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1.
Cell ; 184(12): 3256-3266.e13, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-34048699

RESUMO

Northern East Asia was inhabited by modern humans as early as 40 thousand years ago (ka), as demonstrated by the Tianyuan individual. Using genome-wide data obtained from 25 individuals dated to 33.6-3.4 ka from the Amur region, we show that Tianyuan-related ancestry was widespread in northern East Asia before the Last Glacial Maximum (LGM). At the close of the LGM stadial, the earliest northern East Asian appeared in the Amur region, and this population is basal to ancient northern East Asians. Human populations in the Amur region have maintained genetic continuity from 14 ka, and these early inhabitants represent the closest East Asian source known for Ancient Paleo-Siberians. We also observed that EDAR V370A was likely to have been elevated to high frequency after the LGM, suggesting the possible timing for its selection. This study provides a deep look into the population dynamics of northern East Asia.


Assuntos
Dinâmica Populacional , DNA Antigo/análise , Ásia Oriental , Feminino , Variação Genética , Genética Populacional , Genoma Humano , Geografia , Humanos , Camada de Gelo , Funções Verossimilhança , Masculino , Modelos Genéticos , Filogenia , Análise de Componente Principal , Fatores de Tempo
2.
Cell ; 184(14): 3829-3841.e21, 2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34171307

RESUMO

Past human genetic diversity and migration between southern China and Southeast Asia have not been well characterized, in part due to poor preservation of ancient DNA in hot and humid regions. We sequenced 31 ancient genomes from southern China (Guangxi and Fujian), including two ∼12,000- to 10,000-year-old individuals representing the oldest humans sequenced from southern China. We discovered a deeply diverged East Asian ancestry in the Guangxi region that persisted until at least 6,000 years ago. We found that ∼9,000- to 6,000-year-old Guangxi populations were a mixture of local ancestry, southern ancestry previously sampled in Fujian, and deep Asian ancestry related to Southeast Asian Hòabìnhian hunter-gatherers, showing broad admixture in the region predating the appearance of farming. Historical Guangxi populations dating to ∼1,500 to 500 years ago are closely related to Tai-Kadai and Hmong-Mien speakers. Our results show heavy interactions among three distinct ancestries at the crossroads of East and Southeast Asia.


Assuntos
Genética Populacional , Sudeste Asiático , Ásia Oriental , Geografia , Humanos
3.
Small ; 20(25): e2307281, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38225701

RESUMO

Osteoarthritis (OA) is a typical joint degenerative disease that is prevalent worldwide and significantly affects the normal activities of patients. Traditional treatments using diclofenac (DCF) as an anti-inflammatory drug by oral administration and transdermal delivery have many inherent deficiencies. In this study, a lubricating microneedles (MNs) system for the treatment of osteoarthritis with multistage sustained drug delivery and great reduction in skin damage during MNs penetration is developed. The bilayer dissolvable MNs system, namely HA-DCF@PDMPC, is prepared by designating the composite material of hyaluronic acid (HA) and covalently conjugated drug compound (HA-DCF) as the MNs tips and then modifying the surface of MNs tips with a self-adhesive lubricating copolymer (PDMPC). The MNs system is designed to achieve sustained drug release of DCF via ester bond hydrolysis, physical diffusion from MNs tips, and breakthrough of lubrication coating. Additionally, skin damage is reduced due to the presence of the lubrication coating on the superficial surface. Therefore, the lubricating MNs with multistage sustained drug delivery show good compliance as a transdermal patch for OA treatment, which is validated from anti-inflammatory cell tests and therapeutic animal experiments, down-regulating the expression levels of pro-inflammatory factors and alleviating articular cartilage destruction.


Assuntos
Diclofenaco , Sistemas de Liberação de Medicamentos , Ácido Hialurônico , Agulhas , Osteoartrite , Osteoartrite/tratamento farmacológico , Animais , Diclofenaco/administração & dosagem , Diclofenaco/uso terapêutico , Diclofenaco/farmacologia , Ácido Hialurônico/química , Lubrificação , Humanos , Preparações de Ação Retardada/química
4.
Ecotoxicol Environ Saf ; 249: 114374, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36508824

RESUMO

The Ya-Er Lake is a seriously polychlorinated dibenzo-p-dioxins/dibenzo-furans (PCDD/Fs) and mercury (Hg)-contaminated lake by pesticide and chlor-alkali plants in China. The oxidation pond method has been conducted to control pollution, moreover, the contaminated sediment was dredged and stacked, becoming a sediment stack yard for vegetable cultivation. To assess effects of oxidation pond method and dredging programme on pollution management and long-term risks of PCDD/Fs and Hg, the concentrations of PCDD/Fs, total Hg (THg), and methylmercury (MeHg) in soil and vegetable sampled from the sediment stack yard were measured and analyzed. Significantly positive relationships between concentrations of PCDD/Fs (p < 0.01), THg, and MeHg (p < 0.05) in edible parts of vegetable and soil were found, suggesting that bioaccumulation from contaminated soil derived from sediment dredging is important sources of PCDD/Fs and Hg in vegetable. Much higher PCDD/Fs (12 ± 9 pg/g dw) and Hg (THg, 0.14 ± 0.23 µg/g dw; MeHg,12.63 ± 13.31 ng/g dw) levels in vegetable were found compared with those from other contaminated regions, indicative of serious PCDD/Fs and Hg pollution in vegetable harvested from contaminated soil. Finally, the calculated provisional tolerable daily intake (PTDI) values showed higher health risk of PCDD/Fs and Hg exposure to local residents through consumption of purple and white flowering stalk, and oilseed rape. Our study established a good model to evaluate the long-term risks of PCDD/Fs and Hg. Moreover, the results indicate that the oxidation pond method and dredging programme were not effective to remove PCDD/Fs and Hg in sediment, which shed new light on management strategy of PCDD/Fs and Hg pollution in contaminated regions.


Assuntos
Mercúrio , Dibenzodioxinas Policloradas , Dibenzodioxinas Policloradas/análise , Dibenzofuranos , Verduras , Mercúrio/análise , Sedimentos Geológicos , China , Dibenzofuranos Policlorados , Solo
5.
Molecules ; 28(6)2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36985440

RESUMO

As a new member of the silica-derivative family, modified glass fiber (MGF) has attracted extensive attention because of its excellent properties and potential applications. Surface modification of glass fiber (GF) greatly changes its performance, resulting in a series of changes to its surface structure, wettability, electrical properties, mechanical properties, and stability. This article summarizes the latest research progress in MGF, including the different modification methods, the various properties, and their advanced applications in different fields. Finally, the challenges and possible solutions were provided for future investigations of MGF.

6.
Molecules ; 28(9)2023 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-37175110

RESUMO

Enantioselective labeling of important bioactive molecules in complex biological environments by artificial receptors has drawn great interest. From both the slight difference of enantiomers' physicochemical properties and inherently complexity in living organism point of view, it is still a contemporary challenge for preparing practical chiral device that could be employed in the model animal due to diverse biological interference. Herein, we introduce γ-cyclodextrin onto graphene oxide for fabricating γ-cyclodextrin and graphene oxide assemblies, which provided an efficient nanoplatform for chiral labelling of D-phenylalanine with higher chiral discrimination ratio of KD/KL = 8.21. Significantly, the chiral fluorescence quenching effect of this γ-CD-GO nanoplatform for D-phenylalanine enantiomer in zebrafish was 7.0-fold higher than L-isomer, which exhibiting real promise for producing practical enantio-differentiating graphene-based systems in a complex biological sample.


Assuntos
Grafite , gama-Ciclodextrinas , Animais , Fenilalanina/química , Grafite/química , Peixe-Zebra , Estereoisomerismo
7.
Environ Sci Technol ; 56(13): 9486-9496, 2022 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-35622943

RESUMO

In this work, a typical congener of short-chain chlorinated paraffins (SCCPs) with six chlorine atoms (CP-4, 1,2,5,6,9,10-C10H16Cl6, 250 ng/mL) was selected to elaborate the comprehensive environmental transformation of SCCPs in rice seedling exposure system. CP-4 was quickly absorbed, translocated, and phytovolatilized by seedlings with a small quality of CP-4 (5.81-36.5 ng) being detected in the gas phase. Only 21.4 ± 1.6% of an initial amount (10,000 ng) of CP-4 remained in the exposure system at the end of exposure. Among the transformed CP-4, some were attributed to the degradation of the rhizosphere microorganism (9.1 ± 5.8%), root exudates (2.2 ± 4.2%), and abiotic transformation (3.0 ± 2.8%) that were proved by several transformation products found in the root exudate exposure groups and unplanted controls, and a majority was phytotransformed by rice seedlings. Here, 61 products were determined through complex transformation pathways, including multihydroxylation, -HCl elimination, dechlorination, acetylation, sulfation, glycosylation, and amide acid conjugation. The acetylated and amide acid conjugates of CPs were first observed. Phase I and Phase II phytometabolic reactions of CPs were found intertwining. These findings demonstrate that multiactive transformation reactions contribute to the overlook of CPs accumulated in plants and are helpful for the environmental and health risk assessments of SCCPs in agricultural plants.


Assuntos
Hidrocarbonetos Clorados , Oryza , Amidas , China , Monitoramento Ambiental , Hidroponia , Parafina/análise , Plântula/química
8.
Opt Express ; 28(21): 31808-31820, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33115146

RESUMO

A multi-longitudinal mode fiber laser sensor (MLMFLS) system based on a digital modulation/demodulation technique is proposed. To the best of the authors' knowledge, this is the first digital vibration-demodulation system ever reported by a MLMFLS system. Multiple beat frequency signals (BFS) generated by the MLMFLS work as signal carriers of applied vibration signals. The vibration signals modulated on several BFS at different frequencies are simultaneously demodulated based on a multi-channel digital down-conversion technique by utilizing the digital universal software radio peripheral (USRP). The demodulated vibration signals from different signal channels are superposed by the USRP. Signal-to-noise ratio (SNR) of output vibration signal is highly improved, which increases sensing stability and accuracy of the system. This is really important for sensing of vibration signals that have an extremely low frequency or weak energy. Measurement results demonstrate that the sensing system has an excellent low frequency vibration-sensing capability, simple structure, high SNR, stability and accuracy.

9.
Environ Sci Technol ; 54(16): 9990-9999, 2020 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-32600037

RESUMO

Short-chain and medium-chain chlorinated paraffins (SCCPs and MCCPs) are mixtures of complex chemical compounds with intensive usage. They are frequently detected in various environmental samples. However, the interaction between CPs and plants, especially the biotransformation behaviors of CPs within plants, is poorly understood. In this study, 1,2,5,6,9,10-hexachlorodecane (CP-4, a typical standard of individual SCCP congeners) and 52%-MCCP (a commercial mixture standard of MCCPs with 52% chlorine content by mass) were selected as representative chemicals to explore the metabolic behaviors of SCCPs and MCCPs using suspension rice cell culture exposure systems. Both 79.53% and 40.70% of CP-4 and 52%-MCCP were metabolized by suspension rice cells, respectively. A complementary suspected screening strategy based on the pair mass distances (PMD) analysis algorithm was used to study the metabolism of CPs mediated by the plant cells. Forty and 25 metabolic products for CP-4 and 52%-MCCP, respectively, were identified, including (multi-) hydroxylation, dechlorination, -HCl- elimination metabolites, (hydroxylation-) sulfation, and glycosylation conjugates. Here, we propose a comprehensive metabolic molecular network and provide insight on degradation pathways of SCCPs and MCCPs in plants for the first time, aiding in further understanding of the transformation behaviors of CPs.


Assuntos
Hidrocarbonetos Clorados , Oryza , China , Cloro , Monitoramento Ambiental , Hidrocarbonetos Clorados/análise , Parafina/análise
10.
J Exp Bot ; 70(9): 2561-2574, 2019 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-30825375

RESUMO

Dynamic process-based plant models capture complex physiological response across time, carrying the potential to extend simulations out to novel environments and lend mechanistic insight to observed phenotypes. Despite the translational opportunities for varietal crop improvement that could be unlocked by linking natural genetic variation to first principles-based modeling, these models are challenging to apply to large populations of related individuals. Here we use a combination of model development, experimental evaluation, and genomic prediction in Brassica rapa L. to set the stage for future large-scale process-based modeling of intraspecific variation. We develop a new canopy growth submodel for B. rapa within the process-based model Terrestrial Regional Ecosystem Exchange Simulator (TREES), test input parameters for feasibility of direct estimation with observed phenotypes across cultivated morphotypes and indirect estimation using genomic prediction on a recombinant inbred line population, and explore model performance on an in silico population under non-stressed and mild water-stressed conditions. We find evidence that the updated whole-plant model has the capacity to distill genotype by environment interaction (G×E) into tractable components. The framework presented offers a means to link genetic variation with environment-modulated plant response and serves as a stepping stone towards large-scale prediction of unphenotyped, genetically related individuals under untested environmental scenarios.


Assuntos
Genômica/métodos , Plantas/genética , Ecossistema , Genótipo , Modelos Genéticos , Estresse Fisiológico/genética , Estresse Fisiológico/fisiologia
11.
Fish Shellfish Immunol ; 75: 149-157, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29427715

RESUMO

Protease inhibitors play critical roles in numerous biological processes including host defense in all multicellular organisms. Eighty three evolutionary families of protease inhibitors are currently accommodated in the MEROPS database and the I84 family currently consists of 3 novel serine protease inhibitors from the eastern oyster Crassostrea virginica. In this study, we identified 2 new I84 family members from the Chinese razor clam Sinonovacula constricta, scSI-1 and scSI-2, using cDNA cloning and sequencing. The scSI-1 cDNA consisted of 494 bp with a 282 bp ORF encoding a 93-amino acid polypeptide that was predicted to have a 19-amino acid signal peptide and a 74-residue mature protein with a calculated molecular mass of 8248.5 Da. The scSI-2 cDNA was 490 bp long with a 273 bp ORF encoding a 90-amino acid polypeptide that was predicted to have an 18-amino acid signal peptide and a 72-residue nature protein with a calculated molecular mass of 7528.4 Da. ScSI-1 and scSI-2 shared high sequence similarity with the 3 known members of I84 family and both expressed primarily in the clam digestive glands. Protease inhibitory activity in the clam plasma also exhibited the signature kinetic characteristics of the I84 members from the oyster. In addition, levels of scSI-1 and scSI-2 gene expression in digestive glands and the protease inhibitory activity in plasma elevated significantly in clams challenged by bacterial injections and Vibrio harveyi was more effective than Staphylococcus epidermidis in inducing the gene expression and plasma protease inhibitory activity. Moreover, drastic changes of salinity and temperature also caused significant changes in the gene expression and plasma activity. These results indicated that scSI-1 and scSI-2 represented 2 new members of the I84 family and they likely play a role in clam host defense against infections and in reactions against physiochemical stressors.


Assuntos
Bivalves/genética , Bivalves/imunologia , Expressão Gênica , Imunidade Inata/genética , Inibidores de Proteases , Sequência de Aminoácidos , Animais , Sequência de Bases , Clonagem Molecular , DNA Complementar , Perfilação da Expressão Gênica , Inibidores de Proteases/química , Inibidores de Proteases/imunologia , Inibidores de Proteases/metabolismo , Alinhamento de Sequência , Análise de Sequência de DNA
12.
Respiration ; 93(5): 327-338, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28324873

RESUMO

BACKGROUND: Endobronchial ultrasound (EBUS) elastography is a new imaging procedure for describing the elasticity of intrathoracic lesions and providing important additional diagnostic information. OBJECTIVES: The aim of this study was to utilize the feasibility of qualitative and quantitative methods to evaluate the ability of EBUS elastography to differentiate between benign and malignant mediastinal and hilar lymph nodes (LNs) during EBUS-guided transbronchial needle aspiration (EBUS-TBNA). METHODS: Patients with enlarged intrathoracic LNs required for EBUS-TBNA examination at a clinical center for thoracic medicine from January 2014 to April 2014 were prospectively enrolled. EBUS sonographic characteristics on B-mode, vascular patterns and elastography, EBUS-TBNA procedures, pathological findings, and microbiological results were recorded. Furthermore, elastographic patterns (qualitative method) and the mean gray value inside the region of interest (quantitative method) were analyzed. Both methods were compared with a definitive diagnosis of the involved LNs. RESULTS: Fifty-six patients including 68 LNs (33 benign and 35 malignant nodes) were prospectively enrolled into this study and retrospectively analyzed. Using qualitative and quantitative methods, we were able to differentiate between benign and malignant LNs with high sensitivity, specificity, positive and negative predictive values, and accuracy (85.71, 81.82, 83.33, 84.38, and 83.82% vs. 91.43, 72.73, 78.05, 88.89, and 82.35%, respectively). CONCLUSIONS: EBUS elastography is potentially capable of further differentiating between benign and malignant LNs. These proposed qualitative and quantitative methods might be useful tools for describing EBUS elastography during EBUS-TBNA.


Assuntos
Broncoscopia/métodos , Técnicas de Imagem por Elasticidade , Linfonodos/patologia , Ultrassonografia de Intervenção/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Projetos Piloto , Estudos Retrospectivos , Tórax
13.
Microcirculation ; 23(6): 426-37, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27164060

RESUMO

OBJECTIVE: This study was designed to examine the effect of KDZ, on the BBB disruption in rat underwent MCAO and reperfusion. METHODS: Male Sprague-Dawley rats (260-280 g) were subjected to 60 minutes MCAO followed by reperfusion. KDZ (4 mL/kg) was administrated before ischemia. The Evans blue extravasation, albumin leakage, brain water content, TJ proteins, caveolin-1, p-caveolin-1, Src, and p-Src were evaluated. Neurological scores, cerebral infarction, and CBF were assessed. The binding affinity of KDZ to Src was examined. RESULTS: I/R evoked a range of insults including Evans blue extravasation, albumin leakage, brain water content increase, CBF decrease, cerebral infarction, and neurological deficits, all of which were attenuated by KDZ. Meanwhile, KDZ inhibited TJ proteins down-expression, expression of caveolin-1, phosphorylation of caveolin-1 and Src after I/R. In addition, SPR revealed binding of KDZ to Src with high affinity. CONCLUSIONS: KDZ protects BBB from disruption and improves cerebral outcomes following I/R via preventing the degradation of TJ proteins, caveolin-1 expression, and inhibiting p-caveolin-1 and p-Src, which were most likely attributable to the ability of its main ingredients to bind to Src and inhibit its phosphorylation.


Assuntos
Barreira Hematoencefálica/patologia , Medicamentos de Ervas Chinesas/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Traumatismo por Reperfusão/patologia , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Caveolina 1/antagonistas & inibidores , Caveolina 1/metabolismo , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Masculino , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/farmacologia , Fosforilação/efeitos dos fármacos , Ligação Proteica , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle , Proteínas de Junções Íntimas/efeitos dos fármacos , Quinases da Família src/antagonistas & inibidores , Quinases da Família src/metabolismo
14.
J Dairy Sci ; 99(9): 7313-7318, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27423959

RESUMO

Imputation is a cost-effective approach to augment marker data for genomic selection and genome-wide association studies. However, most imputation studies have focused on autosomes. Here, we assessed the imputation of markers on the X chromosome in Holstein cattle for nongenotyped animals and animals genotyped with low-density (Illumina BovineLD, Illumina Inc., San Diego, CA) chips, using animals genotyped with medium-density (Illumina BovineSNP50) chips. A total of 26,884 genotyped Holstein individuals genotyped with medium-density chips were used in this study. Imputation was carried out using FImpute V2.2. The following parameters were examined: treating the pseudoautosomal region as autosomal or as X specific, different sizes of reference groups, different male/female proportions in the reference group, and cumulated degree of relationship between the reference group and target group. The imputation accuracy of markers on the X chromosome was improved if the pseudoautosomal region was treated as autosomal. Increasing the proportion of females in the reference group improved the imputation accuracy for the X chromosome. Imputation for nongenotyped animals in general had lower accuracy compared with animals genotyped with the low-density single nucleotide polymorphism array. In addition, higher cumulative pedigree relationships between the reference group and the target animal led to higher imputation accuracy. In the future, better marker coverage of the X chromosome should be developed to facilitate genomic studies involving the X chromosome.


Assuntos
Bovinos/genética , Marcadores Genéticos/genética , Estudo de Associação Genômica Ampla/veterinária , Genótipo , Cromossomo X/genética , Animais , Cruzamento/métodos , Feminino , Genoma , Genômica , Masculino , Linhagem , Polimorfismo de Nucleotídeo Único/genética
15.
Org Biomol Chem ; 13(35): 9294-9, 2015 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-26235312

RESUMO

A fluorescent calix[4]arene triazole-linked pyrene (CP) was carefully designed and synthesized via click chemistry. The modification of CP with graphene oxide (GO) by a simple non-covalent interaction strategy is presented. Further inspection by electrochemical impedance spectroscopy reveals that the CP-GO could exhibit a very high supramolecular recognition for carbaryl, in particular in serum samples with a nanomolar concentration detection. Additionally, it is easy to directly observe macroscopic recognition by the contact angle, and expand practical applications.


Assuntos
Calixarenos/química , Carbaril/sangue , Técnicas de Química Analítica/instrumentação , Corantes Fluorescentes/química , Grafite/química , Fenóis/química , Pirenos/química , Triazóis/química , Carbaril/química , Química Click , Modelos Moleculares , Conformação Molecular
16.
Am J Physiol Gastrointest Liver Physiol ; 306(4): G289-300, 2014 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-24356882

RESUMO

Lipopolysaccharide (LPS) is one of the common pathogens that causes mesentery hyperpermeability- and intestinal edema-related diseases. This study evaluated whether ginsenoside Rb1 (Rb1), an ingredient of a Chinese medicine Panax ginseng, has beneficial effects on mesentery microvascular hyperpermeability induced by LPS and the underlying mechanisms. Male Wistar rats were continuously infused with LPS (5 mg · kg(-1) · h(-1)) via the left jugular vein for 90 min. In some rats, Rb1 (5 mg · kg(-1) · h(-1)) was administrated through the left jugular vein 30 min after LPS infusion. The dynamics of fluorescein isothiocynate-labeled albumin leakage from mesentery venules was assessed by intravital microscopy. Intestinal tissue edema was evaluated by hematoxylin and eosin staining. The number of caveolae in endothelial cells of microvessels was examined by electron microscopy. Confocal microscopy and Western blotting were applied to detect caveolin-1 (Cav-1) expression and phosphorylation, junction-related proteins, and concerning signaling proteins in intestinal tissues and human umbilical vein endothelial cells. LPS infusion evoked an increased albumin leakage from mesentery venules that was significantly ameliorated by Rb1 posttreatment. Mortality and intestinal edema around microvessels were also reduced by Rb1. Rb1 decreased caveolae number in endothelial cells of microvessels. Cav-1 expression and phosphorylation, VE-Cadherin phosphorylation, ZO-1 degradation, nuclear factor-κB (NF-κB) activation, and Src kinase phosphorylation were inhibited by Rb1. Rb1 ameliorated microvascular hyperpermeability after the onset of endotoxemia and improved intestinal edema through inhibiting caveolae formation and junction disruption, which was correlated to suppression of NF-κB and Src activation.


Assuntos
Permeabilidade Capilar/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Endotoxemia/tratamento farmacológico , Ginsenosídeos/farmacologia , Lipopolissacarídeos , Mesentério/irrigação sanguínea , Albumina Sérica/metabolismo , Animais , Antígenos CD/metabolismo , Caderinas/metabolismo , Cavéolas/efeitos dos fármacos , Cavéolas/metabolismo , Caveolina 1/metabolismo , Modelos Animais de Doenças , Esquema de Medicação , Edema/induzido quimicamente , Edema/metabolismo , Edema/prevenção & controle , Células Endoteliais/metabolismo , Endotoxemia/induzido quimicamente , Endotoxemia/metabolismo , Endotoxemia/patologia , Ginsenosídeos/administração & dosagem , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Infusões Intravenosas , Interleucina-6/sangue , Masculino , NF-kappa B/metabolismo , Fosforilação , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Fator de Necrose Tumoral alfa/sangue , Vênulas/efeitos dos fármacos , Vênulas/metabolismo , Proteína da Zônula de Oclusão-1/metabolismo , Quinases da Família src/metabolismo
17.
Am J Physiol Heart Circ Physiol ; 307(12): H1764-76, 2014 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-25305180

RESUMO

Cardiac ischemia-reperfusion (I/R) injury remains a challenge for clinicians, which initiates with energy metabolism disorder. The present study was designed to investigate the protective effect of notoginsenoside R1 (NR1) on I/R-induced cardiac injury and underlying mechanism. Male Sprague-Dawley rats were subjected to 30-min occlusion of the left coronary anterior descending artery followed by reperfusion with or without NR1 pretreatment (5 mg·kg(-1)·h(-1)). In vitro, H9c2 cells were cultured under oxygen and glucose deprivation/reoxygenation conditions after NR1 (0.1 mM), Rho kinase (ROCK) inhibitor Y-27632 (10 µM), or RhoA/ROCK activator U-46619 (10 nM) administration. Myocardial infarct size, myocardial histology, and cardiac function were evaluated. Myofibril and mitochondria morphology were observed by transmission electron microscopy. F-actin and apoptosis were determined by immunofluorescence and TUNEL staining. ATP and AMP content were assessed by ELISA. Phosphorylated-AMP-activated protein kinase, ATP synthase subunits, apoptosis-related molecules, and the level and activity of ROCK were determined by Western blot analysis. We found that NR1 pretreatment ameliorated myocardial infarction, histological injury, and cardiac function induced by I/R. Furthermore, similar to the effect of Y-27632, NR1 improved H9c2 cell viability, maintained actin skeleton and mitochondria morphology, and attenuated apoptosis induced by oxygen and glucose deprivation/reoxygenation. Importantly, NR1 prevented energy abnormity, inhibited the expression and activation of ROCK, and restored the expression of the mitochondrial ATP synthase δ-subunit both in vivo and in vitro, whereas U-46619 suppressed the effect of NR1. These results prove NR1 as an agent able to prevent I/R-induced energy metabolism disorder via inhibiting ROCK and enhancing mitochondrial ATP synthase δ-subunits, which at least partially contributes to its protection against cardiac I/R injury.


Assuntos
Cardiotônicos/farmacologia , Ginsenosídeos/farmacologia , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacologia , Actinas/metabolismo , Trifosfato de Adenosina/metabolismo , Amidas/farmacologia , Animais , Apoptose , Cardiotônicos/uso terapêutico , Técnicas de Cultura de Células , Hipóxia Celular , Inibidores Enzimáticos/farmacologia , Ginsenosídeos/uso terapêutico , Masculino , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/ultraestrutura , Miofibrilas/efeitos dos fármacos , Miofibrilas/metabolismo , Miofibrilas/ultraestrutura , Piridinas/farmacologia , Ratos , Ratos Sprague-Dawley , Quinases Associadas a rho/antagonistas & inibidores , Quinases Associadas a rho/genética , Quinases Associadas a rho/metabolismo
18.
Microcirculation ; 21(7): 615-27, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24702968

RESUMO

OBJECTIVE: TSI is a new drug derived from Chinese medicine for treatment of ischemic stroke in China. The aim of this study was to verify the therapeutic effect of TSI in a rat model of MCAO, and further explore the mechanism for its effect. METHODS: Male Sprague-Dawley rats were subjected to right MCAO for 60 minutes followed by reperfusion. TSI (1.67 mg/kg) was administrated before reperfusion via femoral vein injection. Twenty-four hours after reperfusion, the fluorescence intensity of DHR 123 in, leukocyte adhesion to and albumin leakage from the cerebral venules were observed. Neurological scores, TTC staining, brain water content, Nissl staining, TUNEL staining, and MDA content were assessed. Bcl-2/Bax, cleaved caspase-3, NADPH oxidase subunits p47(phox)/p67(phox)/gp91(phox), and AMPK/Akt/PKC were analyzed by Western blot. RESULTS: TSI attenuated I/R-induced microcirculatory disturbance and neuron damage, activated AMPK, inhibited NADPH oxidase subunits membrane translocation, suppressed Akt phosphorylation, and PKC translocation. CONCLUSIONS: TSI attenuates I/R-induced brain injury in rats, supporting its clinic use for treatment of acute ischemic stroke. The role of TSI may benefit from its antioxidant activity, which is most likely implemented via inactivation of NADPH oxidase through a signaling pathway implicating AMPK/Akt/PKC.


Assuntos
Alcenos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Infarto da Artéria Cerebral Média/tratamento farmacológico , Microcirculação/efeitos dos fármacos , NADPH Oxidases/fisiologia , Neurônios/efeitos dos fármacos , Polifenóis/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Proteínas Quinases Ativadas por AMP/fisiologia , Alcenos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Permeabilidade Capilar/efeitos dos fármacos , Infarto Cerebral/etiologia , Infarto Cerebral/patologia , Infarto Cerebral/prevenção & controle , Medicamentos de Ervas Chinesas/farmacologia , Infarto da Artéria Cerebral Média/enzimologia , Infarto da Artéria Cerebral Média/fisiopatologia , Leucócitos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Transtornos dos Movimentos/etiologia , Transtornos dos Movimentos/prevenção & controle , Proteínas do Tecido Nervoso/fisiologia , Neurônios/enzimologia , Fosforilação/efeitos dos fármacos , Polifenóis/farmacologia , Proteína Quinase C/fisiologia , Transporte Proteico/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/fisiologia , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/enzimologia , Traumatismo por Reperfusão/fisiopatologia , Transdução de Sinais/efeitos dos fármacos
19.
Microcirculation ; 21(8): 703-16, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24919947

RESUMO

OBJECTIVE: The purpose of this study was to explore the protective effect of AP on LPS-induced PMD and ALI. METHODS: Male SD rats were continuously infused with LPS (5 mg/kg/h) for one hour to induce PMD and ALI. AP was administrated orally one hour before LPS exposure. Arterial blood pressure and HR were monitored. Blood gas analysis, histological observation, cytokines in plasma, leukocyte recruitment, pulmonary oxidative stress, microvessel permeability, edema, and related proteins were evaluated six hours after LPS challenge. RESULTS: Rats receiving LPS exhibited significant alterations, including hypotension, tachycardia, increase in cytokines, neutrophil adhesion and infiltration, oxidative stress, and microvessel hyperpermeability, resulting in pulmonary injury and dysfunction. AP (0.18 g/kg or 1.8 g/kg) improved rat survival rate, and significantly attenuated all aforementioned insults, and inhibited LPS-induced increase in adhesion molecules, up-regulation of Cav-1 and Src kinase and NADPH oxidase subunits (p47(phox) and p67(phox) ) membrane translocation in lung tissue, and preserved JAM-1 and claudin-5. CONCLUSIONS: The results demonstrated the protective effect of AP on LPS-induced PMD and ALI, suggesting the potential of AP as a prophylactic strategy for LPS-induced ALI.


Assuntos
Lesão Pulmonar Aguda , Anti-Inflamatórios não Esteroides/farmacologia , Diterpenos/farmacologia , Lipopolissacarídeos/toxicidade , Pulmão , Microcirculação/efeitos dos fármacos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Lesão Pulmonar Aguda/fisiopatologia , Lesão Pulmonar Aguda/prevenção & controle , Animais , Moléculas de Adesão Celular/metabolismo , Claudina-5/metabolismo , Citocinas/metabolismo , Pulmão/irrigação sanguínea , Pulmão/metabolismo , Pulmão/patologia , Masculino , NADH NADPH Oxirredutases/metabolismo , NADPH Oxidases/metabolismo , Infiltração de Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Neutrófilos/patologia , Ratos
20.
Artigo em Inglês | MEDLINE | ID: mdl-38249821

RESUMO

Objective: To investigate the knowledge of pulmonary rehabilitation (PR) among physicians involved in pulmonary disease management. Methods: This multi-regional cross-sectional survey was conducted from December 12, 2019 to January 22, 2020. The participants were enrolled and an electronic questionnaire was exclusively sent to the members of the Lung Cancer Special Committee of the China Medicine Education Association through the WeChat platform. Multivariable logistic regression analysis was performed to explore the associated factors of high PR knowledge scores (≥ 18 points). Results: From the 858 valid questionnaires, the routine implementation of PR was only reported for 16.95% of physicians. The main reason hindering the implementation of PR for patients was the limited knowledge and awareness of PR among the physicians involved (69.1%). A total of 618 and 240 physicians had high and low knowledge scores, respectively. Multivariable analysis suggests that the self-perception of PR knowledge (OR = 1.89, 95% CI: 1.32-2.771, P = 0.001) was independently associated with high knowledge scores, while having no theoretical knowledge of PR was associated with poor knowledge scores (OR = 0.43, 95% CI: 0.26-0.72, P = 0.001). Conclusion: Inadequate knowledge of pulmonary rehabilitation is evident among physicians who are involved in pulmonary disease management in China. This underscores the need for more comprehensive and standardized training to bolster their awareness and effective utilization of pulmonary rehabilitation.


Assuntos
Neoplasias Pulmonares , Médicos , Doença Pulmonar Obstrutiva Crônica , Humanos , Estudos Transversais , China
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