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1.
Chin J Nat Med ; 18(2): 123-137, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32172948

RESUMO

Fructus Psoraleae, which is commonly consumed for the treatment of osteoporosis, bone fracture, and leucoderma, induces liver injury. This study investigated the pathogenesis of the ethanol extract of Fructus Psoraleae (EEFP)-induced liver injury in rats. EEFP (1.35, 1.80, and 2.25 g·kg-1) was administrated to Sprague Dawley (SD) rats for 30 d. We measured liver chemistries, histopathology, and quantitative isobaric tags for relative and absolute quantitation (iTRAQ)-based protein profiling. EEFP demonstrated parameters suggestive of liver injury with changes in bile secretion, bile flow rate, and liver histopathology. iTRAQ analysis showed that a total of 4042 proteins were expressed in liver tissues of EEFP-treated and untreated rats. Among these proteins, 81 were upregulated and 32 were downregulated in the treatment group. KEGG pathway analysis showed that the drug metabolic pathways of cytochrome P450, glutathione metabolism, glycerolipid metabolism, and bile secretion were enriched with differentially expressed proteins. The expression of key proteins related to the farnesoid X receptor (FXR), i.e., the peroxisome proliferators-activated receptor alpha (PPAR-α), were downregulated, and multidrug resistance-associated protein 3 (MRP3) was upregulated in the EEFP-treated rats. Our results provide evidence that EEFP may induce hepatotoxicity through various pathways. Furthermore, our study demonstrates changes in protein regulation using iTRAQ quantitative proteomics analysis.

2.
Acta Pharmacol Sin ; 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31937931

RESUMO

Mitochondria serve as sensors of energy regulation and glucose levels, which are impaired by diabetes progression. Catalpol is an iridoid glycoside that exerts a hypoglycemic effect by improving mitochondrial function, but the underlying mechanism has not been fully elucidated. In the current study we explored the effects of catalpol on mitochondrial function in db/db mice and C2C12 myotubes in vitro. After oral administration of catalpol (200 mg·kg-1·d-1) for 8 weeks, db/db mice exhibited a decreased fasting blood glucose level and restored mitochondrial function in skeletal muscle. Catalpol increased mitochondrial biogenesis, evidenced by significant elevations in the number of mitochondria, mitochondrial DNA levels, and the expression of three genes associated with mitochondrial biogenesis: peroxisome proliferator-activated receptor gammaco-activator 1 (PGC-1α), mitochondrial transcription factor A (TFAM) and nuclear respiratory factor 1 (NRF1). In C2C12 myotubes, catalpol significantly increased glucose uptake and ATP production. These effects depended on activation of AMP-activated protein kinase (AMPK)-mediated mitochondrial biogenesis. Thus, catalpol improves skeletal muscle mitochondrial function by activating AMPK-mediated mitochondrial biogenesis. These findings may guide the development of a new therapeutic approach for type 2 diabetes.

3.
ACS Omega ; 4(13): 15560-15566, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31572857

RESUMO

Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer deaths worldwide. Integrin α6 is overexpressed in all stages of CRC which makes it a potential diagnostic biomarker for CRC. Previously, we identified an integrin α6-targeted peptide CRWYDENAC (dubbed RWY) using phage display technology and employed it for nasopharyngeal carcinoma specific nanotherapeutics. In this study, we developed a radiotracer, 18F-RWY, based on this integrin α6-targeted RWY peptide for positron emission tomography (PET) imaging of CRC. Integrin α6 was overexpressed on several CRC cells including HT29 cells where the biotin-labeled RWY peptide colocalized with integrin α6. 18F-RWY PET imaging was performed on subcutaneous, chemically induced, and genetically engineered CRC mice. 18F-RWY generated high PET signals in subcutaneous HT29 tumors, and the tumor uptake of 18F-RWY was reduced by a blocking study using nonradio-labeled RWY. Moreover, 18F-RWY PET imaging enabled detection of CRC in chemically induced and genetically engineered CRC mice. The overexpression of integrin α6 in tumor tissues isolated from chemically induced and genetically engineered CRC mice was confirmed. These results demonstrate the potential clinical application of 18F-RWY for PET imaging of CRC.

