Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 124
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Small ; : e1905703, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32003138

RESUMO

Herein, an all-solid-state sequential self-organization and self-assembly process is reported for the in situ construction of a color tunable luminous inorganic/polymer hybrid with high direct piezoresponse. The primary inorganic self-organization in solid polymer and the subsequent polymer self-assembly are achieved at high pressure with the first utilization of piezo-copolymer (PVDF-TrFE) as the host matrix of guest carbon quantum dots (CQDs). This process induces the spontaneous formation of a highly ordered, microscale, polygonal, and hierarchically structured CQDs/PVDF-TrFE hybrid with multicolor photoluminescence, consisting of very thermodynamic stable polar crystalline nanowire arrays. The electrical polarization-free CQDs/PVDF-TrFE hybrids can efficiently harvest the environmental available kinetic mechanical energy with a new large-scale group-cooperation mechanism. The open-circuit voltage and short-circuit current outputs reach up to 29.6 V cm-2 and 550 nA cm-2 , respectively. The CQDs/PVDF-TrFE-based hybrid nanogenerator demonstrates drastically improved durable and reliable features during the real-time demonstration of powering commercial light emitting diodes. No attenuation/fluctuation of the electrical signals is observed for ≈10 000 continuous working cycles. This study may offer a new design concept for progressively but spontaneously constructing novel multiple self-adaptive complex inorganic/polymer hybrids that promise applications in the next generation of self-powered autonomous optoelectronic devices.

2.
Oncol Res Treat ; 43(3): 96-102, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31945768

RESUMO

INTRODUCTION: The adverse effect of fractures by different aromatase inhibitor (AI) drugs has not been thoroughly assessed in real-world studies. OBJECTIVE: To assess the adverse events of fractures of real-world breast cancer patients caused by AI therapy through the Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: The FAERS data from January 2004 to December 2018 were sorted out and analyzed for correlations between fractures and AI use. Disproportionate analysis and Bayesian analysis were adopted to quantify the signal, the association between the AIs and fractures. The onset time and outcome of fractures after different AI regimens were also compared. RESULTS: Out of 23,064 adverse reports, 657 fracture reports (2.85%) were analyzed. Anastrozole showed a positive association with 4 detection methods, while letrozole and exemestane did so with 2. More exemestane-related reports (44.62%) resulted in initial or prolonged hospitalization than anastrozole (30.12%, p = 0.013) and letrozole (29.43%, p = 0.006). The fracture onset time showed no significant difference among anastrozole, letrozole, and exemestane (median onset time: 46.95, 34.25, and 40.58 months, respectively; p = 0.236). CONCLUSIONS: Anastrozole should be prescribed with more medical care. Analysis of FAERS data identified fracture risk tendencies with AI regimens, which supported continuous monitoring, risk evaluations, and further comparative studies.

3.
Blood ; 135(1): 56-70, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31697837

RESUMO

Lineage-defining transcription factors (TFs) are compelling targets for leukemia therapy, yet they are among the most challenging proteins to modulate directly with small molecules. We previously used CRISPR screening to identify a salt-inducible kinase 3 (SIK3) requirement for the growth of acute myeloid leukemia (AML) cell lines that overexpress the lineage TF myocyte enhancer factor (MEF2C). In this context, SIK3 maintains MEF2C function by directly phosphorylating histone deacetylase 4 (HDAC4), a repressive cofactor of MEF2C. In this study, we evaluated whether inhibition of SIK3 with the tool compound YKL-05-099 can suppress MEF2C function and attenuate disease progression in animal models of AML. Genetic targeting of SIK3 or MEF2C selectively suppressed the growth of transformed hematopoietic cells under in vitro and in vivo conditions. Similar phenotypes were obtained when cells were exposed to YKL-05-099, which caused cell-cycle arrest and apoptosis in MEF2C-expressing AML cell lines. An epigenomic analysis revealed that YKL-05-099 rapidly suppressed MEF2C function by altering the phosphorylation state and nuclear localization of HDAC4. Using a gatekeeper allele of SIK3, we found that the antiproliferative effects of YKL-05-099 occurred through on-target inhibition of SIK3 kinase activity. Based on these findings, we treated 2 different mouse models of MLL-AF9 AML with YKL-05-099, which attenuated disease progression in vivo and extended animal survival at well-tolerated doses. These findings validate SIK3 as a therapeutic target in MEF2C-addicted AML and provide a rationale for developing druglike inhibitors of SIK3 for definitive preclinical investigation and for studies in human patients.

4.
World Neurosurg ; 134: e103-e111, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31568902

RESUMO

OBJECTIVE: To investigate the ultrasonographic characteristics in hourglasslike constriction of peripheral nerve in the upper extremity and to evaluate the value of ultrasonography in the diagnosis. METHODS: Nineteen patients with hourglasslike constriction of peripheral nerve in the upper extremity underwent ultrasonography and the results were compared with surgery. The ultrasonographic characteristics, the accurate rate, and the relation between the ultrasonography and surgery were analyzed. RESULTS: There were 22 affected nerves involved in 19 patients, including 17 radial neuropathies, 4 median neuropathies, and 1 musculocutaneous neuropathy. The accuracy rate of ultrasonography in diagnosing hourglasslike constriction of upper limb nerve was 87.93%. Ultrasonography showed that the constriction sites were completely consistent with the operation. The ultrasonography characteristics of hourglasslike constriction of upper limb nerves were hourglasslike nerve incompleteness or complete constriction, and the nerves at both ends were thickened, and no compression structure was seen around. All lesions with complete constriction diagnosed by ultrasonography were treated with resection of the lesion with or without graft. In addition, 71.43% with incomplete constriction were treated with neurolysis, and 28.57% with resection of the lesion with direct repair. CONCLUSIONS: Ultrasonography could be used as a routine noninvasive examination for hourglasslike constriction of upper limb nerves. Ultrasonography suggests that resection of the lesion rather than neurolysis should be considered in the treatment of complete constriction. For patients with clinical symptoms, ultrasonography showed local nerve enlargement but no constriction; clinicians should be prompted to explore carefully during operation to avoid missing nerve hourglasslike constriction.

5.
J Drug Target ; 28(3): 320-329, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31429596

RESUMO

Background and purpose: The present study aimed to explore the feasibility and efficacy of the targeted non-invasive implantation of mesenchymal stromal cells (MSCs) by low-intensity ultrasound-targeted microbubble destruction (LI-UTMD) assisted blood-brain barrier (BBB) opening and its improvement on neurobehavioural outcomes in brain ischaemic rats.Methods: A transcranial irradiation of low-intensity ultrasound by diagnostic devices was performed, and lipid microbubbles (MBs) and MSCs were simultaneously infused. Then, the MSC transmigration from brain vessels to parenchyma was demonstrated, and MSCs were statistically analysed on days 1, 4, 7 and 14. Behavioural function was statistically analysed.Results: The extra-vascular leakage of lanthanum and EB was observed at the brain ischaemic area receiving ultrasound. MSCs were observed at the ultrasound irradiated brain hemisphere, and the number of MSCs in LI-UTMD assisted MSCs group was significantly higher than that in the MSCs group (p < .01). The attachment, traversing and trans-migration of MSCs across the BBB were recorded. Neuro-behavioural function was improved with this approach.Conclusions: The transcranial irradiation of low intensity ultrasound targeted MBs destruction on brain ischaemic rats might be a safe and efficient BBB opening approach to prompt the successful delivery of MSCs into the targeted area of brain ischaemia, and ameliorate neurological function.

6.
BMC Cancer ; 19(1): 1196, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31805970

RESUMO

BACKGROUND: NF1(Neurofibromatosis type 1) is an autosomal dominant genetic disorder. Patients with NF1 have an increased risk of developing benign or malignant tumours, such as gastrointestinal stromal tumours (GISTs). However, the coexistence of NF1, GIST and colon cancer is very rare, and few cases have been reported in the literature. CASE PRESENTATION: We admitted a case of a 64-year-old man with type 1 neurofibromatosis, GISTs, and ascending colon cancer. This case was characterized by café-au-lait macules, discrete cutaneous neurofibromas, nodular neurofibromas, multiple jejunal tumours, and ascending colon cancer. Laparoscopic exploration revealed ascending colon cancer and multiple jejunal tumours. Laparoscopic right hemicolectomy and local excision of the jejunal tumours were performed successfully. The pathological results confirmed moderate differentiated adenocarcinoma of the ascending colon with multiple jejunal GISTs (low risk, very low risk). Moreover, the immunohistochemistry results of multiple jejunal GISTs suggest that NF1 is positive. Whole-exome sequencing (WES) of colon cancer revealed mutations in more than 20 genes, including KRAS, PIK3CA, APC, SMAD4, etc. The results of whole-exome sequencing (WES) of jejunal GISTs revealed an NF1 mutation and no KIT or PDGFR gene mutation. CONCLUSION: We report a rare case of simultaneous NF1, GIST and colon adenocarcinoma. For patients with NF1, benign and/or malignant tumours are often combined. Therefore, these patients should undergo regular physical examinations so that early detection and early treatment can be achieved.

7.
Plant J ; 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31820831

RESUMO

Phycobilisomes are large light-harvesting complexes attached to the stromal side of thylakoids in cyanobacteria and red algae. They can be remodeled or degraded in response to changing light and nutritional status. Both the core and the peripheral rods of phycobilisomes contain biliproteins. During biliprotein biosynthesis, open-chain tetrapyrrole chromophores are attached covalently to the apoproteins by dedicated lyases. Another set of non-bleaching (Nb) proteins has been implicated in phycobilisome degradation, among them NblA and NblB. We report in vitro experiments with lyases, biliproteins and NblA/B which imply that the situation is more complex than currently discussed: lyases can also detach the chromophores and NblA and NblB can modulate lyase-catalyzed binding and detachment of chromophores in a complex fashion. We show: (i) NblA and NblB can interfere with chromophorylation as well as chromophore detachment of phycobiliprotein, they are generally inhibitors but in some cases enhance the reaction; (ii) NblA and NblB promote dissociation of whole phycobilisomes, cores and, in particular, allophycocyanin trimers; (iii) while NblA and NblB do not interact with each other, both interact with lyases, apo- and holo-biliproteins; (iv) they promote synergistically the lyase-catalyzed chromophorylation of the ß-subunit of the major rod component, CPC; and (v) they modulate lyase-catalyzed and lyase-independent chromophore transfers among biliproteins, with the core protein, ApcF, the rod protein, CpcA, and sensory biliproteins (phytochromes, cyanobacteriochromes) acting as potential traps. The results indicate that NblA/B can cooperate with lyases in remodeling the phycobilisomes to balance the metabolic requirements of acclimating their light-harvesting capacity without straining the overall metabolic economy of the cell.

8.
Environ Pollut ; 255(Pt 2): 113325, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31614327

RESUMO

Associations between single metal and fasting blood glucose (FBG) levels have been reported in previous studies. However, the association between multi-metals exposure and FBG level are little known. To assess the joints of arsenic (As), nickel (Ni), cadmium (Cd), selenium (Se), and zinc (Zn) co-exposure on FBG levels, Bayesian kernel machine regression (BKMR) statistical method was used to estimate the potential joint associations between As, Ni, Cd, Se, and Zn co-exposure and FBG levels among 1478 community-based Chinese adults from two counties, Shimen (n = 696) and Huayuan (n = 782), with different exposure profiles in Hunan province of China. The metals levels were measured in spot urine (As, Ni, and Cd) and plasma (Se and Zn) using inductively coupled plasma-mass spectrometry, respectively. The exposure levels of all the five metals were significantly higher in Shimen area (median: As = 57.76 µg/L, Cd = 2.75 µg/L, Ni = 2.73 µg/L, Se = 112.67 µg/L, Zn = 905.68 µg/L) than those in Huayuan area (As = 41.14 µg/L, Cd = 2.22 µg/L, Ni = 1.88 µg/L, Se = 65.59 µg/L, Zn = 819.18 µg/L). The BKMR analyses showed a significantly positive over-all effect of the five metals on FBG levels when metals concentrations were all above the 50th percentile while a statistically negative over-all effect when metals concentrations were all under the 50th percentile in Shimen area. However, a totally opposite over-all effect of the mixture of the five metals on FBG levels was found in Huayuan area. BKMR also revealed a non-linear exposure-effect of Zn on FBG levels in Huayuan area. In addition, interaction effects of As and Se on FBG level were observed. The relationship between single or combined metals exposure and FBG was different against different exposure profiles. Potential interaction effects of As and Se on FBG levels may exist.


Assuntos
Arsênico/urina , Glicemia/efeitos dos fármacos , Cádmio/urina , Níquel/urina , Selênio/sangue , Zinco/sangue , Adulto , Idoso , Teorema de Bayes , China , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Masculino , Metais Pesados/toxicidade , Pessoa de Meia-Idade , Adulto Jovem
9.
BJR Case Rep ; 5(3): 20180087, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31555467

RESUMO

Bronchial artery embolization is an effective and widely used procedure for controlling hemoptysis. Cerebral infarct after bronchial artery embolization is a rare and severe complication. We report two cases of cerebral infarct complicating bronchial artery embolization, most likely due to errant embolic passage through anastomoses with the ipsilateral subclavian artery.

10.
Med Sci Monit ; 25: 6554-6562, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31473760

RESUMO

BACKGROUND In previous studies, higher expression of PREX1 (PtdIns (3,4,5)P3-dependent Rac exchanger 1) has been detected in some subsets of breast cancer, and activation of PREX1 has been associated with tumor progression in vivo. However, an association between PREX1 and breast cancer prognosis has not been examined. MATERIAL AND METHODS In this study, we investigated the expression and correlation of PREX1 with important clinical factors and prognosis of patients with breast cancer. Immunohistochemical staining was performed for 121 tumor tissue specimens obtained from primary breast cancer lesions. RESULTS We found that 55 tissues exhibited positive staining for PREX1. Moreover, tumors positive for PREX1 were found to have significant association with recurrence rate (P=0.000) and metastasis rate (P=0.001). Univariate and multivariate regression analyses also identified PREX1 expression as an independent variable of disease-free survival. Our analyses indicate that high levels of PREX1 expression were related to longer disease-free survival in patients with breast cancer (P=0.013). CONCLUSIONS PREX1 is a favorable variable of prognosis for breast cancer patients, these study results need to be confirmed in larger research studies.


Assuntos
Neoplasias da Mama/metabolismo , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Adulto Jovem
11.
PeerJ ; 7: e7563, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31523513

RESUMO

Background: To investigate whether SUA is associated with NAFLD in men and women with T2DM. Methods: This cross-sectional study enrolled patients with T2DM at Shanxi High-Tech Development Zone Central Hospital (June 2011 to September 2017). Patients were stratified according to gender and presence/absence of NAFLD. Parameters associated with NAFLD were identified using multivariate stepwise linear regression and univariate/multivariate logistic regression. Results: Among 597 patients (325 males) enrolled, 352 had NAFLD. SUA was higher in the NAFLD group than in the non-NAFLD group for both men and women (P < 0.001). Multiple linear regression showed that body mass index (positively), triglycerides (positively) and estimated glomerular filtration rate (negatively) were independently related to SUA (P < 0.001). Univariate logistic regression revealed increased odds of NAFLD for SUA tertiles 2 (P = 0.022) and 3 (P = 0.001) in women and tertile 3 (P = 0.039) in men. After adjustment for multiple clinical parameters, SUA tertiles were significantly associated with NAFLD for tertile 3 in women (P = 0.014), although there were trends toward associations for tertile 2 in women (P = 0.074) and tertiles 2 and 3 in men (P = 0.085 and 0.054, respectively). Conclusion: SUA is not independently associated with NAFLD in men or women with T2DM after rigorous adjustment for other metabolic parameters.

12.
Neurobiol Dis ; 132: 104567, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31394202

RESUMO

Neurofibrillary tangles of hyperphosphorylated tau protein (p-tau) are a key pathological feature of Alzheimer's disease (AD). Tau phosphorylation is suggested to be secondary to amyloid-beta (Aß) accumulation. However, the mechanism by which Aß induces tau phosphorylation in neurons remains unclear. Neurotrophin receptor p75 (p75NTR) is a receptor for Aß and mediates Aß neurotoxicity, implying that p75NTR may mediate Aß-induced tau phosphorylation in AD. Here, we showed that Aß-induced tau hyperphosphorylation and neurodegeneration, including tau phosphorylation, synaptic disorder and neuronal loss, in the brains of both male wild-type (Wt) mice and male P301L transgenic mice (a mouse model of human tauopathy) were alleviated by genetic knockout of p75NTR in the both mouse models. We further confirmed that the activation or inhibition of cyclin-dependent kinase 5 (CDK5) and glycogen synthase kinase-3ß (GSK3ß) significantly changed Aß/p75NTR-mediated p-tau levels in neurons. Treatment of male P301L mice with soluble p75NTR extracellular domain (p75ECD-Fc), which antagonizes the binding of Aß to p75NTR, suppressed tau hyperphosphorylation. Taken together, our findings suggest that p75NTR meditates Aß-induced tau pathology and is a potential druggable target for AD and other tauopathies.

13.
J Cancer ; 10(18): 4278-4285, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31413747

RESUMO

Background: Chemotherapy impairs ovarian function in premenopausal breast cancer patients. Many breast cancer patients experience menopause earlier and therefore lose their reproductive abilities. The protective effect of gonadotropin-releasing hormone agonist (GnRha) upon the ovary is clearly apparent for hormone receptor (HR) negative patients, although the available data is not consistent for the patient body as a whole when considered regardless of HR status. It is also unknown whether levels of Anti-Mullerian Hormone (AMH) can reflect the influence of chemotherapy upon the ovary. Methods: We randomly assigned 98 premenopausal breast cancer patients regardless HR-positive or -negative to receive either standard chemotherapy with GnRHa (GnRHa group) or standard chemotherapy without GnRHa (control group). Our primary end point was ovarian failure rate (OVF) at 1 year. In addition, we observed the change of AMH level during chemotherapy and the association between AMH and OVF. Results: OVF was significantly lower (44.7%) in the GnRHa group than in the control group (80.6%; P=0.002). Median AMH levels were significantly higher before chemotherapy when compared to after 1/2cycles of chemotherapy, both in the GnRHa group (1.86ng/ml vs 0.12ng/ml; P=0.000) and in the control group (1.57ng/ml vs 0.10ng/ml; P=0.000). OVF was 91.3% in the AMH baseline level <1.1ng/ml group and 63.5% in the AMH baseline level >1.1ng/ml group (P=0.013). Conclusion: Data showed that GnRHa may have a protective effect on young breast cancer patients regardless of HR during chemotherapy. AMH could reflect changes of OVF during chemotherapy and predict OVF after chemotherapy.

14.
Nanoscale ; 11(35): 16515-16522, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31453606

RESUMO

An electrochemical functionalization method is developed to fabricate N- and O-rich graphene films (F-RGO-60) with an expanded interlayer distance. In particular, the functionalization process could be completed within 60 seconds at room temperature, which is conducive to large-scale commercial applications. Electrochemical synthesis of F-RGO-60 leads to two synergetic effects simultaneously: (1) the expansion of the interlayer distance caused by a bubble effect, which leads to more exposure of the active surface area and (2) the introduction of N-doped sites and oxygen-containing functional groups, which not only improves the hydrophilicity of F-RGO-60 but also provides extra pseudocapacitance. It is worth mentioning that after electrochemical functionalization, F-RGO-60 can still maintain a high density of 1.47 g cm-3. Due to their optimal surface area, good electrolyte wettability and massive redox-active sites, the specific capacitance of F-RGO-60 films can reach up to 319.4 F cm-3 (217.3 F g-1) at 1 A g-1 in a three-electrode system, which is about 3.6 times larger than that of RGO films (60 F g-1). The integration of the low-cost preparation method and outstanding performance suggests that F-RGO-60 has great development prospects as supercapacitor electrode materials.

15.
J Alzheimers Dis ; 70(2): 399-412, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31177213

RESUMO

Emerging evidence suggests that gut microbiota dysbiosis plays a role in neurodegenerative disorders. However, whether the composition and diversity of the gut microbiota are altered in tauopathies remains largely unknown. This study was aimed to examine the diversity and composition of the gut microbiota in tauopathies, as well as the correlation with pathological changes in the brain. We collected fecal samples from 32 P301L tau transgenic mice and 32 age- and gender-matched littermate mice at different ages. The 16S ribosomal RNA sequencing technique was used to analyze the microbiota composition in feces. Brain tau pathology levels were measured by immunohistochemistry. The diversity and composition of the gut microbiota significantly changed with aging. At the phylum level, the relative abundance of Bacteroidetes was increased, while Firmicutes were decreased in P301L mice compared with that in Wt mice after 3 months of age. In addition, Actinobacteria was decreased in P301L mice at 3 and 6 months of age, meanwhile Tenericutes was decreased in P301L mice at 10 months of age. Moreover, several specific macrobiota were highly associated with the levels of AT8-tau or pT231-tau protein in the brain. Our findings suggest that gut microbiota changed with aging, as well as in the tauopathy mice model. Modulation of the gut microbiota may be a potential strategy for treatment of tauopathy.

16.
Environ Int ; 129: 497-506, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31158596

RESUMO

BACKGROUND: Metals exposure from natural environment and pollution have been linked to cardiovascular disease (CVD). However, whether associations existing between plasma multiple metals and incident cardiovascular disease in patients with type 2 diabetes (T2D) is unknown. OBJECTIVES: We conducted a prospective cohort study to investigate whether plasma levels of metals are associated with incident CVD risk in patients with T2D. METHODS: In a prospective study of 3897 type 2 diabetes embedded in the Dongfeng-Tongji cohort, fasting blood samples were collected in 2008 at baseline and in 2013 in the first follow-up period. Plasma concentrations of 23 metals were measured by inductively coupled plasma mass spectrometry (ICP-MS). The associations between plasma metal concentrations and CVD risk in patients with T2D were investigated with Cox proportional hazards models. RESULTS: During an average of 6.2 years follow-up, 1114 participants developed CVD. In the single-metal models adjusting for established cardiovascular risk factors, plasma zinc and selenium levels were negatively and strontium was positively associated with incident CVD risk in patients with T2D. Similar results were obtained in the multiple-metal model, the HRs (95% CIs) for zinc, selenium, and strontium comparing extreme quartiles were 0.78 (95% CI: 0.65-0.93; P trend = 0.011), 0.76 (95% CI: 0.64-0.91; P trend = 0.001), and 1.51 (95% CI: 1.26-1.81; P trend <0.001), respectively. In the joint association analyses of two metals, individuals with high plasma levels of zinc and selenium had significantly lower risk of incident CVD in patients with T2D than those with low levels (HR = 0.77, 95% CI: 0.65-0.91). CONCLUSIONS: The present study suggested that plasma levels of zinc and selenium had an inverse association with incident CVD risk in patients with T2D, while strontium had a positive correlation. Plasma zinc and selenium combinedly decreased incident CVD risk in patients with T2D. Further research is still needed to verify these findings in other populations.


Assuntos
Doenças Cardiovasculares/sangue , Diabetes Mellitus Tipo 2/sangue , Metais/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
17.
Environ Pollut ; 252(Pt A): 171-179, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31146232

RESUMO

Organic pollutants are widely detected in surface water, groundwater and irrigation sewage in farmland soil, some of which can form complexes with heavy metal ions as ligands in the environment. Acesulfame (ACE), one of the most popular artificial sweeteners, has been found in wastewater sometimes at tens of microgram per liter. However, the combined effects of heavy metals and ACE are still unclear. In the present study, the effects of ACE on cadmium (Cd) absorption and translocation in rice seedlings (Oryza sativa L.) under different exposure conditions were investigated using hydroponic experiments. Under the combined exposure treatments of ACE and Cd, absorption of Cd and ACE in rice significantly decreased when compared with the single exposure treatments, while the alleviation of oxidative damage in rice was also found. Under the sequential exposure treatments of Cd and ACE, the post-exposed ACE activated the pre-absorbed Cd in plant, and accelerated the release of Cd to the environment as well as its translocation from the roots to shoots. In addition, compared with the single Cd exposure, the accumulated ACE can alleviate the oxidative damage in rice shoots induced by Cd, although the Cd concentrations in shoots changed little. In summary, the combined pollution of artificial sweetener ACE was beneficial to relieve the toxicological damage and ecological risk caused by Cd.


Assuntos
Biodegradação Ambiental/efeitos dos fármacos , Cádmio/metabolismo , Oryza/metabolismo , Poluentes do Solo/análise , Edulcorantes/farmacologia , Tiazinas/farmacologia , Transporte Biológico/efeitos dos fármacos , Cádmio/análise , Poluição Ambiental/análise , Hidroponia , Oryza/efeitos dos fármacos , Raízes de Plantas/efeitos dos fármacos , Plântula/efeitos dos fármacos , Solo
18.
Cancer Res ; 79(11): 2865-2877, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31015230

RESUMO

C/EBPα is an essential transcription factor involved in regulating the expression or function of certain cell-cycle regulators, including in breast cancer cells. Although protein arginine methyltransferases have been shown to play oncogenic roles in a variety of cancers, little is known about the role of arginine methylation in regulating the antiproliferation activity of C/EBPα. Here, we report that the protein arginine methyltransferase 1 (PRMT1) is overexpressed in human breast cancer and that elevated PRMT1 correlates with cancer malignancy. RNA-sequencing analysis revealed that knockdown of PRMT1 in breast cancer cells is accompanied by a decrease in the expression of pro-proliferative genes, including cyclin D1. Furthermore, tandem affinity purification followed by mass spectrometry identified PRMT1 as a component of the C/EBPα complex. C/EBPα associated with and was methylated by PRMT1 at three arginine residues (R35, R156, and R165). PRMT1-dependent methylation of C/EBPα promoted the expression of cyclin D1 by blocking the interaction between C/EBPα and its corepressor HDAC3, which resulted in rapid growth of tumor cells during the pathogenesis of breast cancer. Inhibition of PRMT1 significantly impeded the growth of cancer cells from patients with triple-negative breast cancer. This evidence that PRMT1 mediates C/EBPα methylation sheds light on a novel pathway and potential therapeutic target in breast cancer. SIGNIFICANCE: This study provides novel mechanistic insight of the role of the arginine methyltransferase PRMT1 in breast cancer pathogenesis.

19.
Neurotox Res ; 36(1): 101-107, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30977102

RESUMO

The neurotrophin receptor p75 (p75NTR) plays important roles in regulating amyloid-beta (Aß) metabolism in the brain. The expression of p75NTR is altered in the brain of patients with Alzheimer's disease (AD). In this study, we aimed to evaluate whether p75NTR mRNA level in the peripheral blood cells is changed among AD patients and its potential to be a biomarker for AD. The study subjects included 26 patients with AD (PiB-PET positive) and 28 cognitively normal controls (PiB-PET negative). RNA was extracted from peripheral blood cells of fast blood. p75NTR mRNA was measured using quantitative real-time PCR assay. p75NTR mRNA levels in blood cells were comparable between AD patients and controls. p75NTR mRNA levels in blood cells were not correlated with MMSE scores, ApoE genotypes, gender, and age. p75NTR mRNA expression in blood cells is not changed in AD patients and is unlikely to be a biomarker for AD.


Assuntos
Doença de Alzheimer/sangue , Proteínas do Tecido Nervoso/sangue , Receptores de Fator de Crescimento Neural/sangue , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/genética , Apolipoproteínas E/genética , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/sangue
20.
Angew Chem Int Ed Engl ; 58(18): 5915-5919, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-30840345

RESUMO

Highly efficient detection in the aqueous phase for water-insoluble organic molecule probes is challenging. The bright aggregated-state electrochemiluminescence (ECL) of 1,1-disubstituted 2,3,4,5-tetraphenylsiloles by a co-reactant approach was discovered, and a heterogeneous aggregation-induced emission ECL (HAIE-ECL) was constructed at the electrode surface, showing very high ECL efficiency (37.8 %) and selective recognition for industrially important DNBP plasticizer with a low detection limit of 0.15 nm in the water phase. A mechanistic study indicates that ECL is mainly generated due to the high electron affinity of siloles and restriction of the intramolecular motions caused by their propeller-like noncoplanar structures. This system realizes the sensing of organic-based ECL in the water phase by solving the crucial problems of water insolubility and aggregation-caused quenching (ACQ), and demonstrates potential for further application because of its design and high efficiency.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA