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1.
Aging (Albany NY) ; 122020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32170046

RESUMO

Cervical regional lymph node involvement (CRLNI) is common in papillary thyroid microcarcinoma (PTMC), but the way to deal with cervical lymph node involvement of clinically negative PTMC is controversial. We studied data of patients histologically confirmed PTMC in the Surveillance, Epidemiology, and End Results (SEER) Program and Department of Surgical Oncology in Hangzhou First People's Hospital (China). We screened 6 variables of demographic and clinicopathological characteristics as potential predictors and further constructed a lymph node involvement model based on the independent predictors including age, race, sex, extension, multifocality and tumor size. The model was validated by both the internal and the external testing sets, and the visual expression of the model was displayed by a nomogram. As a result, the C-index of this predictive model in the training set was 0.766, and the internal and external testing sets through cross-validation were 0.753 and 0.668, respectively. The area under the receiver operating characteristic curve (AUC) was 0.766 for the training set. We also performed a Decision Curve Analysis (DCA), which showed that predicting the cervical lymph node involvement risk applying this nomogram would be better than having all patients or none patients use this nomogram.

2.
Medicine (Baltimore) ; 99(5): e18971, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000426

RESUMO

BACKGROUND: We analyzed the scientific outputs of global atrial fibrillation (AF) researches, developed a model to qualitatively and quantitatively evaluate the AF research productions from 2004 to 2018. METHODS: The data was retrieved from the Web of Science Core Collection (WOSCC) on June 15, 2019. Bibliometrics tools-CiteSpace V (Drexel university, Chaomei Chen) and VOSviewer (Leiden University, van Eck NJ) --were used for bibliometric analyzing published outputs and finding research hotspots. RESULTS: There were a total of 21,839 research articles on AF, and the annual publication rate increased over time from 2004 to 2018. The Journal of Cardiovascular Electrophysiology published the greatest number of articles, and the leading country was the United States. The leading institution was the Mayo Clinic, and the most productive researchers were: LIP GYH, Natale A, Chen SA, DI Biase L, and Kuck KH. The keywords analysis showed that catheter ablation, risk, heart failure, stroke, and management were research hotspots. CONCLUSION: Bibliometric analysis of the literature shows that research on AF continues to be a hot spot, and the clinical treatment of AF is an important research frontier. However, further research and collaboration are needed worldwide. Our findings aim to provide valuable information for the editors of journals that publish research on arrhythmia, and to help researchers identify new perspectives for future researches.


Assuntos
Fibrilação Atrial , Bibliometria , Publicações/estatística & dados numéricos , Pesquisa Biomédica/tendências , Humanos
3.
J Cell Physiol ; 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31960961

RESUMO

Numerous studies demonstrate that circular RNAs (circRNAs) are critical regulators of the occurrence and progression of tumors. However, research on the involvement of circRNAs in lung squamous cell carcinoma (LUSC) is limited. In our study, circTIMELESS (also named hsa_circ_0000408 in the Human circRNA Database) was upregulated in both LUSC tissues and LUSC cells, and circTIMELESS expression was positively associated with the TNM stage. Moreover, circTIMELESS silencing markedly suppressed invasion in vitro and disrupted proliferation in vitro as well as in vivo. Additional investigations have shown that circTIMELESS functions as a miR-136-5p "sponge" and regulates miR-136-5p expression. Furthermore, the impact of miR-136-5p upregulation was consistent with the results of circTIMELESS silencing, both of which inhibited the proliferation and invasion of LUSC cells. Additional results showed that Rho-associated coiled-coil containing protein kinase 1 (ROCK1) is targeted by miR-136-5p. The results of recovery experiments showed that ROCK1 overexpression partly rescued the impact of circTIMELESS silencing and miR-136-5p upregulation on proliferation and invasion. Consequently, our findings confirmed that circTIMELESS exists in LUSC and acts as a tumor promoter through the miR-136-5p/ROCK1 axis. Based on these findings, circTIMELESS may be potentially utilized as a therapeutic target for LUSC.

4.
Am J Chin Med ; 48(1): 17-45, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31931596

RESUMO

Licorice is extensively applied in food as well as herbal medicine across the world, possessing a substantial share in the global market. It has made great progress in chemical and pharmacological research in recent years. Currently, Glycyrrhiza uralensis Fisch., Glycyrrhiza inflata Bat., and Glycyrrhiza glabra L. were officially used as Gan-Cao according to the Chinese Pharmacopoeia. Accumulating evidence demonstrated three varieties of licorice have their own special compounds except for two quality markers set by Pharmacopoeia, providing great possibility for better understanding their characteristics, evaluating quality of each species and studying biosynthesis mechanisms of species-specific compounds. As a special "guide drug" in clinic, licorice plays an important role in Chinese herbal formulas. The interaction between licorice with other ingredients and their metabolism in vivo should also be taken into consideration. In addition, draft genome annotation, and success of the final step of glycyrrhizin biosynthesis have paved the way for biosynthesis of other active constituents in licorice, a promising beginning of solving source shortage. Accordingly, we comprehensively explored the nearly 400 chemical compounds found in the three varieties of licorice so far, systematically excavated various pharmacological activities, including metabolism via CYP450 system in vivo, and introduced the complete biosynthesis pathway of glycyrrhizin in licorice. The review will facilitate the further research toward this herbal medicine.

5.
J Cell Mol Med ; 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32000299

RESUMO

Epidemiological studies have found that diabetes and cognitive dysfunction are closely related. Quercetin has been certified with the effect on improving diabetes mellitus (DM) and cognitive impairment. However, the effect and related mechanism of quercetin on diabetic encephalopathy (DE) are still ambiguous. In this study, we used the db/db mice (diabetic model) to discover whether quercetin could improve DE through the Sirtuin1/NLRP3 (NOD-, LRR- and pyrin domain-containing 3) pathway. Behavioural results (Morris water maze and new object recognition tests) showed that quercetin (70 mg/kg) improved the learning and memory. Furthermore, quercetin alleviated insulin resistance and the level of fasting blood glucose. Besides, Western blot analysis also showed that quercetin increased the protein expressions of nerve- and synapse-related protein, including postsynapticdensity 93 (PSD93), postsynapticdensity 95 (PSD95), brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the brain of db/db mice. Quercetin also increased the protein expression of SIRT1 and decreased the expression of NLRP3 inflammation-related proteins, including NLRP3, the adaptor protein ASC and cleaved Caspase-1, the pro-inflammatory cytokines IL-1ß and IL-18. In conclusion, the present results indicate that the SIRT1/NLRP3 pathway may be a crucial mechanism for the neuroprotective effect of quercetin against DE.

6.
Channels (Austin) ; 14(1): 18-27, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31842669

RESUMO

OBJECTIVE: To explore the research status, hotspots, and trends in research on potassium channel. METHODS: The Web of Science core collection database was used as the data source and the visual analysis software Citespace5.4 R3 was used to visualize the studies of potassium channel in the past 10 years. The national/institutional distribution, journal distribution, authors, and related research were discussed. Results 17,392 articles were obtained. The USA, Peoples R China, Germany, England, and Japan were the main countries in the field and University of California was the most important institution for the study of potassium channel. PLoS One was the most productive journal and proceedings of the national academy of sciences of the united states of america was the most frequently cited journal in potassium channel research. The author with the highest number was Colin G Nichols and the author with the highest co- cited frequency was Sanguinetti MC. The three hot spots of potassium channel research were gene expression, Ca2+ activated k+ channel and nitric oxide. The top four research frontiers of potassium channel research were bk channel,blood pressure,oxidative stress and electrophysiology. Conclusion The study provides a perspective for understanding the potassium channel research and provides valuable information for potassium channel researchers to identify potential collaborators, partner institutions, hot topics and research frontiers.

7.
Phytochem Anal ; 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31833631

RESUMO

INTRODUCTION: Ginseng Flos (GF), the flower bud of Panax ginseng, is a worthy functional food with medicinal potential. A few studies have focused on the comprehensive and systematic analysis of its major bioactive constituents. OBJECTIVE: The aims are to develop the methods of ultra-fast liquid chromatography coupled with triple quadrupole-time of flight tandem mass spectrometry (UFLC-Triple TOF-MS/MS) and ultra-fast liquid chromatography coupled with triple quadrupole-linear ion trap tandem mass spectrometry (UFLC-QTRAP-MS/MS) for the qualitative and quantitative analysis of the saponins in GF. METHODOLOGY: UFLC-Triple TOF-MS/MS and UFLC-QTRAP-MS/MS were established for the qualitative and quantitative analysis of the saponins in GF, separately. RESULTS: Fifty-one saponins were identified in GF using UFLC-Triple TOF-MS/MS method; among them, 21 saponins were characterized by comparing with standards. Furthermore, 12 ginsenosides (ginsenoside Re, Rg1 , Rf, 20(S)-Rg2 , 20(R)-Rg2 , Rb1 , Rc, Ro, Rb2 , F1 , Rd, and F2 ) were synchronously determined by UFLC-QTRAP-MS/MS method after the extraction with 70% methanol. This UFLC-QTRAP-MS/MS method showed good linearity (r >0.9991), the interday and intraday precision, repeatability and stability were all satisfied, the average recoveries of standard addition for the compounds were between 94.01% and 105.16%, and the relative standard deviations were less than 5%. CONCLUSION: The results are available for the comprehensive quality control and assessment of GF and its relative products.

8.
Molecules ; 25(1)2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31861777

RESUMO

Preoperative assessment of tumor invasiveness is essential to avoid overtreatment for patients with small-sized ground-glass nodules (GGNs) of 10 mm or less in diameter. However, it is difficult to determine the pathological state by computed tomography (CT) examination alone. Aberrant glycans has emerged as a tool to identify novel potential disease biomarkers. In this study, we used a lectin microarray-based strategy to investigate whether glycosylation changes in plasma immunoglobulin G (IgG) provide additional information about the invasiveness of small GGNs before surgery. Two independent cohorts (discovery set, n = 92; test set, n = 210) of GGN patients were used. Five of 45 lectins (Sambucus nigra agglutinin, SNA; Datura stramonium agglutinin, DSA; Galanthus nivalis agglutinin, GNA; Euonymus europaeus lectin, EEL; and Vicia villosa agglutinin, VVA) were identified as independent factors associated with pathological invasiveness of small GGNs (p < 0.01). Receiver-operating characteristic (ROC) curve analysis indicated the combination of these five lectins could significantly improve the accuracy of CT in diagnosing invasive GGNs, with an area under the curve (AUC) of 0.792 (p < 0.001), a sensitivity of 74.6%, and specificity of 74.4%, which was superior to current clinical biomarkers. These results suggest that the multilectin assay based on plasma IgG glycosylation may be a useful in vitro complementary test to enhance preoperative determination of the invasiveness of GGNs and guide surgeons to select proper clinical management to avoid overtreatment.

9.
Sci Rep ; 9(1): 16666, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31723166

RESUMO

In this study, a fingerprint-activity relationship between chemical fingerprints and hepatoprotective activity was established to evaluate the quality of salt-treated Apocyni Veneti Folium (AVF). Characteristic fingerprints of AVF samples exposed to different concentrations of salt were generated by ultrafast liquid chromatography tandem triple time-of-flight mass/mass spectrometry (UFLC-Triple TOF-MS/MS), and a similarity analysis was performed based on common characteristic peaks by hierarchical clustering analysis (HCA). Then, the hepatoprotective activity of AVF against CCl4-induced acute liver damage in mice was investigated by assessing biochemical markers and histopathology, which showed that a high dose of AVF exposed to low levels of salt stress produced a marked amelioration of hepatic damage compared with the other salt-treated AVF. Finally, fingerprint-activity relationship modeling, which was capable of discovering the bioactive markers used in the quality evaluation, was investigated by the chemical fingerprints and the hepatoprotective activities utilizing multivariate statistical analysis, gray correlation analysis (GCA) and bivariate correlation analysis (BCA). The results showed that the accumulation of polyphenols, such as flavonoids and phenolic acids, in AVF subjected to low levels of salt stress could result in the effective scavenging of free radicals. Therefore, the present study may provide a powerful strategy to holistically evaluate the quality of salt-treated AVF in combination with chemical fingerprint and bioactivity evaluation.

10.
Chem Pharm Bull (Tokyo) ; 67(10): 1104-1115, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31582630

RESUMO

Licorice is one of the ancient and most frequently applied herbs for its diverse phytochemicals. At present, wild resources of licorice have rapidly declined with increasing demand and the proportion of cultivated products in the market is quickly growing. However, the different level in chemical composition between the wild and cultivated licorice may result in the discrepancy in quality and pharmacological activity. Therefore, an ultra-fast liquid chromatography coupled with triple quadrupole-time of flight tandem mass spectrometry (UFLC-Triple TOF-MS/MS) method combined with multivariate statistical analysis technology was employed to explore chemical composition differences. The result showed that total 63 components were identified from licorice samples. The wild and the cultivated licorice are obviously classified into two groups according to principal component analysis (PCA). PCA and partial least squared discrimination analysis (PLS-DA) were also introduced to rapidly find 14 candidate compounds between two ecotypes of licorice. Apart from glycyrrhizin, licorice saponin J2/G2, glyasperin D and dehydroglyasperin D also could be selected as chemical markers based on t-test and variable importance in the projection (VIP) value. Our study successfully established an effective method for exploring metabolite profiling between two ecotypes of licorice and laying the foundation for distinguishing wild and cultivated licorice.


Assuntos
Glycyrrhiza/metabolismo , Extratos Vegetais/metabolismo , Cromatografia Líquida , Glycyrrhiza/química , Estrutura Molecular , Análise Multivariada , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Espectrometria de Massas em Tandem , Fatores de Tempo
11.
Eur J Radiol ; 120: 108690, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31605964

RESUMO

PURPOSE: To characterise the pattern of change of diffusional kurtosis imaging (DKI) parameters (including kurtosis and diffusion parameters) in both white matter and gray matter in normal brain development with a large sample of subjects from term-born neonates to 14-years old children. METHODS: Two hundred and eighteen normal children (136 male, 82 female) underwent conventional magnetic resonance imaging and DKI. Regions of interest (ROIs) were placed in 7 white matter areas and 4 gray matter areas. Then the DKI-derived parameters were automatically calculated, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (Da), radial diffusivity (Dr), mean kurtosis (MK), axial kurtosis (Ka) and radial kurtosis (Kr). The correlation between the DKI parameters and ages were analyzed using nonlinear fit, and the rate of parameter change was computed compared to the baseline value of the neonates. RESULTS: For all ROIs in the white matter and gray matter, the FA, MK, Kr, Ka values increased with age, while the MD and Dr values decreased with age. The correlations were good to excellent, which changed rapidly within the first 2 years and relatively slowly after 2 years. The Da values in peripheral white matters and some gray matter structures (caudate nucleus and putamen) decreased with age. The amplitude of kurtosis parameters variation was greater than that of the diffusion parameters in both white matter and gray matter. CONCLUSIONS: The DKI parameters correlated well with age, and kurtosis parameters showed a potential advantage in detecting the normal brain development of children.


Assuntos
Mapeamento Encefálico/métodos , Encéfalo/anatomia & histologia , Encéfalo/fisiologia , Desenvolvimento Infantil/fisiologia , Imagem de Tensor de Difusão/métodos , Adolescente , Fatores Etários , Algoritmos , Criança , Pré-Escolar , Feminino , Substância Cinzenta/anatomia & histologia , Substância Cinzenta/fisiologia , Humanos , Lactente , Recém-Nascido , Masculino , Valores de Referência , Substância Branca/anatomia & histologia , Substância Branca/fisiologia
12.
Plant Physiol Biochem ; 144: 187-196, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31585397

RESUMO

Apocyni Veneti Folium (AVF) has been raised great interest in the antioxidant properties recently for the preservation of human health. However, little research was found on the integrate metabolites except our previous investigation on the variations of the bioactive constituents. To understand the salt-tolerant mechanisms of the halophyte, metabolomic platform based on ultra-fast liquid chromatography tandem triple time-of-flight mass/mass spectrometer was applied in this study. The results showed that metabolic profiles were separated and differentiated among groups based on multivariate statistical analysis; different metabolites belonged to various chemical classes. Besides, phenylpropanoid pathway and terpenoid biosynthesis were disturbed in all salt-stressed AVF and low salt-treated group appeared to be better than other samples in terms of relative contents (peak areas) of the wide variety of bioactive components and physiological variations of photosynthetic pigments, osmotic homeostasis, lipid peroxidation product and antioxidative enzymes. This study may provide additional insight into the salt-tolerant mechanisms and the quality assessment of AVF in a holistic level based on the plant metabolomics.


Assuntos
Metabolômica/métodos , Folhas de Planta/metabolismo , Flavonoides/metabolismo , Análise Multivariada , Folhas de Planta/genética , Estresse Salino/genética , Estresse Salino/fisiologia , Cloreto de Sódio/farmacologia , Espectrometria de Massas em Tandem
13.
Molecules ; 24(18)2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31487946

RESUMO

Ophiopogonis Radix, also known as Mai-dong in Chinese, was a commonly used traditional Chinese medicine (TCM) and functional health food. Two products of Ophiopogonis Radix are largely produced in the Sichuan and Zhejiang province, which are called "Chuan maidong (CMD)" and "Zhe maidong (ZMD)" respectively. To distinguish and evaluate the quality of CMD and ZMD, an analytical method based on ultra-fast performance liquid chromatography coupled with triple quadrupole-linear ion trap mass spectrometry (UFLC-QTRAP-MS/MS) was established for simultaneous determination of 32 constituents including 4 steroidal saponins, 3 homisoflavonoids, 15 amino acids, and 10 nucleosides in 27 Mai-dong samples from Sichuan and Zhejiang. Furthermore, principal components analysis (PCA), partial least squares discriminant analysis (PLS-DA), t-test, and grey relational analysis (GRA) were applied to discriminate and evaluate the samples from Sichuan and Zhejiang based on the contents of 32 constituents. The results demonstrated that the bioactive constituents in CMD and ZMD were significantly different, and CMD performed better in the quality assessment than ZMD. This study not only provides a basic information for differentiating CMD and ZMD, but offers a new insight into comprehensive evaluation and quality control of Ophiopogonis Radix from two different producing areas.


Assuntos
Acanthaceae/química , Medicina Tradicional Chinesa/normas , Cromatografia Líquida de Alta Pressão , Análise Discriminante , Geografia , Controle de Qualidade , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem
14.
Chem Pharm Bull (Tokyo) ; 67(8): 839-848, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366833

RESUMO

Panacis Japonici Rhizoma (PJR) contains various kinds of saponins, which possesses extensive pharmacological activities, but studies of comprehensive analysis of its saponins were limited. Thus, ultra-fast liquid chromatography coupled with triple quadrupole-time of flight tandem mass spectrometry (UFLC-Triple TOF-MS/MS) and ultra-fast liquid chromatography coupled with triple quadrupole-linear ion trap tandem mass spectrometry (UFLC-QTRAP-MS/MS) methods were established for the qualitative and quantitative analysis of the saponins in PJR, separately. Fifty three saponins in PJR were identified by UFLC-Triple TOF-MS/MS method, 23 saponins of which were unequivocally identified by reference substances. In addition, fragmentation pathways of different types of saponins were preliminarily deduced by fragmentation behavior of 53 saponins. Furthermore, the simultaneous determination of the contents of 13 saponins in PJR samples harvested at different times were analyzed by UFLC-QTRAP-MS/MS method. Furthermore, the quality of the samples was evaluated by grey relational analysis. This study might be beneficial to the quality assessment and control of PJR. Meanwhile, it might provide the basic information for confirming its optimal harvested period.


Assuntos
Rizoma/química , Saponinas/análise , Cromatografia Líquida , Conformação Molecular , Espectrometria de Massas em Tandem , Fatores de Tempo
15.
Biochemistry ; 58(36): 3735-3743, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31424194

RESUMO

The conserved structural motif D is an important determinant of the speed and fidelity of viral RNA-dependent RNA polymerases (RdRps). Structural and computational studies have suggested that conformational changes in the motif-D loop that help to reposition the catalytic lysine represent critical steps in nucleotide selection and incorporation. Conformations of the motif-D loop in the poliovirus RdRp are likely controlled in part by noncovalent interactions involving the motif-D residue Glu364. This residue swivels between making interactions with Lys228 and Asn370 to stabilize the open and closed loop conformations, respectively. We show here that we can rationally control the motif-D loop conformation by breaking these interactions. The K228A variant favors a more active closed conformation, leading to increased nucleotide incorporation rates and decreased nucleotide selectivity, and the N370A variant favors a less active open conformation, leading to decreased nucleotide incorporation rates and increased nucleotide selectivity. Similar competing interactions likely control nucleotide incorporation rates and fidelity in other viral RdRps. Rational engineering of these interactions may be important in the generation of live, attenuated vaccine strains, considering the established relationships between RdRp function and viral pathogenesis.

16.
ACS Appl Mater Interfaces ; 11(36): 33428-33434, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31408316

RESUMO

High-power GaN-based electronics are limited by high channel temperatures induced by self-heating, which degrades device performance and reliability. Increasing the thermal boundary conductance (TBC) between GaN and SiC will aid in the heat dissipation of GaN-on-SiC devices by taking advantage of the high thermal conductivity of SiC substrates. For the typical growth method, there are issues concerning the transition layer at the interface and low-quality GaN adjacent to the interface, which impedes heat flow. In this work, a room-temperature bonding method is used to bond high-quality GaN to SiC directly, which allows for the direct integration of high-quality GaN with SiC to create a high TBC interface. Time-domain thermoreflectance is used to measure the GaN thermal conductivity and GaN-SiC TBC. The measured GaN thermal conductivity is larger than that of grown GaN-on-SiC by molecular beam epitaxy. High TBC is observed for the bonded GaN-SiC interfaces, especially for the annealed interface (∼230 MW m-2 K-1, close to the highest value ever reported). Thus, this work provides the benefit of both a high TBC and higher GaN thermal conductivity, which will impact the GaN-device integration with substrates in which thermal dissipation always plays an important role. Additionally, simultaneous thermal and structural characterizations of heterogeneous bonded interfaces are performed to understand the structure-thermal property relation across this new type of interface.

17.
Metab Brain Dis ; 34(4): 1029-1041, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31152340

RESUMO

Increasing evidence indicates that excessive drug consumption is sufficient for the transition from recreational and controlled drug use to uncontrolled use and addiction. However, the underlying mechanisms are debated. Some neurobehavioral and neuroimaging evidence indicates that dorsolateral striatum (dlStr)-dependent habit learning plays a key role in excessive drug intake and the transition to addiction, but little is known about the molecular events. The present study investigated whether dlStr miR-134, an important regulator of synaptic transmission and plasticity, is involved in excessive methamphetamine intake. We established excessive and uncontrolled methamphetamine self-administration model in rats by permitting animals extended access to drug (6 h/session/d, LgA group), whereas animals that were limited to access to drug (2 h/session/d, ShA group) exhibited low and controlled self-administration. miR-134 expression in dlStr was significantly increased and its target LIMK1 expression was decreased in the LgA group, but not in the ShA group, compared with the saline control group. However, passive methamphetamine exposure did not alter miR-134 and LIMK1 levels in dlStr. We also found that down-regulation of miR-134 in dlStr through local microinjection of a lentivirus carrying miR-134 sponge (LV-miR-134-Sil) significantly reduced methamphetamine infusions and excessive consumption in LgA group, rather than ShA group. These results indicated that dlStr miR-134, perhaps via its target LIMK1, contributed to excessive and uncontrolled methamphetamine intake, supporting the hypothesis that stimulus-response habit formation is an important mechanism underlying the transition from controlled drug use to uncontrolled drug use and addiction.

18.
ACS Appl Mater Interfaces ; 11(20): 18517-18527, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31042348

RESUMO

The development of electronic devices, especially those that involve heterogeneous integration of materials, has led to increased challenges in addressing their thermal operational temperature demands. The heat flow in these systems is significantly influenced or even dominated by thermal boundary resistance at the interface between dissimilar materials. However, controlling and tuning heat transport across an interface and in the adjacent materials has so far drawn limited attention. In this work, we grow chemical vapor-deposited diamond on silicon substrates by graphoepitaxy and experimentally demonstrate tunable thermal transport across diamond membranes and diamond-silicon interfaces. We observed the highest diamond-silicon thermal boundary conductance (TBC) measured to date and increased diamond thermal conductivity due to strong grain texturing in the diamond near the interface. Additionally, nonequilibrium molecular dynamics simulations and a Landauer approach are used to understand the diamond-silicon TBC. These findings pave the way for tuning or increasing thermal conductance in heterogeneously integrated electronics that involve polycrystalline materials and will impact applications including electronics thermal management and diamond growth.

19.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1864(8): 1124-1133, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31054325

RESUMO

Hypercholesterolemia is a preventable risk factor for atherosclerosis and cardiovascular disease. However, the mechanisms of diosgenin (DG) that promote cholesterol homeostasis and alleviate hypercholesterolemia remain elusive. To investigate the effects and molecular mechanisms of the promotion of cholesterol metabolism by DG, a rat model of hypercholesterolemia was induced by providing a high-fat diet for 4 weeks. After 4 weeks, the rats were intragastrically administered high-dose DG (0.3 g/kg/d), low-dose DG (0.15 g/kg/d) or simvastatin (4 mg/kg/d) once a day for 8 weeks. The serum and hepatic cholesterol were tested, the mRNA and protein expression levels of Niemann-Pick C1-Like 1 (NPC1L1), liver X receptor-α (LXR-α) and the ATP-binding cassette G5/G8 (ABCG5/G8) transporters were measured. The results indicate that DG could reduce body weight, decrease the serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, liver total cholesterol and free cholesterol levels compared to those in the controls. Simultaneously, liver tissue pathological morphology analyses revealed that DG could attenuate hepatic steatosis compared to that in the high-fat diet group. Further investigation demonstrated that DG significantly decreased the expression of NPC1L1 and LXR-α in the intestine and markedly increased the expression of ABCG5/G8 in the liver and intestine. Compared to the high-fat diet group, the rats in the DG-treated groups ameliorated hypercholesterolemia in a dose- and time-dependent manner. These data suggest that DG may not only inhibit intestinal cholesterol absorption by downregulating NPC1L1 but also enhance cholesterol excretion by increasing the expression of ABCG5/G8. DG could be a new candidate for the prevention of hypercholesterolemia.


Assuntos
Membro 5 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/agonistas , Membro 8 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/agonistas , Colesterol/metabolismo , Diosgenina/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Proteínas de Membrana Transportadoras/efeitos dos fármacos , Animais , Anticolesterolemiantes , Colesterol/sangue , Diosgenina/farmacologia , Hipercolesterolemia/metabolismo , Hipercolesterolemia/prevenção & controle , Mucosa Intestinal/metabolismo , Intestinos , Fígado/metabolismo , Ratos
20.
Biomed Res Int ; 2019: 4805926, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30937311

RESUMO

Shuangyu Tiaozhi Granule (STG) is composed of two kinds of Chinese medicinal herbs in dioscorea, which are used for managing cholesterol levels in patients with hypercholesterolemia in traditional Chinese medicine (TCM). However, the potential molecular mechanisms of administration of STG in hypercholesterolemia remain unknown. In this study, we investigated the effects of STG on hepatic cholesterol metabolism in high cholesterol (HC) diet-induced hypercholesterolemic rat models and simvastatin was used as a positive control. Male Sprague Dawley (SD) rats were fed general or HC diet, respectively. After 4 weeks of feeding, HC diet-induced hypercholesterolemic rats were fed HC diet, STG at 5% (w/w) or 10% (w/w) mixed in the HC diet, or HC diet combined with simvastatin gavages (4 mg·kg-1·d-1) for 4 or 8 weeks. STG treatment decreased body weight gain, liver weight ratio, serum lipids levels and hepatic lipids accumulation in rats fed a HC diet. Moreover, the effects of STG on decreasing body weight and lowering liver cholesterol levels were in dose- and time-dependent. Furthermore, STG or simvastatin treatment decreased the mRNA and protein levels of HMGCR and SREBP-2 in liver. The ACAT-2 and CYP7A1 mRNA expression were significantly decreased in HC diet supplemented with STG, while the mRNA levels of LDLR were markedly increased. STG attenuates hypercholesterolemia via inhibiting SREBP-2 signaling pathway activation and increasing hepatic uptake genes expression, providing a novel idea of TCM keeping cholesterol levels down for the clinical application.


Assuntos
Colesterol na Dieta/administração & dosagem , Colesterol/biossíntese , Medicamentos de Ervas Chinesas/uso terapêutico , Comportamento Alimentar , Hipercolesterolemia/tratamento farmacológico , Animais , Peso Corporal/efeitos dos fármacos , Fígado Gorduroso/tratamento farmacológico , Fígado Gorduroso/patologia , Hidroximetilglutaril-CoA Redutases/metabolismo , Hipercolesterolemia/sangue , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Modelos Biológicos , Tamanho do Órgão/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo
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