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1.
Redox Biol ; 29: 101404, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31926627

RESUMO

BACKGROUND: C-reactive protein (CRP) is a well-recognized biomarker of inflammation, which can be used as a predictor of cardiovascular disease. Evidence have suggested exposure to multiple metals/metalloids may affect immune system and give rise to cardiovascular disease. However, it is lack of study to comprehensively evaluate the association of multiple metals and CRP, the interactions between metals, and the gene-metal interaction in relation to CRP levels. AIMS: To explore the associations of multiple plasma metals with serum CRP, and to test the interactions between metals, and gene-metal interactions on the levels of serum CRP. METHODS: We included 2882 participants from the Dongfeng-Tongji cohort, China, and measured 23 plasma metals and serum CRP concentrations. The genetic risk score (GRS) was calculated based on 7 established CRP-associated variants. For metals which were associated with the levels of CRP, we further tested the interactions between metals on CRP, and analyzed the gene-metal interactions on CRP. RESULTS: The median level for CRP in the total population was 1.17 mg/L. After multivariable adjustment, plasma copper was positively associated with serum CRP (FDR < 0.001), whereas selenium was negatively associated with serum CRP (FDR = 0.01). Moreover, selenium and zinc attenuated the positive association between high plasma copper and CRP (P for interaction < 0.001). Participants with a higher GRS had a higher CRP level, with the increase in ln-transformed CRP per increment of 5 risk alleles were 0.64 for weighted GRS, and 0.54 for unweighted GRS (both P < 0.001). Furthermore, the genetic association with CRP was modified by copper concentration (P for interaction < 0.001). CONCLUSIONS: Our results suggest that serum CRP is positively associated with plasma concentration of copper, and inversely associated with selenium. Plasma zinc, selenium and CRP genetic predisposition would modify the associations between plasma copper and serum CRP.

2.
Carbohydr Polym ; 232: 115810, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31952604

RESUMO

In the present work, lotus root amylopectin (LRA)-chitosan (CS) composite hydrogel was developed as a delivery system for curcumin (CUR). Results exhibited that a stable LRA-CS-CUR hydrogel was formed using LRA and CS in the ratio of 3:2 (w/w) at pH 4.0. Under this condition, the particle size, polydispersity index and zeta potential of the LRA-CS-CUR was 410.3 nm, 0.211 and +26.47 mV, respectively. The analysis of transmission electron microscopy, fourier transform infrared spectroscopy and X-ray diffractometer revealed that curcumin was successfully encapsulated in the LRA-CS hydrogel, giving a high encapsulation efficiency of 90.3 %. Moreover, this composite hydrogel could significantly improve the solubility and stability of curcumin. The release characteristics of encapsulated curcumin in simulated gastric fluid and simulated intestinal fluid were further investigated. Results exhibited that the LRA-CS hydrogel enabled curcumin to be stable in stomach and release in small intestine.

3.
Am J Clin Nutr ; 2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31927564

RESUMO

BACKGROUND: The association between circulating folate concentrations and risk of coronary artery disease (CAD) has been evaluated in Western populations with inconsistent results; however, the observational and causal associations in Chinese populations with relatively low folate concentrations remain unclear. OBJECTIVES: We aimed to examine the association of circulating folate concentrations with incident CAD in Chinese adults, and further evaluated the causal relation using Mendelian randomization (MR) analysis. METHODS: We measured baseline serum folate in 1605 incident CAD cases and 1605 age- and sex-matched controls nested within the Dongfeng-Tongji (DFTJ) cohort, which recruited 27,009 individuals with a mean age of 63.6 y in 2008-2010 and followed up until the end of 2013 (mean: 4.4 y). We quantified the observational association between folate and incident CAD using conditional logistic regression models. A 2-sample MR analysis was performed using summary statistics obtained for genetic variants identified from a genome-wide association study (GWAS) of circulating folate concentrations in participants of European ancestry (n = 37,341) and from the CardiogramplusC4D 1000 genomes-based GWAS meta-analysis (n = 184,305). We also conducted 1-sample MR among 1545 incident CAD cases and 1444 controls with genotyping data in the DFTJ cohort. RESULTS: In the DFTJ cohort, higher serum folate concentrations were associated with a lower risk of CAD: the OR (95% CI) across sex-specific quartiles of folate (from lowest to highest concentrations) was 1.00 (reference), 0.78 (0.63, 0.97), 0.77 (0.61, 0.97), and 0.75 (0.60, 0.95), respectively (P-trend = 0.01). In the MR analysis, the OR of CAD per SD increase in genetically predicted serum folate was 0.99 (0.82, 1.20) and 0.88 (0.59, 1.32) for European and Chinese populations, respectively. CONCLUSIONS: We found an inverse association between circulating folate concentrations and incident CAD among Chinese populations. However, we confirmed that there was no genetic evidence to support the causal relation in both European and Chinese populations.

5.
Mol Cell Biol ; 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31964753

RESUMO

Cdk2-dependent TopBP1/Treslin interaction is critical for DNA replication initiation. However, it remains unclear how this association is terminated after replication initiation is finished. Here we demonstrate that phosphorylation of TopBP1 by Akt coincides with Cyclin A activation during S and G2 phases, and switches TopBP1-interacting partner from Treslin to E2F1, which results in the termination of replication initiation. Premature activation of Akt in G1 phase causes early switch and inhibits DNA replication. TopBP1 is often overexpressed in cancer and can bypass the control by Cdk2 to interact with Treslin, leading to the enhanced DNA replication. Consistent with this notion, reducing the levels of TopBP1 in cancer cells restores the sensitivity to a Cdk2 inhibitor. Together, our study links Cdk2 and Akt pathways to the control of DNA replication through the regulation of TopBP1/Treslin interaction. These data also suggest an important role for TopBP1 in driving abnormal DNA replication in cancer.

6.
J Chin Med Assoc ; 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31972830

RESUMO

BACKGROUND: Microelectrode recording (MER) for target refinement is widely used in deep brain stimulator insertion for Parkinson disease. Signals may be influenced by anesthetics when patients receive general anesthesia (GA). This study determined the inhibitory concentration of propofol on MER signals when it was coadministered with dexmedetomidine. METHODS: Patients were anesthetized with dexmedetomidine (0.5 µg·kg loading, followed by infusion at 0.4 µg·kg·h) and propofol through target-controlled infusion for general anesthesia with tracheal intubation. The surgeon conducted the online scoring of the background signals, spiking frequency, amplitude, and pattern of single-unit activities by using a 0-10 verbal numerical rating scale (NRS; 0, maximal suppression; 10, minimal suppression), and responses were grouped into suppression (NRS ≤ 6) and nonsuppression (NRS > 6). The median inhibitory concentration (IC50) of propofol (as target effect-site concentrations: Ceprop) was determined using modified Dixon's up-and-down method (UDM). Probit regression analysis was further used to obtain the dose-response relationship, and IC05 and IC95 were calculated. RESULTS: Twenty-three adult patients participated in this study. Under the concomitant infusion of dexmedetomidine, the predicted IC50 value (95% confidence interval; CI) of Ceprop for neuronal suppression during MER was 1.29 (1.24-1.34) µg·mL as calculated using modified Dixon's UDM. Using probit analysis, the estimated IC05, IC50, and IC95 values (95% CIs) were 1.17 (0.87-1.23), 1.28 (1.21-1.34), and 1.40 (1.33-1.85) µg·mL, respectively. CONCLUSION: Our data provided reference values of propofol for dosage adjustment to avoid interference on MER under GA when anesthetics have to be continuously infused during recording.

7.
Dalton Trans ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31904068

RESUMO

Two novel thorium-based organic frameworks (Th-IHEP-5 and Th-IHEP-6) were assembled from a hexanuclear thorium cluster, porphyrin derivative ligand and linear carboxylic acid ligands via a mixed-ligand strategy. As a stable heterogeneous catalyst, Th-IHEP-5 exhibited high photocatalytic activity for the oxidation of 2-chloroethyl ethyl sulfide (CEES) and the fixation of CO2. The good catalytic effect is attributed to the large conjugated system of porphyrin and the photosensitizer enhancing effects of bipyridine.

8.
Med Sci Monit ; 25: 9346-9356, 2019 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-31812978

RESUMO

BACKGROUND Long-term exposure to hypertonic and high glucose in peritoneal dialysis fluid can result in peritoneal fibrosis. Spleen tyrosine kinase (SYK) has a role in inflammation and fibrosis. This study aimed to investigate the role of SYK in an in vivo rat model of peritoneal fibrosis and in rat peritoneal mesothelial cells (PMCs) in vitro and to investigate the underlying mechanisms. MATERIAL AND METHODS Sprague-Dawley rats (N=24) were randomized into the sham control group (N=6); the peritoneal fibrosis group (N=6) treated with intraperitoneal chlorhexidine digluconate; the SYK inhibitor group (N=6), treated with chlorhexidine digluconate and fostamatinib; and the TGF-ß inhibitor group (N=6), treated with chlorhexidine digluconate and LY2109761. The rat model underwent daily intraperitoneal injection with 0.5 ml of 0.1% chlorhexidine digluconate. Rat peritoneal mesothelial cells (PMCs) were cultured in vitro in high glucose. SYK expression was measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot. Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR measured inflammatory mediators. Transforming growth factor-ß1 (TGF-ß1) and Smad3 were detected by Western blot. Short hairpin RNA (shRNA) was used to target the SYK gene. RESULTS SYK was upregulated in the rat model of peritoneal fibrosis and was induced rat PMCs cultured in high glucose. Knockdown of SYK and inhibition of TGF-ß1 significantly reduced fibrosis and inflammation. Findings in the in vivo rat model confirmed that SYK mediated peritoneal fibrosis by regulating TGF-ß1/Smad3 signaling. CONCLUSIONS In a rat model and in rat PMCs, expression of SYK increased peritoneal fibrosis through activation of the TGF-ß1/Smad3 signaling pathway.

9.
Environ Int ; 135: 105388, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31837524

RESUMO

BACKGROUND: Residing in greener areas has several health benefits, but no study to date has examined the effects of greenness on metabolic syndrome (MetS). We aimed to assess associations between residential greenness and MetS prevalence in China, and to explore whether air pollution and physical activity mediated any observed associations. METHODS: We analyzed data from 15,477 adults who participated in the 33 Communities Chinese Health Study during 2009. We defined MetS according to standard guidelines for Chinese populations. Residential greenness was estimated using the Normalized Difference Vegetation Index (NDVI), the Soil Adjusted Vegetation Index (SAVI), and the Vegetation Continuous Field (VCF). We used generalized linear mixed models to assess the associations between greenness and MetS, and mediation analyses to explore potential mechanisms underlying the associations. RESULTS: Higher greenness levels were associated with lower odds of MetS [e.g., for every interquartile range increase of NDVI500-m, SAVI500-m, and VCF500-m, the adjusted odds ratio of MetS was 0.81 (95% confidence interval: 0.70-0.93), 0.80 (95% confidence interval: 0.69-0.93), and 0.91 (95% confidence interval: 0.83-1.00), respectively]. The direction and the magnitude of the associations persisted in several sensitivity analyses. Stratified analyses showed that age and household income modified the associations, with greater effect estimates observed in participants younger than 65 years old or those with higher household income. Particulate matter with an aerodynamic diameter ≤10 µm, nitrogen dioxide, and ozone mediated 2.1-20.3% of the associations between greenness and MetS; no evidence of mediation was observed for physical activity. CONCLUSIONS: Our findings suggest a beneficial association for residential greenness and MetS in Chinese urban dwellers, especially for participants younger than 65 years old and those with higher household income. Particulate matter with an aerodynamic diameter ≤10 µm, nitrogen dioxide and ozone, but not physical activity, may only partially mediate the association.

10.
Aging (Albany NY) ; 11(24): 12708-12732, 2019 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-31884419

RESUMO

Epidemiological studies have indicated that blood vitamin D levels are linked to cancer. Here we conducted a dose-response meta-analysis based on published observational studies to evaluate the association of vitamin D intake and blood vitamin D levels with breast cancer susceptibility. PubMed, EMBASE, and Web of Science databases were searched up to January 2019. The pooled odds ratio (OR) and 95% confidence intervals (CIs) were extracted to estimate the risk. We identified 70 relevant studies on blood vitamin D levels (50 studies) and vitamin D intake (20 studies), respectively. Linear and nonlinear trend analyses were performed and showed that an increase in blood vitamin D levels by 5 nmol/l was associated with a 6% decrease in breast cancer risk (OR = 0.94, 95% CI = 0.93-0.96). Similar results were obtained for premenopausal (OR = 0.96, 95% CI = 0.93-0.99) and postmenopausal women (OR = 0.96, 95% CI = 0.94-0.98). The pooled OR of breast cancer risk for a 400IU/day increase in vitamin D intake was 0.97 (95% CI = 0.92-1.02). In conclusion, we found that breast cancer risk was inversely related to blood vitamin D levels; however, no significant association was observed in vitamin D intake.

11.
Chin J Nat Med ; 17(12): 945-952, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31882050

RESUMO

Twenty-one lignans including three new ones (1, 2 and 13) were isolated from Justicia procumbens. The chemical structures of the new lignans were determined by spectroscopic means including 1D and 2D NMR analysis. These compounds were evaluated for their cytotoxic and anti-HIV activities. The new secoisolariciresinol dimethyl ether acetate (13) exhibited anti-HIV-1 activity with an IC50 value of 5.27 µmol·L-1 and a selective index (SI) value of 2.2. The known arylnaphthalene lignan procumbenoside A (3) and diphyllin (8) demonstrated inhibitory activity against HIV-1 with IC50 values of 4.95 (SI > 6.2) and 0.38 µmol·L-1 (SI = 5.3), respectively.

13.
Orthop Surg ; 11(6): 1187-1200, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31762184

RESUMO

OBJECTIVES: To determine the mechanisms of ubiquitination in postmenopausal osteoporosis and investigate the ubiquitinated spectrum of novel targets between healthy postmenopausal women and postmenopausal osteoporosis patients, we performed ubiquitylome analysis of the whole blood of postmenopausal women and postmenopausal osteoporosis patients. METHODS: To obtain a more comprehensive understanding of the postmenopausal osteoporosis mechanism, we performed a quantitative assessment of the ubiquitylome in whole blood from seven healthy postmenopausal women and seven postmenopausal osteoporosis patients using high-performance liquid chromatography fractionation, affinity enrichment, and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). To examine the ubiquitylome data, we performed enrichment analysis using an ubiquitylated amino acid motif, Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. RESULTS: Altogether, 133 ubiquitinated sites and 102 proteins were quantified. A difference of more than 1.2 times is considered significant upregulation and less than 0.83 significant downregulation; 32 ubiquitinated sites on 25 proteins were upregulated and 101 ubiquitinated sites on 77 proteins were downregulated. These quantified proteins, both with differently ubiquitinated sites, participated in various cellular processes, such as cellular processes, biological regulation processes, response to stimulus processes, single-organism and metabolic processes. Ubiquitin conjugating enzyme activity and ubiquitin-like protein conjugating enzyme activity were the most highly enriched in molecular function of upregulated sites with corresponding proteins, but they were not enriched in downregulated in sites with corresponding proteins. The KEGG pathways analysis of quantified proteins with differentiated ubiquitinated sites found 13 kinds of molecular interactions and functional pathways, such as glyoxylate and decarboxylate metabolism, dopaminergic synapse, ubiquitin-mediated proteolysis, salivary secretion, coagulation and complement cascades, Parkinson's disease, and hippo signaling pathway. In addition, hsa04120 ubiquitin-mediated proteolysis was the most highly enriched in proteins with upregulated sites, hsa04610 complement and coagulation cascades was the most highly enriched in proteins with downregulated ubiquitinated sites, and hsa04114 Oocyte meiosis was the most highly enriched among all differential proteins. CONCLUSION: Our study expands the understanding of the spectrum of novel targets that are differentially ubiquitinated in whole blood from healthy postmenopausal women and postmenopausal osteoporosis patients. The findings will contribute toward our understanding of the underlying proteostasis pathways in postmenopausal osteoporosis and the potential identification of diagnostic biomarkers in whole blood.

14.
Can J Hosp Pharm ; 72(5): 369-376, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31692636

RESUMO

Background: Patients receiving intermittent hemodialysis (IHD) are at high risk of acquiring gram-positive infections, which are often treated with IV vancomycin. Despite frequent use of vancomycin in the IHD setting, there is variability in dosing and monitoring practices among clinicians at the study institution. There is also a paucity of evidence regarding optimal vancomycin dosing to achieve target pre-IHD serum concentration. Objectives: The primary objective was to compare the percentage of treatment courses with a serum vancomycin concentration between 15 and 20 mg/L, measured before the third IHD session, before and after implementation of a weight threshold-based dosing protocol. The secondary objectives were to compare the percentage of treatment courses with a pre-third IHD vancomycin concentration between 10 and 22 mg/L and the number of vancomycin measurements per treatment day, before and after protocol implementation. Methods: This quasi-experimental, single-centre study included inpatients and outpatients who underwent IHD and received at least 2 IV doses of vancomycin, with vancomycin being measured in an appropriately drawn sample before the third IHD session. Before protocol implementation, vancomycin dosing was at the clinician's discretion (usual care). After protocol implementation, each patient received a loading dose of 1000, 1500, or 2000 mg and a maintenance dose of 500, 750, or 1000 mg, depending on body weight. Results: The percentage of treatment courses with a pre-third IHD vancomycin concentration between 15 and 20 mg/L was greater after implementation of the protocol than with usual care, but the difference was nonsignificant (44% [8/18] versus 20% [3/15], p = 0.27). However, the percentage of treatment courses with a pre-third IHD vancomycin concentration between 10 and 22 mg/L was significantly higher after protocol implementation (94% [17/18] versus 53% [8/15], p = 0.012). There was no difference in the median number of vancomycin measurements per treatment day before and after protocol implementation (0.133 versus 0.125, p = 0.99). Conclusions: At the study institution, the likelihood of achieving recommended vancomycin concentration increased (relative to previous practice) after implementation of a simplified vancomycin dosing protocol for patients undergoing IHD.

15.
Nat Commun ; 10(1): 5048, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31695122

RESUMO

Metal-organic frameworks (MOFs) have been recognized as compelling platforms for the development of miscellaneous applications because of their structural diversity and functional tunability. Here, we propose that the electrocatalytic properties could be well modified by incorporating missing linkers into the MOF. Theoretical calculations suggest the electronic structure of MOFs can be tuned by introducing missing linkers, which improves oxygen evolution reaction (OER) performance of the MOF. Inspired by these aspects, we introduced various missing linkers into a layered-pillared MOF Co2(OH)2(C8H4O4) (termed as CoBDC) to prepare missing-linker MOFs. Transmission electron microscope and synchrotron X-ray measurements confirmed that the missing linkers in the MOF could be introduced and well controlled by our strategy. The self-supported MOF nanoarrays with missing linkers of carboxyferrocene exhibit excellent OER performance with ultralow overpotential of 241 mV at 100 mA cm-2. This work opens a new prospect to develop efficient MOF-based electrocatalysts by introducing missing linkers.

16.
Cell ; 179(4): 829-845.e20, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31675496

RESUMO

The immune microenvironment of hepatocellular carcinoma (HCC) is poorly characterized. Combining two single-cell RNA sequencing technologies, we produced transcriptomes of CD45+ immune cells for HCC patients from five immune-relevant sites: tumor, adjacent liver, hepatic lymph node (LN), blood, and ascites. A cluster of LAMP3+ dendritic cells (DCs) appeared to be the mature form of conventional DCs and possessed the potential to migrate from tumors to LNs. LAMP3+ DCs also expressed diverse immune-relevant ligands and exhibited potential to regulate multiple subtypes of lymphocytes. Of the macrophages in tumors that exhibited distinct transcriptional states, tumor-associated macrophages (TAMs) were associated with poor prognosis, and we established the inflammatory role of SLC40A1 and GPNMB in these cells. Further, myeloid and lymphoid cells in ascites were predominantly linked to tumor and blood origins, respectively. The dynamic properties of diverse CD45+ cell types revealed by this study add new dimensions to the immune landscape of HCC.

17.
Med Sci Monit ; 25: 8326-8334, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31689287

RESUMO

BACKGROUND This study aimed to explore the transcript preference of PTK7 in adrenocortical cancer (ACC), the prognostic value, and the potential underlying genetic alterations. MATERIAL AND METHODS Data from the Cancer Genome Atlas-Adrenocortical Cancer (TCGA-ACC) and the Genotype-Tissue Expression (GTEx)-normal adrenal gland were used for analysis. RESULTS A non-canonical alternative transcript, ENST00000489707.5, which only encodes an extracellular immunoglobulin (Ig)-like domain and an intracellular kinase domain, is the dominant isoform of PTK7 in both ACC and normal adrenal gland. Its expression percentage was significantly higher in ACC than in normal adrenal gland. ACC tissues showed preferred expression of this transcript compared with other cancers with known PTK7 expression. Prognostic analysis showed that ENST00000489707.5 had independent prognostic value in progression-free survival (PFS) (HR: 1.227, 95%CI: 1.077-1.398, p=0.002) and disease-specific survival (DSS) (HR: 1.419, 95%CI: 1.154-1.745, p=0.001) after adjustment of other risk factors. cg20819617 methylation was negatively correlated with both PTK7 and ENST00000489707.5 expression. CONCLUSIONS ENST00000489707.5 is a preferred alternative splicing product of PTK7, with a significantly increased proportion in ACC compared with other cancers. Its expression shows potential prognostic value in terms of PFS and DSS in ACC patients. The methylation status of cg20819617 might play a critical role in modulating PTK7 transcription and ENST00000489707.5 expression.

