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1.
BMC Cardiovasc Disord ; 23(1): 228, 2023 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-37131145

RESUMO

BACKGROUND: As a novel marker of insulin resistance, the ratio of triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) has been recently reported to be related to the occurrence of coronary artery diseases. However, no research has been conducted to probe whether the TG/HDL-C ratio is associated with the occurrence of coronary microvascular disease (CMVD). AIM: This study investigates the association between the TG/HDL-C ratio and the occurrence of CMVD. METHODS: This study included 175 patients diagnosed with CMVD in the Department of Cardiology of our hospital from October 2017 to October 2021 as the study group and 175 patients with no chest pain, no history of cardiovascular disease and drug use, and negative results of exercise treadmill testing as the non-CMVD group. The clinical data of the two groups were compared. In addition, the risk factors of CMVD were analyzed with logistic regression, and the efficacy of independent risk factors in predicting CMVD was analyzed with a receiver operating characteristic (ROC) curve. RESULTS: Compared with those in the non-CMVD group, the proportion of females, the incidence of hypertension and type 2 diabetes, the level of platelet count, TG, and C-reactive protein, and the ratio of TG/HDL-C were increased in the CMVD group, accompanied by decreased levels of albumin and HDL-C (P < 0.05). Logistic regression results revealed C-reactive protein (the area under the ROC curve [AUC] value: 0.754; 95% confidence interval [CI]: 0.681-0.827), sex (the AUC value: 0.651; 95%CI: 0.571-0.730), albumin (the AUC value: 0.722; 95%CI: 0.649-0.794), and TG/HDL-C ratio (the AUC value: 0.789; 95%CI: 0.718-0.859) as the independent risk factors of CMVD. CONCLUSION: The TG/HDL-C ratio is an independent risk factor for the occurrence of CMVD.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Feminino , Humanos , Triglicerídeos , HDL-Colesterol , Proteína C-Reativa
2.
Acta Pharmacol Sin ; 43(2): 457-469, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33850273

RESUMO

Mantle cell lymphoma (MCL) is a lymphoproliferative disorder lacking reliable therapies. PI3K pathway contributes to the pathogenesis of MCL, serving as a potential target. However, idelalisib, an FDA-approved drug targeting PI3Kδ, has shown intrinsic resistance in MCL treatment. Here we report that a p300/CBP inhibitor, A-485, could overcome resistance to idelalisib in MCL cells in vitro and in vivo. A-485 was discovered in a combinational drug screening from an epigenetic compound library containing 45 small molecule modulators. We found that A-485, the highly selective catalytic inhibitor of p300 and CBP, was the most potent compound that enhanced the sensitivity of MCL cell line Z-138 to idelalisib. Combination of A-485 and idelalisib remarkably decreased the viability of three MCL cell lines tested. Co-treatment with A-485 and idelalisib in Maver-1 and Z-138 MCL cell xenograft mice for 3 weeks dramatically suppressed the tumor growth by reversing the unsustained inhibition in PI3K downstream signaling. We further demonstrated that p300/CBP inhibition decreased histone acetylation at RTKs gene promoters and reduced transcriptional upregulation of RTKs, thereby inhibiting the downstream persistent activation of MAPK/ERK signaling, which also contributed to the pathogenesis of MCL. Therefore, additional inhibition of p300/CBP blocked MAPK/ERK signaling, which rendered maintaining activation to PI3K-mTOR downstream signals p-S6 and p-4E-BP1, thus leading to suppression of cell growth and tumor progression and eliminating the intrinsic resistance to idelalisib ultimately. Our results provide a promising combination therapy for MCL and highlight the potential use of epigenetic inhibitors targeting p300/CBP to reverse drug resistance in tumor.


Assuntos
Classe Ia de Fosfatidilinositol 3-Quinase/efeitos dos fármacos , Linfoma de Célula do Manto/tratamento farmacológico , Purinas/uso terapêutico , Quinazolinonas/uso terapêutico , Fatores de Transcrição de p300-CBP/antagonistas & inibidores , Animais , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Classe Ia de Fosfatidilinositol 3-Quinase/metabolismo , Sinergismo Farmacológico , Feminino , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Humanos , Camundongos , Transplante de Neoplasias
3.
Acta Pharmacol Sin ; 43(2): 470-482, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33850276

