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1.
Micromachines (Basel) ; 12(7)2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34357200

RESUMO

The labyrinth screw pump is a new type of low-flow rotor pump with a simple structure and good sealing performance. It is suitable for the transport of high-viscosity, high-gas-content, and particle-containing media. In this study, a rectangular labyrinth screw pump was used as the research object. The effect of the medium viscosity on the performance of the labyrinth pump was studied through numerical simulations, and the correctness of the simulation method was verified using existing test data. The efficiency and head of the labyrinth screw pump were selected as the optimization objectives, and the pump structural parameters were selected as the optimization parameters. A structural optimization model of the labyrinth screw pump based on response surface theory was established. The structural parameters of the labyrinth pump were reasonably simplified through size correlations, and then parameter sensitivity analysis was performed to determine the important structural parameters that needed to be optimized. The OSFD (optimized space-filling design) was used to combine the optimized parameters and generate the sample space. The response surface theory was combined with a neural network prediction model and a multi-objective genetic algorithm to perform optimization calculations. The results showed that there was an interactive influence between the structural parameters of the stator and rotor of the labyrinth screw pump. Compared with the original model, the optimized model pump had an efficiency increase of 13.55% and a lift increase of 19.53% when conveying a medium with a viscosity of 133 cp.

2.
Carbohydr Polym ; 271: 118427, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34364567

RESUMO

In recent years, chitosan-based biomaterials have been continually and extensively researched by using layer-by-layer (LBL) assembly, due to their potentials in biomedicine. Various chitosan-based LBL materials have been newly developed and applied in different areas along with the development of technologies. This work reviews the recent advances of chitosan-based biomaterials produced by LBL assembly. Driving forces of LBL, for example electrostatic interactions, hydrogen bond as well as Schiff base linkage have been discussed. Various forms of chitosan-based LBL materials such as films/coatings, capsules and fibers have been reviewed. The applications of these biomaterials in the field of antimicrobial applications, drug delivery, wound dressings and tissue engineering have been comprehensively reviewed.

3.
Biomed Res Int ; 2021: 5561734, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34195268

RESUMO

Mineral malnutrition as a prevalent public health issue can be alleviated by increasing the intake of dietary minerals from major staple crops, such as rice. Identification of the gene responsible for mineral contents in rice would help breed cultivars enriched with minerals through marker-assisted selection. Two segregating populations of backcross inbred lines (BIL) were employed to map quantitative trait loci (QTLs) for macronutrient contents in brown and milled rice, BC1F5, and BC2F4:5 derived from an interspecific cross of Xieqingzao B (Oryza sativa) and Dongxiang wild rice (O. rufipogon). Phenotyping the populations was conducted in multiple locations and years, and up to 169 DNA markers were used for the genotyping. A total of 17 QTLs for P, K, Na, Ca, and Mg contents in brown and milled rice distributed on eight regions were identified in the BC1F5 population, which is explained to range from 5.98% to 56.80% of phenotypic variances. Two regions controlling qCa1.1 and qCa4.1 were validated, and seven new QTLs for Ca and Mg contents were identified in the BC2F4:5 population. 18 of 24 QTLs were clustered across seven chromosomal regions, indicating that different mineral accumulation might be involved in common regulatory pathways. Of 24 QTLs identified in two populations, 16 having favorable alleles were derived from O. rufipogon and 10 were novel. These results will not only help understand the molecular mechanism of macronutrient accumulation in rice but also provide candidate QTLs for further gene cloning and grain nutrient improvement through QTL pyramiding.

4.
Aging (Albany NY) ; 13(13): 16957-16973, 2021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-34253690

RESUMO

Many aging related diseases such as cancer implicate the myofibroblast in disease progression. Furthermore genesis of the myofibroblast is associated with manifestation of cellular senescence of unclear significance. In this study we investigated the role of a common regulator, namely telomerase reverse transcriptase (TERT), in order to evaluate the potential significance of this association between both processes. We analyzed the effects of TERT overexpression or deficiency on expression of CDKN2A and ACTA2 as indicators of senescence and differentiation, respectively. We assess binding of TERT or YB-1, a repressor of both genes, to their promoters. TERT repressed both CDKN2A and ACTA2 expression, and abolished stress-induced expression of both genes. Conversely, TERT deficiency enhanced their expression. Altering CDKN2A expression had no effect on ACTA2 expression. Both TERT and YB-1 were shown to bind the CDKN2A promoter but only YB-1 was shown to bind the ACTA2 promoter. TERT overexpression inhibited CDKN2A promoter activity while stimulating YB-1 expression and activation to repress ACTA2 gene. TERT repressed myofibroblast differentiation and senescence via distinct mechanisms. The latter was associated with TERT binding to the CDKN2A promoter, but not to the ACTA2 promoter, which may require interaction with co-factors such as YB-1.


Assuntos
Diferenciação Celular/fisiologia , Senescência Celular/fisiologia , Miofibroblastos/fisiologia , Telomerase/fisiologia , Actinas/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Humanos , Masculino , Regiões Promotoras Genéticas , RNA Interferente Pequeno , Telomerase/biossíntese , Telomerase/genética
5.
Cell Prolif ; 54(8): e13095, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34254370

RESUMO

OBJECTIVES: Scavenger receptor class A, member 3 (Scara3) was involved in adipogenesis. However, the effect of Scara3 on the switch between osteogenesis and adipogenesis of bone marrow mesenchymal stem cells (BMSCs) remains elusive. MATERIALS AND METHODS: The correlations between SCARA3 with the osteogenic-related were analysed based on the GTEx database. The effects of Scara3 on osteogenic or adipogenic differentiation of BMSCs were evaluated by qPCR, Western blot (WB) and cell staining. The mechanisms of Scara3 regulating Foxo1 and autophagy were validated by co-expression analysis, WB and immunofluorescence. In vivo, Scara3 adeno-associated virus was injected into intra-bone marrow of the aged mice and ovariectomized (OVX) mice whose phenotypes were confirmed by micro-CT, calcein double labelling and immunochemistry (HE and OCN staining). RESULTS: SCARA3 was positively correlated with osteogenic-related genes. Scara3 expression gradually decreased during adipogenesis but increased during osteogenesis. Moreover, the deletion of Scara3 favoured adipogenesis over osteogenesis, whereas overexpression of Scara3 significantly enhanced the osteogenesis at the expense of adipogenesis. Mechanistically, Scara3 controlled the cell fate by promoting Foxo1 expression and autophagy flux. In vivo, Scara3 promoted bone formation and reduced bone marrow fat accumulation in OVX mice. In the aged mice, Scara3 overexpression alleviated bone loss as well. CONCLUSIONS: This study suggested that Scara3 regulated the switch between adipocyte and osteoblast differentiation, which represented a potential therapeutic target for bone loss and osteoporosis.


Assuntos
Adipócitos/citologia , Proteína Forkhead Box O1/metabolismo , Células-Tronco Mesenquimais/citologia , Osteoblastos/citologia , Receptores Depuradores Classe A/metabolismo , Adipócitos/metabolismo , Adipogenia , Envelhecimento , Animais , Autofagia , Diferenciação Celular , Células Cultivadas , Feminino , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Osteoblastos/metabolismo , Osteogênese , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Receptores Depuradores Classe A/antagonistas & inibidores , Receptores Depuradores Classe A/genética
6.
BMC Pulm Med ; 21(1): 149, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33952237

RESUMO

BACKGROUND: Several studies demonstrate that endoplasmic reticulum (ER) stress-mediated epithelial-mesenchymal transition (EMT) is involved in the process of bleomycin (BLM)-induced pulmonary fibrosis. Tauroursodeoxycholic acid (TUDCA), a bile acid with chaperone properties, is an inhibitor of ER stress. This study aimed to investigate the preventive effects of TUDCA on BLM-induced EMT and lung fibrosis. METHODS: The model of lung fibrosis was established by intratracheal injection with a single dose of BLM (3.0 mg/kg). In TUDCA + BLM group, mice were intraperitoneally injected with TUDCA (250 mg/kg) daily. RESULTS: BLM-induced alveolar septal destruction and inflammatory cell infiltration were alleviated by TUDCA. BLM-induced interstitial collagen deposition, as determined by Sirius Red staining, was attenuated by TUDCA. BLM-induced elevation of pulmonary α-smooth muscle actin (α-SMA) and reduction of pulmonary E-cadherin were attenuated by TUDCA. BLM-induced pulmonary Smad2/3 phosphorylation was suppressed by TUDCA. BLM-induced elevation of Ki67 and PCNA was inhibited by TUDCA in mice lungs. In addition, BLM-induced elevation of HO-1 (heme oxygenase-1) and 3-NT (3-nitrotyrosine) was alleviated by TUDCA. Finally, BLM-induced upregulation of pulmonary GRP78 and CHOP was attenuated by TUDCA. CONCLUSIONS: These results provide evidence that TUDCA pretreatment inhibits Smad2/3-medited EMT and subsequent lung fibrosis partially through suppressing BLM-induced ER stress and oxidative stress.

7.
Prep Biochem Biotechnol ; : 1-8, 2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34033527

RESUMO

To improve the naringinase production of Aspergillus tubingensis UA13, shorten the fermentation period, and verify its industrial application value, naringinase production conditions were optimized, and 5 L scale-up study in stirred tank bioreactor was carried out. Parameters, including carbon, nitrogen sources and inducer, optimal seed age, inoculum amount, temperature and pH, were adjusted and optimized in shaking flask. Keeping pH at the optimal value 6 in bioreactor, dissolved oxygen was monitored during the fermentation and the optimal stirring rate was investigated. In 5 L scale-up study, the highest naringinase activity was 72.62 U/mL, which was 1.75 times higher than that (41.52 U/mL) in shaking flask and the fermentation period was shortened by 24 h.

8.
Food Funct ; 12(9): 3954-3964, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33977937

RESUMO

The therapeutic effects of water extract of ginseng (WEG) on exercise-induced fatigue (EF) have been reported in several previous studies, but the molecular mechanisms involved remain unexplored. In this study, the anti-EF effects of WEG were studied, and the potential mechanisms were discussed. We characterized the chemical components of WEG by ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry (UHPLC-QqQ-MS/MS) and high performance liquid chromatography coupled with evaporative light scattering detection (HPLC-ELSD), and then examined the anti-EF effects of WEG on a rat model of weight-loaded swimming with a focus on endogenous metabolism and gut microbiota. WEG contains abundant (90.15%, w/w) saccharides and ginsenosides with structurally diverse glycosyls. WEG taken orally showed strong anti-EF effects by ameliorating energy metabolism abnormality, oxidative stress, lipid peroxidation, inflammatory response, disorders in the metabolism of bile acid, amino acid, fatty acid and lipid, as well as the gut microbiota dysbiosis. Given that gut microbiota is significantly associated with energy expenditure, systemic inflammation and host metabolism, these findings suggest a potential central role of the gut microbiota in mediating the anti-EF effect of WEG. That is, the saccharides and ginsenosides in WEG serve as energy substrates for specific intestinal bacteria, thereby beneficially regulating the gut microbiota, and the reshaped gut microbial ecosystem then triggers several molecular and cellular signaling pathways (e.g. butyrate or TGR5 signals) to achieve the therapeutic effects on EF. The outcomes highlighted here enable deeper insight into how WEG overcomes EF.


Assuntos
Fadiga/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Panax , Esforço Físico , Extratos Vegetais/farmacologia , Aminoácidos/metabolismo , Animais , Bacteroidetes/classificação , Bacteroidetes/crescimento & desenvolvimento , Bacteroidetes/isolamento & purificação , Ácidos e Sais Biliares/metabolismo , Disbiose , Fadiga/etiologia , Ácidos Graxos/metabolismo , Firmicutes/classificação , Firmicutes/crescimento & desenvolvimento , Firmicutes/isolamento & purificação , Metabolismo dos Lipídeos , Masculino , Metaboloma , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Ratos , Ratos Sprague-Dawley , Natação
9.
Environ Pollut ; 283: 117134, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-33866216

RESUMO

1-Nitropyrene (1-NP) is one component of atmospheric fine particles. Previous report revealed that acute 1-NP exposure induced respiratory inflammation. This study aimed to investigate whether chronic 1-NP exposure induces pulmonary fibrosis. Male C57BL6/J mice were intratracheally instilled to 1-NP (20 µg/mouse/week) for 6 weeks. Diffuse interstitial inflammation, a-smooth muscle actin (a-SMA)-positive cells, a marker of epithelial-mesenchymal transition (EMT), and an extensive collagen deposition, measured by Masson staining, were observed in 1-NP-exposed mouse lungs. Pulmonary function showed that lung dynamic compliance (Cydn-min) was reduced in 1-NP-exposed mice. Conversely, inspiratory resistance (Ri) and expiratory resistance (Re) were elevated in 1-NP-exposed mice. Mechanistically, cell migration and invasion were accelerated in 1-NP-exposed pulmonary epithelial cells. In addition, E-cadherin, an epithelial marker, was downregulated, and vimentin, a-SMA and N-cadherin, three mesenchymal markers, were upregulated in 1-NP-exposed pulmonary epithelial cells. Although TGF-ß wasn't altered, phosphorylated Smad2/3 were enhanced in 1-NP-exposed pulmonary epithelial cells. Moreover, reactive oxygen species (ROS) were increased and endoplasmic reticulum (ER) stress was activated in 1-NP-exposed pulmonary epithelial cells. N-Acetylcysteine (NAC), an antioxidant, attenuated 1-NP-evoked excess ROS, ER stress and EMT in pulmonary epithelial cells. Similarly, pretreatment with NAC alleviated 1-NP-caused pulmonary EMT and lung fibrosis in mice. These results demonstrate that ROS-evoked ER stress contributes, at least partially, to 1-NP-induced EMT and pulmonary fibrosis.


