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1.
J Geriatr Cardiol ; 20(6): 448-458, 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37416521

RESUMO

BACKGROUND: Nocturnal hypertension is reported as a risk factor for cardiovascular disease. This study aimed to explore the potential association between nocturnal hypertension and heart failure (HF) rehospitalization in patients with HF with preserved ejection fraction (HFpEF). METHODS: A total of 538 patients with HFpEF from May 2018 to December 2021 were consequently recruited in this study and followed up until they were readmitted for HF or the end of this study. Cox regression analysis was used to reveal the potential association between nighttime blood pressure (BP) levels, nocturnal hypertension and nocturnal BP patterns and HF rehospitalization. Kaplan-Meier curve was used to assess the cumulative event-free survival rate between groups. RESULTS: There were 537 patients with HFpEF were included in the final analysis. The mean age of the study population was 77.14 ± 8.68 years, and 41.2% of patients were men. After a median follow-up duration of 10.93 (4.19-21.13) months, 176 patients (32.7%) with HFpEF were readmitted for HF. Cox regression analysis had revealed that nighttime systolic BP level [hazards ratio (HR) = 1.018, 95% CI: 1.008-1.028, P = 0.001], nighttime diastolic BP level (HR = 1.024, 95% CI: 1.007-1.042, P = 0.007), nocturnal hypertension (HR = 1.688, 95% CI: 1.229-2.317, P = 0.001) were associated with HF rehospitalization. Kaplan-Meier analysis had demonstrated that patients with nocturnal hypertension had significantly lower event-free survival rate (log-rank P < 0.001). Furthermore, patients with a riser pattern had a higher risk of HF rehospitalization (HR = 1.828, 95% CI: 1.055-3.166, P = 0.031) and lower event-free survival rate (log-rank P = 0.003) than those with a dipper pattern. These findings were also confirmed in patients with HFpEF and hyperuricemia. CONCLUSIONS: Nighttime BP levels, nocturnal hypertension and a riser pattern are independently associated with HF rehospitalization in patients with HFpEF, and prominently in patients with HFpEF and hyperuricemia. Well controlled nighttime BP levels should be emphasized and considered in patients with HFpEF.

2.
Biomed Pharmacother ; 162: 114661, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37068333

RESUMO

Kruppel-like factors (KLFs) are a family of zinc finger transcription factors that have been found to play an essential role in the development of various human tissues, including epithelial, teeth, and nerves. In addition to regulating normal physiological processes, KLFs have been implicated in promoting the onset of several cancers, such as gastric cancer, lung cancer, breast cancer, liver cancer, and colon cancer. To inhibit cancer progression, various existing medicines have been used to modulate the expression of KLFs, and anti-microRNA treatments have also emerged as a potential strategy for many cancers. Investigating the possibility of targeting KLFs in cancer therapy is urgently needed, as the roles of KLFs in cancer have not received enough attention in recent years. This review summarizes the factors that regulate KLF expression and function at both the transcriptional and posttranscriptional levels, which could aid in understanding the mechanisms of KLFs in cancer progression. We hope that this review will contribute to the development of more effective anti-cancer medicines targeting KLFs in the future.


Assuntos
Neoplasias da Mama , Fatores de Transcrição , Humanos , Feminino , Fatores de Transcrição/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Regulação da Expressão Gênica
3.
J Am Heart Assoc ; 12(4): e026586, 2023 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-36789853

RESUMO

Background Severe hindlimb ischemia is a chronic disease with poor prognosis that can lead to amputation or even death. This study aimed to assess the therapeutic effect of liraglutide on hind-limb ischemia in type 2 diabetic mice and to elucidate the underlying mechanism. Methods and Results Blood flow reperfusion and capillary densities after treatment with liraglutide or vehicle were evaluated in a mouse model of lower-limb ischemia in a normal background or a background of streptozotocin-induced diabetes. The proliferation, migration, and tube formation of human umbilical vein endothelial cells were analyzed in vitro upon treatment with liraglutide under normal-glucose and high-glucose conditions. Levels of phospho-Akt, phospho-endothelial nitric oxide synthase, and phospho-extracellular signal-related kinases 1 and 2 under different conditions in human umbilical vein endothelial cells and in ischemic muscle were determined by western blotting. Liraglutide significantly improved perfusion recovery and capillary density in both nondiabetic and diabetic mice. Liraglutide also promoted, in a concentration-dependent manner, the proliferation, migration, and tube formation of normal glucose- and high glucose-treated human umbilical vein endothelial cells, as well as the phosphorylation of Akt, endothelial nitric oxide synthase, and extracellular signal-related kinases 1 and 2 both in vitro and in vivo. The liraglutide antagonist exendin (9-39) reversed the promoting effects of liraglutide on human umbilical vein endothelial cell functions. Furthermore, exendin (9-39), LY294002, and PD98059 blocked the liraglutide-induced activation of Akt/endothelial nitric oxide synthase and extracellular signal-related kinases 1 and 2 signaling pathways. Conclusions These studies identified a novel role of liraglutide in modulating ischemia-induced angiogenesis, possibly through effects on endothelial cell function and activation of Akt/endothelial nitric oxide synthase and extracellular signal-related kinases 1 and 2 signaling, and suggested the glucagon-like peptide-1 receptor may be an important therapeutic target in diabetic hind-limb ischemia.


Assuntos
Diabetes Mellitus Experimental , Liraglutida , Camundongos , Humanos , Animais , Liraglutida/farmacologia , Liraglutida/uso terapêutico , Óxido Nítrico Sintase Tipo III/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Neovascularização Fisiológica , Células Endoteliais da Veia Umbilical Humana/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Isquemia/metabolismo , Glucose/metabolismo , Membro Posterior/irrigação sanguínea
4.
Nutrients ; 14(22)2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36432403

RESUMO

Our previous study revealed that the bone anabolic effects of the lignan-rich fraction (SWCA) from Sambucus williamsii Hance was involved in modulating the metabolism of tryptophan in vivo and inhibiting serotonin (5-HT) synthesis in vitro. This study aimed to determine how SWCA modulates bone metabolism via serotonin in vivo. The effects of SWCA were evaluated by using 4-month-old Sprague-Dawley (SD) ovariectomized rats. The serum levels of 5-HT and kynurenine, the protein expressions of tryptophan hydroxylase 1 (TPH-1) and TPH-2, the genes and proteins related to the 5-HT signaling pathway as well as gut microbiota composition were determined. SWCA treatment alleviated bone loss and decreased serum levels of serotonin, which was negatively related to bone mineral density (BMD) in rats. It suppressed the protein expression of TPH-1 in the colon, and reversed the gene and protein expressions of FOXO1 and ATF4 in the femur in OVX rats, while it did not affect the TPH-2 protein expression in the cortex. SWCA treatment escalated the relative abundance of Antinobacteria and modulated several genera relating to BMD. These findings verified that the bone protective effects of lignans were mediated by serotonin, and provided evidence that lignans might be a good source of TPH-1 inhibitors.


Assuntos
Microbioma Gastrointestinal , Lignanas , Sambucus , Ratos , Animais , Serotonina , Lignanas/farmacologia , Ratos Sprague-Dawley
5.
Ann Noninvasive Electrocardiol ; 27(4): e12934, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35481720

RESUMO

OBJECTIVE: To explore the clinical significance of intracavitary electrocardiogram positioning technology in preventing catheter ectopic position during peripherally inserted central catheter (PICC) catheterization in children with tumors. METHODS: A retrospective analysis of the clinical data of 62 children who required PICC catheterization was performed. The intracavitary electrocardiogram (ECG) positioning technology was used during the tube placement of the child patients. After the tube was successfully placed, the chest radiograph was taken. The ECG positioning result was compared with the chest radiograph positioning result after the tube was inserted, and the sensitivity and specificity of the ECG positioning were calculated. RESULTS: The intracavitary electrocardiogram results of 62 children with PICC catheters showed that 56 cases (90.32%) had characteristic P waves, and six cases (9.68%) had no characteristic P waves. The chest radiographs of 56 children with characteristic P wave showed that 33 cases (58.93%) of the catheter tip position was appropriate, 22 cases (39.29%) of the catheter tip was too deep, and 1 case was in a non-superior vena cava; six cases of chest radiographs of children with no characteristic P wave showed: one case was too deep at T8 level, one case was too shallow at T4 level, four cases were at non-superior vena cava, one case was contralateral internal jugular vein, two cases in the contralateral brachiocephalic vein, and one case was the contralateral subclavian vein. CONCLUSION: Intracavitary ECG positioning assisted catheter placement in infants can effectively improve the accuracy of catheter tip position.


Assuntos
Cateterismo Venoso Central , Cateterismo Periférico , Cateteres Venosos Centrais , Neoplasias , Cateterismo Venoso Central/métodos , Cateterismo Periférico/métodos , Criança , Eletrocardiografia/métodos , Humanos , Lactente , Neoplasias/tratamento farmacológico , Estudos Retrospectivos
6.
J Phys Chem B ; 126(8): 1700-1708, 2022 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-35188781

RESUMO

Accurate calculation of the binding free energies between a protein and a ligand is the primary objective of structure-based drug design, but it still remains a challenging problem. In this work, we apply the screening molecular mechanics/Poisson Boltzmann surface area (MM/PBSA) method to calculate the binding affinity of protein-ligand interactions. Our results show that the performance of the screening MM/PBSA is better than that of the standard MM/PBSA, especially in a charged-ligand system. In addition, we also investigate the effect of the solute dielectric constant on the results, and find that the optimal solute dielectric constants are different between the neutral-ligand system and the charged-ligand system. Moreover, we also evaluate the effect of the atomic-charge methods on the performance of the screening MM/PBSA. The present study demonstrates that the screening MM/PBSA should be a reliable method for calculating binding energy of biosystems.


Assuntos
Simulação de Dinâmica Molecular , Ligantes , Ligação Proteica , Termodinâmica
7.
Ann Noninvasive Electrocardiol ; 27(2): e12918, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34951713

RESUMO

BACKGROUND: We compared the methods of electrocardiogram (ECG) and X-ray localization of the peripherally inserted central catheter (PICC) tip position, in order to find a more convenient, practical, and safe method. OBJECTIVE: To investigate the value of applying electrocardiographic localization of the PICC tip position in critically ill patients with advanced cancer in Hebei Province, China. METHOD: Enrolled 137 advanced cancers requiring PICC placement. The position of the catheter tip was localized with the bedside electrocardiogram in real time. Then, the localization was performed using a chest X-ray (the gold standard). The accuracy of electrocardiographic location was checked. RESULTS: Specific P waves were observed in 130 patients. No change in the P waves was observed for the remaining seven patients. The age of the latter group of patients was more advanced (87.29 [5.15] years), a significant difference to that of the 130 patients with specific P waves (71.58 [14.84] years) (t = -6.704, p < .001). Specific P waves not only involve ascendance in P waves but also ascendance in QRS waves. CONCLUSIONS: The use of an ECG to localize the PICC tip in critically ill patients with advanced cancer may replace the unnecessary use of chest X-rays. Specific P waves not only involve an increase in P waves but also an increase in QRS waves. If there is no change in the P wave, a chest X-ray film must be obtained. In elderly patients, because there is a possibility of catheter tip malposition, a comprehensive evaluation should be performed before surgery.


Assuntos
Cateterismo Venoso Central , Cateterismo Periférico , Cateteres Venosos Centrais , Neoplasias , Idoso , Cateterismo Venoso Central/efeitos adversos , Cateterismo Venoso Central/métodos , Cateterismo Periférico/efeitos adversos , Cateterismo Periférico/métodos , Pré-Escolar , Estado Terminal , Eletrocardiografia/métodos , Humanos , Neoplasias/diagnóstico por imagem , Neoplasias/etiologia
8.
Ann Noninvasive Electrocardiol ; 27(1): e12904, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34825734

RESUMO

PURPOSE: To explore the application of ECG-guided localization technology in PICC catheterization and the clinical significance of different maps of intracavitary ECG in PICC tip localization. METHODS: In the process of catheter placement under the guidance of ultrasound, the technique of intracavitary ECG location was used. The length of the catheter was measured on the body's surface. The amplitude of the P-wave and the QRS-wave groups of electrocardiograms before and during catheter placement was recorded. Nine hundred sixty-one patients who underwent X-ray chest film examination after catheterization were imaged on the chest film at the tip of the catheter. RESULTS: Eight hundred four cases had a characteristic P wave, 83.66%, of which, 331 cases (50% < P/R ≤80%) had 99.09%; 425 cases (80% < P/R ≤100%) had 99.29%; 48 cases (P/R >100%) had 100%. One hundred eighteen cases of non-specific P wave accounted for 12.28% and 79.66% of chest radiographs, of which 72 cases of P/R <50% were 100%; 46 cases of unchanged P wave were 47.83%; 34 cases of special cases accounted for 3.54% and 55.88% of chest radiographs; five cases of interference wave accounted for 0.25%, and the chest radiographs were self-control. The in-place rate of the body contrast catheter was 80%. CONCLUSIONS: The accuracy of the ECG characteristic map in guiding the location of the PICC tip is higher than that of the non-characteristic P wave, and it has more clinical significance in locating the best position of the PICC tip.


Assuntos
Cateterismo Venoso Central , Cateterismo Periférico , Cateteres Venosos Centrais , Eletrocardiografia , Humanos
9.
Biomed Pharmacother ; 137: 111372, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33761598

RESUMO

Menopausal women are susceptible to have high risk of cardiovascular diseases, type II diabetes and osteoporosis due to the metabolic disorder caused by estrogen deficiency. Accumulating evidence supports that gut microbiota is a key regulator of metabolic diseases. Our previous metabolomics study interestingly demonstrated that the anti-osteoporotic effects of lignan-rich fraction (SWCA) from Sambucus wialliamsii Hance were related to the restoration of a series of lipid and glucose metabolites. This study aims to investigate how SWCA modulates lipid and glucose metabolism and the underlying mechanism. Our results show that oral administration of SWCA (140 mg/kg and 280 mg/kg) for 10 weeks alleviated dyslipidemia, improved liver functions, prevented glucose tolerance and insulin actions, attenuated system inflammation and improved intestinal barrier in OVX rats. It also induced a high abundance of Actinobacteria, and restored microbial composition. We are the first to report the protective effects of the lignan-rich fraction from S. williamsii on dyslipidemia and insulin resistance. Our findings provide strong evidence for the application of this lignan-rich fraction to treat menopausal lipid disorder and insulin resistance-related diseases.


Assuntos
Dislipidemias/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Hipolipemiantes/farmacologia , Resistência à Insulina , Lignanas/farmacologia , Sambucus/química , Administração Oral , Animais , Citocinas/metabolismo , Feminino , Glucose/metabolismo , Teste de Tolerância a Glucose , Fígado/efeitos dos fármacos , Ovariectomia , Extratos Vegetais/farmacologia , Caules de Planta/química , Ratos , Ratos Sprague-Dawley
10.
Huan Jing Ke Xue ; 28(6): 1377-83, 2007 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-17674753

RESUMO

Chemical forms of Cr, Cu, Mn, Ni, Pb and Zn in the surface sediments of Nansihu Lake and its main inflow rivers are determined by the BCR sequential extraction method. The chemical fractionation composition characteristics, pollution state and potential ecological effects of the heavy metals are discussed. Cr, Cu, Ni and Zn in the sediments of Sihe River, Jinghang Canal, Zhuzhaoxin River, Guangfu River, south area of the Upper Lakes, and Down Lakes mainly exist in residual fraction, which account for 80% - 90% of their content, mainly reflecting the natural characteristics of the heavy metals; but for the sediment of Old Canal, Guangfu River estuary, Baima River, nearly 80% of Cr, Cu, Ni and Zn exist in extractable fractions due to human pollution, especially with high oxidizable and acid extractable fractions content. Pb and Mn mainly exist in residual fraction and oxidizable fraction in the sediment of Nansihu Lake and its main inflow rivers, which account for 95% and 70% of the content of Pb and Mn, similar to other unpolluted sediments. With the mineralization and decomposition of organic matter and change of environment condition of the surface sediment, the extractable fractions of Cr, Cu, Ni, Zn in the polluted sediment can be reactivated, bringing on ecological harm to the water ecological system.


Assuntos
Água Doce/química , Sedimentos Geológicos/química , Metais Pesados/química , Poluentes Químicos da Água/química , Fracionamento Químico , China , Sedimentos Geológicos/análise , Metais Pesados/análise , Poluentes Químicos da Água/análise
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