Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 252
Filtrar
1.
J Hazard Mater ; 392: 122500, 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32208316

RESUMO

1D spindle-like iron oxides with controllable phase were synthesized by using MIL-88A-templated pyrolysis under different atmospheres, thermal annealing in N2 to obtain Fe3O4 and in air to obtain α-Fe2O3. Then, 2D/1D core-shell heterostructures (ZnIn2S4@Fe3O4 and ZnIn2S4@α-Fe2O3) were constructed by in-situ self-assembly strategy. Characterizations indicated that the 2D ultra-thin ZnIn2S4 shell with 0.3 µm was homogeneously coated on the surface of 1D Fe3O4/α-Fe2O3 core with 1 µm, and ZnIn2S4@Fe3O4 exhibited higher BET surface area (84.5 m2 g-1) compared with ZnIn2S4@α-Fe2O3 (17.8 m2 g-1), providing more exposed active sites and larger contact area. The ZnIn2S4@Fe3O4-5 showed the best photocatalytic activity of RhB degradation as compared to ZnIn2S4, Fe3O4 and ZnIn2S4@α-Fe2O3. In addition, the degradation rates of MB, BPA and MO over ZnIn2S4@Fe3O4 were much higher than that of ZnIn2S4@α-Fe2O3. The proposed photocatalytic mechanism was also discussed: the Fe3O4 as an electron acceptor caused Fe3+/Fe2+ cycle in ZnIn2S4@Fe3O4 and ZnIn2S4@α-Fe2O3 followed the Z-scheme mechanism.

2.
Lipids Health Dis ; 19(1): 33, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32131838

RESUMO

BACKGROUND: Previous studies have revealed that triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) is one of major risk factors of insulin resistance and diabetes. However, study on the association between TG/HDL-C and diabetes mellitus (DM) risk is limited, especially in Chinese people. This study was undertaken to investigate the relationship between TG/HDL-C and incident of diabetes in a large cohort in Chinese population. METHODS: The present study was a retrospective cohort study. A total of 114,787 adults from Rich Healthcare Group in China, which includes all medical records for participants who received a health check from 2010 to 2016. The target independent variable and the dependent variable were triglyceride to high-density lipoprotein cholesterol ratio measured at baseline and incident of diabetes mellitus appeared during follow-up respectively. Covariates involved in this study included age, gender, body mass index, diastolic blood pressure, systolic blood pressure, fasting plasma glucose, total cholesterol, low density lipoprotein cholesterol, serum creatinine, smoking and drinking status and family history of diabetes. Cox proportional-hazards regression was used to investigate the association of TG/HDL-C and diabetes. Generalized additive models was used to identify non-linear relationships. Additionally, we also performed a subgroup analysis. It was stated that the data had been uploaded to the DATADRYAD website. RESULT: After adjusting age, gender, body mass index, systolic blood pressure, diastolic blood pressure, fasting blood glucose, total cholesterol, low density lipoprotein cholesterol, serum creatinine, smoking and drinking status and family history of diabetes, result showed TG/HDL-C was positively associated with incident of diabetes mellitus (HR = 1.159, 95%CI (1.104, 1.215)). A non-linear relationship was detected between TG/HDL-C and incident of diabetes, which had an inflection point of TG/HDL-C was 1.186. The effect sizes and the confidence intervals on the left and right sides of the inflection point were 1.718(1.433,2.060) and 1.049(0.981,1.120), respectively. Subgroup analysis showed, the stronger association can be found in the population with fasting plasma glucose (FPG) < 6.1 mmol/L (P for interaction< 0.0001; HR = 1.296 with FPG < 6.1 mmol/L vs HR = 1.051 with FPG ≥ 6.1 mmol/L).The same trend was also seen in the population with body mass index (BMI)(≥18.5, < 24 kg/m2) (P for interaction = 0.010,HR = 1.324) and family history without diabetes(P for interaction = 0.025, HR = 1.170). CONCLUSION: TG/HDL-C is positively associated with diabetes risk. The relationship between TG/HDL-C and incident of diabetes is also non-linear. TG/HDL-C was strong positively related to incident of diabetes when TG/HDL-C is less than 1.186.

