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1.
Int J Biol Macromol ; 190: 463-473, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34506859

RESUMO

Xanthine oxidase (XO) plays a vital role in inducing hyperuricemia and increasing the level of superoxide free radicals in blood, and is proved as an important target for gout. Chrysoeriol (CHE) is a natural flavone with potent XO inhibitory activity (IC50 = 2.487 ± 0.213 µM), however, the mechanism of interaction is still unclear. Therefore, a comprehensive analysis of the interaction between CHE and XO was accomplished by enzyme kinetics, isothermal titration calorimetry (ITC), multi-spectroscopic methods, molecular simulation and ADMET. The results showed that CHE acted as a rapid reversible and competitive-type XO inhibitor and its binding to XO was driven by hydrogen bonding and hydrophobic interaction. Moreover, CHE exhibited a strong fluorescence quenching effect through a static quenching procedure and induced conformational changes of XO. Its binding pattern with XO was revealed by docking study and the binding affinity to XO was enhanced by the interactions with key amino acid residues in the active pocket of XO. Further, CHE showed good stability and pharmacokinetic behavior properties in molecule dynamic simulation and ADMET prediction. Overall, this study shed some light on the mechanism of interaction between CHE and XO, also provided some valuable information concerning the future therapeutic application of CHE as natural XO inhibitor.

2.
Comput Math Methods Med ; 2021: 5221111, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34589137

RESUMO

Trigeminal neuralgia is a neurological disease. It is often treated by puncturing the trigeminal nerve through the skin and the oval foramen of the skull to selectively destroy the pain nerve. The process of puncture operation is difficult because the morphology of the foramen ovale in the skull base is varied and the surrounding anatomical structure is complex. Computer-aided puncture guidance technology is extremely valuable for the treatment of trigeminal neuralgia. Computer-aided guidance can help doctors determine the puncture target by accurately locating the foramen ovale in the skull base. Foramen ovale segmentation is a prerequisite for locating but is a tedious and error-prone task if done manually. In this paper, we present an image segmentation solution based on the multiatlas method that automatically segments the foramen ovale. We developed a data set of 30 CT scans containing 20 foramen ovale atlas and 10 CT scans for testing. Our approach can perform foramen ovale segmentation in puncture operation scenarios based solely on limited data. We propose to utilize this method as an enabler in clinical work.

3.
Acta Virol ; 65(3): 273-278, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34565155

RESUMO

African swine fever (ASF) is an acute and severe infectious disease that seriously endangers the global porcine industry. In order to develop ASF serodiagnostic reagents with high specificity and sensitivity, in the present study, the antigenic epitopes of P72 protein of African swine fever virus (ASFV) were analyzed, and the ASFV multi-epitope fusion gene MeP72 in tandem with the dominant linear epitopes was constructed. The recombinant multi-epitope fusion MeP72 (reMeP72) was prepared in Escherichia coli. A colloidal gold-based immunochromatographic assay (CGIA) based on reMeP72 was developed for the detection of antibodies against ASFV. A total of 139 pig clinical serum samples were used for assessment of the potential diagnostic value of reMeP72. The results showed that CGIA did not cross-react with positive sera of viruses, such as classical swine fever virus (CSFV), porcine circovirus type 2 (PCV2), pseudorabies virus (PRV), porcine reproductive and respiratory syndrome virus (PRRSV) and swine influenza virus (SIV), showing high specificity. Sensitivity analysis showed that CGIA could detect ASFV-positive serum at a dilution of 1:64. Compared with commercial ASFV kits, the sensitivity and specificity of ASFV CGIA based on reMeP72 protein were 85.7% and 97.6%, respectively. The agreement rate of the two methods was 96.4%, showing a good detection performance. The results indicated that the reMeP72 was of potential value for the serodiagnosis of ASF. Keywords: African swine fever virus; P72 gene; antigenic protein; colloidal gold-based immunochromatographic assay.


Assuntos
Vírus da Febre Suína Africana , Febre Suína Africana , Vírus da Síndrome Respiratória e Reprodutiva Suína , Febre Suína Africana/diagnóstico , Vírus da Febre Suína Africana/genética , Animais , Epitopos , Testes Sorológicos , Suínos
4.
ESC Heart Fail ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34545695

RESUMO

AIMS: Rheumatic heart disease (RHD) remains a major global health problem. Renin-angiotensin-aldosterone system inhibitors (RAASi) are commonly administered in the treatment of cardiovascular disease, but its role in RHD patients is still limited. We performed a retrospective study to determine the effect of RAASi on long-term outcomes for RHD patients. METHODS AND RESULTS: A 1:1 propensity score matching was implemented to balance baseline characteristics between groups RAASi and non-RAASi. Cox proportional hazards regression model was used to investigate the associations of RAASi with the risks of all-cause mortality, cardiovascular death (CVD), and cerebrovascular death. Binary logistic regression analysis was used to evaluate the associations of RAASi with the risks of 1, 3, and 5 year heart failure (HF) rehospitalization, new-onset atrial fibrillation (AF), and new-onset stroke. A total of 734 RHD patients were enrolled as study participants; nearly half of these participants had combined valve damage (54.4%), worse New York Heart Association functional class status (III and IV, 55.2%), surgical treatment (54.2%), and AF (65.0%). After propensity score matching, 514 RHD patients were finally analysed. RAASi treatment was associated with decreased risks of all-cause mortality [adjusted hazard ratio (HR) = 0.52, 95% confidence interval (CI): 0.37-0.73, P < 0.001], CVD (adjusted HR = 0.48, 95% CI: 0.30-0.76, P = 0.002), and cerebrovascular death (adjusted HR = 0.22, 95% CI: 0.08-0.60, P = 0.003). Further subgroup analysis showed that RAASi treatment was associated with decreased risks of all-cause mortality (adjusted HR = 0.50, 95% CI: 0.31-0.79, P = 0.004), CVD (adjusted HR = 0.48, 95% CI: 0.25-0.91, P = 0.025), and cerebrovascular death (adjusted HR = 0.19, 95% CI: 0.05-0.65, P = 0.008) in RHD patients without surgical treatment, and better effect was observed in RHD patients with surgical treatment on the risks of all-cause mortality (adjusted HR = 0.47, 95% CI: 0.26-0.85, P = 0.012) and CVD (adjusted HR = 0.43, 95% CI: 0.21-0.90, P = 0.024) except cerebrovascular death (adjusted HR = 0.52, 95% CI: 0.08-3.36, P = 0.491). RAASi treatment was associated with decreased HF rehospitalization risk of 1 year [adjusted odds ratio (OR) = 0.38, 95% CI: 0.23-0.61, P < 0.001], 3 year (adjusted OR = 0.43, 95% CI: 0.28-0.68, P < 0.001), and 5 year (adjusted OR = 0.48, 95% CI: 0.30-0.77, P = 0.002) as well as new-onset AF risk (adjusted OR = 0.38, 95% CI: 0.21-0.68, P = 0.001). RAASi treatment had nothing to do with new-onset stroke risk (adjusted OR = 0.80, 95% CI: 0.47-1.38, P = 0.428). CONCLUSION: Renin-angiotensin-aldosterone system inhibitor treatment was significantly associated with decreased risks of mortality, HF rehospitalization, and new-onset AF in RHD patients in median 5.9 year follow-up.

5.
J Agric Food Chem ; 69(32): 9407-9418, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34369753

RESUMO

The profiles of soluble and insoluble phenolic compounds in 11 commercial red sorghums (B11, B12, B13, B14, J124, J127, J138, J140, J142, J152, and J158) were investigated using ultraperformance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) analysis. A total of 48 phenolic compounds including 35 phenolic acids and their derivatives, 12 flavonoids, and 1 proanthocyanidin were identified, and 8 phenolic compounds were reported for the first time in sorghums. Four major 3-deoxyanthocyanidins were also quantified, with their soluble forms accounting for 99.75-99.87% of the total contents. Pearson's correlation analyses indicated that 3-deoxyanthocyanidins significantly contributed to the antioxidant capacities of the red sorghums and that 5-methoxy-luteolinidin showed the strongest correlation. Besides, the soluble phenolic fraction of B13 dose-dependently inhibited the proliferation of Caco-2 cells and the secretion of IL-1ß and NO in RAW264.7 macrophages, which might be attributed to its relatively high total phenolic (TPC), flavonoid (TFC), and proanthocyanidin content (TPAC) values and radical scavenging capacities.


Assuntos
Sorghum , Antioxidantes , Células CACO-2 , Cromatografia Líquida de Alta Pressão , Flavonoides/análise , Humanos , Fenóis , Extratos Vegetais/farmacologia
7.
Medicine (Baltimore) ; 100(33): e26946, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34414956

RESUMO

ABSTRACT: This study aimed to investigate the association between serum uric acid (SUA) level and nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes (T2DM).T2DM patients hospitalized in the Department of Hepatology, Yantai Qishan Hospital, between April 2012 and December 2018 were classified into the NAFLD group and the non-NAFLD group. Clinical data, glucose and lipid metabolism biomarkers, and liver and kidney function parameters were retrospectively collected.Five hundred eighty-three T2DM patients met the inclusion and exclusion criteria; 227 patients were included in the non-NAFLD group and 356 patients were included in the NAFLD group. Multiple linear regression analyses showed that SUA was positively correlated with body mass index (P = .003), triglycerides (P = .009), aspartate aminotransferase (P = .036), and alanine aminotransferase (P = .038) and negatively correlated with estimated glomerular filtration rate (P < .001) in T2DM patients. Multivariate regression analyses demonstrated that after adjusting for confounding factors, the SUA tertile was still significantly associated with NAFLD occurrence in T2DM patients (P for trend = .008). With reference to SUA tertile I, the odds ratios for NAFLD in the SUA tertile II and tertile III groups were 1.729 (95% confidence interval [CI]: 1.086-2.753) and 2.315 (95% CI: 1.272-4.213), respectively.The level of SUA in T2DM patients was associated with the occurrence of NAFLD. Elevated SUA was associated with a significantly increased prevalence of NAFLD. The SUA level was an independent risk factor for NAFLD occurrence in patients with T2DM.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Hepatopatia Gordurosa não Alcoólica/sangue , Ácido Úrico/sangue , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/complicações , Feminino , Taxa de Filtração Glomerular , Humanos , Metabolismo dos Lipídeos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Fatores de Risco
8.
J Vet Sci ; 22(4): e50, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34170091

RESUMO

BACKGROUND: Bovine papillomatosis is a type of proliferative tumor disease of skin and mucosae caused by bovine papillomavirus (BPV). As a transboundary and emerging disease in cattle, it poses a potential threat to the dairy industry. OBJECTIVES: The aim of this study is to detect and clarify the genetic diversity of BPV circulating in dairy cows in Xinjiang, China. METHODS: 122 papilloma skin lesions from 8 intensive dairy farms located in different regions of Xinjiang, China were detected by polymerase chain reaction. The genetic evolution relationships of various types of BPVs were analyzed by examining this phylogenetic tree. RESULTS: Ten genotypes of BPV (BPV1, BPV2, BPV3, BPV6, BPV7, BPV8, BPV10, BPV11, BPV13, and BPV14) were detected and identified in dairy cows. These were the first reported detections of BPV13 and BPV14 in Xinjiang, Mixed infections were detected, and there were geographical differences in the distribution of the BPV genotypes. Notably, the BPV infection rate among young cattle (< 1-year-old) developed from the same supply of frozen sperm was higher than that of the other young cows naturally raised under the same environmental conditions. CONCLUSIONS: Genotyping based on the L1 gene of BPV showed that BPVs circulating in Xinjiang China displayed substantial genetic diversity. This study provided valuable data at the molecular epidemiology level, which is conducive to developing deep insights into the genetic diversity and pathogenic characteristics of BPVs in dairy cows.


Assuntos
Doenças dos Bovinos/virologia , Deltapapillomavirus/genética , Deltapapillomavirus/isolamento & purificação , Variação Genética , Infecções por Papillomavirus/veterinária , Animais , Bovinos , Doenças dos Bovinos/epidemiologia , Indústria de Laticínios , Feminino , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia
9.
Hypertens Res ; 44(9): 1158-1167, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34035483

RESUMO

Although emerging data suggest that circulating lipoprotein (a) [Lp (a)] could predict cardiovascular events (CVEs) in patients with cardiovascular disease, no study is currently available regarding the prognostic linkage of Lp (a) and hypertension in patients with coronary artery disease (CAD). This study sought to evaluate the association of Lp (a), hypertension and cardiovascular outcomes in patients with stable CAD. A total of 8668 patients with stable CAD were consecutively enrolled. Baseline Lp (a) concentrations were measured. All subjects were categorized according to Lp (a) levels of <10 (low), 10-30 (medium) and ≥30 mg/dL (high) and were further stratified by hypertension status. They were regularly followed-up for the occurrence of cardiovascular death, nonfatal myocardial infarction, and stroke. Over an average of 54.81 ± 18.60 months of follow-up, 584 (6.7%) CVEs occurred. Kaplan-Meier and multivariate Cox regression analyses showed that elevated Lp (a) levels had a significant association with CVEs in hypertensive patients, regardless of the control status of blood pressure, but not in normotensive subjects. Moreover, when analyzed by subgroups according to both Lp (a) category and hypertension status, the risk of CVEs was only significantly elevated in the high Lp (a) plus hypertension group compared with the reference group with low Lp (a) levels and normotension (hazard ratio: 1.80, 95% confidence interval: 1.11-2.91). Elevated Lp (a) was associated with an increased risk of CVEs in stable CAD patients with hypertension. Moreover, the coexistence of high Lp (a) concentrations and hypertension greatly worsened the clinical prognosis in patients with CAD, which may suggest a prognostic correlation between Lp (a) and hypertension.

10.
Pest Manag Sci ; 77(10): 4383-4392, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33969944

RESUMO

BACKGROUND: Tobacco mosaic virus (TMV) is one of destructive plant viruses, causing serious economic losses in the world. Using antiviral proteins or elicitors to inhibit viral infection or promote plant immunity is one of the efficient strategies against TMV. Our previous study identified that the fermentation broth of Brevibacillus laterosporus strain B8 showed strong antiviral activity against TMV. However, the active antiviral ingredient is still unclear. RESULTS: Here, BLB8 (B. laterosporus strain B8 protein, BLB8), an antiviral protein from B. laterosporus strain B8 was isolated and characterized. BLB8 showed protective, inactive and curative effects against TMV, and the inhibition rate reached up to 63%, 83% and 55%, respectively. BLB8 infiltrated around the infection site of the recombinant virus TMV-GFP inhibited the systemic extend and movement of TMV. Pretreatment of the bottom leaves with BLB8 inhibited the spread and accumulation of TMV in upper systemic leaves. Furthermore, BLB8 caused hypersensitive response (HR) in a dose-dependent way, promoted H2 O2 accumulation, and induced the expression of defense-relative genes in Nicotiana benthamiana. CONCLUSION: The antiviral protein BLB8 from B. laterosporus strain B8 effectively inhibits TMV infection in inactivation, protective and curative effects through triggering plant immunity in tobacco. Therefore, the present study provides a new antiviral agent for prevention and control of viral disease. © 2021 Society of Chemical Industry.


Assuntos
Vírus do Mosaico do Tabaco , Antivirais/farmacologia , Brevibacillus , Doenças das Plantas , Imunidade Vegetal , Tabaco
11.
Environ Sci Technol ; 55(11): 7376-7385, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33998794

RESUMO

Both decabromodiphenyl ether (BDE 209) and decabromodiphenyl ethane (DBDPE) are still produced in large quantities in China, especially in the Shandong Province closed to the Bohai Sea (BS). This study conducted a comprehensive investigation of the distribution and budget of brominated flame retardants (BFRs) in the BS. BDE 209 was the predominant BFR in most of the investigated rivers flowing into the BS, although DBDPE exceeded BDE 209 in certain rivers as a result of the replacement of BDE 209 with DBDPE in North China. The spatial distributions of BFRs in the rivers were controlled by the proximity of the BFR manufacturing base and the extent of urbanization. BFRs' spatial distribution in the BS was influenced by a combination of land-based pollution sources, environmental parameters (e.g., suspended particulate matter, particulate organic carbon, and particulate black carbon), and hydrodynamic conditions. The spatial variation trend of BDE 209/DBDPE ratios in various environmental media provided useful information. Vertically, the BDE 209/DBDPE ratio decreased from the seawater surface layer to the sediment, indicating their differential transport in the BS. A multi-box mass balance model and analysis of BDE 209 showed that degradation was the primary sink of BFRs in seawater (∼68%) and surface sediment (∼72%) in the BS.


Assuntos
Monitoramento Ambiental , Retardadores de Chama , Bromobenzenos/análise , China , Retardadores de Chama/análise , Éteres Difenil Halogenados/análise
12.
Pharmacol Res ; 169: 105615, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33872808

RESUMO

Naturally occurring coumestans are known as a collection of plant-derived polycyclic aromatic secondary metabolites which are characterized by the presence of an oxygen heterocyclic four-ring system comprising a coumarin moiety and a benzofuran moiety sharing a CË­C bond. Recently, there is an increasing attention in excavating the medicinal potential of coumestans, particularly coumestrol, wedelolactone, psoralidin and glycyrol, in a variety of diseases. This review is a comprehensive inventory of the chemical structures of coumestans isolated from various plant sources during the period of 1956-2020, together with their reported biological activities. 120 molecules were collected and further classified as coumestans containing core skeleton, dimethylpyranocoumestans, furanocoumestans, O-glycosylated coumestans and others, which showed a wide range of pharmacological activities including estrogenic, anti-cancer, anti-inflammatory, anti-osteoporotic, organ protective, neuroprotective, anti-diabetic and anti-obesity, antimicrobial, immunosuppressive, antioxidant and skin-protective activities. Furthermore, this review focuses on the counteraction of coumestans against bone diseases and organ damages, and the involved molecular mechanisms, which could provide important information to better understand the medicinal values of these compounds. This review is intended to be instructive for the rational design and development of less toxic and more effective drugs with a coumestan scaffold.

13.
J Agric Food Chem ; 69(15): 4542-4549, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33843233

RESUMO

3-Monochloropropane 1,2-diol (3-MCPD) esters are toxicants formed during food thermal processing, and their testicular toxicities were widely reported. In this 90 day in vivo study, Sprague-Dawley rats were treated with 3-MCPD 1-monooleate at 10 and 100 mg/kg body weight (bw)/day or 1-monostearate at 15 and 150 mg/kg bw/day. Histological results indicated that testicular impairment was observed, and the level of serum testosterone was decreased dose dependently, while the levels of serum transforming growth factor beta and interferon-γ in rats' serum were increased dose dependently. To address the molecular mechanisms leading to testicular toxicities of 3-MCPD esters, testes samples were investigated with a mass spectrometry proteomic approach. The deregulated proteins affected by 3-MCPD esters include many enzymes related with the inflammatory necrosis pathways. While verifying the results in cellular level, 3-MCPD 1-monooleate and 3-MCPD 1-monostearate showed almost similar testicular cytotoxicity, and they could activate RIPK1 and MLKL pathways at the cellular level. All of these results showed the possible mechanisms about the toxicity of 3-MCPD esters in rats' testes and play a vital role in understanding the toxic effects of 3-MCPD esters both in vivo and in vitro.


Assuntos
Proteômica , alfa-Cloridrina , Animais , Ésteres , Contaminação de Alimentos/análise , Masculino , Ratos , Ratos Sprague-Dawley , Testículo , alfa-Cloridrina/toxicidade
14.
Molecules ; 26(5)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33803186

RESUMO

In the current study, the chemical composition and total phenolic content of tomato seed flours, along with potential health beneficial properties, including free radical scavenging capacities, anti-inflammatory capacities, and gut microbiota profile modulation, were examined using two different batches. Eight compounds were identified in the tomato seed flour, including malic acid, 2-hydroxyadipic acid, salicylic acid, naringin, N-acetyl-tryptophan, quercetin-di-O-hexoside, kaempferol-di-O-hexoside, and azelaic acid. The total phenolic contents of tomato seed flour were 1.97-2.00 mg gallic acid equivalents/g. Oxygen radical absorbing capacities (ORAC), 2,2-diphenyl-1-picrylhydrazyl radical scavenging capacities (DPPH), and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) cation radical scavenging capacities (ABTS) were 86.32-88.57, 3.57-3.81, and 3.39-3.58 µmoles Trolox equivalents/g, respectively, on a per flour dry weight basis. The mRNA expression of the pro-inflammatory markers, interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α), were dose-dependently suppressed by tomato seed flour extracts. The extracts altered five of the eight bacterial phyla and genera evaluated. The results may provide some scientific support for the use of tomato seed flour as value-added food ingredients.


Assuntos
Lycopersicon esculentum/química , Sementes/química , Animais , Anti-Inflamatórios/análise , Antioxidantes/análise , Bactérias/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão/métodos , Fezes/microbiologia , Sequestradores de Radicais Livres/química , Microbioma Gastrointestinal/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fenóis/química , Extratos Vegetais/química
15.
J Exp Child Psychol ; 208: 105147, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33862531

RESUMO

Asymmetries in social status, specifically social status related to wealth and relational power, appear to influence the ways in which children allocate resources. However, the impact of wealth and relational power status on children's resource allocation decisions has yet to be examined among children developing within a Chinese cultural context. In addition, how children weight the relative importance of these factors when they exist concurrently is not well understood. In Study 1, we examined the impact of recipients' wealth and relational power status on Chinese children's (3- to 8-year-olds; N = 199) allocation decisions. We found that across both categories of social status, 3- and 4-year-olds gave more to high-status individuals, whereas 7- and 8-year-olds gave more to low-status individuals, despite younger children also showing a strong egalitarian preference when the resources could be allocated equally. In Study 2, we investigated how children (3- to 8-year-olds; N = 219) weigh the relative importance of these two types of social status in situations where the level of recipients' wealth and relational power were either consistent or in conflict. When they needed to allocate the resources unequally, the youngest children were found to place greater emphasis on wealth over relational power and favored the high-status individual, whereas older children tended to favor the low-status individual and placed greater importance on relational power over wealth. Overall, we found a consistent age-related shift from favoring high-status individuals toward compensating low-status individuals, suggesting a developing concern for social equity.

16.
Future Med Chem ; 13(9): 769-784, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33759552

RESUMO

Aim: Butyrylcholinesterase (BChE) is a crucial therapeutic target because it is associated with multiple pathological elements of Alzheimer's disease (AD). An integrated computational strategy was employed to exploit effective BChE inhibitors. Methods & results: Ten compounds derived from the Enamine database by structure-based pharmacophore virtual screening were further evaluated for biological activity; out of the ten, only five had an IC50 of less than 100 µM. Among these five compounds, a new molecule, 970180, presented the most potency against BChE, with an IC50 of 4.24 ± 0.16 µM, and acted as a mixed-type inhibitor. Molecular dynamic simulations and absorption, distribution, metabolism and excretion prediction further confirmed its high potential as a good candidate of BChE inhibitor. Furthermore, cytotoxicity of molecule 970180 was not observed at concentrations up to 50 µM, and the molecule also showed a prominent neuroprotective effect compared with tacrine at 25 and 50 µM. Conclusion: This study provides an effective structure-based pharmacophore virtual screening method to discover BChE inhibitors and provide new choices for the development of BChE inhibitors, which may be beneficial for AD patients.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Butirilcolinesterase/metabolismo , Inibidores da Colinesterase/química , Fármacos Neuroprotetores/química , Sobrevivência Celular/efeitos dos fármacos , Inibidores da Colinesterase/farmacologia , Bases de Dados de Compostos Químicos , Avaliação Pré-Clínica de Medicamentos , Humanos , Concentração Inibidora 50 , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Fármacos Neuroprotetores/farmacologia , Ligação Proteica , Relação Estrutura-Atividade
17.
Hepatol Int ; 15(2): 413-423, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33740211

RESUMO

BACKGROUND: Although non-invasive liver fibrosis scores (LFSs) have already been considered as effective tools for estimating cardiovascular risk, their roles in predicting disease severity and cardiovascular event (CVEs) in patients with stable coronary artery disease (CAD) are not comprehensively evaluated. The aim of the present study was to investigate whether non-alcoholic fatty liver disease fibrosis score (NAFLD-FS) and fibrosis-4 (FIB-4) are associated with CVEs in a large cohort with long-term follow-up. METHODS: A cohort of 5143 patients with angiography-proven stable CAD were consecutively enrolled and followed up for CVEs. The degree of coronary severity was assessed using the number of diseased vessels, Gensini, Syntax, and Jeopardy scores. The predictive values of NAFLD-FS and FIB-4 scores to coronary severity, coronary calcification (CAC), and CVEs were assessed, respectively. RESULTS: During a median follow-up of 7 years, 435 CVEs were recorded. Both NAFLD-FS and FIB-4 were predictors for the presence of CAC. The degree of coronary stenosis was significantly higher in high NAFLD-FS categories while FIB-4 was only positively associated with the number of diseased vessels and Gensini score. In Kaplan-Meier analysis, the patients with intermediate and high NAFLD-FS and FIB-4 had higher risk of CVEs and cardiovascular mortality. In multivariate Cox regression analysis, NAFLD-FS and FIB-4 were independently associated with CVEs [hazard ratio (95% confidence interval): 1.150 (1.063-1.244), p < 0.001 and 1.128 (1.026-1.240), p = 0.012]. CONCLUSION: The current data first indicated that both NAFLD-FS and FIB-4 scores were not only significantly related to coronary severity but also associated with CAC and CVEs. CLINICAL TRIALS REGISTRATION: None.

18.
Zhongguo Zhong Yao Za Zhi ; 46(3): 635-637, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33645030

RESUMO

Three compounds, including scolosprine C(1), uracil(2) and hypoxanthine(3), were isolated and purified from the ethyl acetate fraction of centipede by silica gel normal-phase column chromatography, reversed-phase medium pressure preparation chromatography, and high-pressure semi-preparative HPLC. The structure was elucidated through a combination of spectroscopic analyses [such as nuclear magnetic resonance(NMR) and mass spectrometry(MS)] and literature review. Among them, compound 1 was a new quinoline alkaloid. In previous reports, we have described the isolation and structure elucidation of one new and two known quinoline alkaloids. In this paper, we would report the isolation and structure elucidation of scolosprine C in detail.


Assuntos
Alcaloides , Artrópodes , Quinolinas , Animais , Quilópodes
19.
Medicine (Baltimore) ; 100(6): e24627, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33578576

RESUMO

RATIONALE: Steroid-resistant nephrotic syndrome (SRNS) is a special kidney disease. SRNS is characterized by steroid-resistant, clinical variability, and genetic heterogeneity. Patients with SRNS often may eventually need renal transplantation. PATIENT CONCERNS: A 10-month-old Chinese male infant presented with oliguria, renal dysfunction, hypertension, and anemia. DIAGNOSES: Combined with clinical manifestations, laboratory testing and sequencing results, the patient was diagnosed as SRNS. INTERVENTIONS: Combined intravenous methylprednisolone and cefoperazone sulbactam did not improve the patient's condition. Thus, SRNS associated with hereditary nephrotic syndrome was strongly suspected. Genetic testing for hereditary renal disease of the patient revealed 2 novel heterozygous mutations in the Nucleoporin 93 (NUP93) gene, which were predicted pathogenic and harmful by bioinformatic softwares of SIFT, PolyPhen_2 and REVEL. OUTCOMES: As general physical health deterioration and renal dysfunction, the patient died of a severe infection. LESSONS: The novel NUP93 heterozygous mutations identified in the current study broadened the genetic spectrum of SRNS and further deepened our insight into pathogenic mutations of NUP93 to improve disease diagnosis.


Assuntos
Síndrome Nefrótica/diagnóstico , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Cefoperazona/administração & dosagem , Cefoperazona/uso terapêutico , Evolução Fatal , Aconselhamento Genético , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Lactente , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Síndrome Nefrótica/tratamento farmacológico , Síndrome Nefrótica/genética
20.
Artigo em Inglês | MEDLINE | ID: mdl-33606490

RESUMO

Gel electrolytes show certain advantages over conventional liquid and solid electrolytes, but their mechanical strength and surface adhesion to the electrode remain to be improved. To address the challenges, we design and fabricate herein the core-shell nanofiber mats in situ on the LiFePO4 electrode as matrices for gel electrolytes, in which the core is poly(m-phenylene isophthalamide) (PMIA) nanofiber and the shell are composite of Al2O3 nanoparticles and poly(vinylidene fluoride-co-hexafluoropropylene) (PVdF-HFP). The mechanical property of the core-shell polymeric nanofiber mats and their surface interaction with LiFePO4 electrode are characterized complementarily using dynamic thermomechanical analysis and scanning electron microscopy. The electrochemical properties of the gel electrolytes based on the as-prepared matrices after being loaded with lithium salt solution are studied systematically on half coin cells. It is found that the ultimate strength of the core-shell PMIA@PVdF-HFP/Al2O3 mat can reach 6.70 MPa, 2 times higher than that of the PVdF-HFP/Al2O3 nanofiber mat. Meanwhile, the shell PVdF-HFP/Al2O3 can ensure manifest surface affinity to the LiFePO4 electrode and enhance lithium-ion conductance. Thus, the as-assembled LiFePO4 half coin cells using PMIA@PVdF-HFP/Al2O3 gel electrolyte show good electrochemical performances, especially the long cycle stability with the capacity retention of 96.6% after 600 cycles under 1C.

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