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1.
J Biomater Sci Polym Ed ; : 1-18, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31724490

RESUMO

Biological modifications of the silk fibroin (silk) material have broad applications, in textiles, biomedical materials and other industrial materials. It is economical to incorporate nanoparticles to the biosynthesis of silk fibroin by adding them to silkworm larval diets. This strategy may result in the rapid stable production of modified-silk. Glucose coated silver nanoparticles (AgNPs) were used to improve the AgNPs' biocompatibility, and the AgNPs were efficiently incorporated into silk by feeding. Larvae fed with AgNPs produced silk with significantly improved antibacterial properties and altered silk secondary structures. Both positive and negative effects on the growth and synthesis of silk proteins were observed after different AgNPs doses. Larvae feeding with low concentration of 0.02% and medium 0.20% AgNPs have greater transfer efficiencies of AgNPs to silk compared with feeding high concentration of 2.00% AgNPs. In addition, the elongation and tensile strength of the produced silk fibers were also significantly increased, with greater mammalian cell compatibility. The appropriate AgNPs concentration in the diet of silkworms can promote the synthesis of silk proteins, enhance their mechanical properties, improve their antibacterial property and inhibit the presence of Gram-negative bacteria.HIGHLIGHTSAgNPs in silkworm diets can be efficiently incorporated into silkDietary AgNPs can produce antibacterial silk with altered mechanical propertiesA low dietary AgNPs concentration can enhance silk fibroin synthesis.

2.
Future Med Chem ; 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31510797

RESUMO

Background: Gefitinib and sorafenib have been proved effective for the treatment of cancers in clinical practice for years. Materials & methods: We intended to integrate the structural features of gefitinib and sorafenib and construct structurally unique 7-aromatic ureido-4-anilinoquinazolines. Results: Most of the targets exhibited promising antitumor activities. 8u showed excellent antitumor activities against the three tested cell lines (IC50, 0.81-2.49 µM). The enzymatic, apoptosis assay of 8u were also performed to study their preliminary action of mechanism. Conclusion: 8u deserve further research as antitumor agents.

3.
Microbiologyopen ; 8(10): e909, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31452349

RESUMO

Many studies have investigated patterns of soil microbial communities over large spatial scales. However, these studies mainly focused on a few sites. Here, we studied the near-surface (0-30 cm) soil microbial communities of 35 soil samples collected from most of the areas of the Qaidam Basin, which is the largest basin on the Qinghai-Tibet Plateau. A total of 32 phyla and 838 genera were detected from all the samples, in which Actinobacteria, Proteobacteria, Bacteroidetes, and Acidobacteria were the most dominant and cosmopolitan phyla. The most abundant phyla (relative abundance > 5%) detected in all 35 soil samples were also the most dominant, which could be explained by their great dispersal ability. The microbial community structures correlated strongly with variations in pH and Mg2+ and were distinct between the high Mg2+ content (>20 g/kg) samples and other samples (Acidobacteria, Actinobacteria, and Chloroflexi were significantly less abundant in the high Mg2+ content group, but the abundance of Firmicutes was significantly greater). Finally, the microbial spatial pattern was influenced by both the local environment and spatial distance, but environmental factors were the primary drivers of microbial spatial patterns in the Qaidam Basin.

4.
Zhongguo Gu Shang ; 32(7): 653-657, 2019 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-31382725

RESUMO

OBJECTIVE: To observe the repair effect of bone marrow mesenchymal stem cells (BMSCs) combined with basic fibroblast growth factor (bFGF) on spinal cord injury in rats and explore its mechanism. METHODS: SD rat BMSCs were obtained by serum culture technique. Eighty healthy 6-week-old male SD rats(weight about 240 g) were randomly divided into 4 groups with 20 each. The sham operation group underwent simple laminectomy without damaging spinal cord and was kept in the same condition as the other 3 groups. The other 3 groups underwent left T9 spinal cord hemisection to establish spinal cord injury model. After 9 days of modeling the local transplantation was performed. The Control group was implanted with gelatin sponge containing normal saline. The BMSCs transplantation group was implanted with gelatin sponge containing BMSCs. The bFGF+BMSCs transplantation group was implanted with gelatin sponge containing bFGF+BMSCs. After 4 and 8 weeks, the expression of NF-200 and GFAP in injured spinal cord tissue was analyzed by Western blotting and the recovery of hind limb function was evaluated by Basso Beattie Bresnahan(BBB) motor function score scale. RESULTS: The BBB scores of BMSCs transplantation group and bFGF+BMSCs transplantation group were better than control group at 4 and 8 weeks after operation (P<0.05) and there was significant difference between bFGF+BMSCs transplantation group and BMSCs transplantation group (P<0.05). After 4 and 8 weeks postoperatively, NF-200 expression was minimal in control group and only a small amount was expressed in BMSCs transplantation group while in bFGF+BMSCs transplantation group NF-200 was highly expressed(P<0.05). GFAP expression was high in control group, middle in BMSCs transplantation group and low in bFGF BMSCs transplantation group(P<0.05). There was significant difference between bFGF+BMSCs transplantation group, BMSCs transplantation group and control group(P<0.05). CONCLUSIONS: The combined transplantation of BMSCs and bFGF can repair the spinal cord injury in rats. The mechanism may be related to the decrease of GFAP expression and the increase of NF-200 expression.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Traumatismos da Medula Espinal , Animais , Células da Medula Óssea , Fator 2 de Crescimento de Fibroblastos , Masculino , Ratos , Ratos Sprague-Dawley , Medula Espinal
5.
Hematol Oncol ; 37(4): 401-408, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31291481

RESUMO

Multiple myeloma (MM) is malignant tumor with abnormal proliferation of bone marrow plasma cells. The existing clinical tools used to determine treatment response and tumor relapse are limited in sensitivity. We investigated the CD138+ microparticles (MPs) of MM patients to find out whether MPs could provide a novel means to monitor the malignant cells in MM patients. Our study showed that the levels of MPs were significantly elevated in MM patients. The MP counts in peripheral blood from new diagnosed MM patients were significantly higher than patients in CR and HD. Consist with the total MPs, the number of the PC-derived MPs (CD138+) increased in BM from MM patients compared with CR and HD. The ratio of the PC-derived MPs (CD138+) in BM increased in MM patients compared with CR and HD. The correlation test revealed that the CD138+ MPs in BM and PB were all positively correlated with the plasmacyte ratio in bone marrow (BMPC) and the ß2 -MG. New diagnosed MM patients and controls were compared, and ROC curves were used to identify cutoff points with optimal sensitivity and specificity concerning the ratios and counts of CD138+ MPs in BM and PB. The AUC of the CD138+ MP counts in BM was 0.767, and in PB was 0.680. The AUC of the CD138+ MP ratios in BM was 0.714, and in PB was 0.666. According to this, the counts of CD138+ MPs in BM showed to be a powerful marker of diagnosis. We demonstrated that CD138+ MPs from the plasma provide support for a potential monitoring biomarker of MM.

6.
J Exp Clin Cancer Res ; 38(1): 283, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31262330

RESUMO

BACKGROUND: Mucins are key components of the mucosal barrier in the stomach that protects epithelia from carcinogenic effects of chronic inflammation. Analysis of The Cancer Genome Atlas database indicated that mucin-17 (MUC17) was more highly expressed in gastric cancer (GC) specimens, with favourable prognosis for patients. To explore the underlying mechanisms, we investigated the potential role of MUC17 in controlling chronic gastric inflammation. METHODS: We initially quantified the expression of MUC17 and inflammatory factor, as well as the association of MUC17 with survive in GC using immunohistochemistry. To establish how the inflammatory factors affect MUC17 expression, we explored luciferase reporter, chromatin immunoprecipitation (ChIP), and electrophoretic mobility shift (EMSA) assays. The role and mechanism that MUC17 plays in inflammation-induced cell proliferation was examined in AGS cells with reduced MUC17 expression and MKN45 cells overexpressing a truncated MUC17. RESULTS: We found MUC17 was induced by inflammatory cytokines in GC cells via CDX1upregulation. MUC17 thus inactivated NFκB to inhibit GC cell proliferation in response to pro-inflammatory cytokines. We also revealed that the function of MUC17 was dependent on its conserved epidermal growth factor domain and on downstream sequences to enable its interaction with myosin-9, resulting in a sustained regulatory feedback loop between myosin-9, p53, and RhoA, and then activation of p38 to negatively regulate the NFκB pathway in GC cells. This mechanism was also confirmed in vivo. CONCLUSIONS: Our study demonstrates MUC17 as a GC suppressor protein which has the therapeutic potential for human GC.

7.
J Psychiatr Res ; 116: 126-132, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31233895

RESUMO

Despite evidence of structural brain abnormalities in schizophrenia, the current study aimed to explore the effects of antipsychotic treatment on gray matter (GM) volume using structural magnetic resonance imaging (MRI) and investigate the relationship between brain structure and treatment response. The GM volumes of 33 patients with first-episode schizophrenia were calculated with voxel-based morphometry (VBM), with 33 matched healthy controls. Longitudinal volume changes within subjects after 4-month antipsychotic treatment were also evaluated. Correlation between volumetric changes and clinical symptoms derived from the Positive and Negative Syndrome Scale (PANSS) were further investigated. Compared with healthy controls, decreased GM volumes in the frontal gyrus were observed in schizophrenia patients. After 4-month treatment, patients showed significantly decreased GM volume primarily in the bilateral frontal, temporal and left parietal brain regions. In addition, the GM volume changes of the left postcentral gyrus was positively correlated with negative symptoms improvement, and the correlation analysis revealed the total PANSS scores changes were associated with GM volume changes in the right inferior frontal gyrus and the right superior temporal gyrus. Besides, non-responders had reduced GM volume in the bilateral middle frontal gyrus and the right superior frontal gyrus compared with responders and healthy controls. Our results suggest that the abnormality in the right frontal gyrus exists in the early stage of schizophrenia. Moreover, the relationship between antipsychotics and structural changes was identified. The GM volume might have the potential to reflect the symptom improvement in schizophrenia patients. And MRI may assist in predicting the antipsychotic treatment response in first-episode schizophrenia patients.

8.
Nat Commun ; 10(1): 2037, 2019 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-31048690

RESUMO

Genome-wide analysis of genomic signatures might reveal novel mechanisms for gastric cancer (GC) tumorigenesis. Here, we analysis structural variations (SVs) and mutational signatures via whole-genome sequencing of 168 GCs. Our data demonstrates diverse models of complex SVs operative in GC, which lead to high-level amplification of oncogenes. We find varying proportion of tandem-duplications (TDs) among individuals and identify 24 TD hotspots involving well-established cancer genes such as CCND1, ERBB2 and MYC. Specifically, we nominate a novel hotspot involving the super-enhancer of ZFP36L2 presents in approximately 10% GCs from different cohorts, the oncogenic role of which is further confirmed by experimental data. In addition, our data reveal a mutational signature, specifically occurring in noncoding region, significantly enriched in tumors with cadherin 1 mutations, and associated with poor prognoses. Collectively, our data suggest that TDs might serve as an important mechanism for cancer gene activation and provide a novel signature for stratification.


Assuntos
Oncogenes/genética , Neoplasias Gástricas/genética , Fatores de Transcrição/genética , Transcriptoma/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/genética , Caderinas/genética , Carcinogênese/genética , Linhagem Celular Tumoral , Elementos Facilitadores Genéticos/genética , Éxons/genética , Feminino , Duplicação Gênica/genética , Variação Estrutural do Genoma , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estômago/patologia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida , Sequenciamento Completo do Genoma
9.
Pathol Res Pract ; 215(6): 152409, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31000383

RESUMO

Pyruvate kinase M2 (PKM2) serves as a key enzyme that promotes aerobic glycolysis. This study investigated the function of PKM2 in tumor growth and maintenance in gastric cancer (GC). Histological staining was applied to detect PKM2 expression in GC tissues. PCR and western blotting were used to measure PKM2 expression in GC cells. PKM2 was knocked down to examine the biological behavior of tumors, glycometabolism, and apoptosis. PKM2 was upregulated in GC tissues (65%, 34/52) compared with that in adjacent normal tissues (27%, 10/37). Moreover, PKM2 knockdown inhibited proliferation of BGC823 GC cells, and elevated PKM2 levels were associated with poor survival of GC patients. Furthermore, knockdown of PKM2 altered the biological behavior of BGC823 cells through induction of apoptosis. In conclusion, the results of this study indicated that inhibition of PKM2 could represent a novel strategy for gastric cancer treatment.

10.
Schizophr Res ; 208: 160-166, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30967317

RESUMO

OBJECTIVE: We aimed to evaluate the functional network properties in first-episode schizophrenia (SZ) patients at baseline and after 4-months treatment with second-generation antipsychotic drugs. METHODS: Resting-state functional magnetic resonance imaging and graph theory approaches were utilized to evaluate the functional integration and segregation of brain networks in 36 first-episode patients (20 male/16 female) with SZ and 36 age and sex matched healthy controls (20 male/16 female). RESULTS: Compared with healthy controls, SZ at baseline showed lower clustering coefficient (Cp) and local network efficiency (Eloc), and this abnormal pattern was modulated with treatment of antipsychotic drugs at follow-up. Longitudinally, the increase of Cp was associated with the improvement of negative symptom. We found that the strength of functional connectivity between brain regions were significantly increased in three connections after treatment, mainly involving the frontal, parietal and occipital lobes. CONCLUSION: The current study suggested that antipsychotic drugs could modulate the faulty local clustering of the functional connectome in SZ. Furthermore, Cp, the parameter that reflects local clustering of topological organization, demonstrated the potential to be a connectome-based biomarker of treatment response to second-generation antipsychotics in patients with SZ.

11.
Cell Rep ; 26(11): 2984-2997.e4, 2019 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-30865888

RESUMO

The CNS plays a pivotal role in energy homeostasis, but whether oligodendrocytes are involved has been largely unexplored. Here, we show that signaling through GPR17, a G-protein-coupled receptor predominantly expressed in the oligodendrocyte lineage, regulates food intake by modulating hypothalamic neuronal activities. GPR17-null mice and mice with an oligodendrocyte-specific knockout of GPR17 have lean phenotypes on a high-fat diet, suggesting that GPR17 regulates body weight by way of oligodendrocytes. Downregulation of GPR17 results in activation of cAMP-protein kinase A (PKA) signaling in oligodendrocytes and upregulated expression of pyruvate dehydrogenase kinase 1 (PDK1), which promotes lactate production. Elevation of lactate activates AKT and STAT3 signaling in the hypothalamic neurons, leading to increased expression of Pomc and suppression of Agrp. Our findings uncover a critical role of oligodendrocytes in metabolic homeostasis, where GPR17 modulates the production of lactate, which, in turn, acts as a metabolic signal to regulate neuronal activity.

12.
Brain Behav ; 9(2): e01211, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30701701

RESUMO

INTRODUCTION: Treatment response at an early stage of schizophrenia is of considerable value with regard to future management of the disorder; however, there are currently no biomarkers that can inform physicians about the likelihood of response. OBJECTS: We aim to develop and validate regional brain activity derived from functional magnetic resonance imaging (fMRI) as a potential signature to predict early treatment response in schizophrenia. METHODS: Amplitude of low-frequency fluctuation (ALFF) was measured at the start of the first/single episode resulting in hospitalization. Inpatients were included in a principal dataset (n = 79) and a replication dataset (n = 44). Two groups of healthy controls (n = 87; n = 106) were also recruited for each dataset. The clinical response was assessed at discharge from the hospital. The predictive capacity of normalized ALFF in patients by healthy controls, ALFFratio , was evaluated based on diagnostic tests and clinical correlates. RESULTS: In the principal dataset, responders exhibited increased baseline ALFF in the left postcentral gyrus/inferior parietal lobule relative to non-responders. ALFFratio of responders before treatment was significantly higher than that of non-responders (p < 0.001). The area under the receiver operating characteristic curve was 0.746 for baseline ALFFratio to distinguish responders from non-responders, and the sensitivity, specificity, and accuracy were 72.7%, 68.6%, and 70.9%, respectively. Similar results were found in the independent replication dataset. CONCLUSIONS: Baseline regional activity of the brain seems to be predictive of early response to treatment for schizophrenia. This study shows that psycho-neuroimaging holds promise for influencing the clinical treatment and management of schizophrenia.


Assuntos
Encéfalo/fisiopatologia , Hospitalização , Imagem por Ressonância Magnética/métodos , Esquizofrenia , Adulto , Cuidado Periódico , Feminino , Humanos , Masculino , Neuroimagem/métodos , Avaliação de Resultados (Cuidados de Saúde) , Prognóstico , Curva ROC , Esquizofrenia/diagnóstico , Esquizofrenia/fisiopatologia , Esquizofrenia/terapia
13.
J Pathol ; 248(3): 304-315, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30737779

RESUMO

Androgen receptor (AR) and its variants (AR-Vs) promote tumorigenesis and metastasis in many hormone-related cancers, such as breast, prostate and hepatocellular cancers. However, the expression patterns and underlying molecular mechanisms of AR in gastric cancer (GC) are not fully understood. This study aimed to detect the expression of AR-Vs in GC and explored their role in metastasis of GC. Here, the AR expression form was identified in GC cell lines and tissues by RT-PCR and qPCR. Transwell assays and experimental lung metastasis animal models were used to assess the function of AR in cell migration and invasion. Downstream targets of AR were screened by bioinformatics, and identified by luciferase reporter assays and electrophoretic mobility shift assays. AR-v12 was identified as the main expression form in GC cell lines and tissues. Different from full length of AR, AR-v12 was localized to the nucleus independent of androgen. Upregulation of AR-v12 in primary GC tissues was significantly associated with metastasis. Overexpression of AR-v12 promoted migration and invasion independent of androgen. Knockdown of AR-v12 inhibited migration and invasion in vitro, as well as metastasis in vivo. Furthermore, AR-v12, serving as a transcription factor, promoted metastasis through regulating the promoter activity of MYLK. In AR-v12 overexpressing cells, knockdown of MYLK inhibited cell migration and invasion, while in AR-v12 knocked-down cells, overexpression of MYLK promoted cell migration and invasion. Collectively, our study demonstrates that AR-v12 is highly expressed in GC tissues and promotes migration and invasion through directly regulating MYLK. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

14.
Genes (Basel) ; 10(2)2019 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-30700037

RESUMO

The uplift of the Qinghai-Tibetan Plateau (QTP) had a profound impact on the plant speciation rate and genetic diversity. High genetic diversity ensures that species can survive and adapt in the face of geographical and environmental changes. The Tanggula Mountains, located in the central of the QTP, have unique geographical significance. The aim of this study was to investigate the effect of the Tanggula Mountains as a geographical barrier on plant genetic diversity and structure by using Lancea tibetica. A total of 456 individuals from 31 populations were analyzed using eight pairs of microsatellite makers. The total number of alleles was 55 and the number per locus ranged from 3 to 11 with an average of 6.875. The polymorphism information content (PIC) values ranged from 0.2693 to 0.7761 with an average of 0.4378 indicating that the eight microsatellite makers were efficient for distinguishing genotypes. Furthermore, the observed heterozygosity (Ho), the expected heterozygosity (He), and the Shannon information index (I) were 0.5277, 0.4949, and 0.9394, respectively, which indicated a high level of genetic diversity. We detected high genetic differentiation among all sampling sites and restricted gene flow among populations. Bayesian-based cluster analysis (STRUCTURE), principal coordinates analysis (PCoA), and Neighbor-Joining (NJ) cluster analysis based on microsatellite markers grouped the populations into two clusters: the southern branch and the northern branch. The analysis also detected genetic barriers and restricted gene flow between the two groups separated by the Tanggula Mountains. This study indicates that the geographical isolation of the Tanggula Mountains restricted the genetic connection and the distinct niches on the two sides of the mountains increased the intraspecific divergence of the plants.

15.
Gastric Cancer ; 22(5): 941-954, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30778796

RESUMO

BACKGROUND AND AIMS: Helicobacter pylori invades the mucosal barrier and infects the mucins of gastric epithelial cells. However, whether gastric carcinogenesis caused by H. pylori infection involves the membrane-bound mucins is unclear. This study explored the role of mucin 17 (MUC17) in gastric cancer (GC) associated with H. pylori infection. METHODS: The expression of MUC17 and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) was examined in human GC cells and tissues with H. pylori infection. Gain- and loss-of-function assays were performed to assess the role of MUC17 in regulating CEACAM1 in H. pylori-infected GC cells. RESULTS: MUC17 was downregulated in H. pylori-infected GC cells and tissues in association with poor survival of GC patients. Downregulation of MUC17 was attributable to MUC17 promoter methylation mediated by DNA methyltransferase 1 (DNMT1) H. pylori-enhanced GC cell proliferation and colony formation associated with MUC17 downregulation. Gain- and loss-of-function assays showed that MUC17 inhibited the H. pylori-enhanced GC cell growth by preventing the translocation of H. pylori CagA into GC cells. Moreover, MUC17 downregulated the expression of CEACAM1 variant 3S (CEACAM1-3S) in GC cells and tissues with H. pylori infection. Additionally, MUC17 downregulated CEACAM1 promoter activity via attenuation of NF-κB activation in GC cells. CONCLUSIONS: MUC17 was epigenetically downregulated in GC with H. pylori infection. MUC17 inhibited H. pylori CagA translocation via attenuation of NF-κB-mediated expression of CEACAM1-3S in GC cells. Thus, MUC17 may serve as a valuable prognostic biomarker for H. pylori-associated GC.

16.
Acta Pharmacol Sin ; 40(8): 1095-1105, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30643208

RESUMO

ß-Arrestins are a small family of proteins important for signal transduction at G protein-coupled receptors (GPCRs). ß-Arrestins are involved in the desensitization of GPCRs. Recently, biased ligands possessing different efficacies in activating the G protein- versus the ß-arrestin-dependent signals downstream of a single GPCR have emerged, which can be used to selectively modulate GPCR signal transduction in such a way that desirable signals are enhanced to produce therapeutic effects while undesirable signals of the same GPCR are suppressed to avoid side effects. In the present study, we evaluated agonist bias for compounds developed along a drug discovery project of ß2-adrenoceptor agonists. About 150 compounds, including derivatives of fenoterol, 2-amino-1-phenylethanol and 2-amino-2-phenylethanol, were obtained or synthesized, and initially screened for their ß-adrenoceptor-mediated activities in the guinea pig tracheal smooth muscle relaxation assay or the cardiomyocyte contractility assay. Nineteen bioactive compounds were further assessed using both the HTRF cAMP assay and the PathHunter ß-arrestin assay. Their concentration-response data in stimulating cAMP synthesis and ß-arrestin recruitment were applied to the Black-Leff operational model for ligand bias quantitation. As a result, three compounds (L-2, L-4, and L-12) with the core structure of 5-(1-amino-2-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one were identified as a new series of ß-arrestin-biased ß2-adrenoceptor agonists, whereas salmeterol was found to be Gs-biased. These findings would facilitate the development of novel drugs for the treatment of both heart failure and asthma.

17.
Molecules ; 24(3)2019 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-30678231

RESUMO

20-Hydroxy-3-oxolupan-28-oic acid (HOA), a lupane-type triterpene, was obtained from the leaves of Mahonia bealei, which is described in the Chinese Pharmacopeia as a remedy for inflammation and related diseases. The anti-inflammatory mechanisms of HOA, however, have not yet been fully elucidated. Therefore, the objective of this study was to characterize the molecular mechanisms of HOA in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. HOA suppressed the release of nitric oxide (NO), pro-inflammatory cytokine tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) in LPS-stimulated RAW264.7 macrophages without affecting cell viability. Quantitative real-time reverse-transcription polymerase chain reaction (RT-qPCR) analysis indicated that HOA also suppressed the gene expression of inducible NO synthase (iNOS), TNF-α, and IL-6. Further analyses demonstrated that HOA inhibited the phosphorylation of upstream signaling molecules, including p85, PDK1, Akt, IκBα, ERK, and JNK, as well as the nuclear translocation of nuclear factor κB (NF-κB) p65. Interestingly, HOA had no effect on the LPS-induced nuclear translocation of activator protein 1 (AP-1). Taken together, these results suggest that HOA inhibits the production of cytokine by downregulating iNOS, TNF-α, and IL-6 gene expression via the downregulation of phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinases (MAPKs), and the inhibition of NF-κB activation. Our findings indicate that HOA could potentially be used as an anti-inflammatory agent for medical use.


Assuntos
Inflamação/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Triterpenos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Inflamação/imunologia , Inflamação/patologia , Mediadores da Inflamação , Lipopolissacarídeos/imunologia , Macrófagos/imunologia , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Células RAW 264.7 , Triterpenos/química
18.
Front Genet ; 9: 492, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30429869

RESUMO

Qinghai-Tibetan Plateau (QTP) is an important biodiversity hub, which is very sensitive to climate change. Here in this study, we investigated genetic diversity and past population dynamics of Lancea tibetica (Mazaceae), an endemic herb to QTP and adjacent highlands. We sequenced chloroplast and nuclear ribosomal DNA fragments for 429 individuals, collected from 29 localities, covering their major distribution range at the QTP. A total of 19 chloroplast haplotypes and 13 nuclear genotypes in two well-differentiated lineages, corresponding to populations into two groups isolated by Tanggula and Bayangela Mountains. Meanwhile, significant phylogeographical structure was detected among sampling range of L. tibetica, and 61.50% of genetic variations was partitioned between groups. Gene flow across the whole region appears to be restricted by high mountains, suggesting a significant role of geography in the genetic differences between the two groups. Divergence time between the two lineages dated to 8.63 million years ago, which corresponded to the uplifting of QTP during the late Miocene and Pliocene. Ecological differences were found between both the lineages represent species-specific characteristics, sufficient to keep the lineages separated to a high degree. The simulated distribution from the last interglacial period to the current period showed that the distribution of L. tibetica experienced shrinkage and expansion. Climate changes during the Pleistocene glacial-interglacial cycles had a dramatic effect on L. tibetica distribution ranges. Multiple refugia of L. tibetica might have remained during the species history, to south of the Tanggula and north of Bayangela Mountains, both appeared as topological barrier and contributed to restricting gene flow between the two lineages. Together, geographic isolation and climatic factors have played a fundamental role in promoting diversification and evolution of L. tibetica.

19.
Gastric Cancer ; 2018 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-30178386

RESUMO

BACKGROUND: Recurrence is a primary cause of gastric cancer (GC)-related deaths. We reported previously that low expression of miR-142-5p could predict recurrence in GC. The present study aimed to investigate the function and mechanism of miR-142-5p in metastasis of GC. METHODS: MiR-142-5p expression was detected in 101 GC samples by qRT-PCR. Its clinical significance was statistically analyzed. The roles of miR-142-5p and its candidate target gene CYR61 in metastasis were determined both in vivo and in vitro. RESULTS: MiR-142-5p downregulation was significantly associated with the recurrence (P = 0.031) and poor prognosis of GC (P = 0.043). MiR-142-5p inhibited cancer cell migration and invasion both in vitro and in vivo. CYR61 was identified as a novel direct target of miR-142-5p by bioinformatics analysis of target prediction and luciferase reporter assay. The re-expression and knockdown of CYR61 could, respectively, rescue the effects induced by miR-142-5p overexpression and knockdown. MiR-142-5p attenuated GC cell migration and invasion, at least partially, by inactivation of the canonical Wnt/ß-catenin signaling pathway through CYR61. CONCLUSIONS: The newly identified miR-142-5p-CYR61-Wnt/ß-catenin axis partially illustrates the molecular mechanism of GC recurrence and represents a novel prognosis biomarker for GC.

20.
Curr Med Sci ; 38(3): 387-397, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30074203

RESUMO

Firstly discovered in 1980s, human immunodeficiency virus (HIV) continues to affect more and more people. However, there is no effective drug available for the therapy of HIV infection. Betulinic acid existing in various medicinal herbs and fruits exhibits multiple biological effects, especially its outstanding anti-HIV activity, which has drawn the attentions of many pharmacists. Among the derivatives of betulinic acid, some compounds exhibited inhibitory activities at the nanomolar concentration, and have entered phase II clinical trials. This paper summarizes the current investigations on the anti-HIV activity of betulinic acid analogues, and provides valuable data for subsequent researches.


Assuntos
Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , HIV-1/efeitos dos fármacos , Triterpenos/química , Triterpenos/farmacologia , Animais , Humanos , Relação Estrutura-Atividade , Replicação Viral/efeitos dos fármacos
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