RESUMO

Aerobic glycolysis, also known as the Warburg effect, is a hallmark of cancer cell glucose metabolism and plays a crucial role in the activation of various types of immune cells. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) catalyzes the conversion of D-glyceraldehyde 3-phosphate to D-glycerate 1,3-bisphosphate in the 6th critical step in glycolysis. GAPDH exerts metabolic flux control during aerobic glycolysis and therefore is an attractive therapeutic target for cancer and autoimmune diseases. Recently, GAPDH inhibitors were reported to function through common suicide inactivation by covalent binding to the cysteine catalytic residue of GAPDH. Herein, by developing a high-throughput enzymatic screening assay, we discovered that the natural product 1,2,3,4,6-penta-O-galloyl-ß-D-glucopyranose (PGG) is an inhibitor of GAPDH with Ki = 0.5 µM. PGG blocks GAPDH activity by a reversible and NAD+ and Pi competitive mechanism, suggesting that it represents a novel class of GAPDH inhibitors. In-depth hydrogen deuterium exchange mass spectrometry (HDX-MS) analysis revealed that PGG binds to a region that disrupts NAD+ and inorganic phosphate binding, resulting in a distal conformational change at the GAPDH tetramer interface. In addition, structural modeling analysis indicated that PGG probably reversibly binds to the center pocket of GAPDH. Moreover, PGG inhibits LPS-stimulated macrophage activation by specific downregulation of GAPDH-dependent glucose consumption and lactate production. In summary, PGG represents a novel class of GAPDH inhibitors that probably reversibly binds to the center pocket of GAPDH. Our study sheds new light on factors for designing a more potent and specific inhibitor of GAPDH for future therapeutic applications.


Assuntos
Gliceraldeído-3-Fosfato Desidrogenases/antagonistas & inibidores , Taninos Hidrolisáveis/farmacologia , Animais , Avaliação Pré-Clínica de Medicamentos/métodos , Glucose/metabolismo , Gliceraldeído-3-Fosfato Desidrogenase (Fosforiladora)/antagonistas & inibidores , Humanos , Espectrometria de Massa com Troca Hidrogênio-Deutério , Ácido Láctico/metabolismo , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Compostos Organometálicos , Reação em Cadeia da Polimerase em Tempo Real
4.
Acta Pharmacol Sin ; 43(4): 941-953, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34341511

RESUMO

Nonalcoholic steatohepatitis (NASH) is a common chronic liver disease that is increasingly prevalent worldwide. Liver inflammation is an important contributor to disease progression from nonalcoholic fatty liver (NAFL) to NASH, but there is a lack of efficient therapies. In the current study we evaluated the therapeutic potential of givinostat, a histone deacetylase (HDAC) inhibitor, in the treatment of NASH in vivo and in vitro. Liver inflammation was induced in mice by feeding a methionine- and choline-deficient diet (MCD) or a fructose, palmitate, cholesterol diet (FPC). The mice were treated with givoinostat (10 mg·kg-1·d-1, ip) for 8 or 10 weeks. At the end of the experiment, the livers were harvested for analysis. We showed that givoinostat administration significantly alleviated inflammation and attenuated hepatic fibrosis in MCD-induced NASH mice. RNA-seq analysis of liver tissues form MCD-fed mice revealed that givinostat potently blocked expression of inflammation-related genes and regulated a broad set of lipid metabolism-related genes. In human hepatocellular carcinoma cell line HepG2 and human derived fetal hepatocyte cell line L02, givinostat significantly decreased palmitic acid-induced intracellular lipid accumulation. The benefit of givinostat was further confirmed in FPC-induced NASH mice. Givinostat administration significantly attenuated hepatic steatosis, inflammation as well as liver injury in this mouse model. In conclusion, givinostat is efficacious in reversing diet-induced NASH, and may serve as a therapeutic agent for the treatment of human NASH.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Carbamatos , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Fígado/metabolismo , Cirrose Hepática/patologia , Metionina , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/metabolismo
5.
BMC Musculoskelet Disord ; 22(1): 112, 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33499842

RESUMO

BACKGROUND: Carpal tunnel syndrome (CTS) is the most common entrapment symptom in the peripheral nerves. High-frequency ultrasound (HFUS) is widely used in the diagnosis of CTS. Virtual Touch Tissue Imaging and Quantification (VTIQ), which provides more information about the hardness of organization, is used to diagnose CTS. However, the data of diagnostic value of them in various degrees of CTS are limited. Whether the combination of HFUS and VTIQ can improve the diagnostic efficiency also remains unknown. The study aimed to explore the diagnostic value of HFUS and VTIQ in various degrees of CTS and whether combination of HFUS and VTIQ could improve the diagnostic efficiency of CTS. METHODS: A collection and analysis of 133 CTS patients and 35 volunteers from January 2016 to January 2019 were performed. We compared the clinical characteristics, cross-sectional area (CSA) value and shear wave velocity SWVmean value of CTS group with volunteer group. RESULTS: The CSA value and SWVmean value of CTS cohort were significantly higher than volunteer group (10.79 ± 2.88 vs. 8.06 ± 1.39, p < 0.001, 4.36 ± 0.95 vs. 3.38 ± 1.09, p < 0.001, respectively). The area under the curve (AUC) of receiver operating characteristic (ROC) curve of CSA value and SWVmean value were 0.794 and 0.757, respectively. Hierarchical analysis of CSA value and SWVmean value showed that the AUC in the moderate and severe CTS group were higher than in mild CTS group. Furthermore, the CSA value combined with SWVmean value used to diagnose mild CTS was 0.758, which was higher than that of single CSA value or single SWVmean value. CONCLUSIONS: Both HFUS and VTIQ technology were feasible to evaluate CTS. HFUS was suitable for use in diagnosis of moderate and severe CTS. For mild CTS, combination of HFUS and VTIQ was relevant to improve the diagnostic efficiency of CTS.


Assuntos
Síndrome do Túnel Carpal , Área Sob a Curva , Síndrome do Túnel Carpal/diagnóstico por imagem , Testes Diagnósticos de Rotina , Humanos , Nervo Mediano/diagnóstico por imagem , Curva ROC , Sensibilidade e Especificidade , Ultrassonografia
6.
Acta Pharmacol Sin ; 41(2): 286-292, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31253937

RESUMO

The cAMP-responsive element binding protein (CREB) binding protein (CBP) and adenoviral E1A-binding protein (P300) are two closely related multifunctional transcriptional coactivators. Both proteins contain a bromodomain (BrD) adjacent to the histone acetyl transferase (HAT) catalytic domain, which serves as a promising drug target for cancers and immune system disorders. Several potent and selective small-molecule inhibitors targeting CBP BrD have been reported, but thus far small-molecule inhibitors targeting BrD outside of the BrD and extraterminal domain (BET) family are especially lacking. Here, we established and optimized a TR-FRET-based high-throughput screening platform for the CBP BrD and acetylated H4 peptide. Through an HTS assay against an in-house chemical library containing 20 000 compounds, compound DC_CP20 was discovered as a novel CBP BrD inhibitor with an IC50 value of 744.3 nM. This compound bound to CBP BrD with a KD value of 4.01 µM in the surface plasmon resonance assay. Molecular modeling revealed that DC_CP20 occupied the Kac-binding region firmly through hydrogen bonding with the conserved residue N1168. At the celluslar level, DC_CP20 dose-dependently inhibited the proliferation of human leukemia MV4-11 cells with an IC50 value of 19.2 µM and markedly downregulated the expression of the c-Myc in the cells. Taken together, the discovery of CBP BrD inhibitor DC_CP20 provides a novel chemical scaffold for further medicinal chemistry optimization and a potential chemical probe for CBP-related biological function research. In addition, this inhibitor may serve as a promising therapeutic strategy for MLL leukemia by targeting CBP BrD protein.


Assuntos
Antineoplásicos/farmacologia , Proteína de Ligação a CREB/antagonistas & inibidores , Ensaios de Triagem em Larga Escala , Leucemia/tratamento farmacológico , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Sítios de Ligação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Descoberta de Drogas/métodos , Transferência Ressonante de Energia de Fluorescência , Humanos , Concentração Inibidora 50 , Leucemia/patologia , Modelos Moleculares , Domínios Proteicos , Bibliotecas de Moléculas Pequenas
7.
Zhongguo Zhong Yao Za Zhi ; 42(14): 2820-2823, 2017 Jul.
Artigo em Zh | MEDLINE | ID: mdl-29098844

RESUMO

Coding rules for Chinese medicines and their codes (GB/T 31774-2015) was issued by General Administration of Quality Supervision, Inspection and Quarantine of the People's Republic of China (AQSIQ) and Standardization Administration of the People's Republic of China (SAC) in 2015. Coding system for Chinese medicines (ISO 18668-1, 2, 3 and 4) series were issued one after another by International Organization for Standardization in 2016 and 2017. In this paper, the comparative study on the GB/T 31774 and ISO 18668-1, 2, 3 to 4 would be conducted to expound the similarities and differences among them. This essay aims at promoting the application of national and international standards of coding system in production and operation enterprises and the medical institutions of traditional Chinese medicine (TCM), reducing their repetitive investment to meet the Chinese medicine import and export trade requirement in future. Moreover, it provides the cornerstone and support for TCM standardization, and makes Chinese medicines standard gain dominance in field of international TCM standards, occupying the high ground of international market in the traditional medicine field of the world. It may promote the "Internet + TCM service" in our country, and let the Chinese medicine industry go out of the country and into the world to contribute to human health.


Assuntos
Medicina Tradicional Chinesa/normas , China , Humanos , Padrões de Referência
8.
Zhongguo Zhong Yao Za Zhi ; 41(15): 2922-2926, 2016 Aug.
Artigo em Zh | MEDLINE | ID: mdl-28914038

RESUMO

Neobavaisoflavone is one of flavonoids of traditional Chinese medicine Psoralea corylifolial. It has numerous biological properties such as antibacterial, anti-inflammatory, anti-cancer, and anti-osteoporosis effects. This paper aimed to investigate the absorption mechanism of neobavaisoflavone in Caco-2 cell monolayer model. The analyte and osalmide were separated on Thermo Syncronis C18 column with methanol-0.1% formic acid solution (90∶10) as the mobile phase, at a flow rate of 0.2 mL•min⁻¹. The concentration of neobavaisoflavone was determined in eletrospray ionization(ESI) positive ion mode with osalmide as an the internal standard. The effects of time, concentration, P-gp inhibitor verapamil, MRP-2 inhibitor MK-571 and BCRP inhibitor Ko143 on the absorption of neobavaisoflavone were investigated. According to the results, neobavaisoflavone showed a good linearity within the concentration of 10-2 000 µg•L⁻¹, and the results of its specificity, matrix effect, extraction recovery, precision, accuracy and stability all met the requirements. In the Caco-2 cell monolayer model, the transport volume of neobavaisoflavone was correlated positively with the time and concentration. The ER values of 15, 30, 50 µmol•L⁻¹ neobavaisoflavone were 1.64, 1.94,0.99, respectively. As compared with the control group, all of verapamil hyduochloride, MK-571 and Ko143 could promote the transportation of neobavaisoflavone, and the effect was more obvious in verapamil hyduochloride and Ko143. The absorption of neobavaisoflavone may be mainly of active transport in Caco-2 cell monolayer model, and also involve passive transport. Excretion mechanism of intestinal transport protein may be also involved.


Assuntos
Isoflavonas/farmacocinética , Transporte Biológico , Células CACO-2 , Dicetopiperazinas/farmacologia , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Humanos , Absorção Intestinal , Proteína 2 Associada à Farmacorresistência Múltipla , Propionatos/farmacologia , Quinolinas/farmacologia
9.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 37(5): 580-4, 2015 Oct.
Artigo em Zh | MEDLINE | ID: mdl-26564511

RESUMO

OBJECTIVE: To investigate the role of high-frequency ultrasound (HFUS) in evaluating in the effectiveness of conservative treatment for professional athletes with patellar tendon enthesiopathy. METHODS: According to different treatment intensities, 24 professional athletes with patellar tendon enthesiopathy were randomly divided into painless group, slightly-painful group and extremely-painful group. Then changes of the HFUS findings [including ranges of two-dimensional diseases and blood conditions by Color Doppler Flow Imaging (CDFI)] of patellar tendon before and after the treatment were recorded. The results were also compared with conventional clinical treatment evaluations. RESULTS: After two courses of treatment,the percentage of athletes whose pain was resolved or disappeared was 37.5% in painless group, 87.5% in slightly-painful group, and 62.5% in extremely-painful group. The pain score was 4.50 ± 2.07, 4.88 ± 1.13, and 6.13 ± 1.55 in painless group,slightly-painful group,and extremely-painful group, respectively,before treatment and 4.88 ± 2.17, 3.00 ± 1.77,and 5.13 ± 2.36 after treatment. The average pain score remarkably decreased in the slightly-painful group and extremely-painful group,and such difference was statistically significant in the slightly-pain group (P<0.05). The effective rate (defined as thinner patellar,decreased hypoecho area and fewer blood distribution in the lesion) was 38%, 50%, and 62% in the painless group, slightly-painful group,and extremely-painful group, and the rates in the slightly-painful group and extremely-painful group were significantly higher than that in painless group (both P<0.05). CONCLUSIONS: HFUS can display the ultrasonographic changes of patellar tendon enthesiopathy after conservative treatments in an objective and quantitative manner. Compared with conventional clinical evaluations, it can more accurately reflect the disease recovery status.


Assuntos
Traumatismos em Atletas/diagnóstico por imagem , Ligamento Patelar , Atletas , Seguimentos , Humanos , Dor , Tendinopatia , Ultrassonografia
10.
Zhongguo Zhong Yao Za Zhi ; 40(6): 1119-22, 2015 Mar.
Artigo em Zh | MEDLINE | ID: mdl-26226756

RESUMO

OBJECTIVE: An accurate and reliable analytical method for-simultaneous determination of six active components (scopolin, chlorogenic acid, scopoletin, isochlorogenic acid A, isochlorogenic acid B and isochlorogenic acid C) in plants of Erycibe was developed. METHOD: Scopolin, chlorogenic acid, scopoletin, isochlorogenic acid A, isochlorogenic acid B and isochlorogenic acid C in the samples were well separated in analytical HPLC by gradual elution with methanol-0.1% formic acid solution. The chromatographic condictions: Agilent Poroshell 120 EC-C18 column, flowing rate being 1 mL x min(-1), detecting wavelength at 345 nm. RESULT: Good linearities of scopolin, chlorogenic acid, scopoletin, isochlorogenic acid A, isochlorogenic acid B and isochlorogenic acid C were in the range of 0.026 8-2.68, 0.027 0-2.70, 0.008 1-0.81, 0.018 8-1.88, 0.017 6-1.76, 0.019 6-1.96 µg, respectively (r > 0.999 6). The average recoveries of the six components were 98.1%, 98.7%, 100.8%, 100.4%, 99.7%, 101.1%; the relative standard deviations were 2.67%, 2.86%, 2.62%, 1.98%, 2.76%, 2.19%. CONCLUSION: The method is simple, feasible and reproducible and can be used for the quality control of plants of Erycibe.


Assuntos
Ácido Clorogênico/análogos & derivados , Ácido Clorogênico/análise , Cromatografia Líquida de Alta Pressão/métodos , Convolvulaceae/química , Cumarínicos/análise , Medicamentos de Ervas Chinesas/análise , Glucosídeos/análise , Escopoletina/análise , China
11.
Mitochondrial DNA B Resour ; 8(8): 836-840, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37554696

RESUMO

Duck breed Longshengcui (Anas platyrhynchos Linnaeus, 1758 breed Longshengcui, LSC) is one of the famous native breed of the Guangxi Zhuang Nationality Autonomous Region in China. In this study, we report the complete mitochondrial genome of LSC. The mitogenome (GenBank accession no. MZ895120) has 16,602 bp in length and consisted of the well-known 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and the control region. The phylogenetic analysis showed that LSC and Zhijiang duck have highly similar genetic relationship. These results are helpful for the conservation of genetic resources and phylogeny of this species.

12.
Am J Hum Genet ; 85(2): 194-203, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19664746

RESUMO

Nasopharyngeal carcinoma (NPC) is a multifactorial malignancy closely associated with genetic factors and Epstein-Barr virus infection. To identify the common genetic variants linked to NPC susceptibility, we conducted a genome-wide association study (GWAS) in 277 NPC patients and 285 healthy controls within the Taiwanese population, analyzing 480,365 single-nucleotide polymorphisms (SNPs). Twelve statistically significant SNPs were identified and mapped to chromosome 6p21.3. Associations were replicated in two independent sets of case-control samples. Two of the most significant SNPs (rs2517713 and rs2975042; p(combined) = 3.9 x 10(-20) and 1.6 x 10(-19), respectively) were located in the HLA-A gene. Moreover, we detected significant associations between NPC and two genes: specifically, gamma aminobutyric acid b receptor 1 (GABBR1) (rs29232; p(combined) = 8.97 x 10(-17)) and HLA-F (rs3129055 and rs9258122; p(combined) = 7.36 x 10(-11) and 3.33 x 10(-10), respectively). Notably, the association of rs29232 remained significant (residual p < 5 x 10(-4)) after adjustment for age, gender, and HLA-related SNPs. Furthermore, higher GABA(B) receptor 1 expression levels can be found in the tumor cells in comparison to the adjacent epithelial cells (p < 0.001) in NPC biopsies, implying a biological role of GABBR1 in NPC carcinogenesis. To our knowledge, it is the first GWAS report of NPC showing that multiple loci (HLA-A, HLA-F, and GABBR1) within chromosome 6p21.3 are associated with NPC. Although some of these relationships may be attributed to linkage disequilibrium between the loci, the findings clearly provide a fresh direction for the study of NPC development.


Assuntos
Carcinoma/genética , Cromossomos Humanos Par 6 , Estudo de Associação Genômica Ampla , Antígenos HLA/genética , Neoplasias Nasofaríngeas/genética , Alelos , Povo Asiático/genética , Povo Asiático/estatística & dados numéricos , Carcinoma/imunologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Frequência do Gene , Haplótipos , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Imuno-Histoquímica , Desequilíbrio de Ligação , Masculino , Neoplasias Nasofaríngeas/imunologia , Polimorfismo de Nucleotídeo Único , Receptores de GABA-B/genética , Receptores de GABA-B/metabolismo , Taiwan
13.
Clin Cardiol ; 45(9): 936-942, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35770315

RESUMO

BACKGROUND: Triglyceride glucose index (TyG index) is a novel marker of insulin resistance. Studies have shown that TyG index is closely associated with the occurrence of hypertension and cardiovascular disease. However, little is known about the correlation between TyG index and the occurrence of heart failure with preserved ejection fraction (HFpEF) in hypertensive patients. HYPOTHESIS: Our study assumes that TyG index strongly correlates with occurence of HFpEF in hypertensive patients. METHODS: This research enrolled 559 hypertensive patients (273 patients with HFpEF and 286 without HFpEF) admitted to the Department of Cardiology of Jiading Branch of Shanghai General Hospital from 2020 to 2021 as the study subjects. Gender, age, diastolic blood pressure, systolic blood pressure (SBP), and heart rate (HR) were recorded at admission. Medication history and fasting blood samples were harvested after admission to detect laboratory index. Cardiac function and ventricular structure index were measured by echocardiography. Pearson correlation analysis was conducted to identify the correlation of TyG index with cardiac function and ventricular structure. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of TyG index in HFpEF with hypertension. RESULTS: HFpEF patients had higher diuretic use frequencies, fasting plasma glucose, NT-proBNP, triglycerides, TyG index, left atrial diameter (LAD), left ventricular mass index (LVMI), the ratio of peak E-velocity of mitral orifice to peak velocity of early diastolic mitral annulus (E/e'), and SBP but lower ratio of peak E of early diastolic maximum blood flow velocity to peak A of late diastolic maximum blood flow velocity of mitral orifice (E/A) and average e' than non-HFpEF patients. Moreover, TyG index was correlated with LAD, left ventricular ejection fraction (LVEF), LVMI, average e', E/e', and NT-proBNP. The multivariate regression analysis suggested that TyG index, E/e', and NT-proBNP were independent risk factors for HFpEF in hypertensive patients. Compared with E/e' and NT-proBNP, the area under the ROC curve (0.778 [95% confidence interval: 0.707-0.849]) was the largest for TyG index. CONCLUSION: TyG index is higher in HFpEF patients than in non-HFpEF patients and related to cardiac diastolic function, which strongly correlates with occurrence of HFpEF in hypertensive patients.


Assuntos
Insuficiência Cardíaca , Hipertensão , China/epidemiologia , Glucose/uso terapêutico , Humanos , Hipertensão/complicações , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Volume Sistólico/fisiologia , Triglicerídeos , Função Ventricular Esquerda/fisiologia
14.
Front Physiol ; 13: 839217, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35356076

RESUMO

Current experiment was designed to check the effect of dietary supplementation of ramie powder on the growth performance, carcass and meat qualities and antioxidative capacity of Linwu ducks. A total of 312 ducks at 21-day-age were equally divided into 4 groups, fed with control diet, control diet supplemented of 3, 6, or 12% ramie powder, respectively. The results showed that dietary supplementation of 6 and 12% ramie powder increased the final weight and daily body weight gain (P < 0.05), and dietary supplementation of 6% ramie improved the cooking loss of the leg meat 45-mins-postmortem compared with the control group (P < 0.05). Moreover, dietary supplementation of 6% ramie powder promoted the antioxidative capacity of the ducks by increasing the serum activities of superoxide dismutase and glutathione (P < 0.05), as well as the mRNA expressions of glutathione peroxidase 1 in the breast meat and superoxide dismutase 1 in the leg meat (P < 0.05). This experiment demonstrated that dietary supplementation of ramie powder showed beneficial efficacy on the growth performance of Linwu ducks. It corroborated the potential of dietary ramie being used as poultry feed ingredient and suggested that 6% was the proper supplementation rate of ramie powder in Linwu ducks' feed.

15.
Bioengineered ; 13(4): 10914-10930, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35499161

RESUMO

Liver fibrosis occurs following inflammation triggered by the integrated actions of activated liver-resident macrophages (Kupffer cells) and hepatic stellate cells (HSCs), and the multiplicity of these mechanisms complicates drug therapy. Here, we demonstrate that the selective bromodomain and extra-terminal (BET) bromodomain inhibitor compound38 can block both the Janus kinase-signal transducer and activator of transcription and mitogen-activated protein kinase signaling pathways in macrophages, which decreased their secretion of proinflammatory cytokines in a dose-dependent manner. The inactivation of macrophages attenuated lipopolysaccharide-induced injurious inflammation concurrent with a reduction in F4/80+ cells, proinflammatory cytokine levels, and neutrophil infiltration. Moreover, compound 38 inhibited the Wnt/ß-catenin and transforming growth factor-beta/SMAD signaling pathways to abolish the activation of HSCs. In vivo, compound 38 significantly decreased the collagen deposition and fibrotic area of a CCl4-induced liver fibrosis model, and restored the deficiency of activated HSCs and the upregulation of liver inflammation. These results highlight the potential role of compound 38 in treating liver fibrosis considering its simultaneous inhibitory effects on liver inflammation and related fibrosis.


Assuntos
Células Estreladas do Fígado , Cirrose Hepática , Citocinas/metabolismo , Células Estreladas do Fígado/metabolismo , Humanos , Inflamação/metabolismo , Cirrose Hepática/tratamento farmacológico , Macrófagos/metabolismo
16.
Ying Yong Sheng Tai Xue Bao ; 32(1): 289-298, 2021 Jan.
Artigo em Zh | MEDLINE | ID: mdl-33477237

RESUMO

Evapotranspiration is the key element of hydrological energy cycle and climate system. It is of great significance to estimate the spatiotemporal variation of evapotranspiration and its response to climate and land use changes for understanding the effects of water cycle and ecological processes in urban basins. Based on the three-temperature model and MODIS Image, we estimated and analyzed the spatiotemporal variation of evapotranspiration in Nanning City from 2001 to 2018, and examined the influence and driving mode of main climate factors and land use types on evapotranspiration. The results showed that the annual average evapotranspiration of Nanning City ranged from 495.7 to 781.1 mm during 2001-2018, with the inter annual relative variability ranging from -22.5% to 23.1%, showing an overall upward trend. The regional evapotranspiration showed a distribution pattern of high north-south and low middle, with the urban evapotranspiration being significantly lower than suburban area. The evapotranspiration had a significant multiple correlation with climate factors. The influence of temperature on the evapotranspiration was stronger than precipita-tion. Evapotranspiration was temperature driven in suburbs, but was driven by multiple factors in urban area. The average evapotranspiration of different land use types in Nanning was forests (823.4 mm) > grasslands (675.6 mm) > croplands (582.9 mm) > urban area (346.6 mm). The change of land use type was the main underlying surface factor leading to the significant change of regional evapotranspiration.


Assuntos
Clima , Florestas , China , Temperatura , Ciclo Hidrológico
17.
World J Clin Cases ; 9(36): 11265-11275, 2021 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-35071557

RESUMO

BACKGROUND: Severe craniocerebral injury (STBI) is a critical physical trauma caused by a sudden external force acting on the head. The condition is complex and changeable, and disability and mortality rates are high. Although the life of STBI patients can be saved through treatment, the sequelae of consciousness, speech, cognitive impairment, stiffness, spasm, pain and abnormal behavior in the early rehabilitation stage can be a heavy burden to a family. In the past, routine nursing was often used to treat/manage STBI; however, problems, such as improper cooperation and untimely communication, reduced therapeutic effectiveness. AIM: To investigate the effect of a proposed care bundle to optimize the first aid process and assess its effectiveness on the early rehabilitation nursing of patients with STBI. METHODS: From January 2019 to December 2020, 126 STBI patients were admitted to the emergency department of Chongqing Emergency Medical Center. These patients were retrospectively selected as the research participants in the current study. The study participants were then divided into a control group (61 cases) and a study group (65 cases). The control group was treated with routine nursing. The study group adopted the proposed care bundle. The National Institutes of Health Stroke Scale/Score and Glasgow Coma Scale (GCS) were used to evaluate neurological function before and after emergency treatment. After 3 mo of rehabilitation, experimental outcomes were assessed. These included the GCS, Barthel Index, complication rate, muscle strength grade and satisfaction. RESULTS: There was no significant difference in gender, age, cause of injury and GCS between the two groups. After emergency, the National Institutes of Health Stroke Scale/Score of the study group (10.23 ± 3.26) was lower than that of the control group (14.79 ± 3.14). The GCS score of the study group (12.48 ± 2.38) was higher than that of the control group (9.32 ± 2.01). The arrival time of consultation in the study group was 20.56 ± 19.12, and the retention time in the emergency room was 45.12 ± 10.21, which were significantly shorter than those in the control group. After 3 mo of rehabilitation management, the GCS and Barthel Index of the study group were 14.56 ± 3.75 and 58.14 ± 12.14, respectively, which were significantly higher than those of the control group. The incidence of complications in the study group (15.38%) was significantly lower than that in the control group (32.79%). The proportion of muscle strength ≥ grade III in the study group (89.23%) was significantly higher than that in the control group (50.82%). The satisfaction of patients in the study group was significantly higher than that in the control group. CONCLUSION: Care bundles are used to optimize the nursing process. During first-aid, care bundles can effectively improve the rescue effect and improve neurological function of STBI patients as well as shorten the treatment time. In early rehabilitation, they can effectively improve the consciousness of STBI patients, improve the activities of daily living, reduce the risk of complications, accelerate the recovery of muscle strength and improve their satisfaction.

18.
Mol Med Rep ; 23(5)2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33649839

RESUMO

Hepatic fibrosis, a common pathological manifestation of chronic liver injury, is generally considered to be the end result of an increase in extracellular matrix produced by activated hepatic stellate cells (HSCs). The aim of the present study was to target the mechanisms underlying HSC activation in order to provide a powerful therapeutic strategy for the prevention and treatment of liver fibrosis. In the present study, a high­throughput screening assay was established, and the histone deacetylase inhibitor givinostat was identified as a potent inhibitor of HSC activation in vitro. Givinostat significantly inhibited HSC activation in vivo, ameliorated carbon tetrachloride­induced mouse liver fibrosis and lowered plasma aminotransferases. Transcriptomic analysis revealed the most significantly regulated genes in the givinostat treatment group in comparison with those in the solvent group, among which, dermokine (Dmkn), mesothelin (Msln) and uroplakin­3b (Upk3b) were identified as potential regulators of HSC activation. Givinostat significantly reduced the mRNA expression of Dmkn, Msln and Upk3b in both a mouse liver fibrosis model and in HSC­LX2 cells. Knockdown of any of the aforementioned genes inhibited the TGF­ß1­induced expression of α­smooth muscle actin and collagen type I, indicating that they are crucial for HSC activation. In summary, using a novel strategy targeting HSC activation, the present study identified a potential epigenetic drug for the treatment of hepatic fibrosis and revealed novel regulators of HSC activation.


Assuntos
Carbamatos/farmacologia , Células Estreladas do Fígado/efeitos dos fármacos , Cirrose Hepática/prevenção & controle , Fígado/efeitos dos fármacos , Animais , Tetracloreto de Carbono , Linhagem Celular , Feminino , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Inibidores de Histona Desacetilases/farmacologia , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/genética , Mesotelina , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Uroplaquina III/genética , Uroplaquina III/metabolismo
19.
J Clin Nurs ; 18(11): 1632-9, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19490299

RESUMO

AIMS AND OBJECTIVES: This study aimed to evaluate the effectiveness of a comprehensive discharge-planning service for hip fracture patients, including length of stay, functional status, self-care knowledge and quality of life (QOL). BACKGROUND: Hip fractures are the most devastating result of osteoporosis. Care of these patients from the moment they enter the hospital until discharge and postdischarge is a challenging task, requiring a coordinated approach by an interdisciplinary team. DESIGN: An experimental design was used. Methods. Fifty hip fracture patients were recruited from a medical centre in Taipei, Taiwan and randomly divided into two groups. The control group received routine discharge nursing care and the experimental group received comprehensive discharge planning. After patient admission, researchers assessed discharge-planning needs, provided discharge nursing instruction, coordinated services and determined discharge placement based on assessment results. RESULTS: (i) Mean age of 50 hip fracture patients was 78.75 (SD 6.99) years. Mean length of stay was 6.04 (SD 2.41) days for the experimental group and 6.29 (SD 2.17) for the control group. Difference between groups was not significant (t = -0.394, p = 0.696). (ii) The self-care knowledge of the experimental group was higher than that of the control group (F = 11.569, p = 0.001). (iii) Significant improvements were observed in functional status of both groups at three months postdischarge, with no significant differences observed between groups. However, the functional status of experimental group patients showed a slightly better trend than that of the control group. (iv) At three months postdischarge, QOL of experimental group patients was better than control group patients. CONCLUSIONS: A comprehensive discharge-planning service can improve hip fracture patients' self-care knowledge and QOL. RELEVANCE TO CLINICAL PRACTICE: Results of this study can be used clinically as a basis for practical implementation of discharge-planning services in fracture patients.


Assuntos
Fraturas do Quadril/terapia , Alta do Paciente , Avaliação de Programas e Projetos de Saúde , Idoso , Fraturas do Quadril/fisiopatologia , Humanos , Tempo de Internação , Pessoa de Meia-Idade , Satisfação do Paciente , Qualidade de Vida , Taiwan
20.
ChemSusChem ; 12(16): 3808-3816, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31216377

RESUMO

Organic-inorganic halide perovskite solar cells (PSCs) have reached certified efficiencies of over 23 % with expensive organic hole-transporting materials. However, the use of an inorganic hole-transport layer (HTL) remains crucial as it would reduce cost combined with higher mobility and stability. In this direction, the application of Cu2 O as the top layer in PSCs is still complicated owing to the difficulty of solution processing. Herein, a solution-processing method is reported for preparing Cu2 O nanocubes as a p-type HTL in regular structure (n-i-p) PSCs. The controlled synthesis of Cu2 O nanocubes in a size range of 60-80 nm is achieved without using any surfactants, which are usually toxic and tricky to remove. The new structure of these Cu2 O nanocubes enhances the carrier mobility with preferable energy alignment to the perovskite layer and superb stability. The PSCs based on these Cu2 O nanocubes HTMs could achieve an efficiency exceeding 17 % with high stability, whereas organic P3HT-based PSCs display an efficiency of 15.59 % with a poorer running stability. This indicates that Cu2 O nanocubes are a promising HTM for efficient and stable PSCs.

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