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1.
Arch Oral Biol ; 163: 105941, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38599038

RESUMO

OBJECTIVE: Crown dimensions data of deciduous teeth hold anthropological, forensic, and archaeological value. However, such information remains scarce for the Chinese population. This multi-center study aimed to collect a large sample of deciduous crown data from Chinese children using three-dimensional measurement methods and to analyze their dimensions. DESIGN: A total of 1592 children's deciduous dentition samples were included, and the sample size was distributed according to Northeast, North, East, Northwest, Southwest and South China. Digital dental models were reconstructed from plaster dental models. Independent sample t test, paired t test, principal component analysis (PCA), and factor analysis (FA) were used to analyze the tooth crown dimensions. RESULT: 18,318 deciduous teeth from 1592 children were included. Males exhibited slightly larger values than females. The range of sexual dimorphism percentages for each measurement was as follows: mesiodistal diameter (0.40-2.08), buccolingual diameter (0.13-2.24), and maxillogingival diameter (0.48-3.37). The FA results showed that the main trend of crown dimensions changes was the simultaneous increase or decrease in mesiodistal diameter, buccolingual diameter and maxillogingival diameter in three directions. CONCLUSION: This is the first large-scale survey of deciduous tooth crown dimensions in China, which supplements the data of deciduous tooth measurement and provides a reference for clinical application.


Assuntos
Coroa do Dente , Dente Decíduo , Humanos , Dente Decíduo/anatomia & histologia , China , Masculino , Feminino , Estudos Transversais , Criança , Coroa do Dente/anatomia & histologia , Análise de Componente Principal , Modelos Dentários , Pré-Escolar , Imageamento Tridimensional/métodos , Odontometria/métodos , Análise Fatorial , Caracteres Sexuais
2.
Chem Commun (Camb) ; 60(1): 75-78, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38018515

RESUMO

Herein, a novel class of transfer hydrogenation agent, cycloheptanone, was successfully employed in metal-free hydrogenation facilitated by iodine. A series of alkenes, triphenylmethyl derivatives, and diphenylmethyl derivatives were reduced to the desired compounds in moderate to excellent yields. The transfer hydrodeuteration of alkenes using α-deuterated cyclododecanone exhibited high regioselectivity. Preliminary mechanism studies confirmed the origins of the two hydrogen atoms involved in the reduction of alkenes. The current study paves the way for the use of ketones as unique transfer hydrogenation agents in chemical synthesis.

3.
Front Immunol ; 14: 1192940, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37197654

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disease and linked to abnormal deposition of amyloid-ß (Aß), neurofibrillary tangles (NFTs), synaptic dysfunction, and neuroinflammation. Despite significant progress in unravelling the pathogenesis of AD, currently main therapeutic interventions is limited to symptomatic alleviation. Methylprednisolone (MP), a synthetic glucocorticoid, is recognized for its extensive anti-inflammatory properties. Our study assessed the neuroprotective effect of MP (25 mg/kg) administration to an Aß1-42-induced AD mouse model. Our findings demonstrate that MP treatment can ameliorate cognitive impairment in Aß1-42-induced AD mice and suppress microglial activation in the cortex and hippocampus. RNA-Sequencing analysis reveals that MP ultimately rescues cognitive dysfunction through improving the synapse function and inhibiting the immune and inflammatory processes. Our study suggests that MP could be a promising drug alternative for the treatment of AD, either alone or in combination with other existing drugs.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Camundongos , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Metilprednisolona/efeitos adversos , Doenças Neuroinflamatórias , Peptídeos beta-Amiloides/farmacologia , Cognição
4.
Medicine (Baltimore) ; 102(11): e33302, 2023 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-36930115

RESUMO

The objective of this study was to explore the relevant factors affecting the 5-year survival rate of patients after radical colon cancer surgery, and to provide some basis for improving the quality of life and prognosis of colon cancer patients. The clinical data of 116 colon cancer patients who underwent treatment in our hospital from January 2017 to December 2017 were retrospectively selected. Using the date of performing surgical treatment as the starting point and the completion of 5 years after surgery or patient death as the end point, all patients were followed up by telephone to count the 5-year survival rate and analyze the influence of each factor with the prognosis of colon cancer patients. Of the 116 patients, 14 patients were lost to follow-up. Of the 102 patients with complete follow-up, 33 patients were died, with an overall 5-year survival rate of 67.6%. After univariate analysis, it was found that distant metastasis (χ2 = 10.493, P = .001), lymph node metastasis (χ2 = 25.145, P < .001), depth of muscle infiltration (χ2 = 14.929, P < .001), alcohol consumption (χ2 = 15.263, P < .001), and preoperative obstruction (χ2 = 9.555, P = .002) were significantly associated with the prognosis of colon cancer patients. Multivariate logistic analysis showed that distant metastasis (odds ratio [OR]: 1.932, 95% confidence intervals [CI]: 1.272-2.934, P = .002), lymph node metastasis (OR: 1.219, 95% CI: 1.091-1.362, P < .001), and obstruction (OR: 1.970, 95% CI: 1.300-2.990, P < .001) were significant independent risk factors affecting the prognosis in patients after radical colon cancer surgery. In summary, preoperative obstruction, lymph node metastasis, and distant metastasis are independent factors influencing 5-year survival rate after radical colon cancer surgery. Patients with risk factors should be followed up more closely and reasonable postoperative adjuvant chemotherapy regimens should be used to improve long-term survival.


Assuntos
Neoplasias do Colo , Qualidade de Vida , Humanos , Estudos Retrospectivos , Estadiamento de Neoplasias , Metástase Linfática , Correlação de Dados , Prognóstico , Neoplasias do Colo/cirurgia , Neoplasias do Colo/patologia , Taxa de Sobrevida
5.
J Med Chem ; 64(13): 9120-9140, 2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34176264

RESUMO

A series of novel anaplastic lymphoma kinase (ALK) degraders were designed and synthesized based on proteolysis-targeting chimera (PROTAC) technology by linking two alectinib analogs (36 and 37) with pomalidomide through linkers of different lengths and types. The most promising degrader 17 possessed a high ALK-binding affinity and potent antiproliferative activity in the ALK-dependent cell lines and did not exhibit obvious cytotoxicity in ALK fusion-negative cells. More importantly, the efficacy of compound 17 in a Karpas 299 xenograft mouse model was further evaluated based on its ALK-sustained degradation ability in vivo. The reduction in tumor weight in the compound 17-treated group (10 mg/kg/day, I.V.) reached 75.82%, while alectinib reduced tumor weight by 63.82% at a dose of 20 mg/kg/day (P.O.). Taken together, our findings suggest that alectinib-based PROTACs associated with the degradation of ALK may have promising beneficial effects for treating ALK-driven malignancies.


Assuntos
Quinase do Linfoma Anaplásico/antagonistas & inibidores , Antineoplásicos/farmacologia , Carbazóis/farmacologia , Desenvolvimento de Medicamentos , Piperidinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Quinase do Linfoma Anaplásico/metabolismo , Animais , Antineoplásicos/química , Carbazóis/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos , Estrutura Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Piperidinas/química , Inibidores de Proteínas Quinases/química , Proteólise/efeitos dos fármacos , Ratos , Relação Estrutura-Atividade
6.
Colloids Surf B Biointerfaces ; 167: 509-515, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-29729628

RESUMO

Polyethyleneimine (PEI) has long been considered as "golden standard" for polymeric gene delivery carriers. To get a better understanding on the molecular basis of PEI cytotoxicity, dynamic light scattering, zeta-potential measurement, fluorescence emission, Fröster resonance energy transfer and anisotropy measurement were conducted to reveal the interaction between PEI and dimyristoylphosphatidylcholine (DMPC) liposome and the influence on the structural properties of the membrane. PEI was found to bind onto the surface of the liposome, inducing an aggregation of the vesicle and an increase in surface potential at low PEI concentration up to 0.05 mg mL-1. A further increase in PEI concentration made little change on the surface potential, however reduced the aggregation of the vesicle due to the repulsion between the adsorbed PEI chains. PEI binding slightly increased the fluidity of lipid in interface region and decreased its packing density, and thus resulted in an enhanced leakage of calcein through the membrane. The polymer size played an important role in PEI-DMPC liposome interaction. PEI of higher molecular weight was more favorable to interact with DMPC and more efficient to perturb the structural properties of the membrane.


Assuntos
Dimiristoilfosfatidilcolina/química , Lipossomos/química , Lipídeos de Membrana/química , Polietilenoimina/química , Adsorção , Dimiristoilfosfatidilcolina/metabolismo , Fluoresceínas/química , Fluoresceínas/metabolismo , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo , Lipossomos/metabolismo , Fluidez de Membrana , Permeabilidade , Polietilenoimina/metabolismo , Propriedades de Superfície
7.
Immunol Lett ; 182: 18-23, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28062218

RESUMO

Autophagic activation mediated inflammation contributes to brain injury of intracerebral hemorrhage (ICH). MiRNAs play a key role in inflammation, which negatively and posttranscriptionally regulate gene expression and function. Modulating the mTOR signal, a central regulator of autophagy, could be of great significance for ICH. However, the specific of miRNA is unknown. In the current study, we detected the miRNA-144 expression, autophagic activity and inflammation of microglia in ICH. We also knocked down endogenous miRNA-144 to regulate autophagy and inflammation in ICH. In addition, we assessed the neurological damge in ICH mice. We found that ICH promoted miRNA-144 expression but downregulated mTOR expression. In addition, upregulation of mTOR attenuated microglial autophagy and inflammation in ICH. Furthermore, downregulation of miRNA-144 also inhibited inflammation, brain edema and improved neurological functions in ICH mice. Taken together, our findings suggested that miRNA-144 was a crucial regulator of autophagy via regulation of mTOR, and represented a promising therapeutical strategy for ICH.


Assuntos
Autofagia/genética , Hemorragia Cerebral/complicações , Inflamação/etiologia , MicroRNAs/genética , Microglia/metabolismo , Animais , Hemorragia Cerebral/etiologia , Hemorragia Cerebral/metabolismo , Hemorragia Cerebral/patologia , Expressão Gênica , Inflamação/metabolismo , Inflamação/patologia , Camundongos , Microglia/patologia , Microglia/ultraestrutura , Serina-Treonina Quinases TOR/metabolismo
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