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1.
Postgrad Med J ; 100(1181): 142-150, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38055906

RESUMO

BACKGROUND: Contrast-induced nephropathy has become increasingly prevalent as the age and prevalence of comorbidities in the general population have increased. Most cases of contrast-induced nephropathy are reversible; however, some may progress to acute kidney disease, and subsequently, to chronic kidney disease. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are known for their renoprotective effects. However, whether the use of these inhibitors affects the risk of contrast-induced kidney injury remains unclear. METHODS: Data were collected from the Taipei Medical University Clinical Research Database. We included patients with diabetes who had contrast exposure between 2016 and 2020 because of computed tomography or coronary angiography. The primary outcome was the risk of a major adverse kidney event (MAKE), which encompassed acute kidney disease, chronic kidney disease progression, and the need for renal replacement therapy. Overlap weighting was performed to reduce the effects of potential confounders. RESULTS: This study included 12 421 patients, who were divided into two groups: SGLT2i users (n = 920) and nonusers (n = 11 501). The follow-up period after contrast exposure was 6 months. The risk of a MAKE was lower in SGLT2i users than in nonusers (incidence, 36.9 vs. 49.9 per 1000 person-months, respectively; P = .0011). Furthermore, the incidence of acute kidney disease or chronic kidney disease progression was significantly lower in the SGLT2i users than in nonusers. However, no significant between-group difference was noted in the incidence of other MAKEs. CONCLUSIONS: SGLT2i may be safely used in diabetic patients needing contrast exposure. The risk of a MAKE may be lower in SGLT2i users than in nonusers.


Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Rim , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/epidemiologia , Glucose , Sódio , Estudos Retrospectivos
2.
Radiol Med ; 128(6): 784-797, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37154999

RESUMO

OBJECTIVE: We aimed at building and testing a multiparametric clinic-ultrasomics nomogram for prediction of malignant extremity soft-tissue tumors (ESTTs). MATERIALS AND METHODS: This combined retrospective and prospective bicentric study assessed the performance of the multiparametric clinic-ultrasomics nomogram to predict the malignancy of ESTTs, when compared with a conventional clinic-radiologic nomogram. A dataset of grayscale ultrasound (US), color Doppler flow imaging (CDFI), and elastography images for 209 ESTTs were retrospectively enrolled from one hospital, and divided into the training and validation cohorts. A multiparametric ultrasomics signature was built based on multimodal ultrasomic features extracted from the grayscale US, CDFI, and elastography images of ESTTs in the training cohort. Another conventional radiologic score was built based on multimodal US features as interpreted by two experienced radiologists. Two nomograms that integrated clinical risk factors and the multiparameter ultrasomics signature or conventional radiologic score were respectively developed. Performance of the two nomograms was validated in the retrospective validation cohort, and tested in a prospective dataset of 51 ESTTs from the second hospital. RESULTS: The multiparametric ultrasomics signature was built based on seven grayscale ultrasomic features, three CDFI ultrasomic features, and one elastography ultrasomic feature. The conventional radiologic score was built based on five multimodal US characteristics. Predictive performance of the multiparametric clinic-ultrasomics nomogram was superior to that of the conventional clinic-radiologic nomogram in the training (area under the receiver operating characteristic curve [AUC] 0.970 vs. 0.890, p = 0.006), validation (AUC: 0.946 vs. 0.828, p = 0.047) and test (AUC: 0.934 vs. 0.842, p = 0.040) cohorts, respectively. Decision curve analysis of combined training, validation and test cohorts revealed that the multiparametric clinic-ultrasomics nomogram had a higher overall net benefit than the conventional clinic-radiologic model. CONCLUSION: The multiparametric clinic-ultrasomics nomogram can accurately predict the malignancy of ESTTs.


Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Humanos , Nomogramas , Estudos Retrospectivos , Estudos Prospectivos , Fatores de Risco , Neoplasias de Tecidos Moles/diagnóstico por imagem
3.
Plant Physiol ; 184(4): 1731-1743, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33023939

RESUMO

During the course of evolution of land plants, different classes of flavonoids, including flavonols and anthocyanins, sequentially emerged, facilitating adaptation to the harsh terrestrial environment. Flavanone 3ß-hydroxylase (F3H), an enzyme functioning in flavonol and anthocyanin biosynthesis and a member of the 2-oxoglutarate-dependent dioxygenase (2-ODD) family, catalyzes the hydroxylation of (2S)-flavanones to dihydroflavonols, but its origin and evolution remain elusive. Here, we demonstrate that functional flavone synthase Is (FNS Is) are widely distributed in the primitive land plants liverworts and evolutionarily connected to seed plant F3Hs. We identified and characterized a set of 2-ODD enzymes from several liverwort species and plants in various evolutionary clades of the plant kingdom. The bifunctional enzyme FNS I/F2H emerged in liverworts, and FNS I/F3H evolved in Physcomitrium (Physcomitrella) patens and Selaginella moellendorffii, suggesting that they represent the functional transition forms between canonical FNS Is and F3Hs. The functional transition from FNS Is to F3Hs provides a molecular basis for the chemical evolution of flavones to flavonols and anthocyanins, which contributes to the acquisition of a broader spectrum of flavonoids in seed plants and facilitates their adaptation to the terrestrial ecosystem.


Assuntos
Antocianinas/biossíntese , Antocianinas/genética , Embriófitas/genética , Embriófitas/metabolismo , Flavonas/genética , Flavonas/metabolismo , Flavonóis/biossíntese , Flavonóis/genética , Evolução Química , Evolução Molecular , Regulação da Expressão Gênica de Plantas , Genes de Plantas
4.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(6): 1016-1021, 2021 Nov.
Artigo em Zh | MEDLINE | ID: mdl-34841771

RESUMO

OBJECTIVE: To investigate the primary diseases and the distribution of the clinical characteristics of pediatric retinal detachment. METHODS: Clinical records of patients aged 0-14 years old who had retinal detachment and who were hospitalized at the Department of Ophthalmology, West China Hospital, Sichuan University between January 2015 and December 2020, were retrospectively analyzed. The information on the demographic data, history, the scope of retinal detachment, and prognosis was retrieved and documented. RESULTS: A total of 464 eyes of 393 patients were included in this study, including 261 male and 132 female patients at a ratio of 1.98:1. The most common type of primary disease causing pediatric retinal detachments was associated with ocular dysplasia (227 cases, 57.8%), followed by trauma (78 cases, 19.8%) and myopia (56 cases, 14.2%). For infants and preschool children, the primary disease was predominantly ocular dysplasia at a rate of 81.8% (126 cases) and 55.8% (43 cases), respectively. For school-age children, in addition to ocular dysplasia (58 cases, 35.8%), myopia (49 cases, 30.2%) and ocular trauma (43 cases, 26.5%) also accounted for a large proportion of the primary diseases. The most common type of pediatric retinal detachment was rhegmatogenous retinal detachment (184 cases, 46.8%), and ocular trauma and myopia were the most common primary diseases, accounting for 37.5% (69/184) and 30.4% (56/184), respectively. 170 patients were diagnosed with traction retinal detachment, the second most common type of pediatric retinal detachment, and familial exudative vitreoretinopathy (FEVER) was the main primary disease, accounting for 47.6% (81/170). Exudative retinal detachment (39 cases, 9.9%) was the least common type of pediatric retinal detachment. Coats disease was the main primary disease causing exudative retinal detachment, accounting for 71.8% (28/39). After the first repair surgery, patients who had complete traction retinal detachment generally had poorer anatomical outcomes compared with those with complete rhegmatogenous retinal detachments (| Z|=3.026, P=0.002). The retinal break was most commonly seen on the temporal side in pediatric rhegmatogenous retinal detachments. In the retinal detachments caused by trauma, the most common type of retinal break was retinal tear, followed by ora serrata dialysis. Myopic rhegmatogenous retinal detachments were most commonly found in the round holes in lattice degeneration region. CONCLUSION: In the current study, boys were found to be more susceptible to retinal detachment than girls did. Ocular dysplasia, ocular trauma and myopia were major etiologic factors for pediatric retinal detachment. Appropriate information and education measures should be emphasized for different age groups.


Assuntos
Miopia , Descolamento Retiniano , Perfurações Retinianas , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Retina , Descolamento Retiniano/epidemiologia , Estudos Retrospectivos
5.
Molecules ; 24(11)2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31141940

RESUMO

There is growing evidence that neuroinflammation is closely linked to depression. Honokiol, a biologically active substance extracted from Magnolia officinalis, which is widely used in traditional Chinese medicine, has been shown to exert significant anti-inflammatory effects and improve depression-like behavior caused by inflammation. However, the specific mechanism of action of this activity is still unclear. In this study, the lipopolysaccharide (LPS) mouse model was used to study the effect of honokiol on depression-like behavior induced by LPS in mice and its potential mechanism. A single administration of LPS (1 mg/kg, intraperitoneal injection) increased the immobility time in the forced swimming test (FST) and tail suspension test (TST), without affecting autonomous activity. Pretreatment with honokiol (10 mg/kg, oral administration) for 11 consecutive days significantly improved the immobility time of depressed mice in the FST and TST experiments. Moreover, honokiol ameliorated LPS-induced NF-κB activation in the hippocampus and significantly reduced the levels of the pro-inflammatory cytokines; tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), and interferon γ (IFN-γ). In addition, honokiol inhibited LPS-induced indoleamine 2,3-dioxygenase (IDO) activation and quinolinic acid (a toxic product) increase and reduced the level of free calcium in brain tissue, thereby inhibiting calcium overload. In summary, our results indicate that the anti-depressant-like effects of honokiol are mediated by its anti-inflammatory effects. Honokiol may inhibit the LPS-induced neuroinflammatory response through the NF-κB signaling pathway, reducing the levels of related pro-inflammatory cytokines, and furthermore, this may affect tryptophan metabolism and increase neuroprotective metabolites.


Assuntos
Antidepressivos/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Depressão/tratamento farmacológico , Lignanas/uso terapêutico , Animais , Antidepressivos/farmacologia , Sistema Nervoso Autônomo/efeitos dos fármacos , Compostos de Bifenilo/farmacologia , Encéfalo/metabolismo , Cálcio/metabolismo , Citocinas/sangue , Depressão/fisiopatologia , Modelos Animais de Doenças , Elevação dos Membros Posteriores , Imobilização , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Mediadores da Inflamação/sangue , Cinurenina/metabolismo , Lignanas/farmacologia , Lipopolissacarídeos , Camundongos Endogâmicos ICR , NF-kappa B/genética , NF-kappa B/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Natação , Triptofano/metabolismo
6.
Molecules ; 23(3)2018 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-29518887

RESUMO

Selaginella is an extant lycopodiophyte genus, which is representative of an ancient lineage of tracheophytes. The important evolutionary status makes it a valuable resource for the study of metabolic evolution in vascular plants. 4-coumarate: CoA ligase (4CL) is the pivotal enzyme that controls the flow of carbon through the phenylpropanoid metabolic pathway into the specific lignin, flavonoid, and wall-bound phenolics biosynthesis pathways. Although 4CLs have been extensively characterized in other vascular plants, little is known of their functions in Selaginella. Here, we isolated two 4CL genes (Sm4CL1 and Sm4CL2) from Selaginella moellendorffii. Based on the enzymatic activities of the recombinant proteins, both of these genes encoded bona fide 4CLs. The 4CL isoforms in S. moellendorffii have different activities: Sm4CL2 was more active than Sm4CL1. The enzymatic properties and gene expression patterns indicated that the 4CL genes have been conserved in the evolution of vascular plants.


Assuntos
Clonagem Molecular , Coenzima A Ligases/genética , Coenzima A Ligases/metabolismo , Expressão Gênica , Selaginellaceae/genética , Selaginellaceae/metabolismo , Sequência de Aminoácidos , Cromatografia Líquida de Alta Pressão , Coenzima A Ligases/química , Ativação Enzimática , Regulação da Expressão Gênica de Plantas , Especificidade de Órgãos , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Propanóis/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Selaginellaceae/classificação , Análise de Sequência de DNA
7.
Molecules ; 22(11)2017 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-29088080

RESUMO

The aerial organs of most terrestrial plants are covered by a hydrophobic protective cuticle. The main constituent of the cuticle is the lipid polyester cutin, which is composed of aliphatic and aromatic domains. The aliphatic component is a polyester between fatty acid/alcohol and hydroxycinnamoyl acid. The BAHD/HxxxD family enzymes are central to the synthesis of these polyesters. The nature of this class of enzymes in bryophytes has not been explored to date. Here, a gene encoding a fatty ω-hydroxyacid/fatty alcohol hydroxycinnamoyl transferase (HFT) has been isolated from the liverwort Marchantia emarginata and has been functionally characterized. Experiments based on recombinant protein showed that the enzyme uses ω-hydroxy fatty acids or primary alcohols as its acyl acceptor and various hydroxycinnamoyl-CoAs-preferentially feruloyl-CoA and caffeoyl-CoA-as acyl donors at least in vitro. The transient expression of a MeHFT-GFP fusion transgene in the Nicotiana benthamiana leaf demonstrated that MeHFT is directed to the cytoplasm, suggesting that the feruloylation of cutin monomers takes place there.


Assuntos
Aciltransferases/metabolismo , Marchantia/enzimologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Acil Coenzima A/metabolismo , Citoplasma/metabolismo , Regulação da Expressão Gênica de Plantas , Concentração de Íons de Hidrogênio , Marchantia/genética , Filogenia , Plantas Geneticamente Modificadas , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Especificidade por Substrato , Temperatura , Nicotiana/genética
8.
Exp Physiol ; 100(8): 967-76, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26053378

RESUMO

NEW FINDINGS: What is the central question of this study? Higher levels of positive end-expiratory pressure (PEEP) have recently been used in patients with acute respiratory distress syndrome (ARDS). In normal physiological conditions, the ability of the diaphragm to generate pressure is reduced when the lung volume is elevated beyond its functional residual capacity. It is unknown whether higher levels of PEEP will have a negative impact on diaphragmatic contraction in the presence of the pathophysiology of ARDS. What is the main finding and its importance? Mechanical ventilation with higher levels of PEEP reduced lung injury, improved diaphragmatic contractility and increased the expression of both dihydropyridine receptor and ryanodine receptor in the diaphragms of rats with ARDS. Higher levels of positive end-expiratory pressure (PEEP) have recently been used in patients with acute respiratory distress syndrome (ARDS). In normal physiological conditions, the ability of the diaphragm to generate pressure is reduced when the lung volume is elevated beyond its functional residual capacity. Thus, it is critical to understand whether higher levels of PEEP will have a negative impact on diaphragmatic contraction in the presence of the pathophysiology of ARDS. This study was designed to determine whether higher levels of PEEP reduce diaphragmatic contractility in a rat model of ARDS generated using i.p. lipopolysaccharide. Forty rats were randomly assigned to the following five groups: a control group with no special treatment; an ARDS group with no mechanical ventilation; and three ARDS groups with mechanical ventilation with PEEP at 0, 5 or 10 cmH2 O, respectively. We found that mechanical ventilation with PEEP reduced lung injury, improved diaphragmatic contractility and increased the expression of both dihydropyridine receptor and ryanodine receptor in the diaphragms of rats with ARDS. These changes were most significant at a PEEP of 10 cmH2 O among all applied levels of PEEP. In conclusion, using a rat ARDS model, this study confirmed that diaphragmatic contractility was preserved by mechanical ventilation with high levels of PEEP.


Assuntos
Diafragma/fisiologia , Contração Muscular/fisiologia , Respiração com Pressão Positiva/métodos , Síndrome do Desconforto Respiratório/fisiopatologia , Síndrome do Desconforto Respiratório/terapia , Animais , Masculino , Técnicas de Cultura de Órgãos , Ratos , Ratos Sprague-Dawley
9.
Cell Physiol Biochem ; 34(5): 1477-84, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25322729

RESUMO

BACKGROUND/AIMS: Previous studies suggested that high leptin level might increase risk of endometrial cancer, but available data were conflicting and whether high leptin level was an independent risk factor of endometrial cancer was still unclear. Therefore, a meta-analysis was performed to assess whether high leptin level was an independent risk factor of endometrial cancer. METHODS: PubMed, Web of Science, and Embase databases were searched for epidemiological studies published up to June 26, 2014. The pooled risk ratio (RR) with 95% confidence interval (95%CI) was used to assess the association between leptin level and risk of endometrial cancer. RESULTS: Six studies with a total of 3136 individuals were finally included into the meta-analysis. Meta-analysis of total 6 studies showed that high leptin level was associated with increased risk of endometrial cancer (RR = 2.55, 95%CI 1.91-3.41, P < 0.001). After adjusting for confounding factors, high leptin level was also associated with increased risk of endometrial cancer (RR =1.59, 95%CI 1.27-1.98, P < 0.001). Sensitivity analysis proved the stability of the pooled estimates. The RR of endometrial cancer was 1.10 (95%CI, 1.03-1.18, P = 0.005) per 5 ng/mL increment in leptin levels. There was no obvious risk of publication bias (P Egger = 0.54). CONCLUSION: Our findings suggest that high leptin level is an independent risk factor of endometrial cancer. More prospective studies are needed to further confirm the association in the future.


Assuntos
Neoplasias do Endométrio/metabolismo , Leptina/metabolismo , Estudos de Casos e Controles , Estudos Epidemiológicos , Feminino , Humanos , Risco , Fatores de Risco
10.
Biomed Environ Sci ; 27(2): 97-105, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24625399

RESUMO

OBJECTIVE: To investigate the bioeffects of extremely low frequency (ELF) magnetic field (MF) (50 Hz, 400 µT) and magnetic nanoparticles (MNPs) via cytotoxicity and apoptosis assays on PC12 cells. METHODS: MNPs modified by SiO2 (MNP-SiO2) were characterized by transmission electron microscopy (TEM), dynamic light scattering and hysteresis loop measurement. PC12 cells were administrated with MNP-SiO2 with or without MF exposure for 48 h. Cytotoxicity and apoptosis were evaluated with MTT assay and annexin V-FITC/PI staining, respectively. The morphology and uptake of MNP-SiO2 were determined by TEM. MF simulation was performed by Ansoft Maxwell based on the finite element method. RESULTS: MNP-SiO2 were identified as ~20 nm (diameter) ferromagnetic particles. MNP-SiO2 reduced cell viability in a dose-dependent manner. MF also reduced cell viability with increasing concentrations of MNP-SiO2. MNP-SiO2 alone did not cause apoptosis in PC12 cells; instead, the proportion of apoptotic cells increased significantly under MF exposure and increasing doses of MNP-SiO2. MNP-SiO2 could be ingested and then cause a slight change in cell morphology. CONCLUSION: Combined exposure of MF and MNP-SiO2 resulted in remarkable cytotoxicity and increased apoptosis in PC12 cells. The results suggested that MF exposure could strengthen the MF of MNPs, which may enhance the bioeffects of ELF MF.


Assuntos
Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Campos Magnéticos/efeitos adversos , Nanopartículas de Magnetita/toxicidade , Animais , Microscopia Eletrônica de Transmissão , Células PC12 , Ratos , Dióxido de Silício
12.
Int J Biol Macromol ; 253(Pt 6): 127267, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37820903

RESUMO

Diabetes mellitus (DM) as one chronic metabolic disease was greatly increased over recent decades. The major agents treating diabetes have noticeable side effects as well as the tolerability problems. The bioactive dietary polysaccharides from abundant natural resources exhibit good hypoglycemic effect with rare adverse effects, which might serve as a candidate to prevent and treat diabetes. However, the correlations between the hypoglycemic mechanism of polysaccharides and their structure were not mentioned in several studies, what's more, most of the current hypoglycemic studies on polysaccharides were based on in vitro and in vivo experiments, and there was a lack of knowledge about the effects in human clinical trials. The aim of this review is to discuss recent literature about the variety of dietary polysaccharides with hypoglycemic activity, as well the mechanism of action and the structure-function relationship are highlighted. Meanwhile, the application of dietary polysaccharides in functional foods and clinical medicine are realized with an in-depth understanding. So as to promote the exploration of dietary polysaccharides in low glycemic healthy foods or clinical medicine to prevent and treat diabetes.


Assuntos
Diabetes Mellitus , Hipoglicemiantes , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/química , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Polissacarídeos/química , Diabetes Mellitus/tratamento farmacológico , Carboidratos da Dieta/uso terapêutico , Alimento Funcional
13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(1): 77-83, 2022 Feb.
Artigo em Zh | MEDLINE | ID: mdl-35123607

RESUMO

OBJECTIVE: To analyze the expression and clinical characteristics of CD68 in bone marrow and peripheral blood of patients with acute myeloid leukemia (AML). METHODS: The expression of CD68 in bone marrow blast cells was detected by four-color flow cytometry in 50 newly diagnosed AML patients and 23 controls. The expression of CD68 in peripheral blood of 85 newly diagnosed AML patients, 29 remission AML patients and 24 controls was detected by ELISA. The correlation between the expression rate of non-M3 AML bone marrow CD68, peripheral blood CD68 concentration and white blood cell count and other clinical data was compared respectively. RESULTS: The median CD68 expression rate in myeloid leukemia cells of non-M3 AML patients was 19.7%, significantly higher than control (0.2%) (P<0.001). The median concentration of non-M3 CD68 in peripheral blood was 67.97 pg/ml, significantly higher than in control (29.94 pg/ml)(P<0.01). There was no statistically significant difference in the plasma CD68 concentration of the peripheral blood between the newly diagnosed (45.72 pg/ml) and the remission stage (55.12 pg/ml) of non-M3 AML patients by paired analysis (P>0.05). The results showed that the higher the expression rate of CD68 in bone marrow, the higher the count of white blood cells in peripheral blood, and the lower the count of hemoglobin and platelet in peripheral blood. The higher the plasma concentration of CD68 in peripheral blood, the higher the white blood cell count and the lower the complete remission rate. CONCLUSION: The expression of CD68 both in bone marrow and peripheral blood of patients with non-M3 AML is higher than that of control group. Patients with high expression of CD68 show a low rate of complete remission, suggesting that the expression level of CD68 is correlated with treatment response.


Assuntos
Leucemia Mieloide Aguda , Medula Óssea , Citometria de Fluxo , Humanos , Leucócitos , Prognóstico , Indução de Remissão
14.
J Med Chem ; 65(23): 15967-15990, 2022 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-36394994

RESUMO

UDPG/P2Y14R signaling pathway has been considered as a potential therapeutic target for innate immune system diseases. Based on the scaffold hopping strategy, a series of pyrazole analogues were designed and synthesized as novel P2Y14R antagonists with improved physicochemical properties, together with potential anti-inflammatory activities. Additionally, we designed and synthesized a fluorescent probe based on highly selective and potent PPTN to study the affinity of synthesized compounds. The optimized compound 16 (1-(4-fluorobenzyl)-5-(4-methylbenzamido)-1H-pyrazole-3-carboxylic acid, P2Y14R IC50 = 1.93 nM) showed strong binding ability to P2Y14R, high selectivity, notably improved solubility, and more favorable pharmacokinetic profiles. Moreover, compound 16 possessed extremely low cytotoxicity and anti-inflammatory effect in vitro. In an acute peritonitis model, compound 16 could effectively reduce the levels of inflammatory factor IL-6, IL-1ß, and TNF-α of mice induced by LPS. Compound 16, with potent in vitro and in vivo efficacy and favorable druggability, can be a promising candidate for further research.


Assuntos
Amidas , Anti-Inflamatórios , Animais , Camundongos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico
15.
Asia Pac Allergy ; 12(3): e31, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35966156

RESUMO

Background: The rising prevalence of food allergy reported in the United States, UK, and Australia may be attributable to the rise in peanut allergy prevalence. The food allergy prevalence in other parts of the world such as Asia is, however, less well documented. Objective: This study aimed to evaluate the prevalence of cow's milk, egg, and peanut allergies in a general population of Singaporean children below 30 months of age. Methods: A total of 4,115 children from the general population who attended well-baby visits between 2011 and 2015 completed standardized questionnaires to elicit a convincing history of food allergy to estimate the population prevalence of food allergies. Results: The prevalence of a convincing history of cow's milk allergy was 0.51% (95% confidence interval [CI], 0.3-0.7), hen's egg allergy 1.43% (95% CI, 1.1-1.8), and peanut allergy 0.27% (95% CI, 0.12-0.42). Of the 15 of 59 children with a convincing history of hen's egg allergy who consented, 12 (80%) had corroborative positive skin prick tests. Conclusion: The prevalence of food allergy, in particular peanut allergy, in children below 2 years of age is lower in this South East Asian population than reported in Western cohorts. Further research should focus on deciphering differential risk factors for food allergy across different geographical locations.

16.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 40(5): 559-66, 2011 09.
Artigo em Zh | MEDLINE | ID: mdl-21984162

RESUMO

HIF-1 is composed of HIF-1α and HIF-1ß subunits. It promotes target genes transcription under hypoxia and plays essential roles in cell development, physiological adaptations, and pathological processes. In the past 10 years, the research on signaling pathways of HIF-1 in response to cell hypoxia stress, especially on HIF-1α-mediated gene transcription has made great progress.


Assuntos
Fator 1 Induzível por Hipóxia/metabolismo , Transdução de Sinais , Animais , Hipóxia Celular/fisiologia , Humanos
17.
J Agric Food Chem ; 69(1): 474-482, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33372794

RESUMO

In this work, spiral dextrin/resveratrol (SD/Res) crystal, a new colon-specific drug-delivery system, was established by a novel method of encapsulation and cocrystallization to improve the antidigestion ability compared with the SD/Res inclusion complex (SD/Res IC) prepared by encapsulation and coprecipitation. X-ray diffraction (XRD) and scanning electron microscopy (SEM) revealed that the SD/Res crystal formed a more regular and perfect crystallite than SD/Res IC. Moreover, the encapsulation ability and thermostability of the SD/Res crystal were enhanced as the chain length of SD was increased. In vitro digestion indicated that SD/Res IC merely achieved small intestine-targeted release of resveratrol, while the SD/Res crystal could act as a colon-specific delivery system to protect resveratrol from degradation by gastric acid and pancreatic enzymes. The SD-1/Res crystal presented much higher thermal stability and stronger gastrointestinal stability than other SD/Res crystals and SD/Res ICs, which facilitated its application as a novel colon-target delivery system for resveratrol.


Assuntos
Colo/efeitos dos fármacos , Dextrinas/química , Sistemas de Liberação de Medicamentos/métodos , Extratos Vegetais/química , Resveratrol/química , Resveratrol/farmacologia , Composição de Medicamentos , Liberação Controlada de Fármacos , Humanos , Tamanho da Partícula , Difração de Raios X , Zea mays/química
18.
Hepatobiliary Pancreat Dis Int ; 9(3): 280-6, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20525556

RESUMO

BACKGROUND: Post-hepatitic cirrhosis is regarded as common and severe form of liver damage. Interferon gamma-inducible protein 10 (IP-10), a member of the non-ELR (glutamic-leucine-arginine) motif CXC chemokine family, has recently been shown to recruit and activate specific subsets of leukocytes to sites of inflammation or an immune response during the development of hepatic cirrhosis. However, the effects of IP-10 and IP-10 mRNA on inflammatory infiltration at local sites and in the peripheral blood of patients with post-hepatitic cirrhosis as well as their relationship with viral load are still poorly defined. This study aimed to detect the relationship between the expression of IP-10 in serum, IP-10 mRNA in peripheral blood mononuclear cells (PBMCs), and the levels of HBV DNA in the serum of patients, and to explore their role in the pathogenesis of cirrhosis. METHODS: Typical patients with cirrhosis after HBV infection were selected, and their serum IP-10 concentrations were evaluated with ELISA, the content of IP-10 mRNA in PBMCs was measured by real-time PCR, and the load of HBV DNA in serum and PBMCs was assessed by semi-quantitative analysis of gel imaging. RESULTS: The levels of IP-10 in serum and IP-10 mRNA in PBMCs of patients with cirrhosis were 299.9+/-77.2 pg/ml and 0.7500+/-0.1495, respectively. They were higher than those of controls (P<0.05) and also increased in the HBV DNA(+) groups (P<0.05, P<0.01) to 343.0+/-80.3 pg/ml and 0.8465+/-0.1528, respectively. The levels of IP-10 in serum and IP-10 mRNA in PBMCs were clearly correlated with the load of HBV DNA (P<0.01). CONCLUSIONS: The levels of IP-10 and IP-10 mRNA in the peripheral blood of patients with cirrhosis increase are closely correlated with the load of HBV DNA in serum, and play a key role in the progression of post-hepatitic cirrhosis.


Assuntos
Quimiocina CXCL10/sangue , DNA Viral/sangue , Vírus da Hepatite B/genética , Hepatite B/diagnóstico , Mediadores da Inflamação/sangue , Leucócitos Mononucleares/virologia , Cirrose Hepática/virologia , RNA Mensageiro/sangue , Adulto , Biomarcadores/sangue , Quimiocina CXCL10/genética , China , Ensaio de Imunoadsorção Enzimática , Feminino , Hepatite B/complicações , Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Humanos , Leucócitos Mononucleares/imunologia , Cirrose Hepática/imunologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Carga Viral
19.
Acta Crystallogr Sect E Struct Rep Online ; 66(Pt 10): m1247, 2010 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-21587397

RESUMO

The asymmetric unit of the title compound, (C(11)H(15)N(4)O(4))[FeCl(4)], contains two independent protonated 7-(1,3-dioxolan-2-ylmeth-yl)-3,7-dihydro-1,3-dimethyl-1H-purine-2,6-dione (doxofyllinium) and two tetrahedral tetra-chlorido-ferrate(III) anions. In the doxofyllinium, two disordered methyl-ene C atoms are observed in each dioxolane ring with an occupancy ratio of 0.54 (4):0.46 (4). In the crystal, mol-ecules are connected by N-H⋯O hydrogen bonds and weak C-H⋯O and C-H⋯Cl inter-actions.

20.
Carbohydr Polym ; 228: 115389, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31635730

RESUMO

The modified rice starches by octenyl succinic anhydride (OS-RSs) with the same degree of substitution of 0.033 were prepared in aqueous solution using 3% or 20% (w/w) NaOH as a catalyst (OS-RS 3 or OS-RS 20). The results indicated that 20% of NaOH could destroy the structure of starch more seriously and led to more OS groups travelling to interior of starch granules. Furthermore, the storage stability and rheological properties of Pickering emulsions formulated by RS, OS-RS 3 and OS-RS 20 were investigated. Emulsion index of OS-RS 20 were always lower than OS-RS 3 during the storage time, while G', G" and viscosity of O/W Pickering emulsion formulated by OS-RS 20 particles were greater than those of OS-RS 3. OS-RS 3 with more hydrophobic groups in the granule surface could form more compact oil/water layers which contributed greater to the storage stability of Pickering emulsion due to the formation of more compact oil/water layers. However, OS-RS 20 with homogeneous distribution of OS groups in the whole particles resulted in the formation of a tighter droplet network structure that was more resistant to external impacts, which showed OS-RS 20 could improve the shear stability of Pickering emulsion.

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