Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 706
Filtrar
1.
Mol Ther Nucleic Acids ; 18: 476-484, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31670197

RESUMO

Cytogenetically normal acute myeloid leukemia (CN-AML) presents with diverse outcomes in different patients and is categorized as an intermediate prognosis group. It is important to identify prognostic factors for CN-AML risk stratification. In this study, using the TCGA CN-AML dataset, we found that the scavenger receptor stabilin-1 (STAB1) is a prognostic factor for poor outcomes and validated it in three other independent CN-AML datasets. The high STAB1 expression (STAB1high) group had shorter event-free survival compared with the low STAB1 expression (STAB1low) group in both the TCGA dataset (n = 79; p = 0.0478) and GEO: GSE6891 dataset (n = 187; p = 0.0354). Differential expression analysis between the STAB1high and STAB1low groups revealed that upregulated genes in the STAB1high group were enriched in pathways related to cell adhesion and migration and immune responses. We confirmed that STAB1 suppression inhibits cell growth in KG1a and NB4 leukemia cells. Expression correlation analyses between STAB1 and cancer drug targets suggested that patients in the STAB1low group are more sensitive to the BCL2 inhibitor venetoclax, and we confirmed it in cell lines. In conclusion, we identified STAB1 as a prognostic factor for CN-AML in multiple datasets, explored its underlying mechanism, and provided potential therapeutic indications.

2.
Sci Rep ; 9(1): 17460, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31767907

RESUMO

Long non-coding RNAs (lncRNAs) which have little or no protein-coding capacity, due to their potential roles in the cancer disease, caught a particular interest. Our study aims to develop an lncRNAs-based classifier and a nomogram incorporating the lncRNAs classifier and clinicopathologic factors to help to improve the accuracy of recurrence prediction for head and neck squamous cell carcinoma (HNSCC) patients. The HNSCC lncRNAs profiling data and the corresponding clinicopathologic information were downloaded from TANRIC database and cBioPortal. Using univariable Cox regression and Least absolute shrinkage and selection operator (LASSO) analysis, we developed 15-lncRNAs-based classifier related to recurrence. On the basis of multivariable Cox regression analysis results, a nomogram integrating the genomic and clinicopathologic predictors was built. The predictive accuracy and discriminative ability of the inclusive nomogram were confirmed by calibration curve and a concordance index (C-index), and compared with TNM stage system by C-index, receiver operating characteristic (ROC) analysis. Decision curve analysis (DCA) was conducted to evaluate clinical value of our nomogram. Consequently, fifteen recurrence-free survival (RFS) -related lncRNAs were identified, and the classifier consisting of the established 15 lncRNAs could effectively divide patients into high-risk and low-risk subgroup. The prediction ability of the 15-lncRNAs-based classifier for predicting 3- year and 5-year RFS were 0.833 and 0.771. Independent factors derived from multivariable analysis to predict recurrence were number of positive LNs, margin status, mutation count and lncRNAs classifier, which were all embedded into the nomogram. The calibration curve for the recurrence probability showed that the predictions based on the nomogram were in good coincide with practical observations. The C-index of the nomogram was 0.76 (0.72-0.79), and the area under curve (AUC) of nomogram in predicting RFS was 0.809, which were significantly higher than traditional TNM stage and 15-lncRNAs-based classifier. Decision curve analysis further demonstrated that our nomogram had larger net benefit than TNM stage and 15-lncRNAs-based classifier. The results were confirmed externally. In summary, a visually inclusive nomogram for patients with HNSCC, comprising genomic and clinicopathologic variables, generates more accurate prediction of the recurrence probability when compared TNM stage alone, but more additional data remains needed before being used in clinical practice.

3.
Biochim Biophys Acta Mol Cell Res ; : 118574, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31682865

RESUMO

During keratinocyte stratification and wound healing, keratinocytes undergo a switch between differentiation and motility. However, limited knowledge exists on the mechanisms of the switch. We have previously demonstrated that the expression of CD9 was changed in different wound stages and involved in the regulation of keratinocyte migration. In this study, we showed that CD9 expression was increased in both human and mouse keratinocytes undergoing differentiation. CD9 overexpression in keratinocytes stimulated terminal differentiation and reduced cell motility. CD9 silencing inhibited calcium-induced keratinocyte differentiation and increased cell motility. Furthermore, CD9 overexpression recruited E-cadherin to the plasma membrane and subsequently activated PI3K/Akt signaling, while CD9 knockdown inhibited the recruitment of E-cadherin to the plasma membrane and PI3K/Akt activation. Importantly, silencing E-cadherin expression or inhibiting PI3K/Akt signaling reversed CD9 overexpression-induced differentiation and -reduced motility. These results demonstrate that CD9 acts as an important node that regulates keratinocyte differentiation and motility. The recruitment of E-cadherin to the plasma membrane and activation of the PI3K/Akt signaling pathway mediated by CD9 play an important role in these processes.

4.
Psychoneuroendocrinology ; : 104483, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31757429

RESUMO

Infidelity is the major cause of breakups and individuals with a history of infidelity are more likely to repeat it, but may also present a greater opportunity for short-term sexual relationships. Here in a pre-registered, double-blind study involving 160 subjects we report that while both sexes valued faithful individuals most for short-term and long-term relationships, both single men and those in a relationship were more interested in having short-term relationships with previously unfaithful individuals than women. Oxytocin administration resulted in men rating the faces of unfaithful women as more attractive and likeable but in women rating those of unfaithful men as less attractive and also finding them less memorable. Oxytocin also increased single men's interest in having short-term relationships with previously unfaithful women whereas it increased single women's interest in having long-term relationships with faithful men. Thus, oxytocin release during courtship may first act to amplify sex-dependent priorities in attraction and mate choice before subsequently promoting romantic bonds.

5.
Cell Death Differ ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666685

RESUMO

The retrosplenial cortex (Rsp) is a transitional cortex located between the neocortex and archicortex, but the molecular mechanism specifying Rsp from the archicortex remains elusive. We here report that the transcription factor Satb2 is required for specifying Rsp identity during its morphogenesis. In Satb2 CKO mice, the boundary between the Rsp and archicortex [i.e., subiculum (SubC)] disappears as early as E17.5, and Rsp efferent projection is aberrant. Rsp-specific genes are lost, whereas SubC-specific genes are ectopically expressed in Rsp of Satb2 CKO mice. Furthermore, cell-autonomous role of Satb2 in maintaining Rsp neuron identity is revealed by inactivation of Satb2 in Rsp neurons. Finally, Satb2 represses the transcription of Nr4a2. The misexpression of Nr4a2 together with Ctip2 induces expression of SubC-specific genes in wild-type Rsp, and simultaneous knockdown of these two genes in Rsp Satb2-mutant cells prevents their fate transition to SubC identity. Thus, Satb2 serves as a determinant gene in the Rsp regionalization by repressing Nr4a2 and Ctip2 during cortical development.

6.
Neuroimage ; : 116315, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31669409

RESUMO

Non-invasive quantitative imaging of cerebral oxygen metabolism (CMRO2) in small animal models is crucial to understand the role of oxidative metabolism in healthy and diseased brains. In this study, we developed a multimodal method combining near-infrared spectroscopy (NIRS) and MRI to non-invasively study oxygen delivery and consumption in the cortex of mouse and rat models. The term CASNIRS is proposed to the technique that measures CMRO2 with ASL and NIRS. To determine the reliability of this method, CMRO2 values were compared with reported values measured with other techniques. Also, the sensitivity of the CASNIRS technique to detect changes in CMRO2 in the cortex of the animals was assessed by applying a reduction in core temperature, which is known to reduce CMRO2. Cerebral blood flow (CBF) and CMRO2 were measured in five mice and five rats at a core temperature of 37 °C followed by another measurement at 33 °C. CMRO2 was 7.8 ±â€¯1.8 and 3.7 ±â€¯0.9 (ml/100 g/min, mean ±â€¯SD) in mice and rats respectively. These values are in good agreement with reported values measured by 15O PET, 17O NMR, and BOLD fMRI. In hypothermia, we detected a significant decrease of 37% and 32% in CMRO2 in the cortex of mice and rats, respectively. Q10 was calculated to be 3.2 in mice and 2.7 in rats. In this study we showed that it is possible to assess absolute values of metabolic correlates such as CMRO2, CBF and oxygen extraction fraction (OEF) noninvasively in living brain of mice and rats by combining NIRS with MRI. This will open new possibilities for studying brain metabolism in patients as well as the many mouse/rat models of brain disorders.