3.
Fitoterapia ; 143: 104544, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32151638

RESUMO

Two new polyoxygenated cyclohexenes (1-2), one new benzoate derivative (3), and one new dineolignan (4) together with one known neolignan (5) were isolated from whole plants of Piper pleiocarpum. The structures of these compounds were determined by extensive spectroscopic methods including 1D, 2D NMR, HR-ESI-MS, and by comparison with the literature. The 13C NMR spectra of the known compound 5 were completely assigned for the first time. All isolated compounds (1-5) were evaluated for their cytotoxic activities against five human cancer cell lines (including A-549, SMMC-7721, HL-60, MCF-7, and SW-480), Only compound 4 showed inhibitory activity against MCF-7 cell line with IC50 value of 18.24 ± 0.69 µM.

4.
Cell Mol Life Sci ; 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32008086

RESUMO

BACKGROUND: Small bowel vascular malformation disease (SBVM) is the most common cause of obscure gastrointestinal bleeding (OGIB). Several studies suggested that EGFL6 was able to promote the growth of tumor endothelial cells by forming tumor vessels. To date, it remains unclear how EGFL6 promotes pathological angiogenesis in SBVM and whether EGFL6 is a target of thalidomide. METHODS: We took advantage of SBVM plasma and tissue samples and compared the expression of EGFL6 between SBVM patients and healthy people via ELISA and Immunohistochemistry. We elucidated the underlying function of EGFL6 in SBVM in vitro and by generating a zebrafish model that overexpresses EGFL6, The cycloheximide (CHX)-chase experiment and CoIP assays were conducted to demonstrate that thalidomide can promote the degradation of EGFL6 by targeting CRBN. RESULTS: The analysis of SBVM plasma and tissue samples revealed that EGFL6 was overexpressed in the patients compared to healthy people. Using in vitro and in vivo assays, we demonstrated that an EMT pathway triggered by the EGFL6/PAX6 axis is involved in the pathogenesis of SBVM. Furthermore, through in vitro and in vivo assays, we elucidated that thalidomide can function as anti-angiogenesis medicine through the regulation of EGFL6 in a proteasome-dependent manner. Finally, we found that CRBN can mediate the effect of thalidomide on EGFL6 expression and that the CRBN protein interacts with EGFL6 via a Lon N-terminal peptide. CONCLUSION: Our findings revealed a key role for EGFL6 in SBVM pathogenesis and provided a mechanism explaining why thalidomide can cure small bowel bleeding resulting from SBVM.

5.
J Cell Mol Med ; 2020 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-31983065

RESUMO

Chemokines and their receptors have been reported to drive immune cells into tumours or to be directly involved in the promotion or inhibition of the development of tumours. However, their expression in regional lymph node (LN) tissues in melanoma patients remains unknown. The present study investigated the relationship between the expression of mRNA of chemokines and their receptors and clinicopathology of the regional LN tissues of skin cutaneous melanoma (SKCM) patients available in The Cancer Genome Atlas. The relationship between chemokines and their receptors and the composition of immune cells within the tumour was analysed. In SKCM regional LN tissues, the high expression of 32 types of chemokines and receptors, namely CCL2, 4-5, 7-8, 13, 22-25, CCR1-9, CXCL9-13, 16, CXCR3, 5, 6, XCL1-2 and XCR1 in LN was associated with favourable patient prognosis. Conversely, high expression of CXCL17 was an indicator of poor prognosis. The expression of mRNA for CXCL9-11, 13, CXCR3, 6, CCL2, 4, 5, 7, 8, 25, CCR1, 2, 5, and XCL1, 2 in regional LN tissues was positively correlated with the fraction of CD8-positive T cells and M1 macrophages, and was negatively correlated with M0 macrophages. CCR4, 6-9, CCL13, 22, 23 and XCR1 were positively correlated with the fraction of memory B cells and naive T cells, and negatively correlated with M0 macrophages and resting mast cells, suggesting that chemokines and their receptors may affect the prognosis of patients by guiding immune cells into the tumour microenvironment to eliminate tumour cells.

6.
Oncologist ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31922308

RESUMO

BACKGROUND: Superficial colorectal cancer (SCRC) is defined as colorectal cancer (CRC) confined to the mucosa or submucosa. Endoscopic resection (ER) is widely used to resect differentiated SCRC from patients without lymph node metastasis (LNM). However, it is unclear whether ER is suitable for use with patients with differentiated early-onset SCRC because early-onset CRC is more aggressive. Therefore, we aimed to investigate the association between age of CRC onset and LNM. MATERIALS AND METHODS: We retrieved data for patients with surgically resected differentiated-type SCRCs from the Surveillance, Epidemiology, and End Results (SEER) database. Rate of LNM was compared among patients aged 18-39, 40-49, 50-59, 60-69, and ≥70 years. The association between age and LNM was further examined using multivariate logistic regression. RESULTS: We retrieved 34,506 records of differentiated SCRCs from the SEER database, including 667 patients aged 18-39 years, 2,385 aged 40-49, 8,075 aged 50-59 years, 9,577 aged 60-69 years, and 13,802 aged ≥70 years. Rates of LNM were 15.74%, 14.13%, 10.67%, 8.07%, and 6.76% for patients aged 18-39, 40-49, 50-59, 60-69, and ≥70 years, respectively. We found an inverse correlation between age at diagnosis and risk of LNM from the univariate analysis (p < .001). Compared with patients aged 18-39, the odds ratios with 95% confidence interval (CI) for patients aged 40-49, 50-59, 60-69, and ≥70 years were 0.90 (0.71-1.15, p = .376), 0.69 (0.56-0.87, p = .001), 0.54 (0.43-0.68, p < .001), and 0.47 (0.38-0.60, p < .001), respectively. CONCLUSION: In differentiated SCRCs, younger age at diagnosis was associated with higher risk of LNM. IMPLICATIONS FOR PRACTICE: Endoscopic resection (ER) is widely used to resect differentiated superficial colorectal cancer (SCRC) without lymph node metastasis (LNM). However, no study has ever investigated risk of LNM of early-onset SCRC compared with average onset SCRC to explore whether ER is suitable for early-onset SCRC. To the authors' knowledge, this population-based study is the first study to find inverse correlation between age at diagnosis and risk of LNM in differentiated SCRCs. This finding indicates that ER may not be suitable for young patients with differentiated SCRC. Because the 30-day operative mortality after surgery is higher but the risk of LNM is lower in older patients compared with younger patients, ER for differentiated SCRCs may be advantageous over surgery for older patients.

7.
Int J Infect Dis ; 92: 241-246, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31978580

RESUMO

OBJECTIVES: To compare the prevalence of levofloxacin (LFX) resistance and the population structure of Mycobacterium tuberculosis (MTB) with different mutations conferring LFX resistance between 2005 and 2015. METHODS: A total 542 MTB isolates were randomly selected from pulmonary tuberculosis (TB) patients in 2005 and 2015 and analyzed regarding minimum inhibitory concentrations (MICs) and quinolone resistance-determining regions (QRDR). RESULTS: One hundred and eleven of the 542 MTB isolates analyzed (20.5%) were resistant to LFX. There were 42 and 69 LFX-resistant isolates from 2005 and 2015, respectively, and MIC high-level LFX resistance was significantly higher in 2015 (40.6%, 28/69) than in 2005 (16.7%, 7/42) (p = 0.02). There were 87 (78.4%) mutations of these 111 LFX-resistant isolates. In addition, a significant difference in proportion was observed in the isolates with mutations in codon 90 of the gyrA gene between 2005 and 2015 (11.9% in 2005 versus 29.0% in 2015, p = 0.04). CONCLUSIONS: There was an alarming increase in prevalence of LFX-resistant TB in China between 2005 and 2015. This dynamic change is mostly attributed to the increase in high-level LFX resistance. Moreover, a significant difference was noted in the proportion of LFX-resistant isolates harboring specific mutations within the gyrA gene between 2005 and 2015.


Assuntos
Farmacorresistência Bacteriana , Levofloxacino/uso terapêutico , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Tuberculose Pulmonar/tratamento farmacológico , Adulto , China/epidemiologia , DNA Girase/genética , Feminino , Fluoroquinolonas/farmacologia , Fluoroquinolonas/uso terapêutico , Humanos , Levofloxacino/farmacologia , Masculino , Testes de Sensibilidade Microbiana , Mutação , Mycobacterium tuberculosis/isolamento & purificação , Prevalência , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/microbiologia
8.
Artigo em Inglês | MEDLINE | ID: mdl-31905129

RESUMO

OBJECTIVE: Fluorescence molecular tomography (FMT) is a promising medical imaging technology aimed at the non-invasive, specific, and sensitive detection of the distribution of fluorophore. Conventional sparsity prior-based methods of FMT commonly face problems such as over-sparseness, spatial discontinuity, and poor robustness, due to the neglect of the interrelation within the local subspace. To address this, we propose an adaptive group orthogonal matching pursuit (AGOMP) method. METHODS: AGOMP is based on a novel local spatial-structured sparse regularization, which leverages local spatial interrelations as group sparsity without the hard prior of the tumor region. The adaptive grouped subspace matching pursuit method was adopted to enhance the interrelatedness of elements within a group, which alleviates the over-sparsity problem to some extent and improves the accuracy, robustness, and morphological similarity of FMT reconstruction. A series of numerical simulation experiments, based on digital mouse with both one and several tumors, were conducted, as well as in vivo mouse experiments. RESULTS: The results demonstrated that the proposed AGOMP method achieved better location accuracy, fluorescent yield reconstruction, relative sparsity, and morphology than state-of-the-art methods under complex conditions for levels of Gaussian noise ranging from 5×25%. Furthermore, the in vivo mouse experiments demonstrated the practical application of FMT with AGOMP. CONCLUSION: The proposed AGOMP can improve the accuracy and robustness for FMT reconstruction in biomedical application.

9.
Nucleic Acids Res ; 48(D1): D977-D982, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31642469

RESUMO

From clinical observations to large-scale sequencing studies, the phenotypic impact of genetic modifiers is evident. To better understand the full spectrum of the genetic contribution to human disease, concerted efforts are needed to construct a useful modifier resource for interpreting the information from sequencing data. Here, we present the PhenoModifier (https://www.biosino.org/PhenoModifier), a manually curated database that provides a comprehensive overview of human genetic modifiers. By manually curating over ten thousand published articles, 3078 records of modifier information were entered into the current version of PhenoModifier, related to 288 different disorders, 2126 genetic modifier variants and 843 distinct modifier genes. To help users probe further into the mechanism of their interested modifier genes, we extended the yeast genetic interaction data and yeast quantitative trait loci to the human and we also integrated GWAS data into the PhenoModifier to assist users in evaluating all possible phenotypes associated with a modifier allele. As the first comprehensive resource of human genetic modifiers, PhenoModifier provides a more complete spectrum of genetic factors contributing to human phenotypic variation. The portal has a broad scientific and clinical scope, spanning activities relevant to variant interpretation for research purposes as well as clinical decision making.

10.
Mol Imaging Biol ; 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31834570

RESUMO

Morphological imaging techniques are typically used in the anti-cancer drug efficacy evaluation process. However, these techniques can evaluate the therapeutic efficacy only when the tumor shows anatomic changes-usually at later stages, when the therapeutic effects are poor. In contrast, molecular imaging allows noninvasive monitoring of tumor growth, assessment of drug metabolism, and evaluation of therapeutic efficacy at the molecular and cellular levels. Multimodality molecular imaging, which combines the advantages of various imaging modalities, provides even more comprehensive therapeutic efficacy assessment in preclinical and clinical studies. This review provides an overview of molecular imaging evaluation of therapeutic efficacy of the anti-tumor drugs in hepatocellular carcinoma (HCC) both in preclinical and clinical research, which holds great promise in guiding HCC treatment into the era of precision medicine.

11.
J Mech Behav Biomed Mater ; 102: 103497, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31669982

RESUMO

Carbon fiber reinforced Polyetheretherketone (PEEK) acquires mechanical strength which is close to human bone, but PEEK is inert, which can affect the bone fixation and osseointegration during dental implantation. To improve the bioactivity of PEEK, surface modification with nitric acid (HNO3) and calcium chloride (CaCl2) were utilized in this work. As the results, the hydrophilicity of the treated samples is significantly improved with the reduced roughness and attached nitro-functional group on its surface. The biological activity of CF/PEEK samples are enhanced by apatite formation evaluation soaking in simulated body fluid (SBF) in vitro after HNO3 and CaCl2 treatment. Moreover, the cytotoxicity experiments results confirm that surface treatment with HNO3 and CaCl2 is not harmful to the compatibility and safety of the cells.

12.
Brief Bioinform ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31750520

RESUMO

In clinical cancer treatment, genomic alterations would often affect the response of patients to anticancer drugs. Studies have shown that molecular features of tumors could be biomarkers predictive of sensitivity or resistance to anticancer agents, but the identification of actionable mutations are often constrained by the incomplete understanding of cancer genomes. Recent progresses of next-generation sequencing technology greatly facilitate the extensive molecular characterization of tumors and promote precision medicine in cancers. More and more clinical studies, cancer cell lines studies, CRISPR screening studies as well as patient-derived model studies were performed to identify potential actionable mutations predictive of drug response, which provide rich resources of molecularly and pharmacologically profiled cancer samples at different levels. Such abundance of data also enables the development of various computational models and algorithms to solve the problem of drug sensitivity prediction, biomarker identification and in silico drug prioritization by the integration of multiomics data. Here, we review the recent development of methods and resources that identifies mutation-dependent effects for cancer treatment in clinical studies, functional genomics studies and computational studies and discuss the remaining gaps and future directions in this area.

13.
J Periodontol ; 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31573683

RESUMO

BACKGROUND: Periodontal ligament stem cells (PDLSCs) play an essential role in periodontal tissue repair. Basic fibroblast growth factor (bFGF) has been used in the clinical treatment of periodontal disease. However, studies have shown that bFGF inhibits the osteogenic differentiation of PDLSCs, which is not conducive to alveolar bone repair. Sulfonated chitosan oligosaccharide (SCOS), a heparan-like compound, can maintain the conformation of bFGF and promote its proliferation activity. This study investigated the effects of bFGF in combination with SCOS on the osteogenic differentiation of hPDLSCs. METHODS: hPDLSCs were isolated from healthy human periodontal ligament and identified by flow cytometry and immunofluorescence. The affinity between SCOS and bFGF was analyzed by surface plasmon resonance. Changes in osteogenic differentiation by combination of bFGF with SCOS were analyzed by alkaline phosphatase activity assay, Sirius Red staining, and Alizarin Red staining. Expression of genes and proteins was investigated by western blotting and reverse transcription-quantitative PCR. RESULTS: Extracted hPDLSCs were mesenchymal stem cells with pluripotent differentiation potential. SCOS exhibited an affinity for bFGF. bFGF (20 ng/mL) promoted the proliferation of hPDLSCs, but inhibited their osteogenic differentiation. SCOS alleviated the inhibitory effect of bFGF on the osteogenic differentiation of hPDLSCs. CONCLUSIONS: SCOS can reduce the inhibitory effect of bFGF on the osteogenic differentiation of hPDLSCs. This study provides evidence for the clinical use of bFGF to repair periodontal tissue.

14.
Cell Metab ; 30(6): 1107-1119.e8, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31607564

RESUMO

Phosphoglycerate mutase 1 (PGAM1) plays a pivotal role in cancer metabolism and tumor progression via its metabolic activity and interaction with other proteins like α-smooth muscle actin (ACTA2). Allosteric regulation is considered to be an innovative strategy to discover a highly selective and potent inhibitor targeting PGAM1. Here, we identified a novel PGAM1 allosteric inhibitor, HKB99, via structure-based optimization. HKB99 acted to allosterically block conformational change of PGAM1 during catalytic process and PGAM1-ACTA2 interaction. HKB99 suppressed tumor growth and metastasis and overcame erlotinib resistance in non-small-cell lung cancer (NSCLC). Mechanistically, HKB99 enhanced the oxidative stress and altered multiple signaling pathways including the activation of JNK/c-Jun and suppression of AKT and ERK. Collectively, the study highlights the potential of PGAM1 as a therapeutic target in NSCLC and reveals a distinct mechanism by which HKB99 inhibits both metabolic activity and nonmetabolic function of PGAM1 by allosteric regulation.

15.
Clin Appl Thromb Hemost ; 25: 1076029619867137, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31364394

RESUMO

To describe the effect of dabigatran on thrombin time (TT) reagents at different concentrations of thrombin. Pooled normal plasma enriched with dabigatran was dissolved in dimethylsulfoxide (DMSO) at concentrations of 0, 20, 50, 100, 200, 300, and 500 ng/mL. Samples with each concentration were evaluated using a semiautomatic coagulation analyzer to assess the effect of dabigatran on internal normalized ratio (INR), thromboplastin time (APTT), and TT, which were purchased from Instrument Laboratory (IL), Sysmex (SYS), and Stago (STA), respectively. Regarding INR, no reagent showed good sensitivity to increasing concentration of dabigatran, despite all reagents showing good linear response curves (P = .012). Regarding APTT, all reagents had low sensitivity to increasing dabigatran concentration, but SYS-APTT showed a better linear response curve (P = .001). Regarding TT, all reagents had a good linear response to the concentration of dabigatran; however, SYS-TT was very sensitive at low concentrations of dabigatran (0-100 ng/mL), while IL (TT-5 mL) and STA-TT were sensitive at medium concentrations of dabigatran (0-300 ng/mL), and IL (TT-2 mL) was less sensitive for a wide concentration of dabigatran (0-500 ng/mL; P = .007). Internal normalized ratio and APTT showed low sensitivity and SYS-TT showed high sensitivity to concentrations of dabigatran that were unsuitable to monitor. Both IL (TT-5 mL) and STA-TT were useful at medium concentrations of dabigatran by semiautomatic coagulation analyzer, which calculated results using the end point method of coagulation. Instrument Laboratory (TT-2 mL), which contains a higher concentration of thrombin, had better sensitivity to the concentration of dabigatran than APTT and was suitable for routine monitoring by an automatic analyzer.


Assuntos
Dabigatrana/farmacocinética , Monitoramento de Medicamentos/métodos , Tempo de Trombina , Antitrombinas/sangue , Antitrombinas/farmacocinética , Testes de Coagulação Sanguínea , Dabigatrana/sangue , Dabigatrana/normas , Monitoramento de Medicamentos/instrumentação , Monitoramento de Medicamentos/normas , Humanos , Indicadores e Reagentes/farmacologia , Tempo de Tromboplastina Parcial , Sensibilidade e Especificidade , Trombina/farmacologia
16.
Nat Commun ; 10(1): 3499, 2019 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375671

RESUMO

Long non-coding RNAs (lncRNAs) contribute to colorectal cancer (CRC). However, the role of lncRNAs in CRC metabolism, especially glucose metabolism remains largely unknown. In this study, we identify a lncRNA, GLCC1, which is significantly upregulated under glucose starvation in CRC cells, supporting cell survival and proliferation by enhancing glycolysis. Mechanistically, GLCC1 stabilizes c-Myc transcriptional factor from ubiquitination by direct interaction with HSP90 chaperon and further specifies the transcriptional modification pattern on c-Myc target genes, such as LDHA, consequently reprogram glycolytic metabolism for CRC proliferation. Clinically, GLCC1 is associated with tumorigenesis, tumor size and predicts poor prognosis. Thus, GLCC1 is mechanistically, functionally, and clinically oncogenic in colorectal cancer. Targeting GLCC1 and its pathway may be meaningful for treating patients with colorectal cancer.


Assuntos
Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Glucose/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Longo não Codificante/metabolismo , Idoso , Animais , Carcinogênese/genética , Carcinogênese/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Feminino , Glicólise/genética , Proteínas de Choque Térmico HSP90/genética , Humanos , Estimativa de Kaplan-Meier , L-Lactato Desidrogenase/genética , L-Lactato Desidrogenase/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Prognóstico , Ubiquitinação/genética , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Exp Mol Med ; 51(7): 76, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31285418

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related mortality worldwide. Sorafenib is the standard first-line treatment for advanced HCC, but its efficacy is limited. Apatinib is a small-molecule tyrosine kinase inhibitor that has shown promising antitumor effects in gastric and non-small cell lung cancers in clinical trials, but there have been only a few studies reporting its anti-HCC effects in vitro and in HCC xenograft models. Hence, our present study systemically investigated and compared the antitumorigenic and antiangiogenic efficacy of apatinib and sorafenib in HCC in vitro and in vivo using multimodality molecular imaging, including bioluminescence imaging (BLI), bioluminescence tomography (BLT), fluorescence molecular imaging (FMI), and computed tomography angiography (CTA). Moreover, the safety and side effects of the two drugs were systemically evaluated. We found that apatinib showed a comparable therapeutic efficacy to sorafenib for the inhibition of HCC. The drug safety evaluation revealed that both of these drugs caused hypertension and mild liver and kidney damage. Sorafenib caused diarrhea, rash, and weight loss in mice, but these effects were not observed in mice treated with apatinib. In conclusion, apatinib has similar antitumorigenic and antiangiogenic efficacy as sorafenib in HCC with less toxicity. These findings may provide preclinical evidence supporting the potential application of apatinib for the treatment of HCC patients.

18.
Orphanet J Rare Dis ; 14(1): 182, 2019 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-31340840

RESUMO

BACKGROUND: Inherited Factor XIII deficiency (FXIIID) is one of the most severe and under-diagnosed rare bleeding disorders. Only 5 large deletions involving one or more exons in F13A1 have been reported, and lacking of multiplex ligation-dependent probe amplification (MLPA) assay might underestimate the copy number variations (CNVs) in F13A1 and F13B. We had characterized the clinical presentation of two unrelated severe FXIIID probands and explored the pathogenic mechanisms. RESULTS: Both probands experienced several episodes of fatal bleeding and delayed wound healings prior to diagnosis. FXIII activity was measured by the ammonia release assay, and FXIII-A and FXIII-B antigens were determined by ELISA. All the exons including exon-intron boundaries and promoter regions of F13A1 and F13B were amplified and directly sequenced. Copy number variations (CNVs) of F13A1 and F13B were detected by the CNVplex® method. Breakpoints of the F13A1 large deletion were identified by quantitative primer walking combined long-range PCR (LR-PCR) strategies. Proband 1 was found to have compound heterozygous mutations of a novel small deletion (c.1147del) and a missense mutation p.Arg383Ser. Proband 2 was compound heterozygous for a novel large deletion (g.[77815_112815del;112837_116628del]) and a missense mutation p.Arg716Gly in F13A1. Bioinformatics analysis of the large deletion breakpoints predicted that two fork stalling and template switching and/or microhomology-mediated break-induced replication (FoSTeS/MMBIR) events with two homologies of TCT and C might be responsible for the complex rearrangement. Prophylactic replacement therapy was immediately administered for the two probands upon establishment of the diagnosis. CONCLUSIONS: We detected two type I FXIIID pedigrees and adopted CNVplex® method to detect CNVs of F13A1 and F13B for the first time. A large heterozygous deletion of g.[77815_112815del;112837_116628del] in F13A1, mediated by two FoSTeS/MMBIR events, was identified.

19.
Neural Regen Res ; 14(11): 1919-1931, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31290450

RESUMO

Objective: To evaluate the efficacy and safety of MK-801 and its effect on lesion volume in rat models of acute brain injury. Data Sources: Key terms were "stroke", "brain diseases", "brain injuries", "brain hemorrhage, traumatic", "acute brain injury", "dizocilpine maleate", "dizocilpine", "MK-801", "MK801", "rat", "rats", "rattus" and "murine". PubMed, Cochrane library, EMBASE, the China National Knowledge Infrastructure, WanFang database, the VIP Journal Integration Platform (VJIP) and SinoMed databases were searched from their inception dates to March 2018. Data Selection: Studies were selected if they reported the effects of MK-801 in experimental acute brain injury. Two investigators independently conducted literature screening, data extraction, and methodological quality assessments. Outcome Measures: The primary outcomes included lesion volume and brain edema. The secondary outcomes included behavioral assessments with the Bederson neurological grading system and the water maze test 24 hours after brain injury. Results: A total of 52 studies with 2530 samples were included in the systematic review. Seventeen of these studies had a high methodological quality. Overall, the lesion volume (34 studies, n = 966, MD = -58.31, 95% CI: -66.55 to -50.07; P < 0.00001) and degree of cerebral edema (5 studies, n = 75, MD = -1.21, 95% CI: -1.50 to -0.91; P < 0.00001) were significantly decreased in the MK-801 group compared with the control group. MK-801 improved spatial cognition assessed with the water maze test (2 studies, n = 60, MD = -10.88, 95% CI: -20.75 to -1.00; P = 0.03) and neurological function 24 hours after brain injury (11 studies, n = 335, MD = -1.04, 95% CI: -1.47 to -0.60; P < 0.00001). Subgroup analysis suggested an association of reduction in lesion volume with various injury models (34 studies, n = 966, MD = -58.31, 95% CI: -66.55 to -50.07; P = 0.004). Further network analysis showed that 0-1 mg/kg MK-801 may be the optimal dose for treatment in the middle cerebral artery occlusion animal model. Conclusion: MK-801 effectively reduces brain lesion volume and the degree of cerebral edema in rat models of experimental acute brain injury, providing a good neuroprotective effect. Additionally, MK-801 has a good safety profile, and its mechanism of action is well known. Thus, MK-801 may be suitable for future clinical trials and applications.

20.
Fitoterapia ; 137: 104269, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31323238

RESUMO

The genus Amoora belongs to the Meliaceae family comprising approximately 25-30 species. Many Amoora species have been used as folk medicines for the treatment of many diseases. This review focuses on diverse chemical constituents from Amoora species as well as significant pharmacological activities. Up to now, a total of 140 compounds including eight sesquiterpenoids, twenty-six diterpenoids, forty-two triterpenoids, twenty-two limonoids, seven steroids, seven alkaloids, seven rocaglamide derivatives, four flavonoids, four glycosides, two coumarins, nine phenols, and two organic acids and esters were reported from Amoora species. Triterpenoids are characteristic components for Amoora species. The extracts and chemical constituents of Amoora species exhibit a broad spectrum of pharmacological activities including cytotoxic, anti-inflammatory, antibacterial and antifungal activity. The present review may provide useful evidence for reasonable utilization of Amoora species as folk medicines and further research in drug discovery.


Assuntos
Meliaceae/química , Compostos Fitoquímicos/farmacologia , Plantas Medicinais/química , Medicina Tradicional
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA