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1.
J Enzyme Inhib Med Chem ; 35(1): 1403-1413, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32588683

RESUMO

Tubulin polymerisation inhibitors that target colchicine binding site were powerful anticancer agents. Although along the years many colchicine binding site inhibitors (CBSIs) have been reported, few piperidine derivatives were identified as CBSIs. In this regard, we focussed efforts on the piperidine as a promising chemotype to develop potent CBSIs. Herein, novel piperidine derivatives were synthesised and evaluated for their antiproliferative activities. Among them, compound 17a displayed powerful anticancer activity with the IC50 value of 0.81 µM against PC3 cells, which was significantly better than 5-fluorouracil. It could inhibit tubulin polymerisation binding at the colchicine site and inhibit the tumour growth in vitro and in vivo. Further biological studies depicted that 17a suppressed the colony formation, induced apoptosis, and inhibited epithelial-mesenchymal transition against PC3 cells. These results revealed that compound 17a is a promising colchicine binding site inhibitor for the treatment of cancer and it is worthy of further exploitation.

2.
Mol Med Rep ; 21(5): 2202-2208, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32323765

RESUMO

The plant extract piperine is used as a traditional Chinese medicine due to its anti­inflammatory effects and efficacy against numerous types of cancer. The aim of the present study was to investigate the antitumor mechanism of piperine in human osteosarcoma U2OS and 143B cell lines. The effects of piperine on cell apoptosis and invasion of human osteosarcoma cells were assessed using flow cytometry and Transwell assays. Moreover, western blotting was used to measure the effects of piperine on the protein expression levels of the metastasis markers matrix metalloproteinase­2 (MMP­2) and vascular endothelial growth factor (VEGF). In addition, the involvement of the Wnt/ß­catenin signaling pathway in modulating the effects of piperine was examined via western blot analysis. The results of MTT and Transwell invasion assays indicated that piperine treatment dose­dependently reduced U2OS and 143B cell viability and invasion. Furthermore, a significant reduction was identified in MMP­2, VEGF, glycogen synthase kinase­3ß and ß­catenin protein expression levels, as well as the expression levels of their target proteins cyclooxygenase­2, cyclin D1 and c­myc, in U2OS cells after piperine treatment. In addition, similar results were observed in 143B cells. Therefore, the present study demonstrated the efficacy of piperine in osteosarcoma, and identified that the Wnt/ß­catenin signaling pathway may modulate the antitumor effects of piperine on human U2OS and 143B cells.

3.
J Enzyme Inhib Med Chem ; 35(1): 1050-1059, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32299262

RESUMO

Tubulin polymerisation inhibitors exhibited an important role in the treatment of patients with prostate cancer. Herein, we reported the medicinal chemistry efforts leading to a new series of benzothiazoles by a bioisosterism approach. Biological testing revealed that compound 12a could significantly inhibit in vitro tubulin polymerisation of a concentration dependent manner, with an IC50 value of 2.87 µM. Immunofluorescence and EBI competition assay investigated that compound 12a effectively inhibited tubulin polymerisation and directly bound to the colchicine-binding site of ß-tubulin in PC3 cells. Docking analysis showed that 12a formed hydrogen bonds with residues Tyr357, Ala247 and Val353 of tubulin. Importantly, it displayed the promising antiproliferative ability against C42B, LNCAP, 22RV1 and PC3 cells with IC50 values of 2.81 µM, 4.31 µM, 2.13 µM and 2.04 µM, respectively. In summary, compound 12a was a novel colchicine site tubulin polymerisation inhibitor with potential to treat prostate cancer.

4.
Br J Pharmacol ; 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32343840

RESUMO

BACKGROUND AND PURPOSE: Anxiety disorder is a common mental health disorder. However, there are few safe and fast-acting anxiolytic drugs available that can treat anxiety disorder. We previously demonstrated that the interaction of neuronal NOS (nNOS) with its carboxy-terminal PDZ ligand (CAPON) is involved in regulating anxiety-related behaviours. Here, we further investigated the anxiolytic effects of nNOS-CAPON disruptors in chronic stress-induced anxiety in animals. EXPERIMENTAL APPROACH: Mice were intravenously treated with nNOS-CAPON disruptors, ZLc-002 or Tat-CAPON12C, at the last week of chronic mild stress (CMS) exposure. We also infused corticosterone (CORT) into the hippocampus of mice to model anxiety behaviours and also delivered ZLc-002 or Tat-CAPON12C on the last week of chronic CORT treatment via pre-implanted cannula. Anxiety-related behaviours were examined using elevated plus maze, open field, novelty-suppressed feeding and light-dark (LD) tests. The level of nNOS-CAPON interaction was determined by co-immunoprecipitation (CO-IP) and proximity ligation assay (PLA). The neural mechanisms underlying the behavioural effects of nNOS-CAPON uncoupling in anxiety animal models were assessed by western blot, immunofluorescence and Golgi-Cox staining. KEY RESULTS: ZLc-002 and Tat-CAPON12C reversed CMS- or CORT-induced anxiety-related behaviours. ZLc-002 and Tat-CAPON12C increased synaptogenesis along with improved dendritic remodelling in CMS mice or CORT-treated cultured neurons. Meanwhile, blocking nNOS-CAPON interaction significantly activated the cAMP response element-binding protein (CREB)-brain-derived neurotrophic factor (BDNF) pathway, which is associated with synaptic plasticity. CONCLUSION AND IMPLICATIONS: Collectively, these results provide evidence for the anxiolytic effects of nNOS-CAPON uncouplers and their underlying mechanisms in anxiety disorders.

5.
Neurology ; 94(15): e1673-e1674, 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32165450
6.
J Infect Dis ; 221(Supplement_2): S139-S147, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32176789

RESUMO

BACKGROUND: Candidemia is the most common, serious fungal infection and Candida antifungal resistance is a challenge. We report recent surveillance of candidemia in China. METHODS: The study encompassed 77 Chinese hospitals over 3 years. Identification of Candida species was by mass spectrometry and DNA sequencing. Antifungal susceptibility was determined using the Clinical and Laboratory Standards Institute broth microdilution method. RESULTS: In total, 4010 isolates were collected from candidemia patients. Although C. albicans was the most common species, non-albicans Candida species accounted for over two-thirds of isolates, predominated C. parapsilosis complex (27.1%), C. tropicalis (18.7%), and C. glabrata complex (12.0%). Most C. albicans and C. parapsilosis complex isolates were susceptible to all antifungal agents (resistance rate <5%). However, there was a decrease in voriconazole susceptibility to C. glabrata sensu stricto over the 3 years and fluconazole resistance rate in C. tropicalis tripled. Amongst less common Candida species, over one-third of C. pelliculosa isolates were coresistant to fluconazole and 5-flucytocine, and >56% of C. haemulonii isolates were multidrug resistance. CONCLUSIONS: Non-albicans Candida species are the predominant cause of candidemia in China. Azole resistance is notable amongst C. tropicalis and C. glabrata. Coresistance and multidrug resistance has emerged in less common Candida species.

7.
J Hazard Mater ; 391: 121642, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32045798

RESUMO

To enhance the photocatalytic activity of TiO2, a new preparation method has been proposed to synthesize the catalysts by introducing Cu-MOF as a precursor and performing a blackening process via a mixture with NaBH4 for TiO2 nanoparticles (CuO-TiO2(mb)). The results showed that the removal efficiency of xylene under ultraviolet and visible light over CuO-TiO2(mb) was 3.45 times higher than that of the catalysts prepared by impregnation of CuO on the surfaces of TiO2 (CuO-TiO2(d)) and 12.12 times higher than that of pure TiO2 nanoparticles. Analyses by the X-ray diffraction, scanning electron microscopy, and transmission electron microscopy indicated that the introduction of Cu-MOF as a precursor on the surface of the catalyst resulted in CuO-TiO2(mb) presenting a lower grain size compared with TiO2 nanoparticles and CuO-TiO2(d). The results of X-ray photoelectron spectroscopy, diffuse reflectance spectrum and photoluminescence indicated that blackening process narrowed the bind gap width and shortened the band gap from 2.95 eV to 1.32 eV, introduced the coexistence of Ti4+, Ti3+, Cu2+ and Cu+ in CuO-TiO2(mb) decreased the recombination rate of e--h+, which greatly improved the light response of CuO-TiO2(mb) under ultraviolet and visible light, resulting in the benefit to the photocatalytic reaction.

8.
ChemSusChem ; 13(7): 1715-1719, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32057192

RESUMO

Efficient borylation reaction of diazonium salts in water is realized for the first time by using easily prepared, highly emissive and crystalline carbon dots. Electron-donating and electron-withdrawing groups on diazonium salts were well tolerated with moderate to good conversion efficiency. Compared with widely used metal complexes, organic dyes and quantum dots, the approach presented herein uses carbon dots, which are nontoxic and possess good biological and medicinal compatibility and high reactivity. Therefore, this approach presents a new prospective use for carbon dots in green chemistry.

9.
Sci Rep ; 10(1): 439, 2020 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-31949205

RESUMO

Flavanomarein (FM) is a major natural compound of Coreopsis tinctoria Nutt with protective effects against diabetic nephropathy (DN). In this study, we investigated the effects of FM on epithelial-mesenchymal transition (EMT) in high glucose (HG)-stimulated human proximal tubular epithelial cells (HK-2) and the underlying mechanisms, including both direct targets and downstream signal-related proteins. The influence of FM on EMT marker proteins was evaluated via western blot. Potential target proteins of FM were searched using Discovery Studio 2017 R2. Gene Ontology (GO) analysis was conducted to enrich the proteins within the protein-protein interaction (PPI) network for biological processes. Specific binding of FM to target proteins was examined via molecular dynamics and surface plasmon resonance analyses (SPR). FM promoted the proliferation of HK-2 cells stimulated with HG and inhibited EMT through the Syk/TGF-ß1/Smad signaling pathway. Spleen tyrosine kinase (Syk) was predicted to be the most likely directly interacting protein with FM. Combined therapy with a Syk inhibitor and FM presents significant potential as an effective novel therapeutic strategy for DN.

10.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(4): 483-488, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31642223

RESUMO

OBJECTIVE: To study the application value of motion-correction phase sensitive inversion recovery (MOCO-PSIR) to evaluate myocardial fibrosis in the patients with heart failure caused by dilated cardiomyopathy (DCM). METHODS: A prospective study included 60 patients who underwent cardiac MRI enhanced scan from June 2017 to November 2018, including 38 patients who were clinically diagnosed with DCM and 22 patients in the normal control group. All patients were scanned with three late gadolinium enhancement (LGE) sequences: segmented-PSIR, single-shot-PSIR, MOCO-PSIR at the same time. The subjective quality score (level 4) and image signal-to-noise ratio (objective evaluation) of normal and abnormal myocardium were analyzed and compared in three scanning technique groups. The detection rate of myocardial fibrosis and image acquisition time of the three scanning techniques were recorded. RESULTS: In the normal control group (sinus rhythm), subjective score showed no statistical significance. Subjective scoring results in the patients with DCM: MOCO-PSIR>single-shot-PSIR> segmented-PSIR (P < 0.05). SNR results PSIR-LGE images in DCM patients as well as control group: segmented-PSIR>MOCO-PSIR> single-shot-PSIR (P < 0.05). In the whole 646 segments analysis of DCM patients, the ratio unable to judge in segmented-PSIR was up to 25.5%, but only 1.4% in MOCO-PSIR. Significant difference was found in the three groups. While in the 374 segments of control group, no statistical difference was found in comparison of incapability to judge. Acquisition time covered left ventricular: (5.6±1.7) min in segmented-PSIR, (0.4±0.2) min in single-shot-PSIR and (4.5±1.1) min in MOCO-PSIR. Pairwise comparison of acquisition time among three scanning techniques was statistically significant (P < 0.001). CONCLUSION: MOCO-PSIR-LGE has better clinical significance than conventional delayed enhanced scan sequences in the diagnosis of myocardial fibrosis in the patients with heart failure caused by dilated cardiomyopathy.


Assuntos
Cardiomiopatia Dilatada/diagnóstico por imagem , Insuficiência Cardíaca/diagnóstico por imagem , Imagem por Ressonância Magnética , Miocárdio/patologia , Estudos de Casos e Controles , Meios de Contraste , Fibrose , Gadolínio , Humanos , Aumento da Imagem , Estudos Prospectivos
11.
FASEB J ; 33(11): 12240-12252, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31431066

RESUMO

It is recognized that stress can induce cardiac dysfunction, but the underlying mechanisms are not well understood. The present study aimed to test the hypothesis that chronic negative stress leads to alterations in DNA methylation of certain cardiac genes, which in turn contribute to pathologic remodeling of the heart. We found that mice that were exposed to chronic restraint stress (CRS) for 4 wk exhibited cardiac remodeling toward heart failure, as characterized by ventricular chamber dilatation, wall thinning, and decreased contractility. CRS also induced cardiac arrhythmias, including intermittent sinus tachycardia and bradycardia, frequent premature ventricular contraction, and sporadic atrioventricular conduction block. Circulating levels of stress hormones were elevated, and the cardiac expression of tyrosine hydroxylase, a marker of sympathetic innervation, was increased in CRS mice. Using reduced representation bisulfite sequencing, we found that although CRS did not lead to global changes in DNA methylation in the murine heart, it nevertheless altered methylation at specific genes that are associated with the dilated cardiomyopathy (DCM) (e.g., desmin) and adrenergic signaling of cardiomyocytes (ASPC) (e.g., adrenergic receptor-α1) pathways. We conclude that CRS induces cardiac remodeling and arrhythmias, potentially through altered methylation of myocardial genes associated with the DCM and ASPC pathways.-Zhang, P., Li, T., Liu, Y.-Q., Zhang, H., Xue, S.-M., Li, G., Cheng, H.-Y.M., Cao, J.-M. Contribution of DNA methylation in chronic stress-induced cardiac remodeling and arrhythmias in mice.

12.
Ying Yong Sheng Tai Xue Bao ; 30(8): 2865-2874, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31418213

RESUMO

Mineral spring water is a top quality potable groundwater resource formed by long-term groundwater-rock interaction in aquifer. Mineral spring water is rich in minerals and trace elements which are beneficial for human health. Given the current serious water pollution and environment deterioration, it is of great significance to re-recognize the ecological and health effects of mineral water based on new scientific and technological achievement. The Wudalianchi scenic area in Heilongjiang Province has abundant mineral water and peloid resources, which supported the development of tourism and convalescence and have been used in medical and health care for more than 100 years. However, it is threatened by resource reduction, environmental pollution, and other problems. Here, we reviewed the formation process, distribution, hydro-biochemical characteristics and health effects of the Wudalianchi mineral springs, with particular focus on the advances of microbial studies in this area. We also proposed the future research prospective for the Wudalianchi mineral water. To better protect and utilize the Wudalianchi mineral water, it was recommended that a green eco-agriculture practice in reducing chemical fertilizers should be adapted in the surrounding farms of Wudalianchi. Along with the development of tourism and recuperation resources, it is necessary to establish a framework of pollution risk assessment and control, and strictly reduce potential emerging pollutants to eco-geological environment.


Assuntos
Monitoramento Ambiental , Água Subterrânea/microbiologia , Águas Minerais/microbiologia , China , Humanos , Estudos Prospectivos , Poluentes Químicos da Água/análise
13.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(7): 663-669, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31315765

RESUMO

OBJECTIVE: To investigate the composition of gut microbiota and its correlation with the severity of behavior symptoms in children with autism spectrum disorder (ASD). METHODS: A total of 30 children with ASD were enrolled as the ASD group, and 20 healthy children matched for age and sex were enrolled as the healthy control group. Related clinical data were analyzed. The V3-V4 hypervariable regions of the bacterial 16S rRNA gene in fecal samples were sequenced. The severity of behavior symptoms in children with ASD was assessed using the autism behavior checklist. The Spearman's correlation analysis was used to investigate the correlation between gut microbiota and the severity of behavior symptoms in children with ASD. RESULTS: There was a significant difference in the composition of gut microbiota between the two groups. Compared with the healthy control group, the ASD group had significant reductions in Shannon index and Shannoneven index (P<0.05), as well as a significant reduction in the percentage of Firmicutes and a significant increase in the percentage of Acidobacteria in feces (P<0.05). In the ASD group, the dominant bacteria were Megamonas, Megasphaera, and Barnesiella, while in the healthy control group, the dominant bacteria were Eubacterium_rectale_group, Ezakiella, and Streptococcus. In the children with ASD, the abundance of Megamonas was positively correlated with the scores of health/physical/behavior and language communication (P<0.05). CONCLUSIONS: The development of ASD and the severity of behavior symptoms are closely associated with the composition of gut microbiota.


Assuntos
Transtorno do Espectro Autista , Microbioma Gastrointestinal , Bactérias , Criança , Fezes , Humanos , RNA Ribossômico 16S
14.
Neural Regen Res ; 14(11): 1994-2002, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31290458

RESUMO

Progranulin is closely related to neuronal survival in a neuroinflammatory mouse model and attenuates inflammatory reactions. Atsttrin is an engineered protein composed of three progranulin fragments and has been shown to have an effect similar to that of progranulin. Atsttrin has anti-inflammatory actions in multiple arthritis mouse models, and it protects against further arthritis development. However, whether Atsttrin has a role in neuroinflammation remains to be elucidated. In this study, we produced a neuroinflammatory mouse model by intracerebroventricular injection of 1 µL lipopolysaccharide (10 µg/µL). Atsttrin (2.5 mg/kg) was administered via intraperitoneal injection every 3 days over a period of 7 days before intracerebroventricular injection of 1 µL lipopolysaccharide (10 µg/µL). In addition, astrocyte cultures were treated with 0, 100 or 300 ng/mL lipopolysaccharide, with 200 ng/mL Atsttrin simultaneously. Immunohistochemistry, enzyme-linked immunosorbent assay and real-time reverse transcription-polymerase chain reaction were performed to examine the protein and mRNA levels of inflammatory mediators and to assess activation of the nuclear factor kappa B signaling pathway. Progranulin expression in the brain of wild-type mice and in astrocyte cultures was increased after lipopolysaccharide administration. The protein and mRNA expression levels of tumor necrosis factor-α, interleukin-1ß and inducible nitric oxide synthase were increased in the brain of progranulin knockout mice after lipopolysaccharide administration. Atsttrin treatment reduced the lipopolysaccharide-induced increase in the protein and mRNA levels of tumor necrosis factor-α, interleukin-1ß, matrix metalloproteinase-3 and inducible nitric oxide synthase in the brain of progranulin knockout mice. Atsttrin also reduced the expression of cyclooxygenase-2, inducible nitric oxide synthase and matrix metalloproteinase 3 mRNA in lipopolysaccharide-treated astrocytes in vitro, and decreased the concentration of tumor necrosis factor a and interleukin-1ß in the supernatant. Furthermore, Atsttrin significantly reduced the levels of phospho-nuclear factor kappa B inhibitor a in the brain of lipopolysaccharide-treated progranulin knockout mice and astrocytes, and it decreased the expression of nuclear factor kappa B2 in astrocytes. Collectively, our findings show that the anti-neuroinflammatory effect of Atsttrin involves inhibiton of the nuclear factor kappa B signaling pathway, and they suggest that Atsttrin may have clinical potential in neuroinflammatory therapy. The study was approved by the Animal Ethics Committee of Qilu Hospital of Shandong University, China (approval No. KYLL-2015(KS)-088) on February 10, 2015.

15.
Infect Drug Resist ; 12: 865-875, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31114266

RESUMO

Introduction: We studied the species distribution and antifungal susceptibilities of Candida isolates causing refractory or recurrent oropharyngeal candidiasis (OPC) in a multicenter study in China (2013-2016). Methods: Species identification was performed using the Bruker Biotyper (Bruker Daltonics, Germany) matrix-assisted laser desorption/ionization time of flight mass spectrometry system supplemented by internal transcribed spacer sequencing as required. Antifungal susceptibilities were determined by the Clinical and Laboratory Standards Institute document (CLSI) M27-A3 broth microdilution methodology. Results: A total of 558 non-duplicate Candida isolates comprising 10 species were obtained from 535 patients. Candida albicans was the most common species (89.6%), followed by C. glabrata (5.2%), C. tropicalis (2.9%), and C. parapsilosis (0.7%). Azoles were active against C. albicans with susceptibility rates of 96% and 95.8% for fluconazole and voriconazole, respectively. MIC50 values of C. albicans to fluconazole, voriconazole, itraconazole, and miconazole were 1, 0.03, 0.25 and 0.12 µg/mL, respectively, higher than those in previous studies of which OPC patients (corresponding MIC50 values of 0.25 , 0.015 , 0.06 , and 0.03 µg/mL). Except for itraconazole, the MIC50 and MIC90 values of 58 non-C. albicans to other azoles were two to threefold higher than C. albicans. Miconazole, amphotericin B, nystatin, and 5-flucytosine had good in vitro antifungal activity for all isolates. Conclusion: The study provides valuable data on the species distribution and antifungal susceptibility of oropharyngeal Candida isolates from geographically diverse areas of China. C. albicans remains the most common species but with increasing rates of azoles resistance.

16.
FEBS Open Bio ; 9(5): 891-900, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30972964

RESUMO

Escin, a natural triterpene saponin mixture obtained from the horse chestnut tree (Aesculus hippocastanum), has been used for the treatment of chronic venous insufficiency (CVI), hemorrhoids, and edema. However, it is unclear how escin protects against endothelial barrier dysfunction induced by pro-inflammatory high mobility group protein 1 (HMGB1). Here, we report that escin can suppress (a) HMGB1-induced overexpression of the aquaporin-1 (AQP1) water channel in endothelial cells and (b) HMGB1-induced increases in endothelial cell permeability. This is the first report that escin inhibits AQP1 and alleviates barrier dysfunction in HMGB1-induced inflammatory response.


Assuntos
Aquaporina 1/genética , Fármacos Cardiovasculares/farmacologia , Escina/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Proteína HMGB1/genética , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Aquaporina 1/metabolismo , Proteína HMGB1/metabolismo , Células Endoteliais da Veia Umbilical Humana/fisiologia , Humanos , Permeabilidade
17.
Int Immunopharmacol ; 72: 138-147, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30981079

RESUMO

Interleukin-17 (IL-17) is the production of T helper type 17 (Th17) cells and has been reported to play a pro-inflammatory role in the immunopathogenesis of intervertebral disc degeneration. Peroxisome proliferator-activated receptor γ (PPAR-γ) activators display anti-inflammatory and anti-degeneration roles in osteoarthritis and rheumatoid arthritis. However, the expression level of PPAR-γ and related regulatory mechanisms in the nucleus pulposus tissues are not clear. Herein we report that PPAR-γ was down-regulated both in the nucleus pulposus tissue of intervertebral disc degeneration patient and in the cultured nucleus pulposus cells stimulated with IL-17. This study was undertaken to investigate the potential therapeutic effect of pioglitazone, as a PPAR-γ ligand, and its underlying molecular mechanism in IL-17-induced human intervertebral disc degeneration model in vitro. Our results indicate that pioglitazone administration suppressed the production of pro-inflammatory cytokines and down-regulated the mRNA expression levels of inflammatory mediators in the cultured human nucleus pulposus cells and tissue. Consistently, pioglitazone decreased the levels of metalloproteinase and maintained the expression of critical matrix components, such as aggrecan and type II collagen. Moreover, the activation of NF-κB signaling in the nucleus pulposus tissue during the intervertebral disc degeneration development was antagonized by pioglitazone administration. In conclusion, our current findings provide scientific evidence for the assessment of pioglitazone as a potential therapeutic approach to treat the intervertebral disc degeneration.


Assuntos
Anti-Inflamatórios , Degeneração do Disco Intervertebral/tratamento farmacológico , Degeneração do Disco Intervertebral/metabolismo , NF-kappa B/metabolismo , PPAR gama/agonistas , Pioglitazona , Adulto , Idoso , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Citocinas/imunologia , Feminino , Humanos , Degeneração do Disco Intervertebral/imunologia , Masculino , Pessoa de Meia-Idade , NF-kappa B/genética , Núcleo Pulposo/citologia , Pioglitazona/farmacologia , Pioglitazona/uso terapêutico , Transdução de Sinais/efeitos dos fármacos
18.
Joint Bone Spine ; 86(5): 643, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30981870
19.
J Microbiol Immunol Infect ; 52(3): 456-464, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30772212

RESUMO

BACKGROUND AND PURPOSE: Bacteroides fragilis group isolates are most frequently isolated anaerobic pathogens. This study aimed to evaluate the accuracy of VITEK MS, Clin-ToF-II MS, Autof MS 1000 and VITEK 2 ANC card on the identification of clinical B. fragilis group isolates, as well as to determine their antimicrobial susceptibilities. METHODS: A total of 138 isolates of B. fragilis group isolates were identified with the three MALDI-TOF MS systems and VITEK 2 ANC cards. 16S rRNA gene sequencing was used as the reference identification method for comparison. Antimicrobial susceptibilities were determined by agar dilution method to 19 antimicrobial agents recommended by Clinical and Laboratory Standards Institute (CLSI). RESULTS: Hundred thirty three isolates of Bacteroides spp. and 5 isolates of Parabacteroides spp. were identified by 16S rRNA sequencing. The rates of accurate identification at species level of VITEK MS, Clin-ToF-II MS, Autof MS 1000 and VITEK 2 ANC card were 94.2%, 94.2%, 98.6% and 94.9%, respectively, while that at genus level were 99.3%, 100%, 100% and 97.8%, respectively. Metronidazole and chloramphenicol were the most susceptible agents (99.3% and 92.8%, respectively), followed by meropenem, ertapenem, imipenem and piperacillin/tazobactam to which the susceptible rates ranged from 76.8% to 79.0%. The susceptible rates to carbapenems decreased 12.4-15.3% from 2010-2013 to 2014-2017. CONCLUSION: All the four systems provided high accurate rate on the identification of B. fragilis group isolates. Metronidazole showed highest activity against these isolates. Attention should be paid to the higher resistant rates to carbapenems, clindamycin, moxifloxacin and tigecycline than the other countries.


Assuntos
Antibacterianos/farmacologia , Técnicas de Tipagem Bacteriana/métodos , Infecções por Bacteroides/microbiologia , Bacteroides fragilis/efeitos dos fármacos , Bacteroides fragilis/isolamento & purificação , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Bacteroides fragilis/classificação , Bacteroides fragilis/genética , Bacteroidetes/classificação , Bacteroidetes/efeitos dos fármacos , Bacteroidetes/genética , Bacteroidetes/isolamento & purificação , Hemocultura , Farmacorresistência Bacteriana/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
20.
J Orthop Sci ; 24(1): 42-49, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30219602

RESUMO

BACKGROUND: Dyslipidaemia is a well-known risk factor for the development of atherosclerosis, however, little is known about the effect of dyslipidaemia on intervertebral disc degeneration (IVDD). Thus, the purpose of this study is to investigate the relationship between dyslipidaemia and IVDD, and to identify the possible mechanism by which dyslipidaemia aggravates the degeneration of intervertebral discs. METHODS: Hyperlipidaemia rats were induced, thirty male Wistar rats were randomly divided into two groups: normal chow diet control group (CON) and high-fat diet group (HFD) for 8 weeks. And then, a rat disc degeneration model was established, rats were divided into three experimental groups: the normal chow diet + sham surgery group (CON-Sham); the normal chow diet + needle puncture group (CON-NP); and the high-fat diet + needle puncture group (HFD-NP), all rats were continually fed with normal chow diet or HFD 8 weeks. At the end of the experiment, the discs were harvested and histomorphological analysis, immunohistochemistry staining, real-time PCR and western blot were performed for all groups. RESULTS: The degenerative histological score of disc in the HFD-NP group was significantly higher than the CON-NP group. Immunohistochemical analysis revealed remarkable reductions in aggrecan and collagen type II expressions, and significant increases in IL-1ß, TNF-α, MMP-13, HIF-1α and P65 expression in the HFD-NP group. RT-PCR and western blot analysis showed that the mRNA levels and protein expressions of MMP-13 and TIMP-1 were higher in the HFD-NP group. CONCLUSIONS: Hyperlipidaemia resulted in an exaggerated degenerative changes and altered expression and transcription of the degeneration-associated molecules in the rat disc tissue. These results raise the possibility that hyperlipidaemia may accelerate the progression of disc degeneration.


Assuntos
Cóccix/lesões , Hiperlipidemias/complicações , Degeneração do Disco Intervertebral/etiologia , Disco Intervertebral/diagnóstico por imagem , Animais , Biópsia , Cóccix/diagnóstico por imagem , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica , Hiperlipidemias/diagnóstico , Hiperlipidemias/metabolismo , Imuno-Histoquímica , Degeneração do Disco Intervertebral/diagnóstico , Degeneração do Disco Intervertebral/metabolismo , Reação em Cadeia da Polimerase , Prognóstico , RNA/genética , Ratos , Ratos Wistar
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