7.
Reproduction ; 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31671404

RESUMO

Uterine peristalsis plays a vital role in fertility and female reproductive health. Although uterine peristalsis is thought to be correlated with some hormones and uterine pathologies, the physiological mechanisms underlying uterine peristalsis remain not quite clear. This study aimed to identify changes in microRNA (miRNA) in the endometrium of patients with abnormally high-frequency (hyper-) and low-frequency (hypo-) peristalsis to clarify whether miRNAs regulate uterine peristalsis. We used a miRNA microarray and RT-qPCR to identify changes in miRNA in endometrial tissue, a collagen gel contraction assay on co-cultured human endometrial stromal cells (ESCs) to analyze how the altered regulation of miRNAs influences uterine smooth muscle (USM) contraction, and western blots and other assays to elucidate the potential mechanisms involved. We found that among several differentially-regulated miRNAs, miR-29c-3p was overexpressed in endometrial samples from patients with hypoperistalsis; oxytocin receptor (OXTR) expression was low in endometrial samples from patients with hypoperistalsis. Bioinformatic analysis and luciferase assays indicated that OXTR is a target of miR-29c-3p, which attenuates its expression. Additionally, downregulation of miR-29c-3p in ESC cultures increased the expression of aldo-keto reductase family 1, member C3 (AKR1C3) and increased release of prostaglandin F2 alpha (PGF2α). Co-cultured ESCs overexpressing miR-29c-3p reduced USM cell contractions; the opposite tendency was found when ESCs were transfected with a miR-29c-3p inhibitor. To conclude, miR-29c-3p in endometrial cells regulates uterine contractility by attenuating expression of OXTR and reducing PGF2α release.

8.
Cancer Biol Ther ; : 1-9, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31690181

RESUMO

Programmed death ligand-1 (PD-L1) expression and the presence of tumor-infiltrating lymphocytes (TILs) in tumor microenvironment were common in chronic inflammatory tumor types and frequently responded to the PD-L1 pathway immune checkpoint blockade in the clinic. Animal models to optimize such immunotherapeutics comprise an important strategy but often fail to predict the efficacy of clinical approaches. To address this, we aimed to establish new mouse models. In this study, we found that the expression of PD-L1was present at the beginning stage but a gradual decline over time in the in vitro cell culture and also in the mouse model. Based upon this finding, we established the IFN-γ-(human peripheral blood mononuclear cell) PBMC-CDX (cell line-derived xenograft) and IFN-γ-PBMC-PDX (patient-derived xenograft) mouse models, which recapitulate human tumor and human immune system interactions. IFN-γ was injected peritumorally to maintain the positivity of PD-L1 in the tumor microenvironment. Under this circumstance, the PD-1 molecule on the human T lymphocyte surface is in contact with the PD-L1 molecule on the human tumor cells and, thus, the formatin of the PD-L1/PD-1 pathway in the tumor microenvironment.Treatment with anti-PD-1 monoclonal antibody (mAb) significantly inhibited the growth of both CDX and PDX tumors, but not non-human NCG models (without allogeneic human PBMCs and IFN-γ) . These experimental data provide an important and promising platform for the development of drugs and the evaluation of the drug efficacy of immunotherapies with anti-PD-1 mAb as well as the basis of preclinical mAb drug research.

9.
Genes Genomics ; 2019 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-31736006

RESUMO

OBJECTIVE: Aim of this study was to detect the expression of miR-15a in rats following chronic constriction injury (CCI) and to investigate the regulatory functions of miR-15a during neuropathic pain (NP) development. METHODS: CCI was performed in adult Sprague-Dawley rats to set up the rat model of neuropathic pain. MiR-15a agomir and scrambled control were delivered into the implanted catheter of rats. The mechanical allodynia and thermal hyperalgesia were assessed in both CCI- and sham-operated groups. Rat lumbar spinal cord tissues were harvested for mRNA and protein analyses. The primary spinal microglia were isolated from adult Sprague-Dawley rats and transfected with miR-15a mimics, scramble miRNA, miR-15a inhibitor or its corresponding negative control. Cell lysates were collected for mRNA and protein analyses. RESULTS: Compared to sham-operated group, the expression of miR-15a in CCI rats was significantly reduced, whereas neuroinflammation in spinal cord tissues was increased. Intrathecal administration of miR-15a agomir significantly attenuated CCI-induced NP and the levels of proinflammatory cytokines, including IL-6, IL-1ß, and TNF-α. AKT3 was predicted and confirmed as a miR-15a-regulated gene. We further demonstrated that miR-15a overexpression downregulated the level of AKT3 in primary rat microglia and rat CCI model. Moreover, the upregulation of miR-15a induced the expressions of autophagy-associated proteins, suggesting that the regulation mechanism of miR-15a in NP development involves AKT3-mediated autophagy via inhibiting the expression of AKT3. CONCLUSION: Our findings indicated that miR-15a might serve as a promising therapeutic target for the management of NP through the stimulation of autophagic process.

10.
Environ Toxicol ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31737983

RESUMO

Nickel oxide nanoparticles (Nano NiO) bears hepatotoxicity, while whether it leads to liver fibrosis remains unclear. The aim of this study was to establish the Nano NiO-induced hepatic fibrosis model in vivo and investigate the roles of transforming growth factor ß1 (TGF-ß1) in Smad pathway activation, epithelial-mesenchymal transition (EMT) occurrence, and extracellular matrix (ECM) deposition in vitro. Male Wistar rats were exposed to 0.015, 0.06, and 0.24 mg/kg Nano NiO by intratracheal instilling twice a week for 9 weeks. HepG2 cells were treated with 100 µg/mL Nano NiO and TGF-ß1 inhibitor (SB431542) to explore the mechanism of collagen formation. Results of Masson staining as well as the elevated levels of type I collagen (Col-I) and Col-III suggested that Nano NiO resulted in hepatic fibrosis in rats. Furthermore, Nano NiO increased the protein expression of TGF-ß1, p-Smad2, p-Smad3, alpha-smooth muscle actin (α-SMA), matrix metalloproteinase9 (MMP9), and tissue inhibitors of metalloproteinase1 (TIMP1), while decreased the protein content of E-cadherin and Smad7 in rat liver and HepG2 cells. Most importantly, Nano NiO-triggered the abnormal expression of the abovementioned proteins were all alleviated by co-treatment with SB431542, implying that TGF-ß1-mediated Smad pathway, EMT and MMP9/TIMP1 imbalance were involved in overproduction of collagen in HepG2 cells. In conclusion, these findings indicated that Nano NiO induced hepatic fibrosis via TGF-ß1-mediated Smad pathway activation, EMT occurrence, and ECM deposition.

11.
Med Sci Monit ; 25: 7728-7734, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31612870

RESUMO

BACKGROUND The aim of this study was to determine the relationship between the expression of CD35 and CD64 from white blood cells (neutrophil, monocytes, and lymphocytes) and acute infectious diseases in children. MATERIAL AND METHODS The blood samples were collected from 104 children with infections (42 viral infections and 62 bacterial infections). Blood samples were stained with CD45-PC5, CD35-FITC, and CD64-PE, and the fluorescence intensities were measured by flow cytometer, and then the ratio of CD35 to CD64 was calculated. RESULTS The ratio of CD64/CD35 on neutrophils (NCD35/NCD64) was significantly different between the bacterial group, the virus group, and the healthy control group. According to receiver operating characteristic (ROC) analysis, a cutoff value of 7.256 (sensitivity: 90.0%, specificity: 93.7%) was determined for the NCD35/NCD64 ratio. CONCLUSIONS This study shows that NCD35/NCD64 is helpful in the differential diagnosis of acute viral infection and bacterial infection in children.

12.
Am J Hypertens ; 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31549136

RESUMO

BACKGROUND: Hypertension and brachydactyly syndrome (HTNB), also called Bilginturan syndrome, is a rare autosomal dominant disorder characterized by severe salt-independent hypertension, a short stature, brachydactyly, and death from stroke before the age of 50 years when untreated. The purpose of the current study was to identify a PDE3A mutation leading to HTNB associated with vertebral artery malformation in a Chinese family. METHODS: Peripheral blood samples were collected from all subjects for DNA extraction. Next generation sequencing and Sanger sequencing were performed to identify the PDE3A mutation. A comparative overview was performed in the probands with HTNB caused by PDE3A mutations. RESULTS: Genetic analysis identified a missense mutation in PDE3A, c.1346G>A, in the proband with HTNB. This mutation, resulting in p.Gly449Asp, was located in a highly conserved domain and predicted to be damaging by different bioinformatics tools. Co-segregation analyses showed that the proband inherited the identified mutation from her father. Antihypertensive therapy was effective for the proband. Comparative overview of HTNB probands with nine different PDE3A mutations revealed phenotypic heterogeneity. CONCLUSIONS: Genetic screening can significantly improve the diagnosis of HTNB patients at an early age. Our study not only adds to the spectrum of PDE3A mutations in the Chinese population and extends the phenotype of HTNB patients to include vertebral malformation but also improves the awareness of pathogenesis in HTNB patients. We emphasize the importance of antihypertensive treatment and long term follow-up to prevent stroke and adverse cardiovascular events.

13.
Artif Cells Nanomed Biotechnol ; 47(1): 3823-3831, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31556325

RESUMO

Cardiovascular complications are the leading cause of mortality and morbidity in type 2 diabetes patients. Diabetes greatly increases the risk of heart disease; therefore, the management of diabetes often involves the prevention of heart disease. DPP-4 inhibitors have been proven to be the effective therapeutic agents of glycaemic control. Recent studies have shown that certain types of DPP-4 inhibitors could also have cardiovascular benefits. In this study, we examined the protective role of the newly developed DPP-4 inhibitor anagliptin in cultured cardiac myocytic cell line H9C2 cells. Our data show that exposure of H9C2 cells to hypoxic conditions induced higher expression of DPP-4, indicating that DPP-4 is a hypoxia-inducible factor. The inhibition of DPP-4 by anagliptin ameliorates hypoxia-induced cytotoxicity and induction of the pro-inflammatory cytokines IL-6 and MCP-1. Anagliptin also suppresses hypoxia-induced oxidative stress as revealed by the detected levels of cellular ROS and reduced GSH. Moreover, anagliptin protects myocytes from hypoxia-associated reduced mitochondrial membrane potential. Mechanistically, we show that anagliptin promotes hypoxia-induced NFR2/HO1 induction but suppresses HMGB1 and MyD88 generation. Collectively, our data indicate that anagliptin-mediated DPP-4 inhibition is a protective mechanism in cardiomyocytes and imply that the DDP-4 inhibitor anagliptin plays dual roles by lowering glucose and protecting cardiomyocytes.

14.
Reprod Biol Endocrinol ; 17(1): 74, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488148

RESUMO

BACKGROUND: There is much value in identifying non-invasive ways of measuring endometrial receptivity, as it has the potential to improve outcomes following in vitro fertilization (IVF). It has been suggested that endometrial echogenicity on the day of hCG administration was a good marker of endometrial receptivity. In the daily practice, we notice that patients with non-homogeneous hyperechoic endometrium on the embryo transfer day usually have lower pregnancy rates. We therefore extended the research onward transformation of echo pattern after hCG trigger to analyze the relationship between endometrial echogenicity transformation and IVF outcomes. METHODS: A total of 146 infertile women undergoing their first IVF cycle were recruited in the prospective cohort study from August 2017 through August 2018. A series of endometrial echo pattern monitoring was carried out in these patients after hCG trigger: hCG day, from 1 through 3 days after ovum pick-up (OPU + 1, OPU + 2, OPU + 3). RESULTS: The endometrial echogenicity value was calculated as the ratio of the hyperechogenic endometrial area over the whole endometrial area. Clinical pregnancy rate and embryo implantation rate had positive relationship with echogenicity value. The ROC curve analysis of endometrial echogenicity showed the area under curve was greatest on the second day after oocyte retrieval (OPU + 1, 2, 3 were 0.738, 0.765, 0.714 respectively) versus pregnancy. Endometrial echogenicity value on OPU + 2 had a higher predictive efficiency, and the cutoff value was 76.5%. The sensitivity was 61.3% and specificity was 82.0%. When putting the cut-off at <60%, the sensitivity was 93.8% and the specificity was 23.1%. CONCLUSIONS: The endometrial echogenicity value on OPU + 2 was recommended to evaluate endometrial receptivity. It seemed appropriate for clinicians to provide a 'freeze all' IVF cycle and transfer in a subsequent frozen-thawed embryos cycle when echogenicity value <60% on OPU + 2. TRIAL REGISTRATION: The registration number was ChiCTR-OOC-17012214 and the registration date was August 1st, 2017.

15.
BMC Oral Health ; 19(1): 203, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477081

RESUMO

BACKGROUND: This systematic review aimed to assess the clinical effects of laser preparation compared to other types of chemical or mechanical preparation of tooth surfaces used in fissure sealant placement. METHODS: A systematic literature search was conducted up to January 2019, through Pubmed, Scopus, Medline/EMBASE via OVID and the Cochrane library. Only randomized clinical trials were included. RESULTS: Five studies were included in the systematic review and three were included in the meta-analysis. All the studies used acid-etching as a comparator to lasers. All the included studies were rated as having an overall high risk of bias introduced by performance bias. Three studies assessed the clinical effects of fissure sealants placed by acid or laser etching, one compared acid etching versus laser combined with acid etching and one investigated the influence of lasers on the objective and subjective parameters of stress during sealant application in children. The meta-analysis showed no significant difference between laser preparation and conventional acid-etching preparation at 3- (P = 0.08), 6- (P = 0.49), and 12-month (P = 0.87) follow-ups. One study reported that laser preparation as an adjunct to acid-etching enhanced the retention rate. No significant difference in the incidence of caries was reported. And no significant differences were found in heart rates, oxygen saturation or degree of the patient dental anxiety between acid-etching and laser preparation. CONCLUSION: The present limited evidence suggests that lasers could be an effective pretreatment method. The retention rate was similar to that of conventional acid etching. However, the included studies had an overall high risk of bias and more rigorously designed research is needed.

16.
Nucleic Acids Res ; 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31511885

RESUMO

Alternative polyadenylation (APA) is an important post-transcriptional regulation that recognizes different polyadenylation signals (PASs), resulting in transcripts with different 3' untranslated regions, thereby influencing a series of biological processes and functions. Recent studies have revealed that some single nucleotide polymorphisms (SNPs) could contribute to tumorigenesis and development through dysregulating APA. However, the associations between SNPs and APA in human cancers remain largely unknown. Here, using genotype and APA data of 9082 samples from The Cancer Genome Atlas (TCGA) and The Cancer 3'UTR Altas (TC3A), we systematically identified SNPs affecting APA events across 32 cancer types and defined them as APA quantitative trait loci (apaQTLs). As a result, a total of 467 942 cis-apaQTLs and 30 721 trans-apaQTLs were identified. By integrating apaQTLs with survival and genome-wide association studies (GWAS) data, we further identified 2154 apaQTLs associated with patient survival time and 151 342 apaQTLs located in GWAS loci. In addition, we designed an online tool to predict the effects of SNPs on PASs by utilizing PAS motif prediction tool. Finally, we developed SNP2APA, a user-friendly and intuitive database (http://gong_lab.hzau.edu.cn/SNP2APA/) for data browsing, searching, and downloading. SNP2APA will significantly improve our understanding of genetic variants and APA in human cancers.

17.
Int J Biol Sci ; 15(9): 1962-1976, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31523197

RESUMO

Both cell migration and proliferation are indispensable parts of reepithelialization during skin wound healing, which is a complex process for which the underlying molecular mechanisms are largely unknown. Here, we identify a novel role for microtubule-associated protein 4 (MAP4), a cytosolic microtubule-binding protein that regulates microtubule dynamics through phosphorylation modification, as a critical regulator of epidermal wound repair. We showed that MAP4 phosphorylation was induced in skin wounds. In an aberrant phosphorylated MAP4 mouse model, hyperphosphorylation of MAP4 (S737 and S760) accelerated keratinocyte migration and proliferation and skin wound healing. Data from both primary cultured keratinocytes and HaCaT cells in vitro revealed the same results. The promigration and proproliferation effects of MAP4 phosphorylation depended on microtubule rearrangement and could be abolished by MAP4 dephosphorylation. We also identified p38/MAPK as an upstream regulator of MAP4 phosphorylation in keratinocytes. Our findings provide new insights into the molecular mechanisms underlying wound-associated keratinocyte migration and proliferation and identify potential targets for the remediation of defective wound healing.

18.
J Sep Sci ; 42(22): 3439-3450, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31544307

RESUMO

We revealed the potential biomarker and pathway of gelanxinning capsule on rat model with coronary heart disease, which aims to clarify holistic therapeutic effect and predict quality-markers of gelanxinning capsule. Ultra-high performance liquid chromatography coupled with mass spectrometry based on metabolomics technique was used to find the biomarkers and related metabolic pathways of coronary heart disease model, which evaluates the intervention effect of gelanxinning capsule. Using serum pharmacochemistry of traditional Chinese medicine and Pearson correlation analysis, effective ingredients in serum is analyzed to characterize the activity of gelanxinning capsule on coronary heart disease under valid state. A total of 20 biomarkers from coronary heart disease were identified and 12 of them were regulated by gelanxinning capsule treatment, which is mainly involved in sphingolipid metabolism and glycerophospholipid metabolism. With the high sensitivity liquid chromatography coupled with mass spectrometry technology, a total of 46 compounds from gelanxinning capsule were identified in vitro and 25 of them were absorbed in blood. The correlation analysis of serum biomarkers and absorbed components was used to find 11 compounds as quality-markers to be responsible for the efficacy of gelanxinning capsule. This strategy was successfully applied to screening of potential mechanism and quality-markers from herbal medicine.

19.
Zhongguo Zhen Jiu ; 39(9): 993-7, 2019 Sep 12.
Artigo em Chinês | MEDLINE | ID: mdl-31544390

RESUMO

The questionnaire of Acupuncture-Moxibustion and Tuina Applying for First-Level Discipline was issued to 24 colleges and universities of TCM in China. The questionnaire systematically investigated the recent disciplinary development of acupuncture-moxibustion and tuina from the aspects of specialty construction, student enrollment, faculty construction, personnel training quality, teaching quality and scientific research results. As a result, from 2013 to October of 2017, the above aspects in 24 colleges and universities of TCM in China showed an increasing trend year by year. Based on this survey, this report aimed to fully reflect the disciplinary development of acupuncture-moxibustion and tuina in China, which could analyze the current situation for education departments and training units, and provide data reference and support for acupuncture and tuina discipline to become a first-class discipline.


Assuntos
Terapia por Acupuntura , Acupuntura , Moxibustão , Acupuntura/educação , China , Humanos , Universidades
20.
MBio ; 10(5)2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31551335

RESUMO

A major challenge in finding a cure for HIV-1/AIDS is the difficulty in identifying and eradicating persistent reservoirs of replication-competent provirus. Long noncoding RNAs (lncRNAs, >200 nucleotides) are increasingly recognized to play important roles in pathophysiology. Here, we report the first genome-wide expression analysis of lncRNAs in HIV-1-infected primary monocyte-derived macrophages (MDMs). We identified an lncRNA, which we named HIV-1-enhanced lncRNA (HEAL), that is upregulated by HIV-1 infection of MDMs, microglia, and T lymphocytes. Peripheral blood mononuclear cells of HIV-1-infected individuals show elevated levels of HEAL Importantly, HEAL is a broad enhancer of multiple HIV-1 strains because depletion of HEAL inhibited X4, R5, and dual-tropic HIV replications and the inhibition was rescued by HEAL overexpression. HEAL forms a complex with the RNA-binding protein FUS, which facilitates HIV replication through at least two mechanisms: (i) HEAL-FUS complex binds the HIV promoter and enhances recruitment of the histone acetyltransferase p300, which positively regulates HIV transcription by increasing histone H3K27 acetylation and P-TEFb enrichment on the HIV promoter, and (ii) HEAL-FUS complex is enriched at the promoter of the cyclin-dependent kinase 2 gene, CDK2, to enhance CDK2 expression. Notably, HEAL knockdown and knockout mediated by RNA interference (RNAi) and CRISPR-Cas9, respectively, prevent HIV-1 recrudescence in T cells and microglia upon cessation of azidothymidine treatment in vitro Our results suggest that silencing of HEAL or perturbation of the HEAL-FUS ribonucleoprotein complex could provide a new epigenetic silencing strategy to eradicate viral reservoirs and effect a cure for HIV-1/AIDS.IMPORTANCE Despite our increased understanding of the functions of lncRNAs, their potential to develop HIV/AIDS cure strategies remains unexplored. A genome-wide analysis of lncRNAs in HIV-1-infected primary monocyte-derived macrophages (MDMs) was performed, and 1,145 differentially expressed lncRNAs were identified. An lncRNA named HIV-1-enhanced lncRNA (HEAL) is upregulated by HIV-1 infection and promotes HIV replication in T cells and macrophages. HEAL forms a complex with the RNA-binding protein FUS to enhance transcriptional coactivator p300 recruitment to the HIV promoter. Furthermore, HEAL knockdown and knockout prevent HIV-1 recrudescence in T cells and microglia upon cessation of azidothymidine treatment, suggesting HEAL as a potential therapeutic target to cure HIV-1/AIDS.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA