Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 113
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Artigo em Inglês | MEDLINE | ID: mdl-31622010

RESUMO

We describe a female patient who received hybrid catheter intervention and occlusion of the patent ductus arteriosus (PDA) and left atrial appendage (LAA). Four hours after the procedure, pericardial tamponade suddenly occurred. Surgical exploration of the heart found that a fixation hook of the WATCHMAN device, had protruded through the LAA wall and tore the dilated pulmonary artery (PA). This is the first case report to describe PA perforation caused by barbs of the WATCHMAN device, and more attention should be paid to the relationship between the LAA and its adjacent structures before LAA closure.

2.
Int J Mol Sci ; 20(21)2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31661772

RESUMO

Our previous research has shown that a fungal immunomodulatory protein from Nectria haematococca (FIP-nha) possesses a wide spectrum of anti-tumor activities, and FIP-nha induced A549 apoptosis by negatively regulating the PI3K/Akt signaling pathway based on comparative quantitative proteomics. This study further confirmed that the anti-lung cancer activity of FIP-nha was significantly stronger than that of the reported LZ-8 and FIP-fve. Subsequently, 1H NMR-based metabolomics was applied to comprehensively investigate the underlying mechanism, and a clear separation of FIP-nha-treated and untreated groups was achieved using pattern recognition analysis. Four potential pathways associated with the anti-tumor effect of FIP-nha on A549 cells were identified, and these were mainly involved in glycolysis, taurine and hypotaurine metabolism, fructose and mannose metabolism, and glycerolipid metabolism. Metabolic pathway analysis demonstrated that FIP-nha could induce A549 cell apoptosis partly by regulating the p53 inhibition pathway, which then disrupted the Warburg effect, as well as through other metabolic pathways. Using RT-PCR analysis, FIP-nha-induced apoptosis was confirmed to occur through upregulation of p53 expression. This work highlights the possible use of FIP-nha as a therapeutic adjuvant for lung cancer treatment.

3.
JMIR Mhealth Uhealth ; 7(9): e13127, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31507269

RESUMO

BACKGROUND: Many university students are lacking adequate physical exercise and are failing to develop physical activity (PA) behaviors in China. PA app use could improve this situation. OBJECTIVE: The aim of this study was to use the unified theory of acceptance and use of technology (UTAUT) to investigate the intention to use PA apps among university students in Guangzhou, China, and how body mass index (BMI) moderates the effects of UTAUT in explaining PA app use intention. METHODS: A cross-sectional study was conducted among 1704 university students from different universities in Guangzhou, China. The UTAUT model was used to measure the determinants of intention to use PA apps. RESULTS: Of the participants, 41.8% (611/1461) intended to use PA apps. All three UTAUT-related scales (performance expectancy, effort expectancy, and social influence) were positively associated with the intention to use PA apps after adjusting for background variables (adjusted odds ratio 1.10-1.31, P<.001). The performance expectancy scale had stronger associations with the intention to use PA apps among those whose BMI were beyond normal range compared with those whose BMI were within normal range (P<.001). CONCLUSIONS: UTAUT is useful for understanding university students' intention to use PA apps. Potential moderating effects should be kept in mind when designing UTAUT-based interventions to improve PA via app use.

4.
Cancer Med ; 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31518054

RESUMO

BACKGROUND: CXCR4 chemokine receptors play an important role in leukemia proliferation, extramedullary migration, infiltration, adhesion, and resistance to chemotherapy drugs. METHODS: The CXCR4 expression by flow cytometry in 122 acute myeloid leukemia (AML) patients between 2010 and 2014 was analyzed. RESULTS: The expression of CXCR4 in AML-M4/M5 was found to be significantly higher than that of other subtypes according to both FAB subtype and WHO classification. The FLT3-ITD mutant was significantly higher in high CXCR4 expression group (P = .0086). Our data also showed that CXCR4 expression was correlated with CD64 expression. Low CXCR4 expression on AML cells was associated with better prognosis, and the median overall survival (OS) for low CXCR4 expression patients was 318 days, compared with 206 days for patients with high CXCR4 expression (P = .045). Multivariate analysis revealed that CXCR4 expression, age, and extramedullary infiltration were independent prognostic factors. CONCLUSIONS: Our study demonstrated that CXCR4 expression in AML was an independent prognostic predictor for disease survival that could be rapidly and easily determined by flow cytometry at disease presentation.

5.
Brain Res Bull ; 153: 239-249, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31542427

RESUMO

Chronic social defeat stress (CSDS) is a widely used behavioural paradigm of psychosocial stress that can be used to research the pathogenesis of depression and seek antidepressant drugs. Dammarane sapogenins (DS), the deglycosylated product of ginsenosides, has a wide range of biological activities, including immunomodulatory, antifatigue, antitumour and antidepressant activities. However, whether DS has antidepressant-like effects in a CSDS mouse model remains unknown. Therefore, the present study was conducted to evaluate the antidepressant properties of DS in CSDS mice and its underlying mechanisms. The results showed that the oral administration of DS (40 and 80 mg/kg) increased the time spent in the interaction zone in the social interaction test and the sucrose intake in the sucrose preference test, decreased the latency in the novelty-suppressed feeding test, and reduced the immobility time in both the tail suspension test and forced swimming test. Biochemical analyses of brain tissue and serum showed that DS treatment significantly decreased serum corticosterone levels and enhanced brain monoamine neurotransmitter levels in CSDS mice. In addition, an impairment in hippocampal neurogenesis that paralleled a reduced BDNF level in the hippocampus was observed in the mice that were subjected with CSDS for 3 weeks, while treatment with DS reversed these changes. Moreover, DS treatment significantly upregulated BDNF, pTrkB/TrkB, pAkt/Akt, pPI3K/PI3K, pCREB/CREB, pERK1/2/ERK1/2 and pmTOR/mTOR protein expression in the hippocampus. In conclusion, our results showed that DS exerts antidepressant-like effects in mice with CSDS-induced depression, that the effects may be mediated by the normalization of monoamine neurotransmitter levels, the prevention of HPA axis dysfunction and the impairment of hippocampal neurogenesis, and that this occurs partly through the ability of DS to enhance BDNF expression by increasing the TrkB/CREB/ERK pathway and the PI3K/AKT/mTOR pathway.

6.
AAPS PharmSciTech ; 20(7): 293, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31432294

RESUMO

In this study, a novel human serum albumin nanoparticle loading silybin-phospholipid complex (SLNPs) was developed for liver targeting after intravenous administration. The preparation of the drug delivery system consisted of two steps; initially, a silybin-phospholipid complex (SLC) was produced to improve the lipophilicity of SLB to then achieve enhanced encapsulation of SLB in albumin nanoparticles. FT-IR and XRD analysis confirmed the successful formation of SLC. The complex ratio of SLC in the first step was 99.6%. The encapsulation efficiency and drug loading of SLNPs in the second step were 96.2% and 5.6%, respectively. SLNPs were spherical and well-dispersed, with a zeta potential of approximately - 10 mV, and a mean particle size around 200 nm. An in vivo tissue distribution experiment and a pharmacodynamic experiment showed that, compared with SLB solution, SLNPs had an improved SLB accumulation in the liver. The hepatoprotective effect of SLNPs on CCl4-induced acute liver damage was evaluated. CCl4-damaged mice showed an increased enzymatic activity of ALT and AST; however, enzyme levels returned to near-normal levels in high-dose SLNP-treated mice. As SLNPs combine the enhanced oil solubility of SLC and the passive targeting of albumin nanoparticles, they possess great potential for the treatment of acute liver damage.

7.
Angew Chem Int Ed Engl ; 58(41): 14666-14672, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31373432

RESUMO

Reported herein is a visible-light-driven intramolecular C-N cross-coupling reaction under mild reaction conditions (metal- and photocatalyst-free, at room temperature) via a long-lived photoactive photoisomer complex. This strategy was used to rapidly prepare the N-substituted polycyclic quinazolinone derivatives with a broad substrate scope (>50 examples) and further exploited to synthesize the natural products tryptanthrin, rutaecarpine, and their analogues. The success of gram-scale synthesis and solar-driven transformation, as well as promising tumor-suppressing biological activity, proves the potential of this strategy for practical applications. Mechanistic investigations, including control experiments, DFT calculations, UV-vis spectroscopy, EPR, and X-ray single-crystal structure of the key intermediate, provides insight into the mechanism.

8.
Phytother Res ; 33(10): 2726-2736, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31353678

RESUMO

20(S)-Protopanaxadiol (PPD) is a basic aglycone of the dammarane triterpenoid saponins and exerts antidepressant-like effects on behaviour in the forced swimming test (FST) and tail suspension test (TST) and in rat olfactory bulbectomy depression models. However, the antidepressant effects of PPD have not been studied thoroughly. The objective of the present study was first to investigate the effect of PPD on depression behaviours induced by chronic social defeat stress (CSDS) in mice. The results showed that CSDS was effective in producing depression-like behaviours in mice, as indicated by decreased responses in the social interaction test, sucrose preference test, TST, and FST, and that this effect was accompanied by noticeable alterations in the levels of oxidative markers (superoxide dismutase, catalase, and lipid peroxidation) and monoamines (5-HT and NE) in the hippocampus and serum corticosterone levels. Additionally, western blot analysis revealed that CSDS exposure significantly downregulated BDNF, p-TrkB/TrkB, p-Akt/Akt, and p-mTOR/mTOR protein expression in the hippocampus. Remarkably, chronic PPD treatment significantly ameliorated these behavioral and biochemical alterations associated withCSDS-induced depression. Our results suggest that PPD exerts antidepressant-like effects in mice with CSDS-induced depression and that this effect may be mediated by the normalization of neurotransmitter and corticosterone levels and the alleviation of oxidative stress, as well as the enhancement of the PI3K/Akt/mTOR-mediated BDNF/TrkB pathway.

9.
Medicine (Baltimore) ; 98(24): e15876, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31192919

RESUMO

BACKGROUND: Lymphocyte-to-monocyte ratio (LMR) was recently proposed as a prognostic factor of ovarian cancer. However, prognostic value of the LMR in ovarian cancer remains inconclusive. The study aimed to assess prognostic value of the LMR in ovarian cancer. METHODS: Seven common databases were comprehensively searched for relevant studies. The analyses were performed for overall survival (OS), progression-free survival (PFS) and clinical parameters. The hazard ratio (HR) and 95% confidence interval (CI) were used to analyze OS and PFS. RESULTS: A total of 2343 patients with ovarian cancer were included in this meta-analysis. The results showed that a low LMR predicted shorter OS (HR = 1.81, 95% CI = 1.38-2.37, P < .01) and PFS (HR = 1.65 95% CI = 1.46-1.85, P < .01) when compared to a high LMR in ovarian cancer. Besides, a low LMR was significantly associated with advanced clinical stage (P < .01), earlier lymph node metastasis (P = .01), higher carbohydrate antigen-125 levels (P < .01), larger residual tumor (P < .01) and worse chemosensitivity (P < .01) when compared to a high LMR in ovarian cancer. CONCLUSION: Low LMR was associated with unfavorable survival in patients with ovarian cancer. LMR could serve as a prognostic biomarker of ovarian cancer.


Assuntos
Carcinoma Epitelial do Ovário/imunologia , Monócitos/citologia , Neoplasias Ovarianas/imunologia , Carcinoma Epitelial do Ovário/patologia , Feminino , Humanos , Contagem de Leucócitos , Metástase Linfática , Contagem de Linfócitos , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Prognóstico , Análise de Sobrevida
10.
J Transl Med ; 17(1): 191, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31171000

RESUMO

BACKGROUND: Elevated protein expressions of CD markers such as IL2RA/CD25, CXCR4/CD184, CD34 and CD56 are associated with adverse prognosis in acute myeloid leukemia (AML). However, the prognostic value of mRNA expressions of these CD markers in AML remains unclear. Through our pilot evaluation, IL2RA mRNA expression appeared to be the best candidate as a prognostic biomarker. Therefore, the aim of this study is to characterize the prognostic value of IL2RA mRNA expression and evaluate its potential to refine prognostification in AML. METHODS: In a cohort of 239 newly diagnosed AML patients, IL2RA mRNA expression were measured by TaqMan realtime quantitative PCR. Morphological, cytogenetics and mutational analyses were also performed. In an intermediate-risk AML cohort with 66 patients, the mRNA expression of prognostic biomarkers (BAALC, CDKN1B, ERG, MECOM/EVI1, FLT3, ID1, IL2RA, MN1 and WT1) were quantified by NanoString technology. A TCGA cohort was analyzed to validate the prognostic value of IL2RA. For statistical analysis, Mann-Whitney U test, Fisher exact test, logistic regression, Kaplan-Meier and Cox regression analyses were used. RESULTS: In AML cohort of 239 patients, high IL2RA mRNA expression independently predicted shorter relapse free survival (RFS, p < 0.001) and overall survival (OS, p < 0.001) irrespective of age, cytogenetics, FLT3-ITD or c-KIT D816V mutational status. In core binding factor (CBF) AML, high IL2RA mRNA expression correlated with FLT3-ITD status (p = 0.023). Multivariable analyses revealed that high IL2RA expression (p = 0.002), along with c-KIT D816V status (p = 0.013) significantly predicted shorter RFS, whereas only high IL2RA mRNA expression (p = 0.014) significantly predicted shorter OS in CBF AML. In intermediate-risk AML in which multiple gene expression markers were tested by NanoString, IL2RA significantly correlated with ID1 (p = 0.006), FLT3 (p = 0.007), CDKN1B (p = 0.033) and ERG (p = 0.030) expressions. IL2RA (p < 0.001) and FLT3 (p = 0.008) expressions remained significant in predicting shorter RFS, whereas ERG (p = 0.008) and IL2RA (p = 0.044) remained significant in predicting shorter OS. Similar analyses in TCGA intermediate-risk AML showed the independent prognostic role of IL2RA in predicting event free survival (p < 0.001) and OS (p < 0.001). CONCLUSIONS: High IL2RA mRNA expression is an independent and adverse prognostic factor in AML and specifically stratifies patients to worse prognosis in both CBF and intermediate-risk AML.

11.
Nanotechnology ; 30(32): 325502, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-30995625

RESUMO

Micro-structured pressure sensors with broad pressure sensing range, high sensitivity and rapid response speeds are highly desired for epidermal electronic skin. The widely used methods to fabricate micro-structured pressure sensors are lithography and biomaterial-replicating, which are either complex in preparation procedure or uncontrollable in micro-structure morphology. In this work, laser micro-structured wearable pressure sensors with high-performance are developed for epidermal electronic skin. Laser micro-engineering, with scalability, high-efficiency, and controllability, is employed to prepare a series of micro-structures on elastomers for modulating and enhancing the sensitivity of the sensors. The device with micro-domes owns a sensitivity of -1.82 kPa-1, which is approximately 17 times better than the one based on long micro-ridges. Due to the reduced viscous properties of the elastomers by laser micro-engineering, the sensor based on micro-domes demonstrates rapid response/relaxation speeds of 0.036 and 0.052 s, respectively, and a detection limit of 0.001 kPa. Additionally, the device has a good durability (6,000 cycles) with a repeatability deviation of 1.44%, confirming its stability. Combined with near field communication technology, the sensor has been investigated as epidermal electronic skin for health monitoring.

12.
Org Lett ; 21(5): 1438-1443, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30767542

RESUMO

A visible-light-induced/thiourea-mediated intramolecular cyclization of o-nitroarenes under mild conditions is realized for the first time, which provides an efficient and environmentally friendly way to access pharmaceutical relevant quinazolinone derivatives. The reaction can be easily extended to gram level by using a continuous-flow setup with high efficiency. Mechanistic investigation including control experiments, transient fluorescence, UV-vis spectra, and DFT calculations suggests that the formation of active biradical intermediates via intramolecular single electron transfer (SET) is key stage in the catalytic cycle.

13.
Chemosphere ; 222: 399-406, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30711729

RESUMO

Nickel contamination may lead to the destruction of food, ecological safety and its toxicity to plants remains to be studied in depth. In our present study, the translocation factors (TFsoil to root and TFroot to shoot) revealed a significant logarithmic decline with the increase of Ni exposure. In lettuce roots, NiHAC played an important protective role against high Ni stress and the ratio of Ni with high activity (NiE and NiW) in root decreased with the addition of Ni. The activities of antioxidant enzymes (CAT, POD and SOD) in the lettuce roots were increased and might be the way for lettuce to adapt Ni stress. CAT and POD can be great indicators of Ni pollution exhibiting better dose-effect relationships with Ni. Under high Ni stress, lettuce roots contained higher levels of MDA suffering greater pressure than shoots. Expression levels of gene GST 23-like indicated a remarkable (P < 0.05) down-regulation and then this trend would be alleviated after high Ni exposure, and it was positively correlated with GST concentrations (R2 = 0.704). We believe that our research would open up the new avenues for effective understanding ecological risks of Ni.


Assuntos
Tolerância a Medicamentos , Alface/efeitos dos fármacos , Níquel/farmacologia , Antioxidantes/metabolismo , Raízes de Plantas/enzimologia , Solo/química , Poluentes do Solo/farmacologia , Estresse Fisiológico
14.
Clin Genet ; 95(5): 637-639, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30780198

RESUMO

Pedigree chart of hereditary spastic paraplegia (HSP) patients and chromatogram of novel mutations. A. Pedigree chart of 12 Chinese HSP families with mutation. Squares indicate males; circles indicate females; the black symbols indicate affected individuals; arrows indicate the probands; and asterisks indicate the individual with mutation.B. Chromatogram of six novel mutations identified in our cohort. The upper panel in chromatogram depicts the reference sequence. The lower panel represents heterozygous mutated sequence.

16.
J Pharm Biomed Anal ; 165: 31-40, 2018 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-30502550

RESUMO

The pathophysiological mechanism of depression is complex and its etiology remains unclear. Metabolomics can be used to monitor multiple metabolic pathways simultaneously, thereby investigating the mechanisms of depression onset and its regulation. Therefore, we studied the metabolic profile of urine samples from a rat model of depression for identifying potential metabolic biomarkers associated with depression. The depression model of rats was induced by 14-d simulated microgravity (SMG) treatment. Principal component analysis and orthogonal partial least squares discriminate analysis were performed to classify and identify the differences of endogenous metabolites in urine between the normal and depressed rats. Multivariate statistical analysis revealed distinct separation between the urinary metabolic profiles of SMG-treated and control rats. Citric acid, oxalosuccinic acid, creatine, proline, cyclic AMP, L-dihydroxyphenylalanine (DOPA), phenylacetylglycine, 5-hydroxyindole acetaldehyde, succinylcholine, deoxyuridine, 3-hydroxyhippuric acid, glutamine, and 5-hydroxytryptophan levels were significantly reduced, whereas indole-3-acetaldehyde, xanthurenic acid, taurine, kynurenic acid, hippuric acid, 5-hydroxyindoleacetic acid, 2-phenylethanol glucuronide, 2-isopropyl-3-oxosuccinate, and adrenaline levels were elevated significantly in model group. These biochemical changes were related to tryptophan, arginine, proline, and phenylalanine metabolism, and perturbations in energy metabolism. These details of depression will be helpful to the clinical diagnosis of depression caused by space and gravity.

17.
Front Pharmacol ; 9: 1153, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30369882

RESUMO

Genistein (GE) was reported to exert a wide spectrum of biological activities, including antioxidant, anti-inflammatory, anti-mutagenic, anticancer, and cardio-protective effects. In addition, both clinical and preclinical studies have recently suggested GE a potential neuroprotective and memory-enhancing drug against neurodegenerative diseases. The animal model of scopolamine (Scop)-induced amnesia is widely used to study underlying mechanisms and treatment of cognitive impairment in neurodegenerative diseases. However, there is no report about the effects of GE on Scop-induced amnesia in mice. Therefore, the present study was carried out to investigate the beneficial effects and potential mechanism of GE against Scop-induced deficits in mice. The mice were orally pretreated with either GE (10, 20, and 40 mg/kg) or donepezil (1.60 mg/kg) for 14 days. After the pretreatment, the open field test was conducted to assess the effect of GE on the locomotor activity of mice. Thereafter, mice were daily injected with Scop (0.75 mg/kg) intraperitoneally to induce memory deficits and subjected to the cognitive behavioral tests including the Object Location Recognition (OLR) experiment and Morris Water Maze (MWM) task. After the behavioral tests, biochemical parameter assay and western blot analysis were used to examine the underlying mechanisms of its action. The results showed that GE administration significantly improved the cognitive performance of Scop-treated mice in OLR and Morris water maze tests, exerting the memory-enhancing effects. Additionally, GE remarkably promoted the cholinergic neurotransmission and protected against the oxidative stress damage in the hippocampus of Scop-treated mice, as indicated by decreasing AChE activity, elevating ChAT activity and Ach level, increasing SOD activity, lowering the level of MDA and increasing GSH content. Furthermore, GE was found to significantly upregulate the expression levels of p-ERK, p-CREB and BDNF proteins in the hippocampus of Scop-treated mice. Taken together, these results for the first time found that GE exerts cognitive-improving effects in Scop-induced amnesia and suggested it may be a potential candidate compound for the treatment of some neurodegenerative diseases such as Alzheimer's Disease (AD).

18.
Clin Respir J ; 2018 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-30307719

RESUMO

PURPOSE: Third-generation irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), rociletinib (CO-1686), is great efficacy against EGFR-mutated patients bearing the T790M resistance mutation. However, acquired resistance may emerge. There is a need to characterize acquired resistance mechanism(s) and to devise ways to overcome CO-1686 resistance. EXPERIMENTAL DESIGN: MTT assay, ki67 incorporation assay, transwell assay and TUNEL assay were employed to analyze the effects of metformin to reverse CO-1686 resistance in vitro. The NF-κB activity was measured by the antibody of p50, p65, p-IKBɑ, and p-IKKɑ/ß. Western blotting was used to analyze the proteins in cells. RESULTS: We have established CO-1686-resistant cell lines of PC-9GRCOR and H1975COR from two parental cell lines of PC-9GR and H1975 by long-term exposure to increasing doses of CO-1686. Compared with the parental cells, PC-9GRCOR cells and H1975COR cells showed 90-folds and 20-folds higher resistance to CO-1686, respectively. Critically, we showed that the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling molecular proteins subunits of p50, p65 and its inhibitor proteins of IKBɑ, IKKɑ/ß in phosphorylation levels in resistant cells were higher than parental cells. Accordingly, inhibition of NF-κB activity used TPCA-1 effective in decreasing viability and inducing apoptosis of resistant cells. Moreover, metformin overcame the acquired resistance to CO-1686 by reducing cell proliferation and invasion. Metformin combined with CO-1686 synergistically inhibited the p-IKBɑ, p-IKKɑ/ß, p50, and p65. CONCLUSIONS: NF-κB signaling activation induced acquired resistance to CO-1686. Metformin sensitized resistant cells to CO-1686 via inhibiting NF-κB signaling.

19.
Proteomics Clin Appl ; : e1700179, 2018 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-30365225

RESUMO

PURPOSE: To rapidly identify protein abundance changes in biopsy-level fresh-frozen hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: The pressure-cycling technology (PCT) is applied and sequential window acquisition of all theoretical mass spectra (SWATH-MS) workflow is optimized to analyze 38 biopsy-level tissue samples from 19 HCC patients. Each proteome is analyzed with 45 min LC gradient. MCM7 is validated using immunohistochemistry (IHC). RESULTS: A total of 11 787 proteotypic peptides from 2579 SwissProt proteins are quantified with high confidence. The coefficient of variation (CV) of peptide yield using PCT is 32.9%, and the R2 of peptide quantification is 0.9729. Five hundred forty-one proteins showed significant abundance change between the tumor area and its adjacent benign area. From 24 upregulated pathways and 13 suppressed ones, enhanced biomolecule synthesis and suppressed small molecular metabolism in liver tumor tissues are observed. Protein changes based on α-fetoprotein expression and hepatitis B virus infection are further analyzed. The data altogether highlight 16 promising tumor marker candidates. The upregulation of minichromosome maintenance complex component 7 (MCM7) is further observed in multiple HCC tumor tissues by IHC. CONCLUSIONS AND CLINICAL RELEVANCE: The practicality of rapid proteomic analysis of biopsy-level fresh-frozen HCC tissue samples with PCT-SWATH has been demonstrated and promising tumor marker candidates including MCM7 are identified.

20.
Pharmacol Res ; 136: 172-180, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30196102

RESUMO

Artemisinin (Qinghaosu) and its semi-synthetic derivatives have been demonstrated to alleviate neuroinflammatory response in the central nerve system (CNS). In this review, we summarized that artemisinins are capable to treat neuroinflammtion-related CNS diseases in both direct (via regulating inflammatory process in the CNS, exerting anti-oxidative stress and neuroprotective effect, and preventing Aß accumulation) and indirect (via maintaining BBB integrity, suppressing systemic inflammation and alleviating intestinal inflammtion) manner. However, the precise mechanism of their anti-neuroinflammatory effects and potential neurotoxicity, which hindered further progress in these aspects, remains unclear. We suggest that further understanding of the PK/PD properties and structure-action relationship of atemisinin and its derivatives will facilitate the development of new therapeutics with better curative effects and safety.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA