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1.
Pharm Biol ; 57(1): 641-648, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31564190

RESUMO

Context: Caragana pruinosa Kom. (Fabaceae), a commonly used folk medicine, has been found to possess antitumor effects. However, the antiproliferative effect of 2,4-dihydroxy-3'-methoxy-4'-ethoxychalcone (DMEC) derived from C. pruinosa against multiple myeloma (MM) has never been investigated. Objective: This study systematically evaluates the antiproliferative effect of DMEC against MM cells. Materials and methods: The antiproliferative effect of DMEC (1, 2, 4, 8, 16, 32, and 64 µM) on MM cells lines, including RPMI8226, MM.1S, and U266, was examined using Cell counting kit-8 (CCK-8) assay after 24 h incubation. The proapoptotic effect of DMEC (20 µM) was determined using fluorescent microscope and flow cytometer, and its possible underlying mechanisms were further studied by using western blotting analysis. Results: The half maximal inhibitory concentrations (IC50) of DMEC on RPMI8226, MM.1S, and U266 cells were calculated as 25.97, 18.36, and 15.02 µM, respectively. The inhibitory effect of DMEC on MM cells was related to mitochondria-mediated apoptosis via upregulation of the cleaved-caspase-3 (C-3), cleaved-caspase-9 (C-9), Bad, and cytochrome C (Cyto C), but downregulation of the Bcl-2 and poly ADP-ribose polymerase (PARP). Furthermore, DMEC (5, 10, and 20 µM) reduced the expression of phosphatidylinositol-3-kinase (PI3K), phosphorylated (p)-protein kinase B (Akt), and p-mammalian target of rapamycin (p-mTOR), which were further evidenced by pretreatment with IGF-1, a PI3K activator. Conclusion: Collectively, our results indicate that the DMEC could be treated as a new candidate for treatment of multiple myeloma in the future. Also, an in vivo study is warranted in the future.

2.
Mol Med Rep ; 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31545436

RESUMO

The aim of the present study was to investigate whether nuclear factor erythroid 2p45­related factor 2 (Nrf2) overexpression by gene transfer may protect neurons/glial cells and the association between neurons/glial cells and axons in spinal cord injury (SCI). In the present study, Nrf2 recombinant adenovirus (Ad) vectors were constructed. The protein levels of Nrf2 in the nucleus and of the Nrf2­regulated gene products heme oxygenase­1 (HO­1) and NAD (P)H­quinone oxidoreductase­1 (NQO1), were detected using western blot analysis in PC12 cells following 48 h of transfection. Furthermore, the expression of Nrf2 was localized using an immunofluorescence experiment, and the expression of Nrf2, HO­1 and NQO1 were detected using an immunohistochemical experiment in the grey matter of spinal cord in rats. Post­injury motor behavior was assessed via the Basso, Beattie and Bresnahan (BBB) locomotor scale method. In PC12 cells, subsequent to Ad­Nrf2 transfection, nuclear Nrf2, HO­1 and NQO1 levels were significantly increased compared with the control (P<0.01). There was statistically significant changes in the PC12­Ad­Nrf2 group [Nrf2 (1.146±0.095), HO­1 (1.816±0.095) and NQO1 (1.421±0.138)] compared with the PC12­control group [Nrf2 (0.717±0.055), HO­1 (1.264±0.081) and NQO1 (0.921±0.088)] and PC12­Ad­green fluorescent protein group [Nrf2 (0.714±0.111), HO­1 (1.238±0.053) and NQO1 (0.987±0.045); P<0.01]. The BBB scores of the rats indicated that they had improved functional recovery following the local injection of Ad­Nrf2. On the third day following the operation, BBB scores in the adenovirus groups (0.167±0.408) were significantly decreased compared with the SCI group (1±0.894; P<0.05). In the injured section of the spinal cord in the rats, the number of positive cells expressing Nrf2, HO­1 and NQO1 were raised compared with the control and SCI groups, indicating that the adenovirus vector­mediated gene transfer of Nrf2 promotes functional recovery following spinal cord contusion in rats.

3.
Endocrine ; 2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30430352

RESUMO

PURPOSE: Osteoporosis is a condition characterized by decreased bone density and bone strength, commonly observed among older individuals. Caveolin-3 (CAV3) is a principal structural protein of the caveolae membrane domains, which has been reported to participate in cell signaling as well as the maintenance of cell structure. The aim of the current study was to investigate the effects involved with the silencing of CAV3 on bone formation among osteoporotic rat models via the Wnt signaling pathway. METHODS: Osteoporosis was initially induced by means of ovariotomy among rat models in order to determine the expression of CAV3. Then, to confirm the specific function and mechanism of CAV3 from an osteoporosis perspective, the CAV3 expression vector was constructed and transfected into the osteoblasts of the osteoporotic rats. Afterward, the mRNA and protein expressions of CAV3, ß-catenin, low-density lipoprotein receptor-related protein 5 (LRP5), T-cell factor (TCF), and Wnt3a in addition to cell proliferation and apoptosis were detected accordingly. RESULTS: Positive expression of CAV3 exhibited diminished levels in the bone tissues of osteoporotic rats. The osteoblasts of the osteoporotic rats treated with overexpressed CAV3 displayed elevated mRNA and protein expression levels of ß-catenin, LRP5, TCF, and Wnt3a. Increased cell proliferation and decreased cell apoptosis were also observed, while the osteoblasts of the osteoporotic rats treated with si-CAV3 exhibited an opposite result. CONCLUSION: Overexpressed CAV3 promotes bone formation and suppresses the osteoporosis progression via the activation of the Wnt signaling in rat models, suggesting CAV3 as a potential target biomarker in the treatment of osteoporosis.

4.
J Hazard Mater ; 346: 10-18, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29232612

RESUMO

Aliphatic hydrocarbons (AHs) are major petroleum contaminants in the environment. In this study, the AHs bound to various soil endogenetic humus fractions were separated through successive extraction. Most of the AHs (46.1%) in soils were adsorbed onto/into humic acids (HA) and a small quantity of AHs (9.6%) were organic solvent extractable. AHs in B. chinensis were also analyzed since their potential risks to the residents through ingestion. AHs from C21 to C34, so called high molecular weight AHs (HMWAHs), were dominant AHs in B. chinensis (85.5%) and soils (70.4%), followed by AHs from C16 to C21, whose mobility can be enhanced via binding to fulvic acids and then can be taken up by plant root lipids (soil-plant pathway). HMWAHs were mainly HA-bound and then were detained in the top soil layers. HMWAHs associated with fine topsoil particles could be transported to B. chinensis via the soil-air-plant pathway, including resuspension and aboveground plant cuticle capture. Results from Principal Component Analysis combined with Regression Analysis supported this assumption due to the positive correlations between HMWAHs concentration in B. chinensis and fine particle contents in soils. This work presents the distributions of petroleum contaminants that result from previously described behavior mechanisms.


Assuntos
Brassica/química , Substâncias Húmicas/análise , Hidrocarbonetos/análise , Poluentes do Solo/análise , Solo/química , Monitoramento Ambiental , Hidrocarbonetos/química , Poluentes do Solo/química , Verduras/química
5.
Medicine (Baltimore) ; 96(29): e7437, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28723751

RESUMO

INTRODUCTION: High-tension electricity can cause devastating injuries that may result in abdominal wall loss, visceral damage, and sometimes major threat to life. The visceral organ may be exposed after debridement and require flap cover, but the tensile strength of abdominal wall may be lack even if flap transplanted. METHODS: From April 2007 through May 2015, 5 patients with severe abdominal electrical injury were treated at our hospital. Exploratory laparotomy was performed based on their clinical manifestations and debridement findings of abdominal wall at early stage, and decision regarding technique for reconstruction of abdominal wall was based on an assessment of the location and extent of the defect. Medical records were reviewed for these data. RESULTS: Clinical evaluation and debridement findings of the abdomen revealed 4 patients with suspicious visceral damage. Laparotomy was performed in 4 cases, and revealed obvious lesion in 3 cases, including segmental necrosis of small intestine, partial necrosis of diaphragm, left liver and gastric wall, and greater omentum. Five patients underwent abdominal wall reconstruction using island retrograde latissimus dorsi myocutaneous flap or free/island composite anterolateral thigh myocutaneous flap. All flaps survived, abdominal bulging occurred in 3 cases after follow-up of 12 to 36 months. CONCLUSIONS: The clinical manifestations and wound features of abdomen collectively suggest a possible requirement of laparotomy for severe abdominal electrical burns. Retrograde latissimus dorsi myocutaneous flap or composite anterolateral thigh myocutaneous flap is an effective option for reconstruction of abdominal wall loss, the long-term complication of abdominal bulging, however, remains a significant clinical challenge.


Assuntos
Traumatismos Abdominais/cirurgia , Traumatismos por Eletricidade/cirurgia , Laparotomia , Procedimentos Cirúrgicos Reconstrutivos , Traumatismos Abdominais/etiologia , Traumatismos Abdominais/patologia , Adulto , Desbridamento , Traumatismos por Eletricidade/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Retalhos Cirúrgicos/patologia , Fatores de Tempo
6.
J Ethnopharmacol ; 193: 433-444, 2016 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-27664441

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Multiple lines of evidences have suggested that endoplasmic reticulum (ER) stress-related inflammatory responses play a critical role in the pathogenesis of diabetic nephropathy (DN). Moutan Cortex (MC), the root bark of Paeonia suffruticosa Andr., is a well-known traditional Chinese medicine (TCM), which has been used clinically for treating inflammatory diseases in China. The findings from our previous research suggested that terpene glycoside (TG) component of MC possessed favorable anti-inflammatory properties in curing DN. However, the underlying mechanisms of MC-TG for treating DN are still unknown. AIM OF THE STUDY: To explore the role of ER stress-related inflammatory responses in the progression of DN, and to investigate the underlying protective mechanisms of MC-TG in kidney damage. MATERIALS AND METHODS: DN rats and advanced glycation end-products (AGEs) induced HBZY-1 cell dysfunction were established to evaluate the protective effect of MC-TG on ameliorating renal injury. Evaluation of pathological lesions was performed by Masson staining and transmission electron microscopy (TEM). Interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), glucose regulated protein 78 (GRP78/Bip), as well as spliced X box binding protein 1(XBP-1(s)) levels in rat serum were detected by an enzyme-linked immunosorbent assay (ELISA). Furthermore, western blotting (WB) was applied to detect the protein expressions including IL-6, MCP-1, intercellular cell adhesion molecule-1 (ICAM-1), GRP78/Bip, XBP-1 (s), phosphorylated inositol-requiring enzyme-1α (p-IRE1α), cleaved activating transcription factor 6 (ATF6), phosphorylated PKR-like endoplasmic reticulum kinase (p-PERK), and phosphorylated nuclear factor κB p65 (p-NF-κB p65) in vivo and in vitro. Immunohistochemistry (IHC) was carried out to determine the phosphorylation of IRE1α and NF-κB p65 in kidney tissues. RESULTS: Pretreatment with MC-TG could markedly improve renal insufficiency and pathologic changes. It could down-regulate ER stress-related factors GRP78/Bip, XBP-1(s) levels, and also reduce the pro-inflammatory molecules IL-6, MCP-1, and ICAM-1 expressions. Furthermore, a significant decrease in phosphorylation of IRE1α and NF-κB p65 by the treatment of MC-TG. CONCLUSIONS: These findings indicated that MC-TG ameliorated ER stress-related inflammation in the pathogenesis of DN, wherein the protective mechanism might be associated with the inhibition of IRE1/NF-κB activation. Thus, MC-TG might be a potential therapeutic candidate for the prevention and treatment of DN.


Assuntos
Anti-Inflamatórios/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Medicamentos de Ervas Chinesas/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Glicosídeos/farmacologia , Células Mesangiais/efeitos dos fármacos , Insuficiência Renal/prevenção & controle , Terpenos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Produtos Finais de Glicação Avançada/metabolismo , Glicosídeos/química , Glicosídeos/isolamento & purificação , Mediadores da Inflamação/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Células Mesangiais/metabolismo , Células Mesangiais/ultraestrutura , Paeonia/química , Fosforilação , Fitoterapia , Plantas Medicinais , Proteínas Serina-Treonina Quinases/metabolismo , Ratos Sprague-Dawley , Insuficiência Renal/etiologia , Insuficiência Renal/metabolismo , Insuficiência Renal/patologia , Transdução de Sinais/efeitos dos fármacos , Estreptozocina , Terpenos/química , Terpenos/isolamento & purificação , Fator de Transcrição RelA/metabolismo
7.
World J Gastroenterol ; 22(13): 3693-700, 2016 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-27053862

RESUMO

Perivascular epithelioid cell tumor (PEComa) of the pancreas is an unusual tumor deriving from mesenchyma. This paper described a case of pancreatic PEComa, which was initially suspected as neuroendocrine carcinoma by biopsy, and therefore surgical treatment was recommended due to undetermined diagnosis. Examination of the surgical specimen under a microscope showed that the tumor cell's morphology was epithelioid or spindle-shaped, and ranged in a nested pattern. Additionally, these cells had a large extent of acidophilic cytoplasm, no mitotic figures, and expressed HMB-45, melan-p, and smooth muscle actin immunohistochemically. Pathological examination indicated that PEComa originated from the pancreas, but symptoms related to tuberous sclerosis were absent. Since PEComa is extremely rare in the pancreas, it is likely to be ignored in differential diagnosis. In conclusion, our article highlighted the clinicopathological features of PEComa, and we conducted a literature review focusing on PEComa so as to deepen the understanding of this tumor type.


Assuntos
Neoplasias Pancreáticas/patologia , Neoplasias de Células Epitelioides Perivasculares/patologia , Biomarcadores Tumorais/análise , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Feminino , Humanos , Imuno-Histoquímica , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Pancreatectomia , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/cirurgia , Neoplasias de Células Epitelioides Perivasculares/química , Neoplasias de Células Epitelioides Perivasculares/cirurgia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
8.
Zhongguo Zhong Yao Za Zhi ; 41(5): 891-897, 2016 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-28875645

RESUMO

In this study, bovine serum albumin (BSA)/methylglyoxal (MGO) non-enzymatic glycosylation reaction system was used for the evaluation of the inhibitory effects of Moutan Cortex extracts on the formation of AGEs. The HPLC-LC-ESI-MS/MS technology was adopted to test and indentify active components in Moutan Cortex against AGEs formation. The different concentrations of extracts (crude herb concentration 50, 100, 150, 200, 250 g•L⁻¹) from Moutan Cortexwas determined by fluorospectrophotometry, indicating an activity against AGEs formation in different concentrations of extracts, the inhibition ratio were (36.2±5.3)%, (43.5±6.2)%, (55.4±7.8)%, (68.6±6.7)%, (70.4±8.2)%, respectively after 6-day reaction in a dose dependent manner. Besides, the forming speed of AGEs tended to be steady after 24 h reaction. The HPLC technology was used to analyze chromatograms before and after the incubation of Moutan Cortex and methylglyoxal, identify changes in five chromatographic peaks and show decrease or increase in chromatographic peaks. These substances were trigalloyl glucose, tetragalloyl glucose, galloylpaeoniflorin, hexagalloyl glucose and benzoylpaeoniflorin after LC-ESI-MS/MS identification. Extracts from Moutan Cortex showed the remarkable inhibitory effects against formation of AGEs in BSA/glucose system. Furthermore, these potential active components might be associated with the efficacy of Moutan Cortex on treatment of diabetic nephropathy, which enriches basic studies for Moutan Cortex and provides ideas and reference basis for subsequent studies.


Assuntos
Medicamentos de Ervas Chinesas/química , Produtos Finais de Glicação Avançada/química , Paeonia/química , Cromatografia Líquida de Alta Pressão , Aldeído Pirúvico/química , Soroalbumina Bovina/química , Espectrometria de Massas em Tandem
9.
Int J Biol Macromol ; 83: 209-15, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26631636

RESUMO

Recently, there has been a growing research interest on renewable composite due to sustainability concerns. This work demonstrated the possibility of using eucalyptus lignosulfonate calcium (HLS) particles as reinforcement in polyvinyl alcohol (PVA) matrix. 41% and 384.7% improvement of pure PVA tensile strength and Young's modulus were achieved with incorporation of 5 wt% HLS. The above results were ascribed to specific intermolecular interactions between HLS and PVA, suggested by the increasing PVA glass transition and crystalline relaxations temperature, depression of melting point with HLS incorporation. Moreover, this interaction was quantitatively determined by q value of -62.4±10.0 in Kwei equation. Additionally, the remarkable red shift of wavenumber corresponding to hydroxyl group also indicated the formation of strong hydrogen bond in HLS/PVA blend. SEM characterization confirmed that HLS/PVA blends are at least miscible.


Assuntos
Lignina/análogos & derivados , Fenômenos Mecânicos , Álcool de Polivinil/química , Ligações de Hidrogênio , Lignina/química , Temperatura Ambiente
10.
Zhongguo Zhong Yao Za Zhi ; 41(11): 1990-1998, 2016 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-28901091

RESUMO

To evaluate the protective effects of glycosides/phenol component of Moutan Cortex (MC) on renal injury of diabetic nephropathy (DN) rats based on renal function parameters and histopathological examinations(HE staining and transmission electron microscope),and explore its possible mechanism by establishing DN rat models induced by high-sugar high-fat diet combined with streptozotocin (STZ). The results showed that compared with the model group, the MC glycosides/phenol component high and low dose groups(0.808, 0.404 g•kg⁻¹â€¢d⁻¹) could significantly improve serum creatinine, blood urea nitrogen, urine protein and other abnormal renal function parameters. HE staining and transmission electron microscope results showed thickening of glomerular basement membrane, proliferation of mesangial cells and damages of podocyte structure in major rats of model group. However, the intervention of glycosides/phenol component of MC could effectively protect the glomerular injury. To explore its possible mechanism, the expressions of TGF-ß1, fibronectin (FN) and collagen Ⅳ in renal tissues of rats in each group were detected by Western blot and immunohistochemical assay, and the phosphorylation levels of downstream effect factors (Smad2/3, p38MARK) of TGF-ß1 were detected. The results showed that glycosides/phenol component of MC could effectively antagonize the activity of TGF-ß1, lower the expressions of fibronectin (FN) and collagen Ⅳ inextracellular matrix (ECM), and resist against the thickening of glomerular basement membrane. More importantly, its protective effect on renal injury in DN rats may be associated with interfering the conduction of Smad, MARK pathways and resisting against the TGF-ß1-induced ECM accumulation.


Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Glicosídeos/farmacologia , Fenóis/farmacologia , Animais , Colágeno Tipo IV/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Fibronectinas/metabolismo , Rim/efeitos dos fármacos , Rim/fisiopatologia , Paeonia , Ratos , Fator de Crescimento Transformador beta1/metabolismo
11.
Zhongguo Zhong Yao Za Zhi ; 40(5): 920-6, 2015 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-26087557

RESUMO

OBJECTIVE: To study the effect of different composition structures of total paeony glycoside (TPG) component and total phenolic acid of Ligusticum chuanxiong ( TLPA) on sodium dithionite (Na2S2O4) -induced human umbilical vein endothelial cells (HUVEC) hypoxic injury. The baseline geometric proportion was used to design different components structure. And then the best structure of components by cell injury model were optimized. METHOD: A HUVEC hypoxic injury model was established by being induced of Na2S2O4. Cell viability was measured by MTI colorimetric method, intracellular superoxide dismutase (SOD) activity, malondialdehyde (MDA), lactate dehydrogenase( LDH) levels, nitric oxide (NO) contents were measured by kits. At last, Western blot analysis was used to detect the expression of two proteins, Bcl-2 and Bax. RESULT: Compared with the model group, TPG component, TLPA component at different composition structures can significantly increase SOD activity and decrease MDA, LDH, NO levels (P < 0.01, P < 0.05). Paeoniae Radix Rubra and Chuanxiong Rhizoma components can downregulate the expression of Bax protein and upregulate the expression of Bcl-2 protein. The ratio of Bcl-2 and Bax was significantly increased (P < 0 01, P < 0 05), it means that cell apoptosis was inhibited. The results indicate that among all the component composition structures, TPG and TLPA component at the proportion of 8: 2 had the best protection on hypoxic injury of endothelial cells. CONCLUSION: TPG component and TLPA component can resist HUVEC hypoxia injury, the protective effect was the most evident under the structure of 8: 2, which may be due to the inhibition of intracellular lipid peroxidation and cell apoptosis.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Glicosídeos/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Hidroxibenzoatos/farmacologia , Hipóxia/metabolismo , Paeonia/química , Rizoma/química , Apoptose/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/análise , Glicosídeos/análise , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Hidroxibenzoatos/análise , Hipóxia/tratamento farmacológico , Hipóxia/genética , Hipóxia/fisiopatologia , Malondialdeído/metabolismo , Oxigênio/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
12.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 46(2): 173-8, 227, 2015 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-25924424

RESUMO

OBJECTIVE: To explore the protective effect of Cordycepin (3'-deoxyadenosine), a bioactive compound of Cordyceps Sinensis, on injury of podocytes. METHODS: C5b-9-induced podocyte injury was used as a model of membranous nephropathy in vitro. This model was established using mouse podocyte cell line--MPC5. Cordycepin was given as an intervention. Ultra-micro morphological changes were observed by electron microscope. F-actin cytoskeleton and expression of nephrin were observed by fluorescence microscope. The phosphorylation of mitogen-activated protein kinase (MAPK) was measured by Western blot. RESULTS: Stimulated by C5b-9 for 3 h, MPC5 showed secondary foot processes, with cytoskeleton structure damaged, nephrin relocated from the cell surface to the cytoplasm, and cell signal pathway-p38, JNK and ERK activated. Cordycepin protected foot processes and cytoskeleton structures of podocytes, suppressed the redistribution of nephrin, and inhibited p38/JNK action. CONCLUSION: Cordycepin can protect podocyte from C5b-9-induced injury partly through inhibiting the activation of p38/JNK signaling pathway.


Assuntos
Complexo de Ataque à Membrana do Sistema Complemento/fisiologia , Desoxiadenosinas/farmacologia , Podócitos/efeitos dos fármacos , Citoesqueleto de Actina/ultraestrutura , Animais , Linhagem Celular , Sistema de Sinalização das MAP Quinases , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosforilação , Substâncias Protetoras/farmacologia
13.
Asian Pac J Trop Med ; 8(3): 239-42, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25902169

RESUMO

OBJECTIVE: To study the role of microRNA-126 in the development of lung cancer. METHODS: The biological function of microRNA-126 was detected using EdU assay and CCK-8 assay; the target gene of microRNA-126 was analyzed using real time RT-PCR and Western blot assay. RESULTS: In A549 cell line, overexpression of microRNA-126 inhibits the proliferation rate; VEGF is the target gene of microRNA-126; microRNA-126 exerts its function via regulating VEGF protein level. CONCLUSIONS: microRNA-126 inhibits the proliferation in A549 cell line.

14.
Mod Rheumatol ; 25(5): 784-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25736362

RESUMO

OBJECTIVES: A recent genome-wide association study or GWAS identified that anthrax roxin receptor 2 (ANTXR2) was one of the risk loci for ankylosing spondylitis (AS). Previous study also showed that ANTXR2 could potentially affect new bone formation. This study aimed to investigate the possible mechanisms of ANTXR2 involved in AS pathogenesis. METHODS: The expression level of ANTXR2 and miR-124 in peripheral blood was detected by quantitative real-time polymerase chain reaction or qRT-PCR. ANTXR2 was predicted to be a target gene of miR-124 by TargetScan, which was confirmed by luciferase reporter assays. Western blot analysis was used to further investigate the effect of miR-124 on c-Jun N-terminal kinase (JNK) activation and evaluate the activated status of autophagy. RESULTS: We evidenced that ANTXR2 was downregulated and miR-124 was upregulated in peripheral blood from AS patients. Intriguingly, miR-124 targeted ANTXR2 and overexpression of miR-124 in Jurkat cells notably inhibited ANTXR2 expression. ANTXR2 inhibition by miR-124 promoted JNK activation and induced autophagy. CONCLUSIONS: Our results suggested that miR-124 might induce autophagy to participate in AS by targeting ANTXR2, which might be implicated in pathological process of AS.


Assuntos
DNA/genética , Regulação da Expressão Gênica , MicroRNAs/genética , Receptores de Peptídeos/genética , Espondilite Anquilosante/genética , Adulto , Western Blotting , Células Cultivadas , Citometria de Fluxo , Estudo de Associação Genômica Ampla , Humanos , Masculino , MicroRNAs/biossíntese , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Peptídeos/biossíntese , Espondilite Anquilosante/diagnóstico , Espondilite Anquilosante/metabolismo , Tomografia Computadorizada por Raios X
15.
J Biol Chem ; 290(14): 8938-48, 2015 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-25670861

RESUMO

Glioblastoma multiforme (GBM) is known as a highly malignant brain tumor with a poor prognosis, despite intensive research and clinical efforts. In this study, we observed that microRNA-873 (miR-873) was expressed at low levels in GBM and that the overexpression of miR-873 dramatically reduced the cell proliferation, migration, and invasion of GBM cells. Our further investigations of the inhibition mechanism indicated that miR-873 negatively affected the carcinogenesis and metastasis of GBM by down-regulating the expression of IGF2BP1, which stabilizes the mRNA transcripts of its target genes. These results demonstrate that miR-873 may constitute a potential target for GBM therapy.


Assuntos
Neoplasias Encefálicas/patologia , Glioblastoma/patologia , MicroRNAs/fisiologia , Metástase Neoplásica , Proteínas de Ligação a RNA/genética , Animais , Neoplasias Encefálicas/genética , Linhagem Celular Tumoral , Glioblastoma/genética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Regulação para Cima
16.
Zhongguo Gu Shang ; 27(7): 579-82, 2014 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-25338445

RESUMO

OBJECTIVE: To explore the clinical efficacy of self-made Kirschner wire hook in the treatment of severely displaced proximal humerus fractures in children. METHODS: From January 2007 to February 2012,35 children with severely displaced proximal humerus fractures were treated with self-made Kirschner wire hook fixation,including 25 boys and 10 girls with an average age of 13.2 years old ranging from 5 to 17. The duration from injury to operation was 1 to 10 days with an average of 4.5 days. Preoperative diagnoses were confirmed by X-ray films as type III in 26 cases and type IV in 9 according to the Neer-Horwitz classification of the proximal humerus fractures. All fractures were close fracture without nerve or vascular injuries. Anatomical reduction was achieved by open reduction and the fractures were fixed by self-made Kirschner wire hook. Intra-operative and postoperative complications, postoperative radiographic examination, upper extremity length and range of shoulder motion were observed and recorded. Neer score system was used to evaluate shoulder function. RESULTS: All patients were followed up from 6 to 18 months with an average of 12.1 months. The mean Neer score of the injured side was 94.2 +/- 4.8 (ranged, 84 to 99), 30 patients got an excellent result and 5 good according to the Neer scores. The X-ray showed all the fractures healed without shortening deformity or epiphyseal arrest at early stage. There were no complications related to the implant including loosening or breakage of the self-made Kirschner wire hook. The range of shoulder motion in the injuried side was similar to the normal side, except in abductor lift. All the patients could participate in normal physical activities. CONCLUSION: The method of open reduction and fixed with self-made Kirschner wire hook is a safe,effective,convenient treatment for severely displaced proximal humeral fractures in children.


Assuntos
Fios Ortopédicos , Fixação Interna de Fraturas/métodos , Fraturas do Úmero/cirurgia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Fraturas do Úmero/fisiopatologia , Masculino , Amplitude de Movimento Articular
17.
Zhongguo Zhong Yao Za Zhi ; 39(14): 2782-6, 2014 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-25272515

RESUMO

The study on the pharmacokinetics of traditional Chinese medicines (TCMs) is a linking science during the modernization of TCMs, and plays an important role in the studies on the complex material base of TCMs, the in vivo process of ingredient/ component and the pharmacokinetics-pharmacodynamics correlation. However, because of the multi-ingredient/component system of TCMs, how to scientifically reveal the pharmacokinetics that is consistent with TCMs' characteristics has long been a hotspot and difficulty for the exploration. The optimal composition structure of the material basis of TCMs shows the best efficacy, while the difference between the multi-ingredient/component composition structures in the efficacy is closely related to their absorption, transport, metabolism and excretion in vivo. In this article, the authors systematically review the study methods for pharmacokinetics of TCMs and their compounds, and explore the pharmacokinetics of TCMs based on the "component structure theory". As a result, the method for integrating TCM component structure and the TCM pharmacokinetics was proposed to be adopted to intensively study the effect of the component structure on the in vivo TCM multi-ingredient/component pharmacokinetic characteristics, in order to promote the TCM modernization and innovation in China.


Assuntos
Medicina Tradicional Chinesa/métodos , Farmacocinética , Animais , Área Sob a Curva , Química Farmacêutica , Humanos , Relação Estrutura-Atividade
18.
J Ethnopharmacol ; 155(1): 785-95, 2014 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-24953033

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Smilax glabra Roxb. (SGR) is a traditional Chinese herb that has been used in folk for the treatment of diabetic vascular complications. Advanced glycation end products (AGEs)-induced endothelial dysfunction has been thought to be a major cause of diabetic vascular complications. The present study was conducted to investigate the protective effect of SGR extract on AGEs-induced endothelial dysfunction and its underlying mechanisms. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were exposed to 200 µg/ml AGEs to induce endothelial dysfunction. Acridine orange/ethidium bromide (AO/EB) fluorescence assay and Annexin-V/PI double-staining were performed to determine endothelium apoptosis. Dihydroethidium (DHE) fluorescence probe, SOD and MDA kits were used to evaluate oxidative stress. The effect of SGR extract on AGEs-induced TGF-beta1 expression was determined by immunocytochemistry and western blotting. Attenuations of SGR extract on receptor for AGEs (RAGE) expression, extracellular regulated protein kinases (ERK1/2) activation and NF-κB phosphorylation were determined by immunofluorescence assay and western blotting. The blockade assays for RAGE and ERK1/2 were carried out using a specific RAGE-antibody (RAGE-Ab) or a selective ERK1/2 inhibitor PD98059 in immunofluorescence assay. RESULTS: The pretreatment of SGR extract (0.125, 0.25 and 0.5 mg crude drug/ml) significantly attenuated AGEs-induced endothelium apoptosis, and down-regulated TGF-beta1 protein expression in HUVECs. It was also well shown that SGR extract could down-regulate dose-dependently ROS over-generation, MDA content, TGF-beta1 expression, ERK1/2 and NF-κB activation whereas increase significantly SOD activity. Furthermore, the AGEs-induced ERK1/2 activation could be attenuated by the blockade of RAGE-Ab (5 µg/ml) while the NF-κB activation was ameliorated by ERK1/2 inhibitor PD98059 (10 µM). CONCLUSION: These results indicated that SGR extract could attenuate AGEs-induced endothelial dysfunction via RAGE-ERK1/2-NF-κB pathways. Our findings suggest that SGR extract may be beneficial for attenuating endothelial dysfunction in diabetic vascular complications.


Assuntos
Produtos Finais de Glicação Avançada/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Extratos Vegetais/farmacologia , Smilax/química , Anticorpos/imunologia , Apoptose/efeitos dos fármacos , Western Blotting , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Imunofluorescência , Células Endoteliais da Veia Umbilical Humana/patologia , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Receptor para Produtos Finais de Glicação Avançada , Receptores Imunológicos/imunologia , Receptores Imunológicos/metabolismo , Superóxido Dismutase/metabolismo
19.
Zhongguo Zhong Yao Za Zhi ; 39(3): 478-82, 2014 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-24946551

RESUMO

OBJECTIVE: To investigate the effect of Moutan Cortex on mesangial proliferation and basement membrane thickening induced by advanced glycation end products (AGEs). METHOD: The glomerular mesangial cells (MC) injury model was established by inducing by AGEs. The cell were divided into 6 groups: the blank group ( BSA, 200 mg L-1) , the model group (AGEs, 200 mg L-1), the positive control group (AG, 10 mmol L L-1), and drug administration groups, namely the Moutan Cortex-treated high-dose group (2 x 10(-4) g mL(- 1)), the Moutan Cortex-treated medium-dose group (1 x 10(-4) g mL-1 ), and the Moutan Cortex-treated low-dose group (0. 5 x 10(-4) g . mL(-1)). The MTT method was performed to observe the effect of Moutan Cortex on the proliferation of MC. The content of fibronectin (FN) and collagen secretion 1V (Col IV) in cell supernatant were detected by ELISA kits. The western blot analysis was carried out to observe the FN expression. The Real-time PCR analysis was applied to examine the Col IV mRNA expression. RESULT: AGEs significantly increased AGEs-induced MC proliferation and FN and Col 1V secretion. The western blot analysis showed that MC could down-regulate the FN expression of MC secretion. According to the results of the real-time PCR assay, MC could down-regulate AGEs-induced MC secretion Col IV mRNA expression. CONCLUSION: MC had a certain protective effect on MC cultured under AGEs conditions. MC could remarkably inhibit the composition and secretion of Col IV and FN in matrix and the basement membrane thickening, and provide an experimental basis for the treatment of diabetic nephropathy.


Assuntos
Membrana Basal/efeitos dos fármacos , Membrana Basal/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Produtos Finais de Glicação Avançada/efeitos adversos , Células Mesangiais/citologia , Células Mesangiais/efeitos dos fármacos , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Colágeno Tipo IV/genética , Colágeno Tipo IV/metabolismo , Fibronectinas/biossíntese , Regulação da Expressão Gênica/efeitos dos fármacos , Células Mesangiais/metabolismo , Paeonia
20.
Artigo em Inglês | MEDLINE | ID: mdl-24631806

RESUMO

In our research, ultraperformance liquid chromatography/quadrupole-time-of-flight mass spectrometry (U-HPLC/Q-TOF-MS) was established for analyzing the metabolite profiles of Danshensu (DSS) in rat feces, bile, urine, plasma and the possible metabolic pathways were subsequently proposed after the oral dose of 80mg/kg; rat biological samples were collected and pretreated by protein precipitation. Then, the samples were injected into an Acquity ultraperformance liquid chromatography BEHC column with mobile phase consisted of acetonitrile (solvent A)-0.1% formic acid-water (solvent B) with a linear gradient elution program. Totally, 17 metabolites of DSS were identified, including 4, 5, 4 and 4 metabolites in the feces, urine, blood, and bile samples respectively. Most of them were to our knowledge reported for the first time. The results indicated that DSS was metabolized via dehydrogenation, deoxygenation, methylation, glucuronidation, and sulfation pathways in vivo. Among these, methylation was considered as the main physiologic processes of it. This study revealed that U-HPLC/Q-TOF-MS was more accurate and sensitive to detect and identify the possible metabolites and to better understand the metabolism of DSS in vivo.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Lactatos/análise , Lactatos/metabolismo , Animais , Bile/química , Fezes/química , Lactatos/química , Masculino , Espectrometria de Massas/métodos , Redes e Vias Metabólicas , Ratos , Ratos Sprague-Dawley
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