstly evaluated by observing the number of head-scratching of rats, then investigated by determining the levels of nitric oxide (NO), calcitonin gene-related peptide (CGRP) and the expression of c-Fos in the brain of NTG-induced rat models using ELISA and immunohistochemical assessments. In the correlation study, the stir-frying time of RS was set to 5 min, 10 min and 15 min. The scanning electron microscope (SEM) and mercury intrusion method were used to explore the pore structure and main parameters of the pore structure including pore size distribution, pore volume, porosity, surface area and fractal dimension. The compounds dissolution of total flavonoids and five major components containing baicalein, baicalin, scutellarin, wogonin and wogonoside was determined by UV-Vis spectrophotometry and HPLC separately. RESULTS: The animal experiments had shown that wine-processed RS could significantly reduce the head-scratching times of NTG-induced rat models (p < 0.01) and markedly decrease the levels of NO (p < 0.01), CGRP (p < 0.05) and the expression of c-Fos (p < 0.01) compared with model group. The data indicated that wine-processing would affect the dissolution of compounds by changing the pore structure of RS. The order of positive correlation between pore structure parameters and compounds' dissolution was total surface area > fractal dimension (r > 0) and the order of negative correlation was average pore size > total porosity > total volume (r < 0). Compared with the other sample groups (p < 0.05), the wine-processed RS stir-fried for 10 min had a pore structure which was more favorable for compounds dissolution. CONCLUSIONS: Wine-processing could strengthen the anti-migraine effect of RS by changing the pore structure of RS, which is linked to the dissolution of compounds. The RS stir-fried for 10 min may be more effective in treating migraine.


Assuntos
Transtornos de Enxaqueca/induzido quimicamente , Transtornos de Enxaqueca/prevenção & controle , Nitroglicerina/toxicidade , Extratos Vegetais/uso terapêutico , Scutellaria baicalensis , Vinho , Animais , Fractais , Masculino , Extratos Vegetais/isolamento & purificação , Ratos , Ratos Sprague-Dawley , Solubilidade , Vasodilatadores/toxicidade , Vinho/análise
12.
Phytother Res ; 34(10): 2665-2674, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32281178

RESUMO

PURPOSE: The aim of the study was to investigate the effect of liquiritin on neuroendocrine-immune network in menopausal rat model. METHODS: Liquiritin groups were respectively given liquiritin suspension at the dose of 80, 40, and 20 mg/kg, once a day for continuous 30 days after the removal of bilateral ovaries to induce the menopausal rat model. Behavioral experiments were conducted and the organs were weighed for the viscera index. The content of estradiol (E2 ) and follicle-stimulating hormone (FSH) in the serum and 5-hydroxytryptamine (5-HT) and norepinephrine (NE) in hypothalamus were assayed by enzyme linked immunosorbent assay kits. Morphological changes of uterus and adrenal gland were observed by hematoxylin-eosin (HE) staining and estrogen receptor (ER) expression of uterus and spleen were determined by immunohistochemical staining. RESULTS: For the nervous system, liquiritin relieved menopausal depression and up-regulated the levels of 5-HT and NE in hypothalamus; for the endocrine system, it raised the concentrations of E2 and FSH in serum, relieved the histological changes of uterus and adrenal gland and increased the expression of ER in uterus; for the immune system, it increased the thymus index and the expression of ER in spleen. CONCLUSIONS: Liquiritin improved menopausal syndrome in multiple ways by affecting the neuro-endocrine-immune network.


Assuntos
Flavanonas/uso terapêutico , Glucosídeos/uso terapêutico , Glycyrrhiza/química , Menopausa/efeitos dos fármacos , Sistemas Neurossecretores/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Feminino , Flavanonas/farmacologia , Glucosídeos/farmacologia , Ratos , Ratos Wistar
13.
Int Immunopharmacol ; 83: 106384, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32199350

RESUMO

OBJECTIVE: This study aims to select the most effective anti-Rheumatoid Arthritis (RA) component of flavonoids from Daphne genkwa Sieb. et Zucc. by anti-inflammatory and immunomodulatory effects in vitro, and to elucidate the mechanism. METHODS: The anti-inflammatory and immunomodulatory effects of total flavonoids (TF) and four flavonoid components (genkwanin, hydroxygenkwanin, luteolin and apigenin) were determined by pharmacological approach in LPS-induced RAW 264.7 macrophages and ConA-induced T lymphocytes. Principal component analysis (PCA) was used to obtain the optimal anti-RA component in vitro. Western blot and real-time quantitative PCR (q-PCR) were used to explore the mechanisms. Finally, the in vitro anti-RA effect was verified by human rheumatoid arthritis fibroblast-like synoviocytes (FLSs). RESULTS: TF and four flavonoids significantly reduced the expressions of NO, iNOS, TNF-α, IL-6, IFN-γ and IL-2. PCA showed that genkwanin was the most effective anti-RA component in vitro. Genkwanin inhibited nuclear factor-κB (NF-κB) pathway by decreasing the phosphorylation levels of IKK, IκB and NF-κB, and down-regulated the expressions of iNOS, COX-2 and IL-6 mRNA. Genkwanin also inhibited the abnormal proliferation of FLSs and down-regulated the secretions of NO and IL-6. CONCLUSION: The most effective anti-RA component was genkwanin. Genkwanin exerts anti-RA effect through down-regulating the activation of NF-κB pathway and mRNA expressions of inflammatory mediators, and also by inhibiting the abnormal proliferation of FLSs and its NO and IL-6 secretion levels.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Flavonoides/uso terapêutico , Macrófagos/imunologia , Linfócitos T/imunologia , Animais , Citocinas/metabolismo , Daphne/imunologia , Humanos , Imunomodulação , Mediadores da Inflamação , Lipopolissacarídeos/metabolismo , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7 , Transdução de Sinais
14.
Front Neurol ; 11: 621202, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33633659

RESUMO

Background: Atherosclerotic disease of the internal carotid artery (ICA) is a common reason for ischemic stroke. Computed tomography angiography (CTA) is a common tool for evaluation of internal carotid artery (ICA) stenosis. However, blooming artifacts caused by calcified plaques might lead to overestimation of the stenosis grade. Furthermore, the intracranial ICA is more vulnerable to calcification than other ICA segments. The proposed technique, dual-energy computed tomography (DECT) with a modified three-material decomposition algorithm may facilitate the removal of calcified plaques and thus increase diagnostic accuracy. Objectives: The objective of the study is to assess the accuracy of the modified three-material decomposition algorithm for grading intracranial ICA stenosis after calcified plaque removal, with digital subtraction angiography (DSA) used as a reference standard. Materials and Methods: In total, 41 patients underwent DECT angiography and DSA. The three-material decomposition DECT algorithm for calcium removal was applied. We evaluated 64 instances of calcified stenosis using conventional CTA, the previous non-modified calcium removal DECT technique, the modified DECT algorithm, and DSA. The correlation coefficient (r 2) between the results generated by the modified algorithm and DSA was also calculated. Results: The virtual non-calcium images (VNCa) produced by the previous non-modified calcium removal algorithm were named VNCa 1, and those produced by the modified algorithm were named VNCa 2. The assigned degree of stenosis of VNCa 1 (mean stenosis: 39.33 ± 19.76%) differed significantly from that of conventional CTA images (mean stenosis: 59.03 ± 25.96%; P = 0.001), DSA (13.19 ± 17.12%, P < 0.001). VNCa 1 also significantly differed from VNCa 2 (mean stenosis: 15.35 ± 18.70%, P < 0.001). In addition, there was a significant difference between the degree of stenosis of VNCa 2 and conventional CTA images (P < 0.001). No significant differences were observed between VNCa 2 and DSA (P = 0.076). The correlation coefficient (r 2) between the stenosis degree of the VNCa 2 and DSA images was 0.991. Conclusions: The proposed DECT with a modified three-material decomposition algorithm for calcium removal has high sensitivity for the detection of relevant stenoses, and its results were more strongly correlated with DSA than with those of conventional CTA or the previous non-modified algorithm. Further, it overcomes CTA's previous problem of overestimating the degree of stenosis because of blooming artifacts caused by calcified plaques. It is useful to account for calcified plaques while evaluating carotid stenosis.

15.
Virol Sin ; 33(6): 538-544, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30421112

RESUMO

2',3'-dideoxyguanosine (DoG) has been demonstrated to inhibit duck hepatitis B virus (DHBV) replication in vivo in a duck model of HBV infection. In the current study, the in vitro antiviral effects of DoG on human and animal hepadnaviruses were investigated. Our results showed that DoG effectively inhibited HBV, DHBV, and woodchuck hepatitis virus (WHV) replication in hepatocyte-derived cells in a dose-dependent manner, with 50% effective concentrations (EC50) of 0.3 ± 0.05, 6.82 ± 0.25, and 23.0 ± 1.5 µmol/L, respectively. Similar to other hepadnaviral DNA polymerase inhibitors, DoG did not alter the levels of intracellular viral RNA but induced the accumulation of a less-than-full-length viral RNA species, which was recently demonstrated to be generated by RNase H cleavage of pgRNA. Furthermore, using a transient transfection assay, DoG showed similar antiviral activity against HBV wild-type, 3TC-resistant rtA181V, and adefovir-resistant rtN236T mutants. Our results suggest that DoG has potential as a nucleoside analogue drug with anti-HBV activity.


Assuntos
Antivirais/farmacologia , Didesoxinucleosídeos/farmacologia , Vírus da Hepatite B/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Animais , Linhagem Celular , Vírus da Hepatite B do Pato/efeitos dos fármacos , Vírus da Hepatite B da Marmota/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Hepatócitos/virologia , Humanos , Inibidores da Síntese de Ácido Nucleico/farmacologia , Nucleosídeos/farmacologia , RNA Viral/efeitos dos fármacos
16.
Eur J Pharm Biopharm ; 117: 123-131, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28396278

RESUMO

Curcumin (Cur) is a strong natural antioxidant, who can prevent multiple diseases such as anti-cancer, anti-inflammatory, have a resistance to alzheimer's disease and various malignant diseases. But it has poor oral bioavailability due to its poor aqueous solubility, as well as instability. While its novel derivatives (CB and FE), showed better anti-tumor activity, better anti-oxidant activity and better stability than the original drug (Cur). The aim of this study was to study the intestinal transport of Cur, CB and FE using an in vitro Caco-2 cell monolayer model. The results showed that Cur had a lower permeability coefficient (1.13×10-6±0.11×10-6cm/s) for apical-to-basolated (AP-BL) transport at 25µM, while the transport rate for AP to BL flux of CB (3.18×10-6±0.31×10-6cm/s) and FE (5.28×10-6±0.83×10-6cm/s) were significantly greater than that of Cur. The efflux ratio (ER) value at the concentration of 25µM was 1.31 for Cur, 1.26 for CB and 1.33 for FE, suggesting there was no active efflux involved in the translocation across the Caco-2 cell monolayers for the three compounds. Furthermore, the transport flux of CB and FE was in a concentration dependent manner, suggesting the intestinal transport mechanism in them was passive transport. In summary, the results demonstrated that both the intestinal permeability of CB and FE across Caco-2 cell monolayers was significantly improved compare to Cur. Thus they might show a higher oral bioavailability in vivo, and show the potential application in clinic or nutraceutical.


Assuntos
Permeabilidade da Membrana Celular/fisiologia , Curcumina/química , Curcumina/metabolismo , Absorção Intestinal/fisiologia , Antineoplásicos/química , Antineoplásicos/metabolismo , Transporte Biológico/fisiologia , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Humanos
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