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1.
Arch Biochem Biophys ; : 108352, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32240637

RESUMO

Rab1A, a member of the Ras-like protein in rat brain (Rab) family, acts as an oncogene in a variety of malignant tumors. Previous studies reported that Rab1A was highly expressed in GC tissues. However, the function and molecular mechanism of Rab1A in gastric cancer (GC) development remain far from being addressed. Rab1A mRNA and protein levels were detected by qRT-PCR and western blot, respectively. Cell proliferation was evaluated by CCK-8 and BrdU incorporation assays. Apoptosis was estimated by flow cytometry analysis and western blot analysis of B cell lymphoma 2 (Bcl-2), myeloid cell leukemia 1 (Mcl-1), Bcl-2 associated X (Bax), and Bcl-2 homologous antagonist/killer (Bak) expression. Alteration of the mammalian target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase (p70S6K) signaling pathway was detected by western blot. We found that Rab1A expression at both mRNA and protein was upregulated in GC cells. Rab1A knockdown significantly inhibited cell proliferation and induced apoptosis in GC cells. Rab1A overexpression promoted proliferation, inhibited cisplatin-induced apoptosis, and increased xenograft growth. In addition, we found that Rab1A knockdown suppressed the mTOR/p70S6K pathway in GC cells. Moreover, activation of mTOR/p70S6K pathway by MHY1485 abolished the effects of Rab1A knockdown on cell proliferation and apoptosis. In conclusion, Rab1A knockdown repressed proliferation and promoted apoptosis in GC cells by inhibition of the mTOR/p70S6K pathway.

2.
DNA Cell Biol ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32045269

RESUMO

Cervical cancer (CC) is a malignant tumor that could seriously endanger women's life and health, of which cervical squamous cell carcinoma (CESC) accounts for more than 80%. High-risk human papillomavirus (HR-HPV) infection is the primary cause of CC. The 5-year survival rate is low due to poor prognosis. We need to explore the pathogenesis of CC and seek effective biomarkers to improve prognosis. The purpose of this research is to construct an HR-HPV-related long non-coding RNA (lncRNA) signature for predicting the survival and finding the biomarkers related to CC prognosis. First, we downloaded the CESC data from The Cancer Genome Atlas (TCGA) database to find HR-HPV-related lncRNAs in CC. Then, the differentially expressed lncRNAs were analyzed by univariate and multivariate Cox regression. Six lncRNAs were found to be associated with the prognosis and can be used as independent prognostic factors. Next, based on these prognostic genes, we established a risk score model, which showed that patients with higher score had poorer prognosis and higher mortality. Moreover, the Kaplan-Meier curve of the model indicated that the model was statistically significant (p < 0.05). The survival-receiver operating characteristic curve showed that the model could also predict the survival of CC patients (the area under the curve, AUC = 0.65). More importantly, nomogram was drawn with clinical features and risk score, which verified the above conclusion, and its calibration curve and c-index index fully demonstrated that the prediction model could predict the progress of CC. We also validated the risk score model in head and neck cancer, and the results indicated that the model had obvious prognostic ability. Finally, we analyzed the correlation between clinical features and survival, and found that neoplasm cancer (p < 0.000) and risk score (p < 0.000) were independent prognostic factors for CC. In conclusion, the study established HR-HPV-related lncRNA signature, which provided a reliable prognostic tool, and was of great significance for finding the biomarkers related to HR-HPV infection in CC.

3.
Theranostics ; 10(4): 1833-1848, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32042339

RESUMO

Purpose: To determine the role of UCH-L1 in regulating ERα expression, and to evaluate whether therapeutic targeting of UCH-L1 can enhance the efficacy of anti-estrogen therapy against breast cancer with loss or reduction of ERα. Methods: Expressions of UCH-L1 and ERα were examined in breast cancer cells and patient specimens. The associations between UCH-L1 and ERα, therapeutic response and prognosis in breast cancer patients were analyzed using multiple databases. The molecular pathways by which UCH-L1 regulates ERα were analyzed using immunoblotting, qRT-PCR, immunoprecipitation, ubiquitination, luciferase and ChIP assays. The effects of UCH-L1 inhibition on the efficacy of tamoxifen in ERα (-) breast cancer cells were tested both in vivo and in vitro. Results: UCH-L1 expression was conversely correlated with ERα status in breast cancer, and the negative regulatory effect of UCH-L1 on ERα was mediated by the deubiquitinase-mediated stability of EGFR, which suppresses ERα transcription. High expression of UCH-L1 was associated with poor therapeutic response and prognosis in patients with breast cancer. Up-regulation of ERα caused by UCH-L1 inhibition could significantly enhance the efficacy of tamoxifen and fulvestrant in ERα (-) breast cancer both in vivo and in vitro. Conclusions: Our results reveal an important role of UCH-L1 in modulating ERα status and demonstrate the involvement of UCH-L1-EGFR signaling pathway, suggesting that UCH-L1 may serve as a novel adjuvant target for treatment of hormone therapy-insensitive breast cancers. Targeting UCH-L1 to sensitize ER negative breast cancer to anti-estrogen therapy might represent a new therapeutic strategy that warrants further exploration.

4.
J Neurosci Res ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32026519

RESUMO

Hormones such as estrogen, progesterone, and aldosterone all demonstrate vital roles in sustaining auditory function through either the maintenance of cochlear neurons, up/down regulation of critical molecules (i.e., IGF-1, BDNF, etc.), or generation of the endocochlear potential. With disease and/or age, hormone expression begins to decline drastically, which ultimately affects cochlear structures and the integrity of cochlear cells. The following review explores the latest findings as well as realistic outcomes for hormone therapy treatment in the auditory system. This information could serve as a potential guide for patients considering hormone therapy as a medicinal choice to alleviate the signs of onset of presbycusis-age-related hearing loss. Additional scientific investigations could also be carried out to further enhance recent findings.

5.
Dalton Trans ; 49(5): 1674-1680, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-31951247

RESUMO

Elucidations on the structure-activity correlations of non-Pt coordination polymer (CP)-based photocatalysts are highly significant for both the enhancement in catalytic activity and large-scale industrial applications of sustainable hydrogen from water splitting. Herein, three isostructural [Cu(HL)2(R-BDC)]n (denoted as Cu-CP-R, HL = 4'-(4-hydroxyphenyl)-4,2':6',4''-terpyridine, R-BDC = 2-R-1,4-benzenedicarboxylate, R = NO2, OH and Br) CPs were solvothermally synthesized by varying the substituents attached to benzenedicarboxylate, which together with two previously reported analogues (R = NH2 and H) were used as photocatalysts to systematically explore the substitution effect on the hydrogen evolution activity. These five CPs feature isomorphic layered motifs with axially elongated CuII octahedra extended alternately by ditopic HL and R-BDC2- connectors, in which R behaves structurally as a non-coordinate group. The hydrogen production rate over the Cu-CP-R photocatalysts increased from 0.21 to 2.34 mmol g-1 h-1, which followed the order of -NH2 > -NO2 > -H > -OH > -Br. Furthermore, the combined experimental and theoretical investigations reveal that the free R moiety significantly dominates the photocatalytic activity by shifting the d states of the CuII ion towards the Fermi level, controlling the potential of the conduction band and quickening the charge transfer ability. These important findings can provide informative hints for the design of high-performance, earth-abundant non-noble metal CP-based semi-conductive photocatalysts.

6.
Neurochem Int ; 133: 104610, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31778727

RESUMO

Our previous data indicated that tanshinone IIA (tan IIA) improves learning and memory in a mouse model of Alzheimer's disease (AD) induced by streptozotocin via restoring cholinergic function, attenuating oxidative stress and blocking p38 MAPK signal pathway activation. This study aims to estimate whether tan IIA inhibits endoplasmic reticulum (ER) stress-induced apoptosis to prevent cognitive decline in APP/PS1 transgenic mice. Tan IIA (10 mg/kg and 30 mg/kg) was intraperitoneally administered to the six-month-old APP/PS1 mice for 30 consecutive days. ß-amyloid (Aß) plaques were measured by immunohistochemisty and Thioflavin S staining, apoptotic cells were observed by TUNEL, ER stress markers and apoptosis signaling proteins were investigated by western blotting and RT-PCR. Our results showed that tan IIA significantly ameliorates cognitive deficits and improves spatial learning ability of APP/PS1 mice in the nest-building test, novel object recognition test and Morris water maze test. Furthermore, tan IIA significantly reduced the deposition of Aß plaques and neuronal apoptosis, and markedly prevented abnormal expression of glucose regulated protein 78 (GRP78), initiation factor 2α (eIF2α), inositol-requiring enzyme 1α (IRE1α), activating transcription factor 6 (ATF6), as well as suppressed the activation of C/EBP homologous protein (CHOP) and c-Jun N-terminal kinase (JNK) pathways in the parietal cortex and hippocampus. Moreover, tan IIA induced an up-regulation of the Bcl-2/Bax ratio and down-regulation of caspase-3 protein activity. Taken together, the above findings indicated that tan IIA improves learning and memory through attenuating Aß plaques deposition and inhibiting ER stress-induced apoptosis. These results suggested that tan IIA might become a promising therapeutic candidate drug against AD.

7.
Chem Sci ; 10(34): 7982-7987, 2019 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-31673320

RESUMO

Directly introducing a beneficial functional group into biomolecules under mild, clean and easy-to-handle conditions is of great importance in the field of chemical biology and pharmacology. Herein, we described an electrochemical strategy to perform the bioconjugation of tyrosine residues with phenothiazine derivatives in a rapid and simple manner. In this electrochemical system, various polypeptides and proteins were successfully labelled with excellent site- and chemo-selectivity, and metals, oxidants or additives were also avoided.

8.
Int J Biol Markers ; 34(4): 398-405, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31674884

RESUMO

OBJECTIVE: To investigate the role of programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), and P16 in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: A total of 95 paraffin-embedded samples of tumorous tissue of HNSCC were collected. Expression levels of PD-1, PD-L1, and P16 were determined by immunohistochemistry. RESULTS: A significantly higher proportion of PD-1 among patients infected with the human papillomavirus was found. PD-L1 expression is closely associated with the primary site of the tumor, postoperative recurrence, survival, PD-1 expression and P16 expression. Univariable analysis indicated that T stage, N stage, tumor node metastasis stage, tumor differentiation, and PD-L1 expression were all shown to be prognostic variables for overall survival in patients with HNSCC. In the multivariate analysis, only N stage (P = 0.010) and PD-L1 expression (P = 0.001) were found to be independent prognostic variables for overall survival. In addition, for disease recurrence, multivariate analysis showed that only PD-L1 expression was the associated independent risk factor. For the patients with negative PD-L1 expression, Kaplan-Meier analysis revealed that they had significantly worse outcomes in terms of overall survival (P = 0.001). Similarly, compared with the patients with positive PD-L1 expression, those with negative PD-L1 expression had a higher probability of recurrence (P = 0.026). CONCLUSIONS: The expression of PD-L1, PD-1, and P16 in HNSCC is significantly correlated. Human papillomavirus infection (P16 positive) is negatively related to postoperative recurrence. HNSCC patients with positive PD-L1/PD-1 expression tend to have better overall survival outcomes and lower probability of recurrence, providing more evidence for the PD-l-targeted immunotherapy of HNSCC.

9.
Endocr Res ; : 1-8, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31773995

RESUMO

Background: This study aimed to evaluate the association between thyroid parameters and diabetic retinopathy (DR) in euthyroid patients with type 2 diabetes mellitus (T2DM).Materials and Methods: In this cross-sectional study, a total of 911 euthyroid patients with T2DM (539 men and 372 women; mean age, 60.81 ± 12.93 years) were enrolled. Clinical factors were assessed and free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) levels were measured. DR was diagnosed using fundus fluorescein angiography.Results: Compared with patients without DR (n = 718), patients with DR (n = 193) exhibited lower FT3 (4.40 ± 0.58 vs. 4.50 ± 0.51 pmol/L; P = .019) and FT4 (14.86 ± 2.09 vs. 15.91 ± 2.18 pmol/L; P < .001) and higher TSH (1.86 [1.22, 2.66] vs. 1.58 [1.14, 2.34] µIU/mL; P = .015) levels. After adjustment for potential DR risk factors, patients in the highest tertile of plasma FT4 levels had a 0.332-fold likelihood of developing DR compared with those in the lowest tertile of plasma FT4 levels (Ptrend < 0.001). The prevalence of DR showed a significantly decreasing trend across the three tertiles based on FT4 levels (31.35%, 19.08% and 13.16%; Ptrend < 0.001). Similar results were obtained for the presence of proliferative DR.Conclusion: These findings suggest that low-normal FT4 levels are associated with the prevalence of DR in euthyroid patients with T2DM.

10.
Exp Ther Med ; 18(4): 3090-3094, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31555389

RESUMO

One-third of the children who suffer from first-time wheezing are estimated to experience recurrences; however, no standard therapeutic strategy with which to prevent these recurrences currently exists. A few studies have compared the three drugs commonly used for the treatment of persistent asthma in children to identify the most effective one for preventing recurrent wheezing. In this study, in an aim to determine the most effective of these drugs, we recruited patients <5 years of age with recurrent wheezing at our hospital, and assigned them randomly to either the oral montelukast [leukotriene receptor antagonist (LTRA)], the inhaled fluticasone propionate (FP), or the inhaled budesonide suspension (BUD) groups for 12-week treatments. We then determined the treatment efficacy (symptomatic improvement) by recording the number of wheezing episodes and emergency visits, the daily treatment cost, the mean accumulated down time and the patient compliance; we then compared the results among the groups. All treatments were found to be equally effective. The daily cost of inhaled FP was lower than that of oral LTRA and inhaled BUD (P<0.00001). The difference in the mean accumulated down time between these groups was not significant (P=0.132). The adherence (patient compliance) to LTRA was significantly higher than the adherence to inhaled corticosteroids (ICS) (P<0.017). On the whole, the findings of this study indicated that all three treatments prevented recurrent wheezing in our pediatric population. FP was found to be more convenient, to require fewer doses, and that it could be easily adjusted. Patient adherence/compliance to treatment was significantly better with LTRA than with ICS.

11.
Dig Dis Sci ; 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31559550

RESUMO

BACKGROUND: Notoginsenoside R1 (NG-R1) is the predominant active ingredient and a novel triterpene saponin compound extracted from the roots of Panax notoginseng. To date, to the best of our knowledge, there are no previous studies concerning the effect of NG-R1 on hepatocellular carcinoma (HCC). AIMS: To investigate the effects of NG-R1 on HCC cell growth, apoptosis, and invasion and to explore the underlying mechanisms. METHODS: Cell viability and lactate dehydrogenase (LDH) release were evaluated by cell counting kit-8 and LDH assay, respectively. Apoptosis was assessed using flow cytometry analysis and caspase-3/7 activity assay. Cell invasion was detected by Transwell invasion assay and western blot analysis of matrix metallopeptidase (MMP)-2 and MMP-9. The effects of NG-R1 on miR-21 expression and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway were examined by qRT-PCR and western blot, respectively. RESULTS: NG-R1 inhibited the viability, increased LDH release and caspase-3/7 activity, induced apoptosis, and suppressed invasion in HCC cells. NG-R1 reduced miR-21 expression in HCC cells. miR-21 overexpression significantly attenuated the effects of NG-R1 on the viability, LDH release, apoptosis, caspase-3/7 activity, and invasion of HCC cells. We further demonstrated that NG-R1 inhibited the activation of the PI3K/Akt pathway in HCC cells, which was abolished by miR-21 overexpression. CONCLUSIONS: NG-R1 exerted anti-hepatoma activity through inactivation of the PI3K/Akt pathway by downregulating miR-21, contributing to further understanding of the anti-tumor activities of NG-R1 in HCC.

12.
Cell Rep ; 28(10): 2517-2526.e5, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31484065

RESUMO

The endoplasmic reticulum (ER) membrane protein complex (EMC) is a key contributor to biogenesis and membrane integration of transmembrane proteins, but our understanding of its mechanisms and the range of EMC-dependent proteins remains incomplete. Here, we carried out an unbiased mass spectrometry (MS)-based quantitative proteomic analysis comparing membrane proteins in EMC-deficient cells to wild-type (WT) cells and identified 36 EMC-dependent membrane proteins and 171 EMC-independent membrane proteins. Of these, six EMC-dependent and six EMC-independent proteins were further independently validated. We found that a common feature among EMC-dependent proteins is that they contain transmembrane domains (TMDs) with polar and/or charged residues. Mutagenesis studies demonstrate that EMC dependency can be converted in cells by removing or introducing polar and/or charged residues within TMDs. Our studies expand the list of validated EMC-dependent and EMC-independent proteins and suggest that the EMC is involved in handling TMDs with residues challenging for membrane integration.

13.
J Acoust Soc Am ; 145(6): EL521, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31255155

RESUMO

Audio tagging aims to infer descriptive labels from audio clips and it is challenging due to the limited size of data and noisy labels. The solution to the tagging task is described in this paper. The main contributions include the following: an ensemble learning framework is applied to ensemble statistical features and the outputs from the deep classifiers, with the goal to utilize complementary information. Moreover, a sample re-weight strategy is employed to address the noisy label problem within the framework. The approach achieves a mean average precision of 0.958, outperforming the baseline system with a large margin.

14.
Photochem Photobiol Sci ; 18(7): 1823-1832, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31165126

RESUMO

The fluorescence (FL) of calcium-discharged photoprotein (CaDP) can be altered by easily mutating CaDP without modifying coelenteramide (CLM), which is the decarboxylation product of coelenterazine in calcium-regulated photoprotein. The His22-Phe88-Trp92 triad (the ordering numbers of three amino acids are sorted by a crystal structure (PDB: 2F8P) of calcium-discharged obelin, i.e., CaDP-obelin) is closely related to CaDP-obelin FL, since it exists in close proximity to the 5-p-hydroxyphenyl of CLM. Therefore, it is important to thoroughly investigate how the mutations of this triad affect the emission color of CaDP-obelin FL. In this study, by mutating wild-type CaDP-obelin (WT) at the His22-Phe88-Trp92 triad, we theoretically constructed its nine mutants of separable FL colors. Through combined quantum mechanics and molecular mechanics (QM/MM) calculations and molecular dynamics (MD) simulations, the influence of the mutations of this triad on the CaDP-obelin FL was analyzed considering the H-bond effect and the charge effect. This study demonstrated that the mutations at the His22-Phe88-Trp92 triad redistribute the charges on the D-π-A molecule, CLM, change the charge transfer from the D to the (π + A) moiety, and thereby alter the FL emission. Appending more negative charges on the phenolate moiety of CLM benefits the FL redshift.


Assuntos
Cálcio/química , Proteínas Luminescentes/química , Simulação de Dinâmica Molecular , Teoria Quântica , Animais , Ligações de Hidrogênio , Hidrozoários/metabolismo , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Mutagênese Sítio-Dirigida , Conformação Proteica , Espectrometria de Fluorescência
15.
Zygote ; 27(3): 166-172, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31171048

RESUMO

SummaryRabbits play an important role in people's lives due to their high nutritional value and high-quality hair that can be used as raw material for textiles. Furthermore, rabbits are an important animal model for human disease, as genome-edited animals are particularly valuable for studying gene functions and pathogenesis. Somatic cell nuclear transfer (SCNT) is an important technique for producing genome-edited animals and it has great value in saving endangered species and in clone stem cell therapy. However, the low efficiency of SCNT limits its application, with the selection of suitable rabbit oocytes being crucial to its success. In the present study, we collected oocytes from ovarian follicles and stained them with 26 µM brilliant cresyl blue (BCB). We then matured the oocytes in vitro and used them for SCNT. Comparison of the BCB-positive oocytes with BCB-negative oocytes and the control group showed that the BCB-positive group had a significantly higher maturation rate (81.4% vs. 48.9% and 65.3% for the negative and control groups, respectively), cleavage rate (86.6% vs. 67.9% and 77.9%), blastocyst rate (30.5% vs. 12.8% and 19.6%), total number of blastocysts (90±7.5 vs. 65.3±6.3 and 67.5±5.7), and inner cell mass (ICM)/ trophectoderm (TE) index (42.3±4.2 vs. 30.2±2.1 and 33.9±5.1) (P<0.05). The BCB-positive group had a significantly lower apoptosis index (2.1±0.6 vs. 8.2±0.9 and 6.7±1.1 for the negative and control groups, respectively) (P<0.05). These findings demonstrate that BCB-positive oocytes have a higher maturation ability and developmental competence in vitro, indicating that BCB staining is a reliable method for selecting oocytes to enhance the efficiency of SCNT.


Assuntos
Blastocisto/citologia , Fertilização In Vitro/métodos , Oócitos/citologia , Oxazinas/química , Coloração e Rotulagem/métodos , Animais , Células Cultivadas , Clonagem de Organismos , Técnicas de Cultura Embrionária , Desenvolvimento Embrionário , Feminino , Técnicas de Maturação in Vitro de Oócitos , Técnicas de Transferência Nuclear , Oócitos/química , Folículo Ovariano/citologia , Coelhos
16.
Arterioscler Thromb Vasc Biol ; 39(6): 1182-1190, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31070471

RESUMO

Objective- Inflammation is a causal risk factor for cardiovascular disease (CVD). sPLA2-IIA (group IIA secretory phospholipase A2) plays an integral role in regulating vascular inflammation. Although studies investigated sPLA2-IIA in secondary prevention, we prospectively evaluated sPLA2-IIA mass and genetic variants with CVD events in a primary prevention population with chronic inflammation. Approach and Results- The JUPITER trial (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin) randomized participants with LDL (low-density lipoprotein) <130 mg/dL and hsCRP (high-sensitivity C-reactive protein) ≥2 mg/L to high-intensity rosuvastatin versus placebo. Baseline and 1-year plasma sPLA2-IIA mass was measured (N=11 269 baseline; N=9620 1 year). We also identified genetic variants influencing sPLA2-IIA using genome-wide association and examined them with CVD. Three hundred thirteen incident CVD events occurred during follow-up. Baseline sPLA2-IIA mass (median, 25th-75th percentile: 3.81, 2.49-6.03 ng/mL) was associated with increased risk of CVD: risk factor-adjusted hazard ratio (95% CI; P) per SD increment: 1.22 (1.08-1.38; P=0.002). This remained significant (1.18; 1.04-1.35; P=0.01) after incrementally adjusting for hsCRP. Similar estimates were observed in rosuvastatin and placebo groups ( P treatment interaction>0.05). The rs11573156C variant in PLA2G2A (encoding sPLA2-IIA) had the strongest effect on sPLA2-II: median (25th-75th percentile, ng/mL) for CC and GG genotypes: 2.79 (1.97-4.01) and 7.38 (5.38-10.19), respectively; and had nonsignificant trend for higher CVD risk (hazard ratio, 1.11; 95% CI, 0.89-1.38; P=0.34). Conclusions- In the JUPITER population recruited on chronic inflammation, sPLA2-IIA mass was associated with CVD risk relating to vascular inflammation not fully reflected by hsCRP. Additional studies, including larger functional genetic and clinical studies, are needed to determine whether sPLA2-IIA may be a potential pharmacological target for primary prevention of CVD. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT00239681.


Assuntos
Doenças Cardiovasculares/enzimologia , Dislipidemias/enzimologia , Fosfolipases A2 do Grupo II/sangue , Inflamação/enzimologia , Idoso , Anti-Inflamatórios/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/prevenção & controle , Método Duplo-Cego , Dislipidemias/tratamento farmacológico , Dislipidemias/epidemiologia , Dislipidemias/genética , Feminino , Predisposição Genética para Doença , Fosfolipases A2 do Grupo II/genética , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Incidência , Inflamação/tratamento farmacológico , Inflamação/epidemiologia , Inflamação/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Prevenção Primária , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Rosuvastatina Cálcica/uso terapêutico , Fatores de Tempo , Resultado do Tratamento
17.
J Obstet Gynaecol Res ; 45(7): 1277-1285, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31016847

RESUMO

AIM: To study the molecular mechanism of G protein-coupled receptor 30-epidermal growth factor receptor (GPR30-EGFR) signaling pathway on the proliferation of leiomyoma cells exposed with bisphenol A. METHODS: Primary cultures and subcultures of human uterine leiomyoma (UL) cells. The expressions of messenger RNA and proteins of GPR30 and EGFR in 15 leiomyoma tissue specimens and all groups were detected by real-time quantitative polymerase chain reaction assay and Western blot assay. The protein of mitogen-activated protein kinases (MAPK)/extracellular signal-regulated kinases (ERK)/c-fos signaling pathway members was detected by Western blot assay. RESULTS: Bisphenol A promoted the growth of UL cells and the expressions of GPR30, EGFR, c-fos and p-ERK1/2. CONCLUSION: Bisphenol A was found to be a promoter specifically to proliferate the human UL cells by activating the transcription and translation of GPR30-EGFR and MAPK/ERK/c-fos signaling pathway members.


Assuntos
Compostos Benzidrílicos/farmacologia , Estrogênios não Esteroides/farmacologia , Leiomioma/tratamento farmacológico , Fenóis/farmacologia , Receptores Estrogênicos/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Transdução de Sinais/efeitos dos fármacos , Técnicas de Cultura de Células , Proliferação de Células/efeitos dos fármacos , Receptores ErbB/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Humanos , Leiomioma/metabolismo , Sistema de Sinalização das MAP Quinases , RNA Mensageiro/metabolismo
18.
Endocr Connect ; 8(4): 309-317, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30822273

RESUMO

Objective: Thyroid nodules are usually accompanied by elevated thyroglobulin (Tg) level and autoimmune thyroid diseases (AITDs). However, the relationship between Tg and AITDs is not fully understood. Dysfunction of regulatory T cells (Tregs) plays an important role in the development of AITDs. We aimed to evaluate the effects of Tg on the function of Tregs in patients with thyroid nodules. Methods: Tg levels and the functions of Tregs in peripheral blood and thyroid tissues of patients with thyroid nodules from Nanjing First Hospital were evaluated. The effects of Tg on the function of Tregs from healthy donors were also assessed in vitro. The function of Tregs was defined as an inhibitory effect of Tregs on the effector T cell (CD4+ CD25- T cell) proliferation rate. Results: The level of Tg in peripheral blood correlated negatively with the inhibitory function of Tregs (R = 0.398, P = 0.03), and Tregs function declined significantly in the high Tg group (Tg >77 µg/L) compared with the normal Tg group (11.4 ± 3.9% vs 27.5 ± 3.5%, P < 0.05). Compared with peripheral blood, the function of Tregs in thyroid declined significantly (P < 0.01), but the proportion of FOXP3+ Tregs in thyroid increased (P < 0.01). High concentration of Tg (100 µg/mL) inhibited the function of Tregs and downregulated FOXP3, TGF-ß and IL-10 mRNA expression in Tregs in vitro. Conclusions: Elevated Tg level could impair the function of Tregs, which might increase the risk of AITDs in patient with thyroid nodules.

19.
Diabetes Res Clin Pract ; 150: 194-201, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30904742

RESUMO

AIMS: This study aimed to determine the association between lipoprotein-associated phospholipase A2 (Lp-PLA2), a marker for inflammation in the vessel wall and independently associated with atherosclerosis, and the incidence of diabetic kidney disease (DKD) in patients with type 2 diabetes (T2D). METHODS: A total of 1452 patients were enrolled in this retrospective cross­sectional study. We recruited patients with T2D who were tested for glycated hemoglobin, fasting and 2 h post-meal serum C-peptide, blood lipid profile, 24 h urine albumin excretion rate (UAER), blood creatine, blood albumin, uric acid, and Lp-PLA2. RESULTS: Among the patients with T2D, 40.3% were diagnosed with DKD and the correlation between DKD and Lp-PLA2 was the most significant one compared to other diabetic complications (odds ratio = 1.651, P < 0.001). Plasma Lp-PLA2 level in patients with DKD was significantly higher and increased Lp-PLA2 level was independently associated with the incidence of DKD after adjustment for age, gender, duration of diabetes, glycated hemoglobin, body mass index, blood lipids, blood pressure, presence of coronary heart disease and carotid plaque, and use of statins (odds ratio = 1.545, P = 0.013). Lp-PLA2 was found to be positively correlated with UAER (r = 0.123, P < 0.001) and negatively correlated with estimated glomerular filtration rate (eGFR) (r = -0.71, P = 0.009). CONCLUSIONS: Increased plasma level of Lp-PLA2 is associated with incidence and development of DKD in patients with T2D. Lp-PLA2 should be considered as a biomarker for early detection and follow-up of DKD. TRIAL REGISTRATION: clinicaltrials.gov, No. NCT03362112, Registered 30 November 2017, retrospectively registered.


Assuntos
1-Alquil-2-acetilglicerofosfocolina Esterase/sangue , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/diagnóstico , Lipídeos/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/enzimologia , Nefropatias Diabéticas/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
20.
Aging Cell ; 18(3): e12939, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30845368

RESUMO

Estradiol (E) is a multitasking hormone that plays a prominent role in the reproductive system, and also contributes to physiological and growth mechanisms throughout the body. Frisina and colleagues have previously demonstrated the beneficial effects of this hormone, with E-treated subjects maintaining low auditory brainstem response (ABR) thresholds relative to control subjects (Proceedings of the National Academy of Sciences of the United States of America, 2006;103:14246; Hearing Research, 2009;252:29). In the present study, we evaluated the functionality of the peripheral and central auditory systems in female CBA/CaJ middle-aged mice during and after long-term hormone replacement therapy (HRT) via electrophysiological and molecular techniques. Surprisingly, there are very few investigations about the side effects of HRT in the auditory system after it has been discontinued. Our results show that the long-term effects of HRT are permanent on ABR thresholds and ABR gap-in-noise (GIN) amplitude levels. E-treated animals had lower thresholds and higher amplitude values compared to other hormone treatment subject groups. Interestingly, progesterone (P)-treated animals had ABR thresholds that increased but amplitude levels that remained relatively the same throughout treatment. These results were consistent with qPCR experiments that displayed high levels of IGF-1R in the stria vascularis (SV) of both E and P animal groups compared to combination treatment (E + P) animals. IGF-1R plays a vital role in mediating anti-apoptotic responses via the PI3K/AKT pathway. Overall, our findings gain insights into the neuro-protective properties of E hormone treatments as well as expand the scientific knowledge base to help women decide whether HRT is the right choice for them.

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