Assuntos
Transição Epitelial-Mesenquimal , Fibrose Pulmonar , Animais , Bleomicina , Estresse do Retículo Endoplasmático , Masculino , Camundongos , Fibrose Pulmonar/induzido quimicamente , Pirenos , Espécies Reativas de Oxigênio
10.
Rev. bras. med. esporte ; 27(spe): 87-90, Mar. 2021. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1156141

RESUMO

ABSTRACT There are some problems such as few and old equipment in urban community sports fitness facilities, which makes it difficult for community fitness resources to continue to meet the fitness needs of community residents. The opening of university sports resources can alleviate the problem of residents' fitness difficulty to a certain extent. In order to explore the problems faced by the opening of university sports resources, this study established the analytic hierarchy process model based on the analytic hierarchy process (AHP) and Delphi law in the background of national public service of fitness, and combined with the questionnaire survey method to study the influencing factors of opening of college sports. The model modified by the Delphi method contains 6 first-level and 22 second-level influencing factors. It is found that the most important factor in the first level is the hardware factor of college sports resources, and the most important factor of the second level is the spatial layout of university sports resources. The results show that improving the hardware facilities of university sports resources, improving the management mode of sports resources, and increasing the targeted financial subsidies and tax reduction and exemption are helpful to enhance the willingness to open sports resources and improve the quality of opened sports resources. It is hoped that this study can promote the opening of college sports resources and promote the continuous improvement of the service level of sports resources.


RESUMO Há alguns problemas, tais como equipamentos antiquados e em menores quantidades em instalações esportivas na Comunidade urbana, o que dificulta que os recursos de exercícios físicos continuem atendendo as necessidades de atividades físicas dos moradores das comunidades. A abertura de recursos desportivos universitários pode atenuar, em certa medida, o problema da dificuldade dos moradores de praticar atividades físicas. A fim de explorar os problemas enfrentados pela abertura dos recursos desportivos universitários, este estudo estabeleceu o modelo de processo hierárquico analítico baseado no processo hierárquico analítico (Analytic Hierarchy Process — AHP) e na Lei Delphi no contexto do serviço público nacional de atividades físicas, combinado com o método de inquérito por questionário para estudar os fatores que influenciam a abertura dos recursos esportivos universitários. O modelo modificado pelo método Delphi contém 6 fatores influenciadores de primeiro nível e 22 fatores influenciadores de segundo nível. Constata-se que o fator de primeiro nível mais importante é o fator físico dos recursos esportivos universitários, e o fator de segundo nível mais importante é a disposição espacial dos recursos esportivos universitários. Os resultados mostram que a melhoria das instalações físicas dos recursos desportivos universitários, a melhoria do modo de gestão dos recursos desportivos e o aumento dos subsídios financeiros e a redução e isenção de impostos são úteis para aumentar a disponibilidade da abertura dos recursos desportivos e melhorar a qualidade dos recursos desportivos abertos. Espera-se que este estudo possa promover o processo de abertura dos recursos esportivos universitários e promover a melhoria contínua do nível de serviço de recursos esportivos.


RESUMEN Explorar los problemas que enfrenta la apertura de los recursos deportivos universitarios, este estudio estableció el proceso de jerarquía analítica (PJA) y la ley Delphi en el contexto del servicio público nacional de educación física, y los combinó con la encuesta por cuestionario para estudiar los factores que influyen en la apertura de los deportes universitarios. El modelo modificado por el método Delphi contiene 6 factores de influencia de primer nivel y 22 de segundo nivel. Encontramos que el factor más importante en el primer nivel es el factor hardware de los recursos deportivos universitarios, y el factor más importante del segundo nivel es la distribución espacial de los recursos deportivos universitarios. Los resultados muestran que mejorar las instalaciones de hardware de los recursos deportivos universitarios, mejorar el modo de gestión de los recursos deportivos y aumentar los subsidios financieros específicos y la reducción y exención de impuestos son útiles para mejorar la disposición a abrir recursos deportivos y mejorar la calidad de los recursos deportivos abiertos. Esperamos que este estudio pueda promover la apertura de recursos deportivos universitarios y promover la mejora continua del nivel de servicio de los recursos deportivos.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33566774