4.
Molecules ; 24(18)2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31527444

RESUMO

The purpose of this study was to characterize the polysaccharides from Athyrium multidentatum (Doll.) Ching (AMC) rhizome and explore the protective mechanism against d-galactose-induced oxidative stress in aging mice. METHODS: A series of experiments, including molecular weight, monosaccharide composition, Fourier transform infrared (FT-IR) spectroscopy, and 1H nuclear magnetic resonance (1H NMR) spectroscopy were carried out to characterize AMC polysaccharides. The mechanism was investigated exploring d-galactose-induced aging mouse model. Quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) and western blotting assays were performed to assess the gene and protein expression in liver. KEY FINDINGS: Our results showed that AMC polysaccharides were mainly composed of mannose (Man), rhamnose (Rha), glucuronic acid (Glc A), glucose (Glc), galactose (Gal), arabinose (Ara), and fucose (Fuc) in a molar ratio of 0.077:0.088:0.09:1:0.375:0.354:0.04 with a molecular weight of 33203 Da (Mw). AMC polysaccharides strikingly reversed d-galactose-induced changes in mice, including upregulated phosphatidylinositol 3-kinase (PI3K), Akt, nuclear factor-erythroid 2-related factor 2 (Nrf2), forkhead box O3a (FOXO3a), and hemeoxygenase-1 (HO-1) mRNA expression, raised Bcl-2/Bax ratio, downregulated caspase-3 mRNA expression, enhanced Akt, phosphorylation of Akt (p-Akt), Nrf2 and HO-1 protein expression, decreased caspase-3, and Bax protein expression. CONCLUSION: AMC polysaccharides attenuated d-galactose-induced oxidative stress and cell apoptosis by activating the PI3K/AKT pathway, which might in part contributed to their anti-aging activity.


Assuntos
Antioxidantes/farmacologia , Gleiquênias/química , Fosfatidilinositol 3-Quinase/metabolismo , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Envelhecimento/efeitos dos fármacos , Envelhecimento/metabolismo , Animais , Antioxidantes/química , Cromatografia Líquida de Alta Pressão , Galactose/administração & dosagem , Espectroscopia de Ressonância Magnética , Camundongos , Monossacarídeos/química , Extratos Vegetais/química , Polissacarídeos/química
6.
Medicine (Baltimore) ; 98(35): e16999, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464953

RESUMO

RATIONALE: Adenoid cystic carcinoma (ACC) rarely occurs in the digestive tract, particularly in the gastroesophageal junction. PATIENT CONCERNS: A 44-year-old male vomiting blood was admitted to our hospital. Endoscopic ultrasound showed a 2.2 × 3.0 cm submucosal tumor in the gastroesophageal junction. DIAGNOSIS: According to the histopathological examination, the tumor was composed predominantly of ductal epithelial and myoepithelial cells. Immunohistochemical staining revealed that the tumor expressed cytokeratin, cluster of differentiation 117, p63, and calponin. Based on these findings, ACC was diagnosed. INTERVENTIONS: Endoscopic submucosal dissection (ESD) was performed to remove the tumor. As the margins of the ESD specimen were positive, the patient underwent total gastrectomy with D2 lymphadenectomy. Finally, neither residual tumor nor lymphatic metastasis was detected in the surgical specimens. OUTCOMES: No sign of recurrence has been detected during 36 months of follow-up as of October 2018. LESSONS: ESD may be an alternative treatment for cardial ACC invading the submucosa.


Assuntos
Carcinoma Adenoide Cístico/patologia , Junção Esofagogástrica/patologia , Neoplasias Gástricas/patologia , Adulto , Carcinoma Adenoide Cístico/cirurgia , Ressecção Endoscópica de Mucosa/métodos , Gastrectomia/métodos , Humanos , Masculino , Neoplasias Gástricas/cirurgia
7.
J Control Release ; 281: 178-188, 2018 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-29777796

RESUMO

The sodium pump Na+/K+ ATPase a1 subunit(NKA a1), an attractive cancer-related biomarker and therapeutic target, is closely related to the development and progression of several cancers including breast cancer. Currently, a NKA a1 inhibitor, UNBS1450, has already evidenced its great therapeutic potential in personalized cancer treatment. The ability of non-invasive imaging of NKA a1 expression would be useful for selecting cancer patients who may benefit from this drug. Here, we identified an S3 peptide that is specifically homed to breast cancer by phage display. All data of in vitro and in vivo experiments suggested the excellent targeting character of the S3 peptide. As the binding activity of the S3 phage was positively correlated to the level of NKA α1 expression in various breast cancer cells, NKA α1 was validated as the primary target of the S3 peptide. Based on immunohistochemistry staining result of 107 breast cancer patients, NKA α1 was verified to be a novel tracking marker and a prognostic predictor for breast cancer. Importantly, we proposed and validated an S3 peptide-based radiotracer 18F-ALF-NOTA-S3 for PET (Positron Emission Tomography) imaging of breast cancer and other NKA α1-overexpressing cancers, including hepatocellular carcinoma and non-small cell lung cancer, in mouse models. Our findings demonstrated the potential application of 18F-ALF-NOTA-S3 for visualization of NKA α1-positive lesions, which provide a new approach to character tumor phenotypic imaging.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Peptídeos/metabolismo , Compostos Radiofarmacêuticos/química , ATPase Trocadora de Sódio-Potássio/metabolismo , Animais , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Linhagem Celular Tumoral , Feminino , Radioisótopos de Flúor , Xenoenxertos , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Camundongos Endogâmicos C57BL , Imagem Óptica/métodos , Tomografia por Emissão de Pósitrons/métodos , Subunidades Proteicas/metabolismo
8.
Phytother Res ; 31(8): 1265-1272, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28639266

RESUMO

Psoralea corylifolia L. (Fructus Psoraleae) is widely used in Asia, but there are concerns about hepatotoxicity caused by constituents such as psoralens and bakukiol. Bakuchiol (BAK) has antiinflammatory, antipyretic, antibacterial antiviral, anticancer, and estrogenic activity but appears to be hepatotoxic in in vitro tests. This study investigated the hepatotoxicity in vivo in rats. Using intragastrically administered bakuchiol at doses of 52.5 and 262.5 mg/kg for 6 weeks. Bodyweight, relative liver weight, biochemical indicators, histopathology, mRNA expression of CYP7A1, HMG-CoA reductase, BSEP, PPARα, SREBP-2, and MRP3 were measured. Many abnormalities were observed in the bakuchiol-treated groups including suppression of weight gain and food intake, change of some parameters in serum biochemistry, and increased weight of liver. The mRNA expression of CYP7A1, HMG-CoA reductase, PPARα, and SREBP-2 decreased in bakuchiol-treated group, the expression of BSEP increased in bakuchiol-treated low dosage, and the expression of BSEP decreased in bakuchiol-treated high dosage. In conclusion, we provide evidence for the first time that bakuchiol can induce cholestatic hepatotoxicity, suggesting potential hepatotoxicity. The mechanism may be related to effects on liver lipid metabolism, but further investigation is necessary. Copyright © 2017 John Wiley & Sons, Ltd.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , Fenóis/toxicidade , Extratos Vegetais/toxicidade , Psoralea/toxicidade , Animais , Colestase/induzido quimicamente , Fabaceae/química , Frutas/química , Fígado/efeitos dos fármacos , Fígado/fisiopatologia , Masculino , Estrutura Molecular , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley
9.
J Gene Med ; 19(6-7)2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28636766

RESUMO

BACKGROUND: Our previous genome-wide association study of IgA nephropathy (IgAN) in a Chinese Han population suggested that the TNFSF13 gene may be a novel susceptibility gene for IgAN. In the present study, we aimed to further evaluate the associations of single-nucleotide polymorphisms (SNPs) and expression level of the TNFSF13 gene with the risk and clinical parameters of IgAN. METHODS: Six candidate SNPs were selected for genotyping by Sequenom MassARRAY iPLEX in 1000 IgAN cases and 1000 controls. Unconditional logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (95% CI) with adjustment for age and sex. Serum APRIL (encoded by the TNFSF13 gene) level was detected by an enzyme-linked immunosorbent assay. RESULTS: We found that rs3803800 was significantly associated with the susceptibility of IgAN after Bonferroni correction [padditive  = 0.0009, OR (95% CI) = 1.25 (1.09-1.42); precessive  = 0.0006, OR (95% CI) = 1.54 (1.20-1.96)]; however, the association remained only in women after further sex-stratified analysis. Genotype-phenotype correlation analysis showed significant associations of rs3803800 with severe clinicopathological manifestations in IgAN patients after adjusting for age and sex, as well as the other two SNPs (rs4246413 and rs4968210) that were also associated with specific clinical phenotypes. Compared with healthy controls, serum APRIL levels were significantly higher in IgAN patients (p = 0.0001) and associated with severity of disease. CONCLUSIONS: The results of the present study indicate that the genetic variations and gene expression level of TNFSF13 are associated with the susceptibility and severity of IgAN in a Han Chinese population.


Assuntos
Glomerulonefrite por IGA/genética , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética , Estudos de Casos e Controles , China , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Glomerulonefrite por IGA/fisiopatologia , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Fatores Sexuais
10.
Contemp Clin Trials ; 59: 38-43, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28533194

RESUMO

OBJECTIVE: There is initial evidence that the use of volatile anesthetics can reduce the postoperative release of cardiac troponin I, the need for inotropic support, and the number of patients requiring prolonged hospitalization following coronary artery bypass graft (CABG) surgery. Nevertheless, small randomized controlled trials have failed to demonstrate a survival advantage. Thus, whether volatile anesthetics improve the postoperative outcome of cardiac surgical patients remains uncertain. An adequately powered randomized controlled trial appears desirable. DESIGN: Single blinded, international, multicenter randomized controlled trial with 1:1 allocation ratio. SETTING: Tertiary and University hospitals. INTERVENTIONS: Patients (n=10,600) undergoing coronary artery bypass graft will be randomized to receive either volatile anesthetic as part of the anesthetic plan, or total intravenous anesthesia. MEASUREMENTS AND MAIN RESULTS: The primary end point of the study will be one-year mortality (any cause). Secondary endpoints will be 30-day mortality; 30-day death or non-fatal myocardial infarction (composite endpoint); cardiac mortality at 30day and at one year; incidence of hospital re-admission during the one year follow-up period and duration of intensive care unit, and hospital stay. The sample size is based on the hypothesis that volatile anesthetics will reduce 1-year unadjusted mortality from 3% to 2%, using a two-sided alpha error of 0.05, and a power of 0.9. CONCLUSIONS: The trial will determine whether the simple intervention of adding a volatile anesthetic, an intervention that can be implemented by all anesthesiologists, can improve one-year survival in patients undergoing coronary artery bypass graft surgery.


Assuntos
Anestesia em Procedimentos Cardíacos , Anestésicos Inalatórios , Ponte de Artéria Coronária , Doença da Artéria Coronariana/cirurgia , Complicações Pós-Operatórias , Adulto , Anestesia em Procedimentos Cardíacos/efeitos adversos , Anestesia em Procedimentos Cardíacos/métodos , Anestésicos Inalatórios/administração & dosagem , Anestésicos Inalatórios/química , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/métodos , Ponte de Artéria Coronária/mortalidade , Doença da Artéria Coronariana/mortalidade , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Análise de Sobrevida , Volatilização
11.
Phytother Res ; 31(7): 1039-1045, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28524381

RESUMO

Gallic acid (GA) is a polyphenol natural compound found in many medicinal plant species, including pomegranate rind (Punica granatum L.), and has been shown to have antiinflammatory and antibacterial properties. Pomegranate rind is used to treat bacterial and fungal pathogens in Uyghur and other systems of traditional medicine, but, surprisingly, the effects of GA on antifungal activity have not yet been reported. In this study, we aimed to investigate the inhibitory effects of GA on fungal strains both in vitro and in vivo. The minimal inhibitory concentration (MIC) was determined by the NCCLS (M38-A and M27-A2) standard method in vitro, and GA was found to have a broad spectrum of antifungal activity, with MICs for all the tested dermatophyte strains between 43.75 and 83.33 µg/mL. Gallic acid was also active against three Candida strains, with MICs between 12.5 and 100.0 µg/mL. The most sensitive Candida species was Candida albicans (MIC = 12.5 µg/mL), and the most sensitive filamentous species was Trichophyton rubrum (MIC = 43.75 µg/mL), which was comparable in potency to the control, fluconazole. The mechanism of action was investigated for inhibition of ergosterol biosynthesis using an HPLC-based assay and an enzyme linked immunosorbent assay. Gallic acid reduced the activity of sterol 14α-demethylase P450 (CYP51) and squalene epoxidase in the T. rubrum membrane, respectively. In vivo model demonstrated that intraperitoneal injection administration of GA (80 mg/kg d) significantly enhanced the cure rate in a mice infection model of systemic fungal infection. Overall, our results confirm the antifungal effects of GA and suggest a mechanism of action, suggesting that GA has the potential to be developed further as a natural antifungal agent for clinical use. Copyright © 2017 John Wiley & Sons, Ltd.


Assuntos
Antifúngicos/farmacologia , Arthrodermataceae/efeitos dos fármacos , Ácido Gálico/farmacologia , Animais , Candida/efeitos dos fármacos , Candidíase/tratamento farmacológico , Feminino , Fluconazol/farmacologia , Masculino , Camundongos Endogâmicos ICR , Testes de Sensibilidade Microbiana , Trichophyton/efeitos dos fármacos
12.
Mol Med Rep ; 15(2): 635-642, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28000867

RESUMO

Dexmedetomidine (DXM) is a selective α2-adrenoceptor (α2­AR) and imidazoline receptor (IR) agonist that has been reported to regulate inflammatory responses mediated by diverse signaling pathways through α2­AR. The majority of the reported receptors or downstream molecules have been demonstrated to locate with caveolin­1, a protein suggested to participate in regulating Toll­like receptor 4 (TLR4)­mediated inflammatory responses and the pathogen endocytosis capability of macrophages. The present study hypothesized that DXM may influence these pathways by regulating the expression of caveolin­1 and mediating the subsequent effects. Using a cecal­ligation and puncture­induced rat sepsis model, it was initially observed that pre­emptive DXM is able to upregulate and stabilize the amount of caveolin­1 expression, which may be partly antagonized by both α2­AR and the IR antagonist atepamezole (APZ). The pathophysiological parameters indicated that DXM is able to inhibit secondary lung injury, in addition to the rise of body temperature and arterial lactate accumulation, however it marginally increased arterial glucose and the murine sepsis score, which can be largely antagonized by APZ. The overall effect was beneficial and improved the 24­h cumulative survival rate of rats with sepsis. In conclusion, preemptive clinical sedative doses of DXM may upregulate the expression of caveolin­1 downregulated by sepsis, which may contribute to the inhibition of inflammatory pathways such as TLR4­mediated pathways. Furthermore, DXM may favor the improvement of short­term outcomes by the regulation of other metabolic pathways.


Assuntos
Caveolina 1/metabolismo , Dexmedetomidina/farmacologia , Hipnóticos e Sedativos/farmacologia , Pulmão/metabolismo , Sepse/patologia , Regulação para Cima/efeitos dos fármacos , Antagonistas de Receptores Adrenérgicos alfa 2/farmacologia , Antagonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Animais , Gasometria , Temperatura Corporal/efeitos dos fármacos , Caveolina 1/genética , Modelos Animais de Doenças , Imidazóis/farmacologia , Imidazóis/uso terapêutico , Pulmão/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Sepse/tratamento farmacológico , Sepse/mortalidade , Receptor 4 Toll-Like/metabolismo
13.
Contemp Clin Trials ; 59: 38-43, 2017. tab
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: ses-37191

RESUMO

Objective: There is initial evidence that the use of volatile anesthetics can reduce the postoperative release of cardiac troponin I, the need for inotropic support, and the number of patients requiring prolonged hospitalization following coronary artery bypass graft (CABG) surgery. Nevertheless,small Randomized Controlled Trials have failed to demonstrate a survival advantage. Thus, whethervolatile anesthetics improve the postoperative outcome of cardiac surgical patients remains uncertain. An adequately powered randomized controlled trial appears desirable.Design: Single blinded, international, multicenter randomized controlled trial with 1:1 allocation ratio.Setting: Tertiary and University hospitals. (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Anestesia , Mortalidade , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos
14.
J Agric Food Chem ; 64(49): 9381-9389, 2016 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-27960285

RESUMO

Ten novel C21 pregnane glycosides, extensumside C-L (1-10), were isolated as highly sweet-tasting substances from the edible pericarps of Myriopteron extensum (Wight) K. Schum by sensory-guided fractionation and purification. Their structures were determined through 1D and 2D NMR, such as HSQC, HMBC, 1H-1H COSY, HSQC-TOCSY, and ROESY, as well as other spectroscopic analysis combined with chemical evidence. These compounds shared the same aglycone, 3ß,16α-dihydroxy-pregn-5-en-20-one, and contained the deoxysugar chain and the glucose chain which were linked to C-3 and C-16 of the aglycone, respectively. The sweetness potency was evaluated by a human sensory panel test and preliminary structure-taste relationship was discussed. The sweetness intensities of these compounds are between 50 and 400 times greater than that of sucrose. Furthermore, quantitation analyses of compounds 1, 3, 4, and 6 in different parts of M. extensum indicated that the concentrations of these sweet components in the pericarps are obviously higher than those in stems and roots.


Assuntos
Apocynaceae/química , Glicosídeos/química , Extratos Vegetais/química , Pregnanos/química , Edulcorantes/química , Adulto , Feminino , Frutas/química , Glicosídeos/isolamento & purificação , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estrutura Molecular , Extratos Vegetais/isolamento & purificação , Pregnanos/isolamento & purificação , Edulcorantes/isolamento & purificação , Paladar
15.
Int J Ophthalmol ; 9(12): 1719-1724, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28003969

RESUMO

AIM: To determine the role of microRNA (miRNA)-29a and miRNA-29c in the regulation of apoptosis in early rat diabetic cataract formation. METHODS: Streptozotocin (STZ)-induced diabetic Sprague-Dawley (SD) rats were used in the study. The expression level of miRNA-29a, miRNA-29c, and BCL2-modifying factor (BMF) in lens epithelial cells (LECs) samples were measured using quantitative real-time polymerase chain reaction. Prediction algorithms of miRanda, TargetScan 6.2, and mirRDB to perform a miRNA gene network analysis were used for the potential miRNA-29a and miRNA-29c targets. RESULTS: The miRNA-29a and miRNA-29c expression levels were all significantly lower in the control group compared to the 2 and 4wk diabetic samples (P<0.01). The network analysis indicated that one miRNA-29a and miRNA-29c targets was BMF. There was significantly higher expression of BMF mRNA compared to the normal controls (P<0.01). CONCLUSION: Apoptosis occurs in rat LECs following high blood glucose exposure. It is likely that apoptosis during diabetic cataract formation involves the decreased expression of miRNA-29a and miRNA-29c and the increased expression of BMF.

16.
Int J Dev Neurosci ; 53: 10-17, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27224662

RESUMO

Bone morphogenic protein-7 (BMP7) is a multifunctional cytokine with demonstrated neurogenic potential. Oligodendrocytes (OLs) death after spinal cord injury (SCI) contributes to demyelination of spared axons, even leading to a permanent neurological deficit. Therefore, therapeutic approaches to prevent OLs death after SCI should be considered. Since the effects of BMP7 on OLs after injury are largely unknown, we demonstrated the effects of BMP7 on TNF-α-induced OLs apoptosis in vitro. The effects of BMP7 on TNF-α-induced OLs apoptosis were verified by flow cytometry, spectrophotometry and western blotting on primary cultures from spinal cord of postnatal day 1 (P1) to P2 rats. As shown by flow cytometry, apoptosis rate was 25.6% for the control group, 59.0% for the TNF-α group, and 33.5% for the BMP7+TNF-α group; spectrophotometry showed caspase-3 and caspase-8 activity were significantly increased in the TNF-α group than in the control group, and BMP7 could reverse the increase. The involvement of cIAP1 in the protection of BMP7 was determined by western blotting and silencing cIAP1. In summary, our results demonstrated that BMP7 could potently inhibite TNF-α-induced OLs apoptosis and identified the cIAP1 expression level, the activity of caspase-3 and caspase-8 as important mediators of OLs survival after cellular stress and cytokine challenge.


Assuntos
Apoptose/efeitos dos fármacos , Proteína Morfogenética Óssea 7/farmacologia , Oligodendroglia/efeitos dos fármacos , Fator de Necrose Tumoral alfa/toxicidade , Análise de Variância , Animais , Animais Recém-Nascidos , Caspases/metabolismo , Células Cultivadas , Relação Dose-Resposta a Droga , Feminino , Citometria de Fluxo , Gangliosídeos/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Proteínas Inibidoras de Apoptose/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Proteína Básica da Mielina/metabolismo , RNA Interferente Pequeno/farmacologia , Ratos , Fatores de Tempo
17.
Huan Jing Ke Xue ; 37(9): 3290-3299, 2016 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-29964761

RESUMO

Continuous monitoring of gaseous elemental mercury (GEM), reactive gaseous mercury (RGM) and particulate mercury (PBM) was conducted in the Dongtan wetland park in Chongming Island, Shanghai from March 2014 to February 2015. The average concentrations of GEM, RGM, and PBM were (2.75±1.13) ng·m-3, (13.39±15.95) pg·m-3, and (21.89±40.42) pg·m-3, respectively, higher than the background concentrations of Northern Hemisphere. The atmospheric mercury showed obvious seasonal variations, with the highest seasonal average GEM concentration in summer (3.65 ng·m-3), which was mainly influenced by natural sources, while lower GEM concentrations appeared in autumn and winter influenced mainly by anthropogenic sources. The concentration of RGM was highest in spring and lowest in winter, mainly influenced by the wind direction, while PBM showed higher concentrations in autumn and winter, when heavy fine particulate pollution episodes occurred frequently. The concentrations of GEM and PBM were generally elevated in nighttime and lower in daytime caused by the mixing condition of the air masses. Most of the high RGM concentration values occurred in the afternoon of all seasons due to the higher atmospheric oxidation. The concentrations of GEM and PBM were higher in the west wind due to the emission from anthropogenic sources in Shanghai, Jiangsu, etc. The RGM concentration in southeast wind was obviously higher than those in other wind directions. The RGM was mainly from the anthropogenic sources, and the smaller wind in the southeast direction was against the dispersion of RGM.

18.
Huan Jing Ke Xue ; 37(10): 3766-3773, 2016 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-29964407

RESUMO

Municipal solid waste (MSW) incineration is one of the most important atmospheric mercury emission sources. To investigate the mercury concentrations of MSW and mercury emission characteristics in incineration plants, this study analyzed the MSW sampled in 3 typical MSW incineration plants in Shanghai, Guangzhou and Wuhu respectively. The exhaust gas samples in incineration plants were sampled by using OH (Ontario Hydro) method. The mercury concentrations in fly ash, and bottom ash samples were also analyzed. The results indicated that mercury concentrations of MSW in Shanghai, Guangzhou, and Wuhu incineration plants were (0.39±0.04) mg·kg-1, (0.57±0.05) mg·kg-1, and (0.27±0.08) mg·kg-1 respectively. The mercury concentrations of exhaust gas in Guangzhou, Wuhu MSW incineration plants were (9.5±3.9) µg·m-3 and (24.1±6.0) µg·m-3 respectively; Particulate mercury (Hgp), gaseous oxidized mercury (Hg2+), and gaseous elemental mercury (Hg0) represented (0.9±0.8)%, (89.0±5.4)%, (10.1±4.6)% in Guangzhou MSW incineration plant, and (1.0±0.8)%, (65.4±27.6)%, (33.6±27.5)% in Wuhu MSW incineration plant, respectively. Gaseous oxidized mercury (Hg2+) of exhaust gas in different incineration process showed different distribution proportions. Besides, mercury removal efficiency of Guangzhou, Wuhu MWS incineration plants was 96.7% and 33.7%, respectively. The atmospheric mercury emission factors of Shanghai, Guangzhou, and Wuhu MSW incineration plants were (0.156±0.016) mg·kg-1, (0.019±0.002) mg·kg-1, (0.178±0.027) mg·kg-1 respectively. Compared with MSW incineration plants in Japan and Korea, the atmospheric mercury emission factor of Guangzhou incineration plant was slightly lower; Atmospheric mercury emission factors of Shanghai and Wuhu MSW incineration plants were close to those of domestic fractional MSW incineration plants.

19.
Phytother Res ; 29(7): 1019-25, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25919446

RESUMO

Ellagic acid (EA) has been shown to have antioxidant, antibacterial, and anti-inflammatory activities. In Uighur traditional medicine, Euphorbia humifusa Willd is used to treat fungal diseases, and recent studies suggest that it is the EA content which is responsible for its therapeutic effect. However, the effects of EA on antifungal activity have not yet been reported. This study aimed to investigate the inhibitory effect of EA on fungal strains both in vitro and in vivo. The minimal inhibitory concentration (MIC) was determined by the National Committee for Clinical Laboratory Standards (M38-A and M27-A2) standard method in vitro. EA had a broad spectrum of antifungal activity, with MICs for all the tested dermatophyte strains between 18.75 and 58.33 µg/ml. EA was also active against two Candida strains, with MICs between 25.0 and 75.0 µg/ml. It was inactive against Candida glabrata. The susceptibility of six species of dermatophytes to EA was comparable with that of the commercial antifungal, fluconazole. The most sensitive filamentous species was Trichophyton rubrum (MIC = 18.75 µg/ml). Studies on the mechanism of action using an HPLC-based assay and an enzyme linked immunosorbent assay showed that EA inhibited ergosterol biosynthesis and reduced the activity of sterol 14α-demethylase P450 (CYP51) in the Trichophyton rubrum membrane, respectively. An in vivo test demonstrated that topical administration of EA (4.0 and 8.0 mg/cm(2) ) significantly enhanced the cure rate in a guinea-pig infection model of Trichophyton rubrum. The results suggest that EA has the potential to be developed as a natural antifungal agent.


Assuntos
Antifúngicos/farmacologia , Ácido Elágico/farmacologia , Tinha/tratamento farmacológico , Administração Cutânea , Animais , Arthrodermataceae/efeitos dos fármacos , Candida/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Fluconazol , Cobaias , Masculino , Testes de Sensibilidade Microbiana , Estrutura Molecular , Trichophyton/efeitos dos fármacos
20.
Biosens Bioelectron ; 68: 668-674, 2015 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-25660511

RESUMO

Herein, a sensitive and selective sensor for biothiols based on colorimetric assay is reported. S-adenosyl-L-methionine (SAM) could induce the selective aggregation of unmodified gold nanoparticles (AuNPs) by electrostatic interaction. In the presence of biothiols, such as glutathione (GSH), homocysteine (Hcy), and cysteine (Cys), AuNPs prefer to react with thiols of biothiols rather than SAM due to the formation of Au-S bond. Thus, the AuNPs turn from the aggregation to the dispersion state, and the corresponding color variation in the process of anti-aggregation of AuNPs can be used for the quantitative screening of biothiols through UV-vis spectroscopy or by the naked eye. Under optimized conditions, a good linear relationship in the range of 0.4-1.2 µM is obtained for Cys, 0.2-0.9 µM for GSH, and 0.6-3.0 µM for Hcys. The detection limits of this assay for GSH, Cys and Hcys are 35.8 nM, 21.7 nM, and 62.4 nM, respectively. This colorimetric assay exhibits rapid operation (within 5 min), high selectivity and sensitivity towards biothiols with tunable dynamic ranges.


Assuntos
Técnicas Biossensoriais , Cisteína/isolamento & purificação , Glutationa/isolamento & purificação , Homocisteína/isolamento & purificação , Colorimetria , Ouro/química , Humanos , Limite de Detecção , Nanopartículas Metálicas/química , Metionina/análogos & derivados , Metionina/química
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