18.
Chem Commun (Camb) ; 55(95): 14347-14350, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31720630

RESUMO

Herein, we developed a tri-functional MOF heterogeneous catalyst, MIL-IMAc-Br-, by a post-synthesis modification method for the first time. Due to the synergistic role of three functional sites, including Lewis acid sites, Brønsted acid sites and Br- anion sites, MIL-IMAc-Br- displayed an efficient catalytic performance for the cycloaddition reaction of CO2 and epoxides to form cyclic carbonates under mild and co-catalyst free conditions.

19.
Aging (Albany NY) ; 11(19): 8681-8700, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31613226

RESUMO

BACKGROUND: As an important downstream factor in the Hippo pathway, yes-associated protein 1(YAP1) has been detected to be elevated in various cancers and demonstrated to play a role in tumor development. Therefore, we evaluated by a meta-analysis the prognostic value of YAP1 in cancer patients. RESULTS: Sixty-eight studies with 8631 patients were identified. The results indicated that YAP1 overexpression predicted unfavorable patient prognosis in studies with overall survival (OS) (HR=1.76, 95%CI: 1.50-2.06, p<0.001) and disease-free survival (DFS) (HR=1.39, 95%CI: 1.22-1.59, p<0.001), as well as in studies with recurrence-free survival (RFS) (HR=2.38, 95%CI: 1.73-3.27, p<0.001), and disease-specific survival (DSS) (HR=2.04, 95%CI: 1.55-2.70, p<0.001). Meanwhile, YAP1 overexpression was also observed to be significantly associated with worse OS in GEPIA (HR=1.2, p<0.001). CONCLUSIONS: Overexpression of YAP1 showed great association with poorer prognosis in patients with various cancers, particularly liver cancer. Therefore, YAP1 might be an important prognostic marker and a novel target of cancer therapy. METHODS: We searched for potential publications in several online databases and retrieved relevant data. Overall and subgroup analyses were performed. Begg's and Egger's tests were used to assess publication bias. Online dataset GEPIA was used to generate the survival curves and verify the prognostic role of YAP1 in patients with tumors.

20.
Orthop Surg ; 11(5): 784-793, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31663278

RESUMO

OBJECTIVE: For the purpose of providing evidence for the treatment of osteoporosis and osteopenia, this study retrospectively identified succinylation-modified sites and proteins in postmenopausal women, and bioinformatics analysis were performed. METHODS: From January 2016 to June 2018, a total of 30 postmenopausal women aged from 55 to 70 years old were assigned to three groups: 10 cases with osteoporosis; 10 cases with osteopenia; and 10 cases with normal bone mass. Subsequently, the serum samples were collected from all cases for succinyl-proteome. Measures comprised label-free quantitative analysis, succinylation enrichment techniques, the liquid chromatograph-mass spectrometer/mass spectrometer (LC-MS/MS) methods, and bioinformatics. RESULTS: A total of 113 succinylation sites on 35 proteins were identified based on quantitative information. The variation of the different multiple folds were more than 1.2 times as a significant increase for up-regulated and less than 1/1.2 times as a significant decrease for down-regulated. Among the quantified succinylation sites, 66 were up-regulated and 11 down-regulated in the Osteopenia/Normal comparison group, 24 were up-regulated and 44 down-regulated in the Osteoporosis/Osteopenia comparison group, 45 were up-regulated and 32 down-regulated in the Osteoporosis/Normal comparison group. Among the quantified succinylation proteins, 24 were up-regulated and 7 down-regulated in the Osteopenia/Normal comparison group, 15 were up-regulated and 20 down-regulated in the Osteoporosis/Osteopenia comparison group, 20 were up-regulated and 17 down-regulated in the Osteoporosis/Normal comparison group. The percentage of proteins differed in immune response, signaling pathway, proteolysis, lymphocyte, leukocyte, and cell activation. Four differentially expressed proteins (apolipoprotein A-I, apolipoprotein A-II, hemoglobin subunit alpha, and haptoglobin) contained quantitative information; they were mediated with receptors, factors, mechanisms, that related to bone metabolism. Hemoglobin subunit alpha was screened for diagnosis of osteopenia. CONCLUSIONS: The succinyl-proteome experimental data indicated that apolipoprotein A-I, apolipoprotein A-II, hemoglobin subunit alpha, and haptoglobin were valuable for diagnosis and treatment in postmenopausal women with osteoporosis and osteopenia.

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