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1.
Biomed Pharmacother ; 173: 116361, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38428310

RESUMO

Gynura procumbens (Lour.) Merr., utilized in traditional Chinese medicine, is known for its liver-protective, liver-soothing, and depression-alleviating properties. This research examines the antidepressant and anti-hyperprolactinemia potentials of an ethanol extract from G. procumbens stems (EEGS) and specific metabolites. To model depression and hyperprolactinemia, chronic unpredictable mild stress (CUMS) was induced in mice and risperidone was administered to rats, respectively. Treatments involved administering low (5 mg/kg), medium (25 mg/kg), and high (125 mg/kg) doses of EEGS and certain metabolites to both models. Behavioral assessments were conducted in the CUMS-induced mice, while the CA3 neuronal damage in mice and histopathological alterations in rat mammary glands were evaluated using Nissl and Hematoxylin & Eosin staining techniques, respectively. EEGS decreased immobility times in the forced swimming and tail suspension tests in mice, enhancing their exploration of the central zone. It elevated the serum levels of 5-hydroxytryptamine, norepinephrine, estradiol, luteinizing hormone (LH), and testosterone in mice. Moreover, EEGS restored the neuronal cell arrangement in the CA3 area, reduced interleukin-1beta mRNA production, and increased the expression of interleukin-10 and beta-catenin mRNA. In the context of risperidone-induced hyperprolactinemia, EEGS lowered blood prolactin levels, reduced the dimensions of rat nipples, and enhanced LH, progesterone, and dopamine levels, alongside mitigating mammary hyperplasia. Among the EEGS selected metabolites, the combined effect of chlorogenic acid and trans-p-coumaric acid was found to be more effective than the action of each compound in isolation. Collectively, the findings indicate that EEGS and its selected metabolites offer promising antidepressant benefits while counteracting hyperprolactinemia.


Assuntos
Asteraceae , Hiperprolactinemia , Ratos , Camundongos , Animais , Hiperprolactinemia/induzido quimicamente , Hiperprolactinemia/tratamento farmacológico , Risperidona/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , RNA Mensageiro , Depressão/induzido quimicamente , Depressão/tratamento farmacológico , Modelos Animais de Doenças , Estresse Psicológico
2.
Front Oncol ; 13: 1099624, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36937390

RESUMO

Introduction: Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer kind. According to recent research, a fatty liver increases the risk of hepatocellular cancer. Nevertheless, the AMPK signaling pathway is crucial. In addition, 5'-AMP-activated protein kinase (AMPK) is strongly linked to alterations in the tumor microenvironment, such as inflammation, hypoxia, and aging. The objective of this study is to evaluate the impact of the AMPK signaling pathway on the progression of fatty liver to HCC. Methods: In this study, we established a mouse liver cancer model using high-fat diets and nano-nitrosamines (nano-DEN). In addition, we employed a transcriptomic technique to identify all mRNAs detected in liver samples at the 25th weekexpression of proteins linked with the LKB1-AMPK-mTOR signaling pathway, inflammation, aging, and hypoxia was studied in microarrays of liver cancer tissues from mice and humans. These proteins included p-AMPK, LKB1, mTOR, COX-2, ß-catenin, HMGB1, p16, and HIF-1α. Results: Data were collected at different times in the liver as well as in cancerous and paracancerous regions and analyzed by a multispectral imaging system. The results showed that most of the genes in the AMPK signaling pathway were downregulated. Prakk1 expression was upregulated compared to control group but downregulated in the cancerous regions compared to the paracancerous regions. Stk11 expression was downregulated in the cancerous regions. Mtor expression was upregulated in the cancerous regions. During liver cancer formation, deletion of LKB1 in the LKB1-AMPK-mTOR signaling pathway reduces phosphorylation of AMPK. It contributed to the upregulation of mTOR, which further led to the upregulation of HIF1α. In addition, the expression of ß-catenin, COX-2, and HMGB1 were upregulated, as well as the expression of p16 was downregulated. Discussion: These findings suggest that changes in the AMPK signaling pathway exacerbate the deterioration of disrupted energy metabolism, chronic inflammation, hypoxia, and cellular aging in the tumor microenvironment, promoting the development of fatty liver into liver cancer.