RESUMO

Power amplifier (PA) models, such as the neural network (NN) models and the multilayer NN models, have problems with high complexity. In this article, we first propose a novel behavior model for wideband PAs, using a real-valued time-delay convolutional NN (RVTDCNN). The input data of the model is sorted and arranged as a graph composed of the in-phase and quadrature (I/Q) components and envelope-dependent terms of current and past signals. Then, we created a predesigned filter using the convolutional layer to extract the basis functions required for the PA forward or reverse modeling. Finally, the generated rich basis functions are input into a simple, fully connected layer to build the model. Due to the weight sharing characteristics of the convolutional model's structure, the strong memory effect does not lead to a significant increase in the complexity of the model. Meanwhile, the extraction effect of the predesigned filter also reduces the training complexity of the model. The experimental results show that the performance of the RVTDCNN model is almost the same as the NN models and the multilayer NN models. Meanwhile, compared with the abovementioned models, the coefficient number and computational complexity of the RVTDCNN model are significantly reduced. This advantage is noticeable when the memory effects of the PA are increased by using wider signal bandwidths.

12.
J Immunol ; 206(3): 515-523, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33361208

RESUMO

Vitamin D deficiency is associated with increased risks of chronic obstructive pulmonary disease (COPD). Nevertheless, the mechanisms remain unknown. This study analyzed the correlations between vitamin D levels and inflammation in COPD patients. One hundred and one patients with COPD and 202 control subjects were enrolled. Serum 25(OH)D level and inflammatory cytokines were detected. Serum 25(OH)D was decreased and inflammatory cytokines were increased in COPD patients. According to forced expiratory volume in 1 s, COPD patients were divided into three grades. Furthermore, serum 25(OH)D was gradually decreased in COPD patients ranging from grade 1-2 to 4. Serum 25(OH)D was inversely associated with inflammatory cytokines in COPD patients. Further analysis found that NF-κB and AP-1 signaling were activated in COPD patients. Besides, inflammatory signaling was gradually increased in parallel with the severity of COPD. By contrast, pulmonary nuclear vitamin D receptor was decreased in COPD patients. In vitro experiments showed that 1,25(OH)2D3 inhibited LPS-activated inflammatory signaling in A549 cells (human lung adenocarcinoma cell). Mechanically, 1,25(OH)2D3 reinforced physical interactions between vitamin D receptor with NF-κB p65 and c-Jun. Our results indicate that vitamin D is inversely correlated with inflammatory signaling in COPD patients. Inflammation may be a vital mediator of COPD progress in patients with low vitamin D levels.


Assuntos
Inflamação/imunologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Receptores de Calcitriol/metabolismo , Deficiência de Vitamina D/imunologia , Vitamina D/sangue , Células A549 , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Transdução de Sinais , Fator de Transcrição AP-1/metabolismo , Deficiência de Vitamina D/metabolismo
13.
Fundam Clin Pharmacol ; 35(5): 822-831, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33336420

RESUMO

The poor outcomes in advanced non-small-cell lung cancer (NSCLC) necessitate new treatments. Recent studies emphasize anisomycin as a promising anti-cancer drug candidate. In this work, we systematically investigated the efficacy of anisomycin alone and its combination with the standard-of-care drugs in NSCLC. We showed that anisomycin inhibited growth, migration, and survival in NSCLC cells regardless of genetic mutation status, and to a greater extent than in normal lung epithelial cells. Isobologram analysis showed that the combination of anisomycin with cisplatin, paclitaxel, or gefitinib was synergistic in NSCLC but not normal lung cells. We further demonstrated that anisomycin inhibited NSCLC growth in mice. The combination of anisomycin with cisplatin was more effective than cisplatin alone and completely arrested NSCLC growth throughout the whole duration of treatment. JNK and p38 MAPK were not required for anisomycin's action. In contrast, anisomycin inhibits PI3K/Akt/mTOR pathway. Overexpression of constitutively active Akt reversed the pro-apoptotic effect of anisomycin. Our work demonstrates the selective anti-NSCLC activity of anisomycin via suppressing PI3K/Akt/mTOR. Our findings provide preclinical evidence to initialize the clinical trial of using anisomycin to sensitize NSCLC to current therapy.

14.
Zhongguo Zhong Yao Za Zhi ; 45(20): 4867-4874, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33350258

RESUMO

"Dao-di herbs" is the original comprehensive index for the quality evaluation of traditional Chinese medicine, which has the characteristics of high quality and good effect. After more than 30 years of development, a large number of data, including text data, image data and other types, have been generated in the modern research on Dao-di herbs. It has the characteristics of large quantity, variety, scattered content and different structure, and the data types of each feature are isolated or less interrelated. Based on the literature published in CNKI journal database since 1999-2019, the data collection, selection and collation of 34 kinds of Dao-di herbs characteristics, micro characteristics, ecological characteristics and genetic characteristics were carried out. Using the knowledge base construction technology and combining these characteristics of the characteristics data of the herbs, the above characteristics data were standardized and regarded as a part of the knowledge base of the herbs. Based on a large number of data, this paper analyzes the knowledge composition, research status, comparison between modern and traditional producing areas of traditional Chinese medicine, and takes Salvia miltiorrhiza as an example to compare the ecological characteristics of modern and traditional producing areas. The construction of the knowledge base will facilitate the mining and utilization of the scientific data of Dao-di herbs, and provide resource management and basic guarantee for the transformation and promotion of scientific and technological achievements of Dao-di herbs.


Assuntos
Medicamentos de Ervas Chinesas , Plantas Medicinais , Descoberta do Conhecimento , Medicina Tradicional Chinesa , Tecnologia
15.
J Immunother Cancer ; 8(2)2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33203663

RESUMO

OBJECTIVES: Strategies to improve the responsiveness of programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) checkpoint blockade therapy remain an essential topic in cancer immunotherapy. In this study, we developed a new radiolabeled nanobody-based imaging probe 99mTc-MY1523 targeting PD-L1 for the enhanced therapeutic efficacy of PD-L1 blockade immunotherapy by the guidance of 99mTc-MY1523 SPECT/CT imaging. METHODS: The binding affinity and specificity of nanobody MY1523 were measured in vitro. MY1523 was radiolabeled with 99mTc by a site-specific transpeptidation of Sortase-A, and the biodistribution and single photon emission CT (SPECT)/CT were performed in mice bearing different tumors. We used interferon-γ (IFN-γ) as an intervention means to establish animal models with different levels of PD-L1 expression, then investigated the ability of 99mTc-MY1523 SPECT/CT for the in vivo non-invasive measurement of PD-L1 expression in tumors. Finally, the PD-L1 blockade immunotherapies guided by 99mTc-MY1523 SPECT/CT were carried out in MC-38, A20, and 4T1 tumor-bearing mouse models, followed by the testing of tumor infiltration T cells. RESULTS: MY1523 exhibited a high binding affinity and specificity to PD-L1 and had no competitive binding with the therapeutic antibody. 99mTc-MY1523 was prepared with high specific activity and radiochemical purity. It was found that tumor PD-L1 expression was dynamically upregulated by IFN-γ intervention in MC-38, A20, and 4T1 tumor-bearing mouse models, as indicated by 99mTc-MY1523 SPECT/CT. The PD-L1 blockade therapy initiated during the therapeutic time window determined by 99mTc-MY1523 SPECT/CT imaging significantly enhanced the therapeutic efficacy in all animal models, while the tumor growth was effectively suppressed, and the survival time of mice was evidently prolonged. A correlation between dynamically upregulated PD-L1 expression and improved PD-L1 blockade therapy effectiveness was revealed, and the markedly increased infiltration of effector T cells into tumors was verified after the imaging-guided therapy. CONCLUSION: Our results demonstrated that 99mTc-MY1523 SPECT/CT allowed a real-time, quantitative and dynamic mapping of PD-L1 expression in vivo, and the imaging-guided PD-L1 blockade immunotherapy significantly enhanced the therapeutic efficacy. This strategy merits translation into clinical practice for the better management of combination therapies with radiotherapy or chemotherapy.

16.
Acta Pharmacol Sin ; 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33154553

RESUMO

Herbs and dietary supplement-induced liver injury (HILI) is the leading cause of drug-induced liver injury in China. Among different hepatotoxic herbs, the pyrrolizidine alkaloid (PA)-producing herb Gynura japonica contributes significantly to HILI by inducing hepatic sinusoidal obstruction syndrome (HSOS), a liver disorder characterized by hepatomegaly, hyperbilirubinemia, and ascites. In China, G. japonica has been used as one of the plant species for Tu-San-Qi and is often misused with non-PA-producing Tu-San-Qi (Sedum aizoon) or even San-Qi (Panax notoginseng) for self-medication. It has been reported that over 50% of HSOS cases are caused by the intake of PA-producing G. japonica. In this review, we provide comprehensive information to distinguish these Tu-San-Qi-related herbal plant species in terms of plant/medicinal part morphologies, medicinal indications, and chemical profiles. Approximately 2156 Tu-San-Qi-associated HSOS cases reported in China from 1980 to 2019 are systematically reviewed in terms of their clinical manifestation, diagnostic workups, therapeutic interventions, and outcomes. In addition, based on the application of our developed mechanism-based biomarker of PA exposure, our clinical findings on the definitive diagnosis of 58 PA-producing Tu-San-Qi-induced HSOS patients are also elaborated. Therefore, this review article provides the first comprehensive report on 2214 PA-producing Tu-San-Qi (G. japonica)-induced HSOS cases in China, and the information presented will improve public awareness of the significant incidence of PA-producing Tu-San-Qi (G. japonica)-induced HSOS and facilitate future prevention and better clinical management of this severe HILI.

17.
Zhongguo Zhong Yao Za Zhi ; 45(19): 4545-4554, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33164417

RESUMO

In the theories of empirical identification of "arguments on quality" and "five elephants and seven originals", color is regarded as one of the important indicators in the quality evaluation of Chinese medicine. The color of medicinal material including the surface color, the internal color, and the color after processing is caused by the pigment in the cells, which is a characteristic of the "optimal shape". Most pigments have a wide range of pharmacological activities such as anti-oxidation, anti-tumor, anti-atherosclerosis, prevention of coronary heart disease, protection of cardiovascular function, enhancement of immunity, etc. Therefore, the "optimal color" of medicinal materials is unified with the "high quality". This article systematically reviews the research status of "quality discrimination by color", the correlation between L~*, a~*, b~* color space and active ingredients such as alkaloids, flavonoids, terpenes, etc. to explain the "quality discrimination by color" in quantitative characterization. We also summary the research progress on the biosynthesis and regulation of the main pigment components of traditional Chinese medicine, and analyze the biological causes that affect the accumulation of the main pigments. We aim to provide a reference for the theory "quality discrimination by color" in biological knowledge to establish a modern quality control system for Chinese herbal medicines.


Assuntos
Medicamentos de Ervas Chinesas , Cor , Flavonoides , Medicina Tradicional Chinesa , Controle de Qualidade
18.
J Clin Transl Hepatol ; 8(3): 246-254, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33083246

RESUMO

Background and Aims: Coronavirus disease 2019 (COVID-19) is a new respiratory infectious disease caused by severe acute respiratory syndrome coronavirus-2 (commonly known as SARS-CoV-2) with multiple organ injuries. The aim of this study was to analyze COVID-19-associated liver dysfunction (LD), its association with the risk of death and prognosis after discharge. Methods: Three-hundred and fifty-five COVID-19 patients were recruited. Clinical data were collected from electronic medical records. LD was evaluated and its prognosis was tracked. The association between LD and the risk of death was analyzed. Results: Of the 355 COVID-19 patients, 211 had mild disease, 88 had severe disease, and 51 had critically ill disease. On admission, 223 (62.8%) patients presented with hypoproteinemia, 151(42.5%) with cholestasis, and 101 (28.5%) with hepatocellular injury. As expected, LD was more common in critically ill patients. By multivariate logistic regression, male sex, older age and lymphopenia were three important independent risk factors predicting LD among COVID-19 patients. Risk of death analysis showed that the fatality rate was higher in patients with hypoproteinemia than in those without hypoproteinemia (relative risk=9.471, p<0.01). Moreover, the fatality rate was higher in patients with cholestasis than those without cholestasis (relative risk=2.182, p<0.05). Follow-up observation found that more than one hepatic functional index of two-third patients remained abnormal at 14 days after discharge. Conclusions: LD at early disease stage elevates the risk of death of COVID-19 patients. COVID-19-associated LD does not recover completely by 14 days after discharge.

19.
Tissue Cell ; 66: 101386, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32933709

RESUMO

BACKGROUND: Ideal bone defect repair scaffolds should be biodegradable, biocompatible, bioactive, porous, and provide adequate mechanical support. However, it is challenging to fabricate such an ideal bone repair scaffold. Previously, we showed that 5 wt.% strontium-doped hydroxyapatite (Sr-HA) scaffolds prepared by spark plasma sintering (SPS) technology exhibited good biocompatibility. Moreover, unlike pure hydroxyapatite (HA) scaffolds, HA scaffolds containing strontium (Sr) exhibited superior bioactivity, higher proliferation rate of BMSCs and MG-63 osteoblast cells, as well as enhanced BMSCs differentiation. METHODS: In this study, we prepared pure HA scaffolds and 5 wt.% strontium containing Sr-HA scaffolds by SPS technology without adhesive, ammonium bicarbonate as pore former. Subsequently, scanning electron microscope (SEM) and X-Ray diffraction (XRD) were used to characterize the properties of Sr-HA and HA scaffolds. The ability of the scaffolds to repair bone defects was evaluated using a critical-sized rabbit tibia-bone defect rabbit model. Thirty 3-month-old New Zealand white rabbits were randomly divided into three groups (blank control group, Sr-HA scaffolds implanted group and HA scaffolds implanted group) with 10 rabbits in each group. These rabbits are sacrificed after 8 weeks and 16 weeks of surgery, and the repair effects of each scaffold were evaluated with X-ray, micro-CT, and HE staining. The three-point bending test was employed to assess the mechanical property of repaired bones. RESULTS: XRD pattern indicated that Sr-HA and HA scaffolds possess a similar crystal structure after sintering, and that incorporation of strontium did not form impure phase. SEM showed that the porosity of Sr-HA and HA scaffolds was about 40 %. Universal Testing Machine tests showed that Sr-HA scaffolds had better compressive strength than HA scaffolds. Bone defect was obvious, and the fibrous tissue was formed in the bone defects of rabbits in the blank control group after 8 weeks of surgery. Sr-HA and HA scaffolds enhanced osteointegration of the host bone, and extensive woven bone was formed on the surface of the Sr-HA scaffolds. After 16 weeks, the bone strump became blunt and a small amount of callus was formed in the blank control group. Comparatively, the scaffolds were substantially degraded in the Sr-HA scaffolds implanted group while scaffolds shadows still were observed in the HA implanted group. Bone remodeling and cavity recanalization were completely developed in the Sr-HA scaffolds group. The compressive strength of repaired bone in the Sr-HA scaffolds implantation group was higher than that of HA scaffolds implantation group after 8 weeks and 16 weeks of surgery. CONCLUSIONS: Our results show that the Sr-HA composite scaffolds can effectively repair bone defects and have good biodegradable properties.


Assuntos
Regeneração Óssea , Osso e Ossos/patologia , Hidroxiapatitas/química , Estrôncio/química , Engenharia Tecidual/métodos , Tecidos Suporte/química , Animais , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/cirurgia , Varredura Diferencial de Calorimetria , Teste de Materiais , Porosidade , Pós , Coelhos , Termogravimetria , Difração de Raios X , Microtomografia por Raio-X
20.
Zhongguo Zhong Yao Za Zhi ; 45(15): 3651-3658, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32893554

RESUMO

As an important substitute for agarwood, mountain-agarwood, belonging to the family Oleaceae, comes from the root, stem and thick branch of Syringa pinnatifolia, which has a wide range of application in Inner Mongolia, China. It has good clinical efficacy in the use of cardiovascular diseases. However, the formation speed of mountain-agarwood is extremely slow, and its cultivated seedlings have low resin content. Therefore, how to speed up the formation of mountain-agarwood and increase the resin content is a hot research topic in this field. In this work, 16 S rDNA amplicon sequencing method was used to systematically analyze the bacterial communities of different samples of mountain-agarwood. Our data revealed that the samples of mountain-agarwood had more obvious species diversity than the ones of non-mountain-agarwood, especially the wild mountain-agarwood samples. By analysis of bacterial community composition and species abundance, Sphingomonas, Modestobacter and unidentified Cyanobacteria genus were three dominant bacterial genera in all samples. In addition, there are two identified genera of dominant bacteria, namely Actinoplanes and Microbacterium in both wild and cultivated mountain-agarwood, by bacterial community composition and species richness analysis. Meanwhile, Roseomonas was the dominant bacterial genus in both wild and cultivated non-mountain-agarwood samples. Our work could provides basic data for exploring the mechanism of the mountain-agarwood formation, and help to exploit resource of endophytic bacteria reasonably.


Assuntos
Thymelaeaceae , Bactérias/genética , China , DNA Ribossômico , Resinas Vegetais
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