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1.
Chemosphere ; 238: 124602, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31545211

RESUMO

Polybrominated diphenyl ethers (PBDEs) have been known to exhibit neurotoxicity in rats; however, the underlying mechanism remains unknown and there is no available intervention. In this study, we aimed to investigate the role of oxidative and nitrosative stress in the neurotoxicity in the cerebral cortex and primary neurons in rats following the BDE-153 treatment. Compared to the untreated group, BDE-153 treatment significantly induced the neurotoxic effects in rats, as manifested by the increased lactate dehydrogenase (LDH) activities and cell apoptosis rates, and the decreased neurotrophic factor contents and cholinergic enzyme activities in rats' cerebral cortices and primary neurons. When compared to the untreated group, the oxidative and nitrosative stress had occurred in the cerebral cortex or primary neurons in rats following the BDE-153 treatment, as manifested by the increments in levels of reactive oxygenspecies (ROS), malondialdehyde (MDA), nitric oxide (NO), and neuronal nitric oxide synthase (nNOS) mRNA and protein expressions, along with the decline in levels of superoxide dismutase (SOD) activity, glutathione (GSH) content, and peroxiredoxin I (Prx I) and Prx II mRNA and protein expressions. In addition, the ROS scavenger N-acetyl-l-cysteine (NAC) or NO scavenger NG-Nitro-l-arginine (L-NNA) significantly rescued the LDH leakage and cell survival, reversed the neurotrophin contents and cholinergic enzymes, mainly via regaining balance between oxidation/nitrosation and antioxidation. Overall, our findings suggested that oxidative and nitrosative stresses are involved in the neurotoxicity induced by BDE-153, and that the antioxidation is a potential targeted intervention.

2.
J Cell Physiol ; 235(1): 408-420, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31230347

RESUMO

The atypical protein kinase C isoform ι (PKCι) is upregulated, which cooperates with mutated KRAS (mu-KRAS) to promote the development of pancreatic cancers. However, the exact role of PKCι in KRAS-mediated pancreatic tumorigenesis is not fully defined. In the present study, we demonstrate that mu-KRAS upregulates and activates PKCι, accompanied by dephosphorylation of large tumor suppressor (LATS), a key member of the growth-inhibiting Hippo signaling pathway. As a result, Yes-associated protein 1 (YAP1; a transcriptional coactivator) is dephosphorylated and translocates to the nucleus, which promotes transcription of downstream target genes to sustain the transformed growth of pancreatic cancer cells. In contrast, when PKCι is suppressed by the chemical inhibitor or small-hairpin RNA, the levels of phosphorylated LATS and YAP1 are elevated and YAP1 is excluded from the nucleus, which enhances the susceptibility of pancreatic cancer cells harboring mu-KRAS to apoptosis. These findings shed new light on the mechanisms underlying the pancreatic tumorigenesis initiated by mu-KRAS, and suggest that the PKCι-YAP1 signaling may potentially be therapeutically targeted for restricting the growth and inducing apoptosis in pancreatic tumors expressing mu-KRAS.

3.
J Hazard Mater ; 383: 121160, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31518812

RESUMO

The application of current soil quality standards based on total arsenic (As) fails to assess the ecological risks of soil arsenic or to ensure the safety of crops and foods. In this study, bioavailable arsenic instead of total arsenic was applied to improve predictive models for arsenic transfer from soil to wheat (Triticum turgidum L.). The stepwise multiple-linear regression analysis showed that bioavailable arsenic and amorphous iron oxides (FeOX) were the two most important factors contributing to arsenic accumulation in wheat grain, with the explained percentage of variation being up to 82%. Compared with the bioavailable arsenic extracted by NH4H2PO4, bioavailable arsenic extracted by HNO3 from soils generated better predictions of the amount of arsenic in grain. The best reliable model was log[Asgrain] = 0.917 log[HNO3-As] - 0.452 log[FeOX] - 1.507 (R2 = 0.82, P <  0.001). Consistently, bioavailable arsenic and FeOX were also the key factors to predict arsenic accumulation in wheat straw, leaves and spikes. Our prediction models was successfully verified for three independent soils. Our results highlight the role of soil bioavailable heavy metals in predicting their transfer in soil-plant systems and can be used to improve existing Chinese soil quality standards.

4.
Bioinformatics ; 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31710672

RESUMO

MOTIVATION: Eosinophils are phagocytic white blood cells with a variety of roles in the immune system. In situations where actual counts are not available, high quality approximations of their cell proportions using indirect markers are critical. RESULTS: We develop a Bayesian measurement error model to estimate proportions of eosinophils in cord blood, using the cord blood DNA methylation profiles, based on markers of eosinophil cell heterogeneity in blood of adults. The proposed method can be directly extended to other cells across different reference panels. We demonstrate the method's estimation accuracy using B cells and show that the findings support the proposed approach. The method has been incorporated into the estimateCellCounts function in the minfi package to estimate eosinophil cells proportions in cord blood. AVAILABILITY: estimateCellCounts function is implemented and available in Bioconductor package minfi. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31753657

RESUMO

Piceatannol (PIC) displays a wide spectrum of biological activities, such as antioxidation, antibacterial activity and anti-inflammation, but the biochemical and molecular mechanism is not fully understood. In this study, the interaction of PIC with bovine serum albumin (BSA) was studied by fluorescence spectroscopy, ultraviolet-visible absorption spectroscopy, circular dichroism spectroscopy and molecular simulation. The effects of PIC on BSA non-enzymatic glycosylation, fibrillation, thermal stability, and structure information were also studied. The results showed that the formation of PIC-BSA complex by mainly hydrogen-bonding forces resulted in the conformational changes of protein. PIC inhibited the formation of ß-sheets structures of BSA. BSA still maintained the esterase-like good activity in the presence of PIC. In addition, PIC significantly reduced the degree of BSA glycosylation. These results provided a basis for the molecular interaction between PIC and protein, and suggested the potential effect of PIC in preventing the progression of diabetes mellitus.

6.
Vascul Pharmacol ; : 106613, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31678650

RESUMO

Metformin (Met) can improve atherosclerosis (As). Abnormal endothelin receptors [including endothelin type A (ETA) or type B (ETB) receptor] in vascular smooth muscle cells (VSMCs) are involved in As. Hyperhomocysteinemia (HHcy) is an independent risk factor for As. The present study was designed to test our hypothesis that Met inhibits the upregulation of endothelin receptors induced by homocysteine (Hcy) in VSMCs. Rat superior mesenteric artery (SMA) without endothelium, as an in vitro model, was cultured in serum-free medium for 24 h in the presence of Hcy with or without Met or nicotinamide (Nic). In vivo, rats received subcutaneous injections of Hcy in the presence or absence of Met or Nic for 3 weeks. Levels of protein expression were determined by Western blotting. The contractile responses to sarafotoxin 6c (an ETB receptor agonist) or ET-1 (an ETA/ ETB receptor agonist) were studied using a sensitive myograph. The blood pressure of rats was measured using a noninvasive tail-cuff plethysmography method. The results showed that Met could significantly inhibit the Hcy-induced upregulation of endothelin receptors (including ETA and ETB receptor) protein expression and endothelin receptor-mediated vasoconstriction, and it recovered the Hcy-induced decrease in silent information regulator 1 (Sirt1) in a dosage-dependent manner in SMA. However, Nic (a Sirt1 inhibitor) recovered the levels of Met-inhibited endothelin receptors and acetylated p65. Furthermore, the in vivo results showed that Met not only significantly the inhibited HHcy-induced upregulation of endothelin receptors and acetylated p65 but also recovered the HHcy-induced decrease in Sirt1 in a dosage-dependent manner in SMA. In addition, Met significantly inhibited the HHcy-induced blood pressure elevation. However, these effects were reverted by Nic. In conclusion, these data demonstrated that Met inhibited the Hcy-induced increase in endothelin receptor expression by activating Sirt1 and then inhibiting NF-κB in VSMCs. These findings may provide insights into the mechanism underlying of Met-treated cardiovascular diseases induced by Hcy.

7.
Oxid Med Cell Longev ; 2019: 4010764, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31737170

RESUMO

Type 2 diabetes mellitus is a chronic metabolic disorder characterized by elevated blood glucose and/or high serum free fatty acids. Chronic hyperlipidemia causes the dysfunction of pancreatic beta cells, which is aggravated in the presence of hyperglycemia (glucolipotoxicity). Long noncoding RNAs (lncRNAs) have been suggested to play key roles in type 1 diabetes mellitus development. However, their roles in glucolipotoxicity-induced beta cell dysfunction are not fully understood. In the present study, we identified the differentially expressed lncRNAs in INS-1 cells exposed to high glucose and palmitate (HG/PA). Among the dysregulated lncRNAs, NONRATT003679.2 (low expression in glucolipotoxicity-treated beta cells (LEGLTBC)) was involved in glucolipotoxicity-evoked rat islet beta cell damage. LEGLTBC functioned as a molecular sponge of miR-34a in INS-1 cells. Additionally, SIRT1 was identified as a target of miR-34a and LEGLTBC promoted SIRT1 expression by sponging miR-34a. The upregulation of LEGLTBC attenuated HG/PA-induced INS-1 cell injury through the promotion of SIRT1-mediated suppression of ROS accumulation and apoptosis. This is the first study to comprehensively identify the lncRNA expression profiling of HG/PA-treated INS-1 beta cells and to demonstrate that LEGLTBC functions as a competing endogenous RNA and regulates miR-34a/SIRT1-mediated oxidative stress and apoptosis in INS-1 cells undergoing glucolipotoxicity.

8.
Int J Biol Macromol ; 2019 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-31770558

RESUMO

Chitosan-α-lipoic acid (CS-LA) conjugates were prepared by amino reaction. The methotrexate (MTX) was successfully loaded within CS-LA copolymer by the ring-opening polymerizations of disulfide bond under the action of reducing agent. The obtained copolymer was investigated by fourier transform infrared spectrometer (FTIR), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and nuclear magnetic resonance (1H NMR) analysis. The ring-opening polymerization process effects on rheological properties were studied. The graft of LA increased the apparent viscosity of CS-LA, and the loaded of MTX by redox reduced its apparent viscosity enormously. The load of MTX under the action of DTT decreased the apparent viscosity and moduli of CS-LA-MTX hydrogel. In dynamic oscillatory experiment, the package of MTX reduced the rigidity of CS-LA and damaged the gel structure of CS-LA. The antimicrobial ability of CS-LA against E. coli was processed by the inhibition zone and growth curves. The modification of LA raised the antibacterial activity of CS-LA. The cytotoxicity assay of CS-LA-MTX to prostate cancer cells (RM-1) was examined. The load of MTX within CS-LA-MTX greatly enhanced the cytotoxicity to RM-1 cells. In summary, CS-LA hydrogel may provide a new copolymer carrier for drug package in food and biomedical application.

9.
Zhongguo Fei Ai Za Zhi ; 22(11): 687-695, 2019 Nov 20.
Artigo em Chinês | MEDLINE | ID: mdl-31771737

RESUMO

BACKGROUND: In recent years, a number of clinical trials have shown that immunocheckpoint inhibitors (ICI) have brought survival benefits to patients with advanced non-small cell lung cancer (NSCLC), however, such clinical trials comprise cohorts selected based on strict and complex entry and exclusion criteria, and the results cannot fully reflect the real world situation. The purpose of this study was to investigate the clinical efficacy and safety of immunotherapy in the real world, as well as possible prognostic factors. METHODS: Patients with advanced NSCLC receiving immunotherapy in Beijing Chest Hospital from January 2017 to July 2019 were retrospectively collected, and the following information were collected: curative effect, progression-free surival (PFS) and adverse reactions. The occurrence of adverse reactions and clinical curative effect and prognosis factors that may be relevant were explored. RESULTS: 34 patients were enrolled in this study, median PFS was 5.66 months (95%CI: 4.48-6.84), grade 1-2 and 3-4 incidence of adverse events was 61.71% (22/34) and 14.71% (5/34), there were 3 patients (8.82%) experienced fatal immune related adverse events (irAE), 2 cases were immune associated pneumonia, 1 case was immune related myocarditis. Univariate analysis showed that tumor-node-metastasis (TNM) stage and metastatic site were correlated with median PFS (P<0.05), and multivariate analysis showed that patients with extrapulmonary metastasis (OR=6.42, P=0.029) and pleural metastasis (OR=14.14, P=0.006) had shorter median PFS. CONCLUSIONS: In the real world, immunotherapy has good efficacy in patients with advanced NSCLC, but the incidence of severe irAE is also higher. Distant metastasis and pleural metastasis are poor prognostic factors for advanced NSCLC patients receiving immunotherapy.

10.
Lung Cancer ; 139: 118-123, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31775086

RESUMO

OBJECTIVES: The 2015 World Health Organization classification defines pulmonary large-cell neuroendocrine carcinoma (LCNEC) as a high-grade neuroendocrine carcinoma. However, the clinical characteristics and prognostic factors of pure LCNEC and combined LCNEC remain unclear. Hence, we performed a multi-center retrospective study to compare the clinical outcomes of pure versus combined LCNEC. MATERIALS AND METHODS: Data from 381 patients with pulmonary LCNEC admitted to 17 Chinese institutes between 2009 and 2016 were collected retrospectively. Clinical characteristics and prognosis were analyzed among patients receiving adjuvant (adjuvant group; n = 56) and first-line (first-line group; n = 146) chemotherapy, as well as among patients receiving small cell lung cancer (SCLC) and non-SCLC (NSCLC) chemotherapy regimens. The Kaplan-Meier method and multivariable Cox regression were used to identify clinicopathological variables that might influence patient outcomes. RESULTS: Expression levels of neuroendocrine markers (synaptophysin, chromogranin-A, CD56) were associated with patients' prognosis in the total study cohort. In the adjuvant group, median disease-free survival was non-significantly longer for SCLC-based regimens than for NSCLC-based regimens (P = 0.112). In the first-line group, median progression-free survival was significantly longer for SCLC-based regimens than for NSCLC-based regimens (11.5 vs. 7.2 months, P = 0.003). Among patients with combined LCNEC, adenocarcinoma was the most common combined component, accounting for 70.0 % of cases. Additionally, median overall survival was non-significantly shorter for combined LCNEC than for pure LCNEC (P = 0.083). CONCLUSION: The SCLC regimen is a more effective choice, as either first-line or adjuvant chemotherapy, when compared to the NSCLC regimen for LCNEC treatment. Further studies are needed to clarify the survival differences between patients with pure-, and combined LCNEC.

11.
Anticancer Drugs ; 30(10): 1013-1021, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31609763

RESUMO

Antisense non-coding RNA in the INK4A locus (ANRIL) has been recognized as a cancer-related lncRNA in hepatocellular carcinoma previously. This study aimed to reveal the functional effects and mechanisms of ANRIL on hepatocellular carcinoma cells in vitro. The expression of ANRIL in hepatocellular carcinoma cell lines (MHCC97 and Li-7) and non-tumourigenic liver cell line THLE-3 was detected by qRT-PCR. The expression of ANRIL, miR-144 and PBX3 in hepatocellular carcinoma cells was altered simultaneously or respectively by vector/oligonucleotide transfection. Then, cell viability, migration, invasion, apoptotic cell rate, protein expression of apoptosis-related factors were assessed. The correlation between ANRIL, miR-144 and PBX3 was explored. ANRIL was highly expressed in MHCC97 and Li-7 cells when compared to THLE-3 cells. ANRIL overexpression promoted cell viability, migration, invasion and suppressed apoptosis of MHCC97 and Li-7 cells. ANRIL negatively regulated miR-144, and oncogenic effects of ANRIL were attenuated when miR-144 was overexpressed. PBX3 was a direct target of miR-144. miR-144 overexpression blocked PI3K/AKT and JAK/STAT signalling pathways via targeting PBX3. Our data documented that ANRIL promoted hepatocellular carcinoma cells growth, migration and invasion. One of the possible mechanisms responsible for the tumour-promoting actions is that ANRIL sponging miR-144 to derepress PBX3.

12.
Spectrochim Acta A Mol Biomol Spectrosc ; 227: 117662, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31654845

RESUMO

Exploring the protein-nanomaterials interactions is the topic of high relevance for the future applications of new nanomaterials in biological system. Herein, the binding mechanism of bovine serum albumin(BSA) and bovine hemoglobin(BHB) with two-dimensional black phosphorus nanosheets (BP NSs) was reported. Muti-spectral results showed that the combination of BP NPs with protein resulted in the fluorescence quenching of BSA and BHB and induced the extension of the protein peptide chain by van der Waals forces, hydrophobic forces, and electron-transfer forces. Both BSA and BHB retain their structure in α-helix form. The induced circular dichroism (ICD) spectral results showed that the presence of BP NPs partly destroyed the binding domain of BHB with bilirubin and altered the tertiary structure of BHB by BP NPs binding.

13.
Clin Neurol Neurosurg ; 186: 105428, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31581028

RESUMO

The treatment efficacy of galcanezumab for migraine remained controversial. We conducted a systematic review and meta-analysis to explore the influence of galcanezumab versus placebo on the treatment of migraine. We searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through October 2018 for randomized controlled trials (RCTs) assessing the effect of galcanezumab versus placebo for patients with migraine. This meta-analysis was performed using the random-effect model. Six RCTs were included in the meta-analysis. Overall, compared with control group for migraine patients, galcanezumab resulted in greater overall mean reduction in the number of monthly migraine headache day (MHD) (P < 0.05). In contrast, galcanezumab was associated with increased adverse events (risk ratio (RR) = 1.08; 95% CI = 1.01-1.15; P = 0.02), but with no significant impact on serious adverse events between two groups (RR = 2.0; 95% CI = 0.95-4.21; P = 0.07).Galcanezumab showed favorable promotion for the preventive treatment of migraine patients.

14.
Anat Histol Embryol ; 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31571240

RESUMO

The distribution of glucagon-like peptide 1 (GLP-1)-positive cells in digestive tracts and pancreases of aquatic vertebrates was investigated by immunohistochemical staining method. The results suggested that GLP-1-positive cells were distributed in the columnar mucous epithelium and tubular glands of lamina propria in the digestive system. However, GLP-1-positive cells were also found in subepithelial lamina propria of the mucosae and muscularis in each segment of the digestive tract of Rana nigromaculata. The distribution densities of these cells reached peaks in the stomachs, and the middle or end segments of small intestines of Chinese softshell turtle, Bufo gargarizans, R. nigromaculata and catfish, and there was the third distribution density peak in the rectum of catfish. The total amount or overall density of GLP-1-positive cells varied a lot in the digestive tracts of different animal species. The distribution density was relatively low in the digestive tract of chub and reached the maximum in the digestive tracts of snakehead and catfish, but no GLP-1-positive cells were found in the digestive tract of bighead carp. GLP-1-positive cells were densely distributed in the pancreases of Chinese softshell turtle, B. gargarizans and R. nigromaculata. These cells spread over the superficial layers of islets or scattered in exocrine pancreas in the pancreas of B. gargarizans, spread in the endocrine cells or scattered in the pancreas of Chinese softshell turtle, scattered in the pancreas of R. nigromaculata and distributed in the superficial layers of islets in the pancreas of catfish.

15.
Aging (Albany NY) ; 11(17): 6930-6940, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31479417

RESUMO

Backgroud: Bladder cancer (BLCA) is one of the most fatal types of cancer worldwide. However, there are limited methods for us to provide a prognostic prediction of BLCA patients. Therefore, we aimed at developing a lncRNA signature to improve the prognosis prediction of BLCA. RESULTS: An eight-lncRNA signature was significantly associated with recurrence free survival in BLCA patients from both discovery and validation groups. Furthermore, genes involved in the signature were enriched in extracellular matrix organization pathway. Finally, functional experiments demonstrated that six out of the eight lncRNAs significantly regulated the invasion of BLCA cells. METHOD: A total of 343 BLCA patients from The Cancer Genome Atlas (TCGA) were employed and randomly divided into training (n=172) and validating (n=171) groups. The lncRNA expression profiles of BLCA patients were screened and a risk-score formula were created and validated according to the Cox regression analysis. Next, WGCNA method was employed to cluster genes that highly correlated with the risk scores based on the profiling data of TCGA dataset and transwell assay was also performed to further investigate the role of these lncRNAs. CONCLUSIONS: Our results suggested that the eight-lncRNA signature was a candidate prognostic biomarker for predicting tumor recurrence of patients with BLCA.

16.
Cancer Biomark ; 26(2): 203-207, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31403942

RESUMO

OBJECTIVE: To investigate the diagnostic and prognostic values of long non-coding RNA H19 (H19) in patients with papillary thyroid carcinoma (PTC). METHODS: This retrospective, nonrandomised study included 410 patients with PTC and 89 patients with benign thyroid nodes (BTN)who underwent standard total thyroidectomy. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect H19 expression in these tissues. The relationship between H19 expression and the patients' clinicopathological factors, including histopathological characteristics of the tumour, diagnosis and prognosis was explored. RESULTS: Expression of H19 was lower in the PTC tissues (1.259 ± 1.15) compared to the BNT tissues (2.8347 ± 2.176) (p= 0.001). Low expression of H19 was associated with patient's age, tumor size, extrathyroid extension, pathological lateral node metastasis (pN1b), histological aggressive type and poorer disease-free survival (p< 0.0001). The sensitivity for distinguishing PTC from benign was 81.3%. H19 was found to be an independent risk factor for extrathyroidal extension, lymph node metastasis. CONCLUSIONS: H19 may serve as a potential predictor of poor prognoses in patients with PTC.

17.
Int J Biol Macromol ; 139: 521-530, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31377297

RESUMO

Chitosan-1-(mercaptomethyl)-cyclopropane acetic acid (CS-MCA) copolymer was synthesized by amino linkage. The obtained copolymer was characterized by FTIR, 1H NMR, XRD, TGA and SEM. Porous and reticulate morphologies were found on the CS-MCA surface. The effects of pH on the rheological properties of CS-MCA were investigated. On the one hand, the apparent viscosity of CS-MCA indicated a shear-thinning behavior. The graft of MCA enhanced the moduli and the maximum elastic properties were observed at pH = 7.00. The addition of dithiothreitol reduced the viscosity and modulus of CS-MCA hydrogel, and the gelation time, temperature and frequency were obtained in dynamic oscillatory tests. The antibacterial effect of CS-MCA against E. coli was investigated for the inhibition zone and bacterial growth curve. These results showed that CS-MCA had better antibacterial ability than chitosan without modification. Therefore, the rheological behavior and functional activities can be applied for the hydrocolloid gels in food and pharmaceutical applications.

18.
Clin Epigenetics ; 11(1): 128, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31464656

RESUMO

BACKGROUND: Breastfeeding is protective against many long-term diseases, yet the mechanisms involved are unknown. Leptin gene (LEP) is reported to be associated with body mass index (BMI). On the other hand, breastfeeding duration has been found to be associated with DNA methylation (DNAm) of the LEP gene. Therefore, epigenetic regulation of LEP may represent the mechanism underlying the protective effect of breastfeeding duration against obesity. METHODS: In the Isle of Wight Birth Cohort, peripheral blood DNAm at 23 cytosine-phosphate-guanine sites (CpGs) in the LEP locus in 10-year-old (n = 297) samples and 16 CpGs in 18-year-old (n = 305) samples, were generated using the Illumina Infinium MethylationEPIC and HumanMethylation450 Beadchips respectively and tested for association with breastfeeding duration (total and exclusive) using linear regression. To explore the association between breastfeeding durations and genome-wide DNAm, epigenome-wide association studies (EWASs) and differential methylation region (DMR) analyses were performed. BMI trajectories spanning the first 18 years of life were used as the outcome to test the association with breastfeeding duration (exposure) using multi-nominal logistic regression. Mediation analysis was performed for significant CpG sites. RESULTS: Both total and exclusive breastfeeding duration were associated with DNAm at four LEP CpG sites at 10 years (P value < 0.05), and not at 18 years. Though no association was observed between breastfeeding duration and genome-wide DNAm, DMR analyses identified five significant differentially methylated regions (Sidak adjusted P value < 0.05). Breastfeeding duration was also associated with the early transient overweight trajectory. Furthermore, DNAm of LEP was associated with this trajectory at one CpG site and early persistent obesity at another, though mediation analysis was not significant. CONCLUSIONS: Breastfeeding duration is associated with LEP methylation at age 10 years and BMI trajectory. LEP DNAm is also significantly associated with BMI trajectories throughout childhood, though sample sizes were small. However, mediation analysis did not demonstrate that DNAm of LEP explained the protective effect of breastfeeding against childhood obesity.

19.
J Photochem Photobiol B ; 198: 111578, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31408842

RESUMO

In recent years, biological nanomedicine-based biomaterials have an extreme attention for biomedical uses, herein we examined a novel kind advance of photoluminescent Graphene quandum dots encapsulated mesoporous nanoparticles (GND@MSNs) encapsulated by well-known anticancer drugs Doxorubicin (DOX) and Cyclosporin (CsA) for lung carcinoma. Electron microscopic technique exhibit the nanostructure and spherical morphology of GND@MSNs+DOX+CsA with mean size ≈110 nm. Moreover, Dynamic Light Scattering (DLS) exposed that blended GND@MSNs+DOX+CsA nanoparticles were highly stable with extremely negatively charged nanoparticles. Raman investigation was done on the all naturally dynamic nanoparticles containing shed graphene to survey the blend condition of the graphene inside the silica mesoporous nanoparticles. GND@MSNs+DOX+CsA provided an outstanding anti-cancer efficiency against the lung cancer cell lines (i.e., A549 and HEL-299). MTT assay monitored that GND@MSNs, GND@MSNs+DOX and GND@MSNs+DOX+CsA have a robust toxicity behaviour on the A549 and HEL-299 model lung cancer cell lines. Additionally, investigation of the cell death was found on AO-EB, Hoechst 33452 staining and flowcytometry techniques. Furthermore, the DNA damage were confirmed by cell cycle arrest and comet assay. Hence, we suggesting that these GND@MSNs+DOX+CsA could be applied as auspicious drug vesicles for novel lung cancer therapeutic potential and new openings to solve the complexity of lung cancer in the care of cancer patients.


Assuntos
Apoptose/efeitos dos fármacos , Ciclosporina/farmacologia , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Grafite/química , Nanopartículas/química , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Ciclosporina/química , Ciclosporina/uso terapêutico , Dano ao DNA/efeitos dos fármacos , Doxorrubicina/química , Doxorrubicina/uso terapêutico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Porosidade
20.
Int J Immunopathol Pharmacol ; 33: 2058738419869489, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31462112

RESUMO

Polysaccharides from Ganoderma lucidum have been demonstrated to possess diverse biological activities. Despite lots of studies on the biological activities of Ganoderma lucidum polysaccharide (GLP), little is known regarding the medicinal potential of low-molecular weight enzymatically hydrolyzed Ganoderma lucidum polysaccharide (EGLP). EGLP was prepared by enzymatic degradation and its potential effects in U14 cervical tumor-bearing mice were evaluated. Both GLP and EGLP delayed tumor growth of the tumor xenograft. The EGLP was superior to native polysaccharide. Moreover, EGLP treatment could effectively protect the immune organs of U14 cervical carcinoma-bearing mice. In addition, the EGLP treatment ameliorated oxidative stress as compared with cyclophosphamide (CTX). Compared with the MC group, the expression of Bcl-2 and COX-2 was obviously decreased by EGLP treatment, whereas the expression of Bax and cleaved caspase-3 was obviously increased. These results indicated that EGLP showed stronger antitumor activity with lower toxic effects and had the potential to be a novel antitumor agent.

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