3.
Front Oncol ; 12: 959322, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091173

RESUMO

Cancer is one of the most serious diseases threatening human health, so it is particularly important to develop effective tumor-targeting drugs. As the first CDK4/6 inhibitor, palbociclib effectively inhibits tumor proliferation by blocking the cell cycle to the G1 phase. 10-HCPT is a Topo I inhibitor; however, its clinical application has been greatly limited due to its high toxicity. Based on the successful development of double target inhibitors, three novel palbociclib derivatives (HP-1, HP-2, and HP-3) were designed and synthesized from Palbociclib and 10-HCPT, and their biological activities were investigated. At first, the possible binding sites of the three compounds to Topo I and CDK4/6 were predicted by molecular docking. Then, we evaluated the anti-proliferative effects of the three palbociclib derivatives. In general, human lung cancer cells were more sensitive to HP-1, HP-2, and HP-3, especially NCI-H460. In addition, cell cycle arrest and apoptosis induction were investigated by flow cytometry. The three palbociclib derivatives, especially HP-1, had obvious cell cycle arrest phenomenon on NCI-H460 cells and induced apoptosis of NCI-H460 cells significantly. In the end, it was proved that these three drugs had obvious cyclin-dependent kinase inhibitory activities. In short, all the data showed that HP-1, HP-2, and HP-3 could play anti-cancer roles by acting on dual targets and had the characteristics of high efficiencies and low toxicities, which opened up a new idea for the study of palbociclib derivatives.

4.
Curr Eye Res ; 47(10): 1381-1388, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35923150

RESUMO

PURPOSE: To explore the effect of doxycycline on vasculogenic mimicry (VM) formation and the potential mechanism in human pterygium fibroblasts in order to find novel targets for pterygium therapy. METHODS: First, we demonstrate the existence of VM in 73 pterygium specimens by CD31 and periodic acid Schiff (PAS) dual staining. Then we used cell counting kit-8, clone formation assay and flow cytometry to prove the inhibitory effect of doxycycline on cell proliferation and apoptosis. The VM formation was evaluated through wound healing assay, cell transwell assay and three-dimensional cell culture combined with PAS staining. Finally, we used Western blot to testify the correlation of the VM and the factors in protein level preliminarily. RESULTS: Our results showed that VM existed in human pterygium specimens exactly. Otherwise, in human pterygium fibroblasts, doxycycline induced a dose-dependent inhibitory effect on cell proliferation and apoptosis induction. Besides, doxycycline significantly suppressed vasculogenic mimicry tube formation, cell migration and invasion. Furthermore, doxycycline impaired the expression of MMP-9, MMP-2 and VEGF which may related to pterygium VM formation. CONCLUSIONS: Doxycycline decelerated pterygium progression might be through inhibiting VM formation according to the downregulation of MMP-9, MMP-2 and VEGF, which may provide the basis of further studies involving doxycycline for pterygium treatment.


Assuntos
Metaloproteinase 2 da Matriz , Pterígio , Linhagem Celular Tumoral , Túnica Conjuntiva/anormalidades , Doxiciclina/farmacologia , Fibroblastos/metabolismo , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Neovascularização Patológica/metabolismo , Ácido Periódico , Pterígio/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/metabolismo
5.
J Ethnopharmacol ; 285: 114917, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34919988

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Gynura procumbens (Lour.) Merr, (Family Asteraceae), which serves as both medicine and food in traditional ethnic medicine, has the effects of diminishing inflammation, relieving cough, reducing blood glucose and lipids levels, mitigating hepatotoxicity, and can be used for liver cancer prevention and treatment. AIM OF THE STUDY: To explore how the ethanol extract of Gynura procumbens stems (EEGS) can effectively intervene in the tumor microenvironment, it is necessary to study the mechanism of EEGS on the chemical toxicant nanodiethylnitrosamine (nanoDEN) that induces liver cancer. MATERIALS AND METHODS: EEGS contains large quantities of caffeoylquinic acid (CAC) and non-caffeoylquinic acid (n-CAC), which can be separated by high-performance liquid chromatography. The liver cancer model that was induced by the chemical toxin, nanoDEN, was used to clarify the effective mechanism for tumor intervention of the EEGS and its active ingredients. RESULTS: (1) after interventions with the four drugs on liver cancer, the tumor nodules were obviously reduced and inflammation levels improved. (2) The immunohistochemical staining results showed that both the EEGS and its active ingredients could significantly reverse the abnormal changes in inflammation, proliferation, aging and hypoxia-related proteins in mouse liver tissues that were caused by nanoDEN. (3) Real-time PCR results showed that compared with the nanoDEN group, the expression levels of inflammatory, fatty, and fibrosis-related factors in each group after drug intervention were decreased. (4) The transmission electron microscopy measurements showed that the EEGS significantly reversed the nanostructure changes in hepatocytes that were induced by nanoDEN. CONCLUSION: The EEGS component of Gynura procumbens is effective in preventing and treating liver cancer by interfering with the inflammatory microenvironment during oncogenesis induced by nanoDEN.


Assuntos
Asteraceae/química , Dietilnitrosamina/toxicidade , Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Etanol , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Masculino , Camundongos , Nanoestruturas , Extratos Vegetais/química , Distribuição Aleatória , Microambiente Tumoral/efeitos dos fármacos
6.
Nanoscale ; 12(26): 14004-14010, 2020 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-32579652

RESUMO

The development of metal-organic frameworks (MOFs) as high-efficiency electrocatalysts for water splitting has attracted special attention due to their unique structural features including high porosity, large surface areas, high concentrations of active sites, uniform pore sizes and shapes, etc. Most of the related reports focus on the in situ generation of high-efficiency electrocatalysts by annealed MOFs. However, the pyrolysis process usually destroys the porous structure of MOFs and reduces the number of active sites due to the absence of organic ligands and agglomeration of metal centers. In this work, we prepared unique NiCo-MOF hollow nanospheres (NiCo-MOF HNSs) by a solvothermal method and further fabricated Fe-doped NiCo-MOF HNSs (Fe@NiCo-MOF HNSs) by a simple impregnation-drying method. Significant enhancement of electrocatalytic activity of Fe@NiCo-MOF HNSs was witnessed because of the doped Fe. Compared with the parent NiCo-MOF HNSs, the optimized Fe@NiCo-MOF HNSs exhibited a lower overpotential of 244 mV at 10 mA·cm-2 with a smaller Tafel slope of 48.61 mV·dec-1, which was lowered by ca. 90 mV due to the influence of Fe doping on the electronic structure of the active centers of Ni and Co. The above materials also displayed excellent stability without obvious activity decay for at least 16 hours. These findings present a new entry in the design and fabrication of high-efficiency MOF-based electrocatalysts for energy conversion.

7.
Nanoscale ; 12(8): 4816-4825, 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32057061

RESUMO

Pristine metal-organic frameworks (MOFs) have received much attention in recent years due to their high specific surface areas, large porosity, excellent pore size distributions, flexible structure, and remarkable catalytic properties. The design of functional MOFs that can function as efficient HER and OER catalysts is significant in solving the energy crisis but remains a big challenge. Tri-metallic metal-organic frameworks show a good application prospect in water oxidation. In this review, we are going to focus on the latest progress and future trends in the development of pristine trimetallic MOFs with respect to the OER. The synergistic effect between multi-metal active sites is effective at improving the intrinsic activity of MOFs toward the OER. By summarizing the synthesis method of tri-metallic MOFs and observing their performance toward the oxygen evolution reaction, we hope that this review will trigger new developments in coordination chemistry, electrochemistry, nanomaterials and energy materials.

8.
RSC Adv ; 10(21): 12145-12150, 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-35497616

RESUMO

As an important two-dimensional material, layered double hydroxides (LDHs) show considerable potential in electrocatalytic reactions. However, the great thickness of the bulk LDH materials significantly limits their catalytic activity. In this work, we report ultrathin NiFe-LDH nanosheets with sulfate interlayer anions (Ni6Fe2(SO4)(OH)16·7H2O) (U-LDH(SO4 2-)), which can be synthesized in gram-scale by a simple solvothermal method. The U-LDH(SO4 2-) shows excellent stability and great electrocatalytic performance in OER with a current density of 10 mA cm-2 at a low overpotential of 212 mV and a small Tafel slope of 65.2 mV dec-1, exhibiting its great potential for a highly efficient OER electrocatalyst.

9.
Inorg Chem ; 58(16): 11202-11209, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31385509

RESUMO

Design and synthesis of non-noble metal electrocatalysts with high activity and durability for the electrolysis of water is of great significance for energy conversion and storage. In this work, we prepared a series of Fe-doped MoS2 nanomaterials by simple one-pot solvothermal reactions of (NH4)2MoS4 with FeCl3·6H2O. An optimized working electrode of Fe-MoS2-5 displayed high hydrogen evolution reaction (HER) activity with a relatively small overpotential of 173 mV to achieve a current density of 10 mA cm-2 in 0.5 M H2SO4, along with no significant change in catalytic performance even after 1000 cyclic voltammetry (CV) cycles. Fe-MoS2 nanoparticles on nickel foam (NF; denoted as Fe-MoS2/NF) exhibited an overpotential of 230 mV at 20 mA cm-2 for the oxygen evolution reaction (OER) and 153 mV at 10 mA cm-2 for the HER in 1.0 M KOH electrolyte. Fe-MoS2/NF was stable for more than 140 h under these conditions. Furthermore, the two electrode system of Fe-MoS2/NF (anode)//Fe-MoS2/NF (cathode) electrodes demonstrated excellent electrocatalytic activity toward overall water splitting with a low potential of 1.52 V at 10 mA cm-2 in 1.0 M KOH electrolyte.

10.
Dalton Trans ; 48(32): 12186-12192, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31334514

RESUMO

The development of bifunctional non-noble metal electrocatalysts demonstrating high activity and stability for the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is of great significance for renewable and clean energy. In this work, we report hierarchically structured integrated Fe-MoS2/Ni3S2/NF (NF = nickel foam) materials prepared by a facile in situ solvothermal method, and among them, the Fe-doped MoS2 was assembled into spine-like nanorods. The optimized electrocatalyst (denoted as Fe-MoS2/Ni3S2/NF-2) demonstrated excellent activity and durability for performing the HER and OER in an alkaline electrolyte (pH = 14) with low overpotentials of 130.6 mV and 256 mV (vs. RHE) at a current density of 10 mA cm-2, as well as no significant loss in catalytic performance even after 2000 cyclic voltammetry (CV) cycles. An outstanding durability of 180 h could be achieved for OER. The overall water splitting made up of the two-electrode system with Fe-MoS2/Ni3S2/NF-2 as both the anode and the cathode required a voltage of only 1.61 V to drive a current density of 10 mA cm-2 along with an outstanding long-term stability of 20 h, displaying its great potential for application in water splitting. The effective construction of multi-component synergistic structures shows a good pathway for high-performance electrocatalysis and energy storage.

11.
Int J Nanomedicine ; 14: 3283-3295, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31123400

RESUMO

Background and aims: Lipid nanoparticles (LNs) are widely applied in drug delivery systems because they can incorporate and stabilize lipophilic and hydrophilic molecules. LNs are generally considered quite safe and convenient for in vivo applications. However, we previously observed that certain types of LNs could cause a loss of Kupffer cells, a kind of resident macrophage in the liver. As a result, we investigated the details of this phenomenon. Methods: MTT assay, Annexin-V-FITC/PI double staining, JC-1 staining, flow cytometry, Western blot and transmission electron microscopy were used in cell-based experiments. Additionally, serum biochemical analyses, H&E staining and immunofluorescence staining were performed to detect the acute and chronic changes of tissue structure and the number of Kupffer cells in mouse liver tissue samples. Results: Application of LN depolarized and swelled the mitochondria of Raw264.7 cells, and disrupted the balance of Bax/Bcl-2. This led to cleavage and activation of caspase-3 and PARP, and then induced apoptosis of Raw264.7 cells. In addition, either acute or chronic applications of LN were sufficient to disrupt the structure of the hepatic portal vein and reduce the number of Kupffer cells in mice. Conclusions: LNs could induce apoptosis of macrophages through a mitochondrial-dependent pathway.


Assuntos
Apoptose , Lipídeos/química , Macrófagos/metabolismo , Mitocôndrias/metabolismo , Nanopartículas/química , Animais , Sobrevivência Celular , Células Hep G2 , Hepatócitos/citologia , Humanos , Células de Kupffer/citologia , Macrófagos/ultraestrutura , Masculino , Camundongos , Nanopartículas/ultraestrutura , Células RAW 264.7 , Transdução de Sinais , Proteína X Associada a bcl-2/metabolismo
12.
Nanoscale ; 10(43): 20189-20195, 2018 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-30378626

RESUMO

Introducing nanoscale heterostructure interfaces into material matrix is an effective strategy to optimize the thermoelectric performance by energy-dependent carrier filtering effect. In this study, highly (00l)-oriented Bi2Te3/Te heterostructure thin films have been fabricated on single-crystal MgO substrates using a facile magnetron co-sputtering method. Bi2Te3/Te heterostructure thin films with Te contents of 63.8 at% show an optimized thermoelectric performance, which possess a Seebeck coefficient of -157.7 µV K-1 and an electrical conductivity of 9.72 × 104 S m-1, leading to a high power factor approaching 25 µW cm-1 K-2. The partially decoupled behavior of the Seebeck coefficient and electrical conductivity is contributed to Bi2Te3/Te heterostructure interfaces, which causes interfacial barrier filtering and scattering effects; thus, a high level of the Seebeck coefficient is obtained. Meanwhile, carrier transport in a-b plane can benefit from the highly preferred orientation, which guarantees a remarkably high electrical conductivity. We anticipate that our strategy may guide the way for preparing high-performance thermoelectric materials by microstructure design and regulation.

13.
Nanomedicine ; 13(2): 701-711, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27729235

RESUMO

Nano-carriers, especially lipid nanoparticles have been used widely in "a good manner", for instance in the treatment of cancer, by enhancing the targetability and reducing required dose. Here in the contrary, we presented a new possibility: nanoDEN, a nanoparticle-packed "bad guy", which is more effective and efficient in generating liver tumor in mice. We have shown that nanoDEN, same as diethylnitrosamine (DEN), induced overexpression of multiple pivotal factors (including COX-2, ß-catenin and PCNA) during oncogenesis. Moreover, nanoDEN increased the apoptosis of liver cells compared with DEN alone. This apoptotic effect of nanoDEN is more efficient on normal cells than on cancer cells. Taken into consideration the fact that there are endogenous nanoparticles naturally formed inside our body, our research enlarged our views of all the aspects of oncogenic chemicals, while also established a better method of producing animal model of liver cancer, which has future investigational and therapeutical potential.


Assuntos
Carcinogênese , Dietilnitrosamina/farmacologia , Lipídeos , Neoplasias Hepáticas/induzido quimicamente , Nanopartículas , Animais , Proliferação de Células , Dietilnitrosamina/administração & dosagem , Modelos Animais de Doenças , Humanos , Fígado , Camundongos
14.
Chem Biol Drug Des ; 83(3): 334-43, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24118825

RESUMO

A series of shikonin derivatives (1-13) that were acylated selectively by various thiophene or indol carboxylic acids at the side chain of shikonin were synthesized, and their biological activities were also evaluated as potential tubulin inhibitors. Among them, compound 3 ((R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-enyl 3-(1H-indol-3-yl)propanoate) and compound 8 ((R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-enyl 2-(thiophen-3-yl)acetate) exhibited good antiproliferative activity of A875 (IC50  = 0.005 ± 0.001 µm, 0.009  ± 0.002 µm) and HeLa (IC50  = 11.84 ± 0.64 µm, 4.62  ± 0.31 µm) cancer cell lines in vitro, respectively. Shikonin (IC50  = 0.46 ± 0.002 µm, 4.80 ± 0.48 µm) and colchicine (IC50  = 0.75 ± 0.05 µm, 17.79 ± 0.76 µm) were used as references. Meanwhile, they also showed the most potent growth inhibitory activity against tubulin (IC50 of 3.96  ± 0.13 µm and 3.05 ± 0.30 µm, respectively), which were compared with shikonin (IC50  =  15.20 ± 0.25 µm) and colchicine (IC50  = 3.50 ± 0.35 µm). Furthermore, from the results of flow cytometer, we found compound 3 can really inhibit HeLa cell proliferation and has low cell toxicity. Based on the preliminary results, compound 3 with potent inhibitory activity in tumor growth may be a potential anticancer agent.


Assuntos
Indóis/síntese química , Indóis/farmacologia , Naftoquinonas/química , Naftoquinonas/síntese química , Naftoquinonas/farmacologia , Tiofenos/síntese química , Tiofenos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Sítios de Ligação , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Colchicina/síntese química , Colchicina/química , Colchicina/farmacologia , Células HeLa , Humanos , Indóis/química , Simulação de Acoplamento Molecular , Estrutura Terciária de Proteína , Tiofenos/química , Tubulina (Proteína)/química , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/síntese química , Moduladores de Tubulina/química , Moduladores de Tubulina/farmacologia
15.
Ophthalmic Res ; 48(2): 82-88, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22473034

RESUMO

Mesenchymal stem cells (MSCs) can play an active role in there construction of the ocular surface; however, the mechanisms by which the implanted MSCs exert their effects remain elusive. In the present study, we investigated the influences of MSCs on cell proliferation and growth factor expression of corneal limbal epithelial cells (LECs) in vitro. Rat LECs were either cocultured with rat MSCs or cultured in rat MSC condition edmedium. The harvested LECs were subjected to light microscopy, MTT assay, bromodeoxyuridine (BrdU)staining, flow cytometry and real-time quantitative RT-PCR analysis, respectively. Light microscopy showed that coculturing of LECs with MSCs significantly increased the proliferation of LECs. The MTT assay showed that MSC-conditioned medium significantly increased the cell viability of LECs compared to those incubated with plain medium. BrdU immunostaining and flow-cytometric analysis of the cell cycle showed that the cell proliferation rate of LECs cocultured with MSCs was significantly higher than that of LECs cultured alone. Real-time quantitative RT-PCR analysis showed that expression of epidermal growth factor in LECs cocultured with MSCs was significantly higher than that in LECs cultured alone. However, expression of basic fibroblast growth factor showed no difference under the two culture conditions. These results indicate that MSCs promote the survival and proliferation of LECs, and these effects may be mediated ina paracrine manner.


Assuntos
Células da Medula Óssea/fisiologia , Proliferação de Células , Fator de Crescimento Epidérmico/genética , Epitélio Corneano/citologia , Fator 2 de Crescimento de Fibroblastos/genética , Limbo da Córnea/citologia , Células-Tronco Mesenquimais/fisiologia , Animais , Ciclo Celular , Sobrevivência Celular , Técnicas de Cocultura , Ensaio de Imunoadsorção Enzimática , Fator de Crescimento Epidérmico/metabolismo , Epitélio Corneano/metabolismo , Fator 2 de Crescimento de Fibroblastos/metabolismo , Citometria de Fluxo , Técnica Indireta de Fluorescência para Anticorpo , Expressão Gênica , Limbo da Córnea/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real
16.
J Bacteriol ; 194(6): 1464-73, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22228730

RESUMO

Streptococcus suis serotype 2 (S. suis 2) is an important swine and human pathogen responsible for septicemia and meningitis. A novel gene, designated atl and encoding a major autolysin of S. suis 2 virulent strain HA9801, was identified and characterized in this study. The Atl protein contains 1,025 amino acids with a predicted molecular mass of 113 kDa and has a conserved N-acetylmuramoyl-l-alanine amidase domain. Recombinant Atl was expressed in Escherichia coli, and its bacteriolytic and fibronectin-binding activities were confirmed by zymography and Western affinity blotting. Two bacteriolytic bands were shown in the sodium dodecyl sulfate extracts of HA9801, while both were absent from the atl inactivated mutant. Cell chains of the mutant strain became longer than that of the parental strain. In the autolysis assay, HA9801 decreased to 20% of the initial optical density (OD) value, while the mutant strain had almost no autolytic activity. The biofilm capacity of the atl mutant was reduced ∼30% compared to the parental strain. In the zebrafish infection model, the 50% lethal dose of the mutant strain was increased up to 5-fold. Furthermore, the adherence to HEp-2 cells of the atl mutant was 50% less than that of the parental strain. Based on the functional analysis of the recombinant Atl and observed effects of atl inactivation on HA9801, we conclude that Atl is a major autolysin of HA9801. It takes part in cell autolysis, separation of daughter cells, biofilm formation, fibronectin-binding activity, cell adhesion, and pathogenesis of HA9801.


Assuntos
Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , N-Acetil-Muramil-L-Alanina Amidase/genética , N-Acetil-Muramil-L-Alanina Amidase/metabolismo , Streptococcus suis/enzimologia , Animais , Proteínas de Bactérias/química , Biofilmes/crescimento & desenvolvimento , Adesão Celular , Modelos Animais de Doenças , Eletroforese em Gel de Poliacrilamida , Escherichia coli/genética , Fibronectinas/metabolismo , Deleção de Genes , Expressão Gênica , Células Hep G2 , Humanos , Dose Letal Mediana , Peso Molecular , N-Acetil-Muramil-L-Alanina Amidase/química , Ligação Proteica , Estrutura Terciária de Proteína , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Infecções Estreptocócicas/microbiologia , Streptococcus suis/genética , Streptococcus suis/crescimento & desenvolvimento , Streptococcus suis/metabolismo , Análise de Sobrevida , Virulência , Peixe-Zebra
17.
Int J Ophthalmol ; 4(1): 33-6, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22553604

RESUMO

AIM: To investigate the effect of amniotic membrane transplantation (AMT) on the expressions of inflammatory-related, angiogenic-related and growth-related cytokines in rat corneas after chemical injury. METHODS: Alkali wounds were inflicted on the central corneas of rats by applying a round filter paper soaked in 1mol/L NaOH for 40 seconds. One week after alkali burn, 12 rats were randomly divided into 2 groups: the AMT group and the control group, and AMT was performed on the rats in the AMT group. Corneal opacity and neovascularization were observed by slit-lamp microscopy. The protein levels of interleukin (IL)-2, interferon (IFN)-γ, IL-10 and transforming growth factor (TGF)-ß were determined by enzyme-linked immunosorbent assay 2 weeks after AMT. The mRNA levels of matrix metalloproteinase-2 (MMP-2), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) were evaluated by real-time quantitative PCR. RESULTS: In the AMT group, the corneal opacity was improved (P=0.011) and the area of corneal neovascularization was significantly decreased (P=0.005) compared with the control group. The amount of IL-2 and IFN-γ secreted by Th1 cells were decreased after AMT, whereas the amount of IL-10 and TGF-ß secreted by Th2 cells were increased (P<0.05). The level of MMP-2 was significantly down-regulated (P=0.013) at the mRNA level in the AMT group, while the expression of EGF was significantly higher (P=0.022) compared with controls. CONCLUSION: [corrected] AMT may suppress corneal neovascularization after chemical injury by modulating the expressions of soluble factors.

18.
Zhong Xi Yi Jie He Xue Bao ; 5(5): 536-40, 2007 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-17854555

RESUMO

OBJECTIVE: To study the expression of angiopoietin receptor Tie-2 in the renal tissue of diabetic rats and the effects of Astragalus. METHODS: SD rats were randomly divided into normal control group, diabetes group and Astragalus-treated group. The expression of receptor Tie-2 in the renal tissue was assessed by using real-time quantitative polymerase chain reaction and immunohistochemical method. RESULTS: Glomerule Tie-2 protein expression was significantly elevated in the diabetes group as compared with the normal control group (P<0.01). Glomerule Tie-2 protein expression in the Astragalus-treated group was decreased as compared with the diabetes group (P<0.01). CONCLUSION: Tie-2 may play an important role in the pathogenesis of the early stage diabetic renal injury. The reno-protection effect of Astragalus may be mediated by down-regulating the expression of Tie-2 in the kidney tissue of diabetic rats.


Assuntos
Astragalus propinquus/química , Diabetes Mellitus Experimental/metabolismo , Rim/metabolismo , Extratos Vegetais/farmacologia , Receptor TIE-2/metabolismo , Animais , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/metabolismo , Regulação para Baixo , Rim/patologia , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
19.
Zhongguo Zhen Jiu ; 26(12): 851-3, 2006 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-17313004

RESUMO

OBJECTIVE: To explore effect of acupuncture at Zusanli (ST 36) and Xuanzhong (GB 39) on cerebrovascular function in the patient of ischemic stroke. METHODS: Three central, single blind, randomized controlled trial method was adopted, and 160 cases were randomly divided into an acupuncture group and a control group, 80 cases in each group. The two groups were treated by routine treatment for ischemic stroke with acupuncture at Zusanli (ST 36) and Xuanzhong (GB 39) added in the acupuncture group. Changes of TCD cerebrovascular blood flow indexes before and after treatment were evaluated. RESULTS: After treatment, TCD indexes significantly improved in the acupuncture group (P < 0.05, P < 0.01) with a significant difference as compared with that in the control group (P < 0.05). CONCLUSION: Acupuncture at Zusanli (ST 36) and Xuanzhong (GB 39) can significantly improve cerebral vasomotoricity, cerebral blood flow auto-regulative function, cerebral hemisphere collateral circulation comprehental function in the patient of ischemic stroke.


Assuntos
Pontos de Acupuntura , Terapia por Acupuntura/métodos , Isquemia Encefálica/terapia , Circulação Cerebrovascular , Acidente Vascular Cerebral/terapia , Adulto , Idoso , Isquemia Encefálica/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/fisiopatologia , Ultrassonografia Doppler Transcraniana
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