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1.
J Clin Pathol ; 2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32220941

RESUMO

AIMS: The aim of this study is to investigate the expression profiles of cell cycle related proteins in nasal extranodal NK/T cell lymphoma, nasal type (ENKTCL). METHODS: The expression profiles of cell cycle related proteins were assessed with a cell cycle antibody array and validated by immunohistochemistry. Correlations between the expression levels of proteins and clinical outcomes of patients with nasal ENKTCL were evaluated. RESULTS: The expression of full length ataxia telangiectasia mutated (ATM) in nasal ENKTCL significantly decreased compared with that in nasal benign lymphoid proliferative disease (NBLPD), but the expression levels of p-ATM, CHK2 and RAD51 significantly increased in nasal ENKTCL compared with that in NBLPD. Kaplan-Meier analysis showed that the expression levels of p-ATM and CHK2 in nasal ENKTCL were inversely related to overall survival (p=0.011 and p=0.025, respectively). CONCLUSION: Abnormalities in the ATM pathway may play a crucial role in the oncogenesis and chemoradiotherapy resistance of nasal ENKTCL.

2.
Postgrad Med J ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32047103

RESUMO

BACKGROUND: We are currently faced with an increasing burden of cardiovascular disease in China and the inadequacy of the application of guidelines in clinical practice. In the past decade, China has been strengthening the healthcare system, but it still lacked a national performance measurement system and an appropriate quality improvement strategy. Therefore, in order to improve the implementation of guideline recommendations in clinical practice, China has learnt from the successful experience of Get With The Guidelines project in 2014. Under the guidance of the Medical and Health Hospital of the National Health and Family Planning Commission, the Chinese Society of Cardiology and the American Heart Association jointly launched the Improving Care for Cardiovascular Disease in China (CCC) project. The project team provided an analysis report on the completion of key medical quality evaluation indicators of each hospital every month, supplied guidance through education, training, experience exchange and on-site investigation for problems, and certified hospitals with outstanding performance and obvious progress. The circle pattern, including evaluation, training, improvement and re-evaluation, will boost the guidelines compliance on clinical practice in China and improve the quality of medical services. METHODS: This study was conducted in a centre of the Third Xiangya Hospital of Central South University. It included patients with ACS from December 2009 to December 2011 (n=225), patients with ACS in the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project coming from the Third Xiangya Hospital of Central South University (n=665), 12 hospitals in Hunan Province (n=4333) and 150 hospitals in China (n=63 641) from November 2014 to April 2017. It assessed the situation of drug therapy, hospitalisation day, mortality during hospitalisation, median of door-to-needle (D-to-N) time and median of door-to-balloon (D-to-B) time of patients with ST-segment elevation myocardial infarction (STEMI), the proportion of D-to-N within 30 min and D-to-B within 90 min, and the proportion of reperfusion therapy. Patients with ACS from the centre from November 2014 to April 2017 were divided into five groups (every 6 months as a group according to time). The study observed change trends in all the above-mentioned indexes. RESULTS: Compared with before participating in the CCC project, there were increases after participating in the CCC project in the drug usage rates of aspirin, P2Y12 inhibitor (clopidogrel or ticagrelor), ß-blocker, statin and angiotensin converting enzyme inhibitor (ACEI)/angiotensin-receptor blocker (ARB). Hospitalisation day and mortality during hospitalisation were shortened. D-to-N and D-to-B times of patients with STEMI were shorter. Compared with Hunan Province and China, the drug usage rates were higher; hospitalisation day and D-to-N time were shorter; D-to-B time was longer; and the proportion of reperfusion therapy was higher. The trend of drug usage rates was on the rise. There was no significant change in the hospitalisation day and D-to-N and D-to-B times. The mortality during hospitalisation showed a downward trend. The proportion of D-to-N within 90 min and reperfusion therapy showed upward trends. CONCLUSION: Quality of care for patients with ACS improved over time in the CCC project, including taking medicine following the guidelines, increased use of reperfusion therapy and faster time to treatment. Although overall mortality has improved, we also should attach importance to high-risk patients. The influence of the CCC project, which is based on guidelines on prognosis of ACS in the centre, presents an important clinical implication that it is necessary to enhance adherence to the guidelines in the treatment of ACS.

3.
Nucleic Acids Res ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32055844

RESUMO

Formation of a pluripotency-specific chromatin network is a critical event in reprogramming somatic cells into pluripotent status. To characterize the regulatory components in this process, we used 'chromatin RNA in situ reverse transcription sequencing' (CRIST-seq) to profile RNA components that interact with the pluripotency master gene Oct4. Using this approach, we identified a novel nuclear lncRNA Oplr16 that was closely involved in the initiation of reprogramming. Oplr16 not only interacted with the Oct4 promoter and regulated its activity, but it was also specifically activated during reprogramming to pluripotency. Active expression of Oplr16 was required for optimal maintenance of pluripotency in embryonic stem cells. Oplr16 was also able to enhance reprogramming of fibroblasts into pluripotent cells. RNA reverse transcription-associated trap sequencing (RAT-seq) indicated that Oplr16 interacted with multiple target genes related to stem cell self-renewal. Of note, Oplr16 utilized its 3'-fragment to recruit the chromatin factor SMC1 to orchestrate pluripotency-specific intrachromosomal looping. After binding to the Oct4 promoter, Oplr16 recruited TET2 to induce DNA demethylation and activate Oct4 in fibroblasts, leading to enhanced reprogramming. These data suggest that Oplr16 may act as a pivotal chromatin factor to control stem cell fate by modulating chromatin architecture and DNA demethylation.

4.
RNA Biol ; : 1-15, 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32079470

RESUMO

The tight gene expression regulation controls the development and pathogenesis of human malaria parasite Plasmodium falciparum throughout the complex life cycle. Recent studies have revealed the pervasive nascent transcripts in the genome of P. falciparum, suggesting the existence of a hidden transcriptome involved in the dynamic gene expression. However, the landscape and related biological functions of nascent non-coding RNAs (ns-ncRNAs) are still poorly explored. Here we profiled the transcription dynamics of nascent RNAs by rRNA-depleted and stranded RNA sequencing over the course of 48-h intraerythrocytic developmental cycle (IDC). We identified the genome-wide sources of a total of 2252 ns-ncRNAs, mostly originating from intergenic and untranslated regions of annotated genes. By integrating the nascent RNA abundances with ATAC-seq and ChIP-seq analysis, we uncovered the euchromatic microenvironment surrounding the ns-ncRNA loci, and revealed a positive correlation between ns-ncRNAs and corresponding mRNA abundances. Finally, by gene knock-down strategy, we showed that the cooperation of RNA exosome catalytic subunit PfDis3 and PfMtr4 cofactor played a major role in ns-ncRNAs degradation. Collectively, this study contributes to understanding of the potential roles of short-lived nascent ncRNAs in regulating gene expression in malaria parasites.

6.
Theranostics ; 10(1): 353-370, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31903125

RESUMO

Background: Long non-coding RNAs (lncRNAs) constitute an important component of the regulatory apparatus that controls stem cell pluripotency. However, the specific mechanisms utilized by these lncRNAs in the control of pluripotency are not fully characterized. Methods: We utilized a RNA reverse transcription-associated trap sequencing (RAT-seq) approach to profile the mouse genome-wide interaction targets for lncRNAs that are screened by RNA-seq. Results: We identified Peblr20 (Pou5F1 enhancer binding lncRNA 20) as a novel lncRNA that is associated with stem cell reprogramming. Peblr20 was differentially transcribed in fibroblasts compared to induced pluripotent stem cells (iPSCs). Notably, we found that Peblr20 utilized a trans mechanism to interact with the regulatory elements of multiple stemness genes. Using gain- and loss-of-function experiments, we showed that knockdown of Peblr20 caused iPSCs to exit from pluripotency, while overexpression of Peblr20 activated endogenous Pou5F1 expression. We further showed that Peblr20 promoted pluripotent reprogramming. Mechanistically, we demonstrated that Peblr20 activated endogenous Pou5F1 by binding to the Pou5F1 enhancer in trans, recruiting TET2 demethylase and activating the enhancer-transcribed RNAs. Conclusions: Our data reveal a novel epigenetic mechanism by which a lncRNA controls the fate of stem cells by trans-regulating the Pou5F1 enhancer RNA pathway. We demonstrate the potential for leveraging lncRNA biology to enhance the generation of stem cells for regenerative medicine.

7.
J Photochem Photobiol B ; 202: 111680, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31810038

RESUMO

Tissue engineering and stem cell rehabilitation are the hopeful aspects that are being investigated for the management of Myocardial Infarction (MI); cardiac patches have been used to start myocardial rejuvenation. In this study, we engineered p-phenylenediamine surface functionalized (modif-CQD) into the Silk fibroin/PLA (SF/PLA) nanofibrous bioactive scaffolds with improved physico-chemical abilities, mechanical and cytocompatibility to cardiomyocytes. The micrograph results visualized the morphological improved spherical modif-CQD have been equivalently spread throughout the SF/PLA bioactive cardiac scaffolds. The fabricated CQD@SF/PLA nanofibrous bioactive scaffolds were highly porous with fully consistent pores; effectively improved young modulus and swelling asset for the suitability and effective implantation efficacy. The scaffolds were prepared with rat cardiomyocytes and cultured for up to 7 days, without electrical incentive. After 7 days of culture, the scaffold pores all over the construct volume were overflowing with cardiomyocytes. The metabolic activity and viability of the cardiomyocytes in CQD@SF/PLA scaffolds were significantly higher than cardiomyocytes in Silk fibroin /PLA scaffolds. The integration of CQD also influenced greatly and increases the expression of cardiac-marker genes. The results of the present investigations evidently recommended that well-organized cardiac nanofibrous scaffold with greater cardiac related mechanical abilities and biocompatibilities for cardiac tissue engineering and nursing care applications.


Assuntos
Fibroínas/química , Nanofibras/química , Pontos Quânticos/química , Engenharia Tecidual , Tecidos Suporte/química , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Carbono/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Raios Infravermelhos , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Nanofibras/toxicidade , Poliésteres/química , RNA Mensageiro/metabolismo , Ratos , Troponina C/genética , Troponina C/metabolismo
8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(6): 1869-1875, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-31839052

RESUMO

OBJECTIVE: To investigate the prognostic significance of immune changes in patients with newly diagnosed multiple myeloma(MM) after chemothrapy. METHODS: The clinical data of 99 patients with multiple myeloma received treatment in Department of Hematology, Lanzhou University Second Hospital from April 2011 to December 2017 were collected and retrospectively analyzed. The change of immune status was defined by changes of lymphocyte/monocyte ratio(LMR) level. The prognosis value of age, sex, typing, hemoglobin (Hb), ß2-microglobulin (ß2-MG), lactate dehydrogenase (LDH), albumin (albumin, ALB) and LMR changes were investigated in patients with newly diagnosed MM, and the relationship between above inentioned factors and changes of LMR was also explored. Overall survival rate between different subgroups was compared by using Kaplan-Meier curves and detected by Log-rank tests. Univariate and multivariate analysis of prognosis was performed by using the COX proportional hazards regression model. Paired samples Wilcoxon test were used to compare changes in ALC, AMC and LMR before and after chemotherapy, and logistic regression was used to investigate the clinical factors that affect the changes of LMR. RESULTS: The median value of ALC increased from 1.25 (0.84-1.81)×109/L to 1.39 (1.02-1.9)×109/L (P=0.029) after treated for 1 month; the median value of AMC decreased from 0.37 (0.23-0.47) ×109/L to 0.29 (0.2-0.44)×109/L (P=0.026), and the median value of LMR increased from 3.552 (2.405-5.208) to 5.138 (3.22-6.471) (P=0.002). Multivariate survival analysis showed that increasing of LMR (HR 0.459, 95% CI 0.241-0.875, P=0.018) and LDH (HR 2.368, 95% CI 1.123-4.995, P=0.024) were considered to be the independent factors affecting the prognosis of MM patients. CONCLUSION: The increasing of LMR level after treatment indicates a longer survival time of newly prognostic MM patients. Combination with LMR can not only reflect the effect of treatment on the immune status, but also predict the prognosis of MM patients much better.


Assuntos
Mieloma Múltiplo , Humanos , Linfócitos , Monócitos , Mieloma Múltiplo/tratamento farmacológico , Prognóstico , Estudos Retrospectivos
9.
Ecol Evol ; 9(19): 11232-11242, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31641468

RESUMO

Restriction site-associated DNA sequencing (RAD-seq) is one of the most effective high-throughput sequencing technologies for SNP development and utilization and has been applied to studying the origin and evolution of various species. The domestic Bactrian camels play an important role in economic trade and cultural construction. They are precious species resources and indispensable animals in China's agricultural production. Recently, the rapid development of modern transportation and agriculture, and the deterioration of the environment have led to a sharp decline in the number of camels. Although there have been some reports on the evolution history of the domestic Bactrian camel in China, the origin, evolutionary relationship, and genetic diversity of the camels are unclear due to the limitations of sample size and sequencing technology. Therefore, 47 samples of seven domestic Bactrian camel species from four regions (Inner Mongolia, Gansu, Qinghai, and Xinjiang) were prepared for RAD-seq analysis to study the evolutionary relationship and genetic diversity. In addition, seven domestic Bactrian camel species are located in different ecological zones, forming different characteristics and having potential development value. A total of 6,487,849 SNPs were genotyped. On the one hand, the filtered SNP information was used to conduct polymorphism mapping construction, LD attenuation analysis, and nucleotide diversity analysis. The results showed that the number of SNPs in Dongjiang camel was the highest, the LD coefficient decayed the fastest, and the nucleotide diversity was the highest. It indicates that Dongjiang camel has the highest genetic diversity. On the other hand, the filtered SNPs information was used to construct the phylogenetic tree, and F ST analysis, inbreeding coefficient analysis, principal component analysis, and population structure analysis were carried out. The results showed that Nanjiang camel and Beijiang camels grouped together, and the other five Bactrian camel populations gathered into another branch. It may be because the mountains in the northern part of Xinjiang and the desert in the middle isolate the two groups from the other five groups.

11.
J Food Prot ; 82(10): 1744-1750, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31536421

RESUMO

Bacillus cereus is a spore-forming gastrointestinal pathogen that can cause life-threatening diseases. Here, a simple and effective assay to detect B. cereus was developed, using cross-priming amplification (CPA). Amplicons were detected using disposable cartridges that contained nucleic acid detection strips. The sensitivity of CPA assay for B. cereus was assessed using serial dilutions of genomic DNA, which indicated a detection limit of 3.6 × 101 CFU/mL. No cross-reactions were detected when genomic DNA extracted from 12 different B. cereus strains and 20 other bacterial foodborne strains were tested, suggesting that the assay is highly specific. Finally, we evaluated the practical applications of the CPA assay for the detection of B. cereus in 150 food samples and found that its sensitivity and specificity, compared with real-time PCR, were approximately 98.18 and 100%, respectively. In conclusion, CPA combined with nucleic acid detection strips is easy to perform, requires simple equipment, and offers highly specific and sensitive B. cereus detection.

13.
Mol Nutr Food Res ; 63(19): e1900249, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31271251

RESUMO

BACKGROUND: Calorie restriction (CR) is a therapeutically effective method for nonalcoholic fatty liver disease. However, the compliance of the CR method is relatively poor. New CR methods are needed. METHODS AND RESULTS: Each week, mice are given a 5-day high-fat diet (HFD) ad libitum plus 2 days of an intermittent calorie restriction (ICR) diet (50% calorie restriction) consisting of yogurt, fruit, and vegetables, for 16 weeks. The effect of the ICR diet model on the fatty liver of mice is examined. Compared with continuous HFD-fed mice, the mice feeding HFD+ICR have lower body weight and hepatic steatosis, reduced serum lipid and transaminase levels, increased fatty acid oxidation gene of Cpt1a, and decreased hepatic lipid synthesis gene of Pparγ and Srebf-1c, as well as improved insulin resistance and lower level of inflammation. Moreover, ICR reverses the dysbacteriosis in HFD group, including the lower Shannon diversity indexes and lower abundance of Lactobacillus. CONCLUSION: An ICR diet consisting of yogurt, fruit, and vegetables attenuates the development of HFD-induced hepatic steatosis in mice. Furthermore, HFD+ICR diet is associated with a different fecal microbiota that tends to be more similar to normal diet controls.

14.
Nutrients ; 11(7)2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31261807

RESUMO

Modern research has found that Ganoderma lucidum polysaccharides (GLP) and Polyporus umbellatus polysaccharides (PUP) mainly exhibit immunoregulation. However, the immune function of a polysaccharide composition consisting of GLP and PUP has not been studied. In this study, we developed a polysaccharide composition consisting of GLP and PUP in a ratio of 3:1 (named GPP). The immunoregulation of GPP was detected in RAW264.7 macrophages. Then, the acute oral toxicity of GPP and the effect of GPP on immunoregulation in mice was detected. The results showed that GPP enhanced the function of macrophage RAW264.7 cells through improving phagocytic ability, nitric oxide (NO) production and the mRNA expression of inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-α. GPP belonged to the non-toxic grade in mice. Moreover, GPP significantly improved macrophage phagocytic function and the activity of natural killer (NK) cells after being administered to mice at a dose of 0, 3.6, 120, 360 mg/kg body weight (mg/kg BW) orally for 30 days. Taken together, these findings suggested that GPP moderately regulated immune function in mice, which contributes to the further development and utilization of GLP and PUP in immune function.


Assuntos
Adjuvantes Imunológicos/farmacologia , Imunidade Inata/efeitos dos fármacos , Células Matadoras Naturais/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Polyporus , Polissacarídeos/farmacologia , Reishi , Adjuvantes Imunológicos/isolamento & purificação , Animais , Feminino , Interleucina-10/genética , Interleucina-10/metabolismo , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Fagocitose/efeitos dos fármacos , Polyporus/química , Polissacarídeos/isolamento & purificação , Células RAW 264.7 , Reishi/química , Transdução de Sinais , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
15.
Genome Res ; 29(9): 1521-1532, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31315906

RESUMO

Long noncoding RNAs (lncRNAs) can regulate the activity of target genes by participating in the organization of chromatin architecture. We have devised a "chromatin-RNA in situ reverse transcription sequencing" (CRIST-seq) approach to profile the lncRNA interaction network in gene regulatory elements by combining the simplicity of RNA biotin labeling with the specificity of the CRISPR/Cas9 system. Using gene-specific gRNAs, we describe a pluripotency-specific lncRNA interacting network in the promoters of Sox2 and Pou5f1, two critical stem cell factors that are required for the maintenance of pluripotency. The promoter-interacting lncRNAs were specifically activated during reprogramming into pluripotency. Knockdown of these lncRNAs caused the stem cells to exit from pluripotency. In contrast, overexpression of the pluripotency-associated lncRNA activated the promoters of core stem cell factor genes and enhanced fibroblast reprogramming into pluripotency. These CRIST-seq data suggest that the Sox2 and Pou5f1 promoters are organized within a unique lncRNA interaction network that determines the fate of pluripotency during reprogramming. This CRIST approach may be broadly used to map lncRNA interaction networks at target loci across the genome.


Assuntos
Cromatina/genética , Fator 3 de Transcrição de Octâmero/genética , RNA Longo não Codificante/genética , Fatores de Transcrição SOXB1/genética , Análise de Sequência de RNA/métodos , Animais , Sistemas CRISPR-Cas , Linhagem Celular , Reprogramação Celular , Fibroblastos/citologia , Fibroblastos/metabolismo , Camundongos , Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/metabolismo , Regiões Promotoras Genéticas , Sequências Reguladoras de Ácido Nucleico
16.
Medicine (Baltimore) ; 98(30): e16477, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348252

RESUMO

BACKGROUND: Traditional Chinese medicine (TCM) therapy is effective for post-stroke depression (PSD). TCM therapy encompasses various forms of practices. However, the comparative effectiveness of these therapies is still not clear. Here, we provide a network meta-analysis protocol to compare the effects of different types of TCM therapy on PSD, using both direct and indirect evidence. METHODS: Twelve databases investigation will be conducted through the keywords from their inception to June 1, 2019. At least 2 independent reviewers will identify eligible articles. EndNote X7 software is utilized to manage the literatures and RevMan V.5.3 (The Cochrane Collaboration) software is for data processing throughout the review. The package "netmeta" (version 0.5-0) in R (version 3.0.2, The R Foundation for Statistical Computing) will be used to perform network meta-analysis (NMA). In addition, the overall quality of evidence is evaluated by GRADEPro software, and Cochrane Collaboration Risk of Bias Tool is employed for the methodological quality. Generally speaking, this review protocol is reported according to the preferred reporting items for systematic review and meta-analysis protocols 2015 guidelines. RESULTS: According to this protocol, it will provide evidence in support of, or against, the hypothesis that TCM therapy for PSD is more effective than pharmacotherapy. The results of this study will also provide evidence on relative efficacy of different forms of TCM. Furthermore, this analysis will show which form(s) of TCM therapy is (are) the most effective. CONCLUSION: The results will help PSD doctors and patients choose the treatment regimen which is effective, time-saving and economical. PROSPERO REGISTRATION NUMBER: CRD42016041594.


Assuntos
Depressão/etiologia , Depressão/terapia , Medicina Tradicional Chinesa/métodos , Acidente Vascular Cerebral/complicações , Antidepressivos/uso terapêutico , Humanos , Meta-Análise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
17.
BMC Bioinformatics ; 20(Suppl 8): 290, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31182028

RESUMO

BACKGROUND: It is of great clinical significance to develop an accurate computer aided system to accurately diagnose the breast cancer. In this study, an enhanced machine learning framework is established to diagnose the breast cancer. The core of this framework is to adopt fruit fly optimization algorithm (FOA) enhanced by Levy flight (LF) strategy (LFOA) to optimize two key parameters of support vector machine (SVM) and build LFOA-based SVM (LFOA-SVM) for diagnosing the breast cancer. The high-level features abstracted from the volunteers are utilized to diagnose the breast cancer for the first time. RESULTS: In order to verify the effectiveness of the proposed method, 10-fold cross-validation method is used to make comparison among the proposed method, FOA-SVM (model based on original FOA), PSO-SVM (model based on original particle swarm optimization), GA-SVM (model based on genetic algorithm), random forest, back propagation neural network and SVM. The main novelty of LFOA-SVM lies in the combination of FOA with LF strategy that enhances the quality for FOA, thus improving the convergence rate of the FOA optimization process as well as the probability of escaping from local optimal solution. CONCLUSIONS: The experimental results demonstrate that the proposed LFOA-SVM method can beat other counterparts in terms of various performance metrics. It can very well distinguish malignant breast cancer from benign ones and assist the doctor with clinical diagnosis.


Assuntos
Neoplasias da Mama/diagnóstico , Drosophila melanogaster/fisiologia , Máquina de Vetores de Suporte , Animais , Feminino , Humanos , Reprodutibilidade dos Testes
18.
J Exp Med ; 216(8): 1944-1964, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31196982

RESUMO

High bone mass (HBM) is usually caused by gene mutations, and its mechanism remains unclear. In the present study, we identified a novel mutation in the long noncoding RNA Reg1cp that is associated with HBM. Subsequent analysis in 1,465 Chinese subjects revealed that heterozygous Reg1cp individuals had higher bone density compared with subjects with WT Reg1cp Mutant Reg1cp increased the formation of the CD31hiEmcnhi endothelium in the bone marrow, which stimulated angiogenesis during osteogenesis. Mechanistically, mutant Reg1cp directly binds to Krüppel-like factor 3 (KLF3) to inhibit its activity. Mice depleted of Klf3 in endothelial cells showed a high abundance of CD31hiEmcnhi vessels and increased bone mass. Notably, we identified a natural compound, Ophiopogonin D, which functions as a KLF3 inhibitor. Administration of Ophiopogonin D increased the abundance of CD31hiEmcnhi vessels and bone formation. Our findings revealed a specific mutation in lncRNA Reg1cp that is involved in the pathogenesis of HBM and provides a new target to treat osteoporosis.

19.
Ther Adv Med Oncol ; 11: 1758835919843463, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31065295

RESUMO

Without stringent criteria, liver transplantation for hepatocellular carcinoma (HCC) can lead to high cancer recurrence and poor prognosis in the current treatment context. Checkpoint inhibitors can lead to long survival by targeting coinhibitory pathways and promoting T-cell activity; thus, they have great potential for cancer immunotherapy. Therapeutic modulation of cosignaling pathways may shift paradigms from surgical prevention of recurrence to oncological intervention. Herein, we review the available evidence from a therapeutic perspective and focus on immune microenvironment perturbation by immunosuppressants and checkpoint inhibitors. Partial and reversible interleukin-2 signaling blockade is the mainstream strategy of immunosuppression for graft protection. Programmed cell death protein 1 (PD-1) is abundantly expressed on human liver allograft-infiltrating T-cells, which proliferate considerably after programmed death-ligand 1 (PD-L1) blockade. Clinically, checkpoint inhibitors are used in heart, liver, and kidney recipients with various cancers. Rejection can occur after checkpoint inhibitor administration through acute T-cell-mediated, antibody-mediated, or chronic allograft rejection mechanisms. Nevertheless, liver recipients may demonstrate favorable responses to treatment for HCC recurrence without rejection. Pharmacodynamically, substantial degrees of receptor occupancy can be achieved with lower doses, with favorable clinical outcomes. Manipulation of the immune microenvironment is a therapeutic niche that balances seemingly conflicting anticancer and graft protection needs. Additional translational and clinical studies emphasizing the comparative effectiveness of signaling networks within the immune microenvironment and conducting overall assessment of the immune microenvironment may aid in creating a therapeutic window and benefiting future liver recipients with HCC recurrence.

20.
PLoS One ; 14(5): e0216470, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31063496

RESUMO

BACKGROUND: Human B-cell lymphoma 6 (BCL6) gene, usually coding protein of 706 amino acids, is closely associated with large B cell lymphoma. Researches showed that protein mutation or change of expression levels usually happened in the mounting non-hodgkin lymphoma (NHL). Thus BCL6 is considered to be involved in germinal center (GC)-derived lymphoma. RESULTS: The BCL61-350 gene codons were optimized for prokaryotic system. After expression of BCL61-350 in E. coli, the BCL61-350 protein was purified with Ni column. Then the BCL61-350 protein, mixing with QuickAntibody-Mouse5W adjuvant, was injected into Balb/c mice. After immunization and cell fusion, a stable cell line named 1E6A4, which can secrete anti-BCL6 antibody, was obtained. The isotype of 1E6A4 mAb was determined as IgG2a, and the affinity constant reached 5.12×1010 L/mol. Furthermore, the specificity of the mAb was determined with ELISA, western blot and immunohistochemistry. Results indicated that the 1E6A4 mAb was able to detect BCL6 specifically and sensitively. CONCLUSIONS: BCL61-350 antigen has been successfully generated with an effective and feasible method, and a highly specific antibody named 1E6A4 against BCL6 has been screened and characterized in this study, which was valuable in clinical diagnosis.


Assuntos
Anticorpos Monoclonais Murinos , Imunoglobulina G , Linfoma de Células B/diagnóstico , Linfoma de Células B/imunologia , Proteínas Proto-Oncogênicas c-bcl-6/imunologia , Animais , Anticorpos Monoclonais Murinos/química , Anticorpos Monoclonais Murinos/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Centro Germinativo/imunologia , Centro Germinativo/metabolismo , Centro Germinativo/patologia , Humanos , Imunoglobulina G/química , Imunoglobulina G/imunologia , Imuno-Histoquímica , Linfoma de Células B/metabolismo , Linfoma de Células B/patologia , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Proto-Oncogênicas c-bcl-6/biossíntese
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