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1.
Proc Natl Acad Sci U S A ; 121(11): e2319390121, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38437562

RESUMO

Water-energy sustainability will depend upon the rapid development of advanced pressure-driven separation membranes. Although energy-efficient, water-treatment membranes are constrained by ubiquitous fouling, which may be alleviated by engineering self-cleaning membrane interfaces. In this study, a metal-polyphenol network was designed to direct the armorization of catalytic nanofilms (ca. 18 nm) on inert polymeric membranes. The chelation-directed mineralized coating exhibits high polarity, superhydrophilicity, and ultralow adhesion to crude oil, enabling cyclable crude oil-in-water emulsion separation. The in-place flux recovery rate exceeded 99.9%, alleviating the need for traditional ex situ cleaning. The chelation-directed nanoarmored membrane exhibited 48-fold and 6.8-fold figures of merit for in-place self-cleaning regeneration compared to the control membrane and simple hydraulic cleaning, respectively. Precursor interaction mechanisms were identified by density functional theory calculations. Chelation-directed armorization offers promise for sustainable applications in catalysis, biomedicine, environmental remediation, and beyond.

2.
Environ Res ; 232: 116339, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37290628

RESUMO

Chlortetracycline hydrochloride (CTC) is one of the prevailing antibiotic pollutants that harm both environmental ecosystem and human health. Herein, Zr-based metal-organic gels (Zr-MOGs) with lower-coordinated active sites and hierarchically porous structures are fabricated via a facile straightforward room-temperature strategy for CTC treatment. More importantly, we incorporated the powder Zr-MOGs into low-cost sodium alginate (SA) matrix to achieve shaped Zr-based metal-organic gel/SA beads for enhancing the adsorption ability and ameliorating the recyclability. The Langmuir maximum adsorption capacities of Zr-MOGs and Zr-MOG/SA beads could reach 143.9 mg/g and 246.9 mg/g, respectively. What's more, in the manual syringe unit and continuous bead column experiments, Zr-MOG/SA beads could achieve an eluted CTC removal ratio as high as 96.3% and 95.5% in the river water sample, respectively. On top of that, the adsorption mechanisms were put forward as a combination of pore filling, electrostatic interaction, hydrophilic-lipophilic balance, coordination, π-π interaction as well as hydrogen bonding interaction. This study outlines a workable strategy for the facile preparation of candidate adsorbents for wastewater treatment.


Assuntos
Clortetraciclina , Poluentes Químicos da Água , Humanos , Clortetraciclina/química , Água , Temperatura , Alginatos/química , Adsorção , Ecossistema , Metais , Géis/química , Poluentes Químicos da Água/análise , Cinética , Concentração de Íons de Hidrogênio
3.
Zhongguo Zhong Yao Za Zhi ; 48(16): 4421-4428, 2023 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-37802868

RESUMO

This study aimed to provide scientific evidence for predicting quality markers(Q-markers) of Elephantopus scaber by establishing UPLC fingerprint of E. scaber from different geographical origins and determining the content of 13 major components, as well as conducting in vitro anti-cancer activity investigation of the main components. The chromatographic column used was Waters CORTECS UPLC C_(18)(2.1 mm×150 mm, 1.6 µm), and the mobile phase consisted of acetonitrile and 0.1% formic acid solution(gradient elution). The column temperature was set at 30 ℃, and the flow rate was 0.2 mL·min~(-1). The injection volume was 1 µL, and the detection wavelength was 240 nm. The UPLC fingerprint of E. scaber was fitted using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 edition) to determine common peaks, evaluate similarity, identify and determine the content of major components. The CCK-8 assay was used to explore the inhibitory effect of the main components on the proliferation of lung cancer cells. The results showed that in the established UPLC fingerprint of E. scaber, 35 common peaks were identified. Thirteen major components, including neochlorogenic acid(peak 1), chlorogenic acid(peak 2), cryptochlorogenic acid(peak 3), caffeic acid(peak 4), schaftoside(peak 6), galuteolin(peak 9), isochlorogenic acid B(peak 10), isochlorogenic acid A(peak 12), isochlorogenic acid C(peak 18), deoxyelephantopin(peak 28), isodeoxyelephantopin(peak 29), isoscabertopin(peak 31), and scabertopin(peak 32) were identified and quantified, and a quantitative analysis method was established. The results of the in vitro anti-cancer activity study showed that deoxyelephantopin, isodeoxyelephantopin, isoscabertopin, and scabertopin in E. scaber exhibited inhibition rates of lung cancer cell proliferation exceeding 80% at a concentration of 10 µmol·L~(-1), higher than the positive drug paclitaxel. These results indicate that the fingerprint of E. scaber is highly characteristic, and the quantitative analysis method is accurate and stable, providing references for the research on quality standards of E. scaber. Four sesquiterpene lactones in E. scaber show significant anti-cancer activity and can serve as Q-markers for E. scaber.


Assuntos
Asteraceae , Medicamentos de Ervas Chinesas , Neoplasias Pulmonares , Humanos , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Asteraceae/química , Neoplasias Pulmonares/tratamento farmacológico
4.
J Transl Med ; 14: 260, 2016 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-27604550

RESUMO

BACKGROUND: Body mass index (BMI), waist circumference (WC), visceral adiposity index (VAI), triglyceride glucose index (TyG), TyG-BMI, and TyG-WC have been reported as markers of insulin resistance or type 2 diabetes mellitus (T2DM). However, little is known about the associations between the aforementioned markers and the risk of prediabetes and diabetes in first-degree relatives (FDRs) of T2DM patients. METHODS: 1544 FDRs of T2DM patients (635 men and 909 women) were enrolled in the initial cross-sectional study and all of them finished corresponding examinations. Logistic regression analysis and receiver operating characteristic (ROC) curve were used to compare and identify the associations of the six parameters (BMI, WC, VAI, TyG, TyG-BMI and TyG-WC) with the prevalence of prediabetes and diabetes. Subsequently, 452 of them were followed-up for an average of 5 years. Cox proportional hazard regression model was applied to confirm the predictive value of the optimal marker. RESULTS: Among the indices, TyG-WC was more strongly associated with the prevalence of prediabetes and diabetes. Compared with participants in the lowest quartile of TyG-WC, the adjusted odds ratio and 95 % CIs for prediabetes and diabetes was 11.19 (7.62-16.42) for those in the top quartile of TyG-WC. Moreover, the largest AUC was also observed in TyG-WC (0.765, 95 % CIs 0.741-0.789, P < 0.001). The robust predictive value of TyG-WC was further confirmed in the follow-up study (HR: 7.13, 95 % CIs 3.41-14.90, P < 0.001). CONCLUSIONS: TyG-WC is a novel and clinically effective marker for early identifying the risks of prediabetes and diabetes in FDRs of T2DM patients.


Assuntos
Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/metabolismo , Família , Glucose/metabolismo , Triglicerídeos/metabolismo , Circunferência da Cintura , Adulto , Estudos Transversais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estado Pré-Diabético/diagnóstico , Estudos Prospectivos , Curva ROC , Fatores de Risco , Resultado do Tratamento
5.
J Clin Lab Anal ; 30(1): 23-31, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27152377

RESUMO

OBJECTIVE: This meta-analysis aimed to identify the value of serum YKL-40 level for the diagnosis of coronary artery disease (CAD). METHODS: Through searching the following electronic databases: the Cochrane Library Database (Issue 12, 2013), Web of Science (1945 ∼ 2013), PubMed (1966 ∼ 2013), CINAHL (1982 ∼ 2013), EMBASE (1980 ∼ 2013), and the Chinese Biomedical Database (CBM; 1982 ∼ 2013), related articles were determined without any language restrictions. STATA statistical software (Version 12.0, Stata Corporation, College Station, TX) was chosen to deal with statistical data. Standard mean difference (SMD) and its corresponding 95% confidence interval (95% CI) were calculated. RESULTS: Eleven clinical case-control studies that recruited 1,175 CAD patients and 1,261 healthy controls were selected for statistical analysis. The main findings of our meta-analysis showed that serum YKL-40 level in CAD patients was significantly higher than that in control subjects (SMD = 2.79, 95% CI = 1.73 ∼ 3.85, P < 0.001). Ethnicity-stratified analysis indicated a higher serum YKL-40 level in CAD patients than control subjects among China, Korea, and Denmark populations (China: SMD = 2.97, 95% CI = 1.21 ∼ 4.74, P = 0.001; Korea: SMD = 0.66, 95% CI = 0.17 ∼ 1.15, P = 0.008; Denmark: SMD = 1.85, 95% CI = 1.42 ∼ 2.29, P < 0.001; respectively), but not in Turkey (SMD = 4.52, 95% CI = -2.87 ∼ 11.91, P = 0.231). CONCLUSION: The present meta-analysis suggests that an elevated serum YKL-40 level may be used as a promising diagnostic tool for early identification of CAD.


Assuntos
Adipocinas/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico , Lectinas/sangue , Idoso , Proteína 1 Semelhante à Quitinase-3 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Tamanho da Amostra
6.
J Res Med Sci ; 21: 12, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27904558

RESUMO

BACKGROUND: We performed this meta-analysis in order to collect all the relevant studies to clarify the correlations of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) with chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: After a literature search in electronic databases, pertinent case-control studies investigating the correlations of MMP-9 and TIMP-1 protein expressions within a COPD setting were enrolled based on our strict inclusion and exclusion criteria. We used key words such as "chronic obstructive pulmonary disease," "COPD" or "COAD" or "chronic obstructive airway disease" and "matrix metalloproteinases" or "MMPs" to make a searching strategy in this study. STATA software (version 12.0, Stata Corporation, College Station, TX, USA) was utilized for statistical analysis. RESULTS: A total of 20 studies were enrolled into this meta-analysis including 923 COPD patients and 641 healthy controls. The findings of this meta-analysis revealed that serum expression levels of MMP-9 and TIMP-1 protein in COPD patients were higher than those of healthy controls (MMP-9: SMD = 1.44, 95%CI = 0.85 ~ 2.04, P < 0.001; TIMP-1: SMD = 3.53, 95% CI = 2.31 ~ 4.75, P < 0.001). Subgroup analysis based on ethnicity revealed that both Caucasians and Asian COPD patients exhibited higher MMP-9 and TIMP-1 serum protein levels than healthy controls (MMP-9: SMD = 0.81, 95%CI = 0.15~1.48, P = 0.016; TIMP-1: SMD = 4.43, 95%CI = 1.98 ~ 6.87, P = 0.016) and in Caucasians (MMP-9: SMD = 2.30, 95%CI = 1.21 ~ 3.38, P < 0.001; TIMP-1: SMD = 2.86, 95%CI = 1.47 ~ 4.24, P < 0.001). CONCLUSION: The result of this meta-analysis indicates that elevated levels of MMP-9 and TIMP-1 proteins may be correlated with the pathogenesis of COPD, and the two proteins may represent important biological markers for the early diagnosis of COPD.

7.
J Cell Biochem ; 116(11): 2610-9, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25925903

RESUMO

This study aimed to investigate the effect of microRNA-30b (miR-30b) in rat myocardial ischemic-reperfusion (I/R) injury model. We randomly divided Sprague-Dawley (SD) rats (n = 80) into five groups: 1) control group; 2) miR-30b group; 3) sham-operated group; 4) I/R group, and 5) I/R+miR-30b group. Real-time quantitative polymerase chain reaction, immunohistochemical staining and Western blot analysis were conducted. TUNEL assay was employed for testing cardiomyocyte apoptosis. Our results showed that miR-30b levels were down-regulated in I/R group and I/R + miR-30b group compared with sham-operated group (both P < 0.05). However, miR-30b level in I/R + miR-30b group was higher than I/R group (P < 0.05). Markedly, the apoptotic rate in I/R group showed highest in I/R group (P < 0.05). Additionally, the results illustrated that protein levels of Bcl-2, Bax, and caspase-3 were at higher levels in ischemic regions in I/R group, comparing to sham-operated group (all P < 0.05), while Bcl-2/Bax was reduced (P < 0.05). Bcl-2 level and Bcl-2/Bax were obviously increased in I/R + miR-30b group by comparison with I/R group, and expression levels of Bax and caspase-3 were down-regulated (all P < 0.05). We also found that in I/R + miR-30b group, KRAS level was apparently lower and p-AKT level was higher by comparing with I/R group (both P < 0.05). Our study indicated that miR-30b overexpression had anti-apoptotic effect on early phase of rat myocardial ischemia injury model through targeting KRAS and activating the Ras/Akt pathway.


Assuntos
MicroRNAs/genética , MicroRNAs/metabolismo , Isquemia Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Animais , Apoptose , Caspase 3/genética , Caspase 3/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica , Isquemia Miocárdica/genética , Isquemia Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
8.
BMC Endocr Disord ; 15: 21, 2015 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-25924608

RESUMO

BACKGROUND: To explore clinical characteristics and beta cell function in Chinese patients with newly diagnosed drug naive type 2 diabetes mellitus (T2DM) with different levels of serum triglyceride (TG). METHODS: Patients with newly diagnosed T2DM (n = 624) were enrolled and divided into different groups according to levels of serum TG. All patients underwent oral glucose tolerance tests and insulin releasing tests. Demographic data, lipid profiles, glucose levels, and insulin profiles were compared between different groups. Basic insulin secretion function index (homeostasis model assessment for beta cell function index, HOMA-ß), modified beta cell function index (MBCI), glucose disposition indices (DI), and early insulin secretion function index (insulinogenic index, IGI) were used to evaluate the beta cell function. RESULTS: Patients of newly diagnosed T2DM with hypertriglyceridemia were younger, fatter and had worse lipid profiles, glucose profiles, and high insulin levels than those with normal TG. There is no difference in early phase insulin secretion among groups of newly diagnosed T2DM patients with different TG levels. The basal beta cell function (HOMA-ß and MBCI) initially increased along rising TG levels and then decreased as the TG levels rose further. The insulin sensitivity was relatively high in patients with a low level of TG and low with a high level of TG. CONCLUSIONS: Hypertriglyceridemia influences clinical characteristics and ß cell function of Chinese patients with newly diagnosed T2DM. A better management of dyslipidemia may, to some extent, reduce the effect of lipotoxicity, thereby improving glucose homeostasis in patients with newly diagnosed T2DM.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Células Secretoras de Insulina/fisiologia , Triglicerídeos/sangue , Adulto , Idoso , China/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Hipertrigliceridemia/sangue , Hipertrigliceridemia/epidemiologia , Hipertrigliceridemia/fisiopatologia , Insulina/sangue , Resistência à Insulina , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade
9.
Zhong Yao Cai ; 38(6): 1287-9, 2015 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-26762070

RESUMO

OBJECTIVE: To establish a simple and reliable method for rapid separation and identification of chemical components in Polygonum multiflorum Formula Granules. METHODS: An ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometric method( UPLC/Q-TOF MS) was used. The separation was performed on an Agilent Eclipse Plus C18 RRHD(100 mm x 2.1 mm, 1.8 µm) column with a mobile phase of water and acetonitrile in a gradient elution mode. The flow rate was 0.4 mL/min and the column temperature was maintained at 25 degrees C. TOF MS was applied for qualitative analysis under positive ion mode. RESULTS: Five compounds were identified by the time of flight mass spectrometry and literature data. CONCLUSION: This method is accurate, rapid and sensitive, it can provide reference for the quality control of Polygonum multiflorum Formula Granules.


Assuntos
Medicamentos de Ervas Chinesas/química , Fallopia multiflora/química , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas
10.
Int J Mol Sci ; 15(10): 17442-56, 2014 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-25268616

RESUMO

The primary objective of this study investigated the role of microRNA-320 (miR-320) on left ventricular remodeling in the rat model of myocardial ischemia-reperfusion (I/R) injury, and we intended to explore the myocardial mechanism of miR-320-mediated myocardium protection. We collected 120 male Wistar rats (240-280 g) in this study and then randomly divided them into three groups: (1) sham surgery group (sham group: n=40); (2) ischemia-reperfusion model group (I/R group: n=40); and (3) I/R model with antagomir-320 group (I/R+antagomir-320 group: n=40). Value changes of heart function in transesophageal echocardiography were recorded at various time points (day 1, day 3, day 7, day 15 and day 30) after surgery in each group. Myocardial sections were stained with hematoxylin and eosin (H&E) and examined with optical microscope. The degree of myocardial fibrosis was assessed by Sirius Red staining. Terminal dUTP nick end-labeling (TUNEL) and qRT-PCR methods were used to measure the apoptosis rate and to determine the miR-320 expression levels in myocardial tissues. Transesophageal echocardiography showed that the values of left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular systolic pressure (LVSP) and ±dp/dtmax in the I/R group were obviously lower than those in the sham group, while the left ventricular end-diastolic pressure (LVEDP) value was higher than that in the sham group. The values of LVEF, LVFS, LVSP and ±dp/dtmax showed a gradual decrease in the I/R group, while the LVEDP value showed an up tendency along with the extension of reperfusion time. The H&E staining revealed that rat myocardial tissue in the I/R group presented extensive myocardial damage; for the I/R+antagomir-320 group, however, the degree of damage in myocardial cells was obviously better than that of the I/R group. The Sirius Red staining results showed that the degree of myocardial fibrosis in the I/R group was more severe along with the extension of the time of reperfusion. For the I/R+antagomir-320 group, the degree of myocardial fibrosis was less severe than that in the I/R group. Tissues samples in both the sham and I/R+antagomir-320 groups showed a lower apoptosis rate compared to I/R group. The qRT-PCR results indicated that miR-320 expression in the I/R group was significantly higher than that in both the sham and I/R+antagomir-320 groups. The expression level of miR-320 is significantly up-regulated in the rat model of myocardial I/R injury, and it may be implicated in the prevention of myocardial I/R injury-triggered left ventricular remodeling.


Assuntos
MicroRNAs/metabolismo , Traumatismo por Reperfusão/patologia , Animais , Apoptose , Modelos Animais de Doenças , Ecocardiografia , Fibrose/patologia , Hemodinâmica , Masculino , MicroRNAs/antagonistas & inibidores , Miocárdio/metabolismo , Miocárdio/patologia , Oligorribonucleotídeos Antissenso/metabolismo , Ratos , Ratos Wistar , Traumatismo por Reperfusão/genética , Regulação para Cima , Remodelação Ventricular/genética
11.
PLoS One ; 19(4): e0300261, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38568919

RESUMO

Doxorubicin (DOX) is a broad-spectrum, highly effective antitumor agent; however, its cardiotoxicity has greatly limited its use. Hydrogen sulfide (H2S) is an endogenous gaseous transmitter that exerts cardioprotective effects via the regulation of oxidative stress and apoptosis and maintenance of mitochondrial function, among other mechanisms. AP39 is a novel mitochondria-targeted H2S donor that, at appropriate concentrations, attenuates intracellular oxidative stress damage, maintains mitochondrial function, and ameliorates cardiomyocyte injury. In this study, DOX-induced cardiotoxicity models were established using H9c2 cells and Sprague-Dawley rats to evaluate the protective effect of AP39 and its mechanisms of action. Both in vivo and in vitro experiments showed that DOX induces oxidative stress injury, apoptosis, and mitochondrial damage in cardiomyocytes and decreases the expression of p-AMPK/AMPK and UCP2. All DOX-induced changes were attenuated by AP39 treatment. Furthermore, the protective effect of AP39 was significantly attenuated by the inhibition of AMPK and UCP2. The results suggest that AP39 ameliorates DOX-induced cardiotoxicity by regulating the expression of AMPK/UCP2.


Assuntos
Sulfeto de Hidrogênio , Ratos , Animais , Sulfeto de Hidrogênio/farmacologia , Sulfeto de Hidrogênio/metabolismo , Cardiotoxicidade/tratamento farmacológico , Cardiotoxicidade/etiologia , Cardiotoxicidade/prevenção & controle , Proteínas Quinases Ativadas por AMP/metabolismo , Ratos Sprague-Dawley , Linhagem Celular , Doxorrubicina/toxicidade , Miócitos Cardíacos/metabolismo , Estresse Oxidativo , Mitocôndrias/metabolismo , Apoptose
12.
Phytomedicine ; 132: 155545, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38972238

RESUMO

BACKGROUNDS: Idiopathic pulmonary fibrosis (IPF) is a persistent and advanced pulmonary ailment. The roles of innate immunity and adaptive immunity are pivotal in the evolution of IPF. An ill-adjusted interaction between epithelial cells and immune cells is responsible for initiating the epithelial-mesenchymal transition (EMT) process and sustaining chronic inflammation, thereby fostering fibrosis progression. The intricacy of IPF pathogenesis has hindered the availability of efficacious agents. Elephantopus scaber Linn. (ESL) is a canonical Chinese medicine with significant immunoregulatory effects, and its aqueous extract has been proven to attenuate IPF symptoms in bleomycin (BLM)-induced mice. However, the underlying mechanism through which ESL relieves IPF remains unclear. AIM: To validate whether ESL reverses IPF by mediating the immune response and EMT. METHODS: Ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) and UPLC were used to identify the components and determine the concentrations of the specific compounds in the ESL. Network pharmacology and molecular docking were applied to predict the potential mechanism underlying the anti-IPF effect of ESL. BLM-induced IPF mice were used to validate the anti-IPF effect of ESL, and lung tissue was collected to test putative pathways involved in inflammation and EMT via immunohistochemistry (ICH), real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting. RESULTS: Sixty-one compounds were identified, and thirteen main ingredients were quantified in the ESL. In silico experiments predicted that the IPF-mediated reversal of adverse effects by ESL would be related to interruption of the Toll-like receptor 4 (TLR4)/nuclear factor-k-gene binding (NF-ĸB) inflammatory pathway and the transforming growth factor-beta l (TGF-ß1)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/forkhead box O3 (FOXO3a) fibrosis pathway. In vivo experiments showed that ESL alleviates BLM-induced lung inflammation and fibrosis by reducing neutrophil aggregation and fibroblast foci, similar to the effects of the positive control drug pirfenidone (PFD). ESL markedly inhibited the transcription of TNF-α, IL-1ß, and IL-6, which are downstream genes of the NF-κB signaling pathway. Furthermore, the protein levels of TLR4 and p-NF-κB were correspondingly inhibited in response to ESL treatment. Additionally, ESL reverses BLM-induced changes in the expression of EMT-related biological characteristic indicators (collagen I [COLIA1], E-cadherin, and alpha smooth muscle actin [α-SMA]) at the messenger ribonucleic acid (mRNA) level and markedly inhibits the expression of EMT-related upstream proteins (TGF-ß1, p-PI3K, p-Akt, and p-FOXO3a). CONCLUSION: Our research suggested that ESL attenuates BLM-induced IPF through mediating the EMT process via the TGF-ß1/PI3K/Akt/FOXO3a signaling pathway and inhibiting inflammation through the TLR4/NF-κB signaling pathway, highlighting that ESL can serve as an immunoregulator for relieving the abnormal immune response and reversing the EMT in IPF.

13.
Trials ; 24(1): 411, 2023 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-37337229

RESUMO

BACKGROUND: Low-carbohydrate diet (LCD) is an emerging therapy for type 2 diabetes mellitus (T2DM). Although its effect on glucose control has been confirmed in previous clinical trials, most of those studies have focused on comparing calorie-restricted LCD to iso-caloric low-fat diets. In this study, we aim to compare the effects of LCD and canagliflozin, a sodium-glucose cotransporter 2 inhibitor, in patients with T2DM. METHODS: This is a multicenter, randomized controlled trial. We will recruit 120 patients with poor-controlled T2DM. Participants will be randomly divided into canagliflozin and LCD groups in a 1:1 ratio. The primary outcome is the change in hemoglobin A1C levels after the 3-month intervention. The secondary outcomes are the time in range and cost of antihyperglycemic agents. Exploratory outcomes include physical examination, body composition, glucose variability, appetite, glycolipid metabolism, liver lipid content, and urine glucose threshold. DISCUSSION: No previous study has compared an LCD with antihyperglycemic agents. In LoCaT, participants' metabolism will be assessed from multiple perspectives. It is believed that the finding obtained from this trial will optimize the treatments for patients with T2DM. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900027592. Registered on November 20, 2019.


Assuntos
Diabetes Mellitus Tipo 2 , Dieta com Restrição de Carboidratos , Humanos , Glicemia/metabolismo , Canagliflozina/farmacologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
Front Cardiovasc Med ; 10: 1102521, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37057101

RESUMO

Heart failure is a serious threat to human health, with morbidity and mortality rates increasing despite the existence of multiple treatment options. Therefore, it is necessary to identify new therapeutic targets for this disease. Sacubitril/valsartan is a supramolecular sodium salt complex of the enkephalinase inhibitor prodrug sacubitril and the angiotensin receptor blocker valsartan. Its combined action increases endogenous natriuretic peptides while inhibiting the renin-angiotensin-aldosterone system and exerting cardioprotective effects. Clinical evidence suggests that sacubitril/valsartan is superior to conventional renin-angiotensin-aldosterone inhibitor therapy for patients with reduced ejection fraction heart failure who can tolerate angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. The therapy reduces the risk of heart failure hospitalization, cardiovascular mortality, and all-cause mortality and has a better safety and tolerability record. This review describes the potential pathophysiological mechanisms of cardiomyocyte injury amelioration by sacubitril/valsartan. We explore the protective effects of sacubitril/valsartan and outline the therapeutic value in patients with heart failure by summarizing the results of recent large clinical trials. Furthermore, a preliminary outlook shows that sacubitril/valsartan may be effective at treating other diseases, and provides some exploratory observations that lay the foundation for future studies on this drug.

15.
Sci Total Environ ; 862: 160773, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36509275

RESUMO

Levofloxacin (LEV) is prone to be retained in aquifers due to its strong adsorption affinity onto sand, thus posing a threat to groundwater quality. In-situ injection technology for remediating LEV-contaminated soil and groundwater is still challenging owing to the lack of appropriate remedial agents. Herein, two novel multi-component porous covalent-organic polymers (namely, SLEL-1 and SLEL-2) with alkyl chains were constructed through Schiff-base reactions to adsorb LEV from an aqueous solution, in which the kinetics, isotherms, influenced factors were investigated. Plausible adsorption mechanisms were proposed through characterization and experimental analysis, including pore filling effect, π-π electron-donor-acceptor (EDA) interaction, hydrogen bonding force, hydrophobic-hydrophobic interaction as well as electrostatic force. In addition, response surface methodology (RSM) revealed the treatment optimization and reciprocal relationship within multi-variables. Furthermore, taking advantage of favorable dispersion and outstanding competitive behavior, SLEL-1 was established as an in-situ adsorptive agent in dynamic saturated columns on a laboratory scale to investigate the removal of LEV from water-bearing stratum. Overall, the findings of this work provided an insight into the fabrication of SLELs as long-term mobile and reusable adsorptive agents for practical in-situ applications in the future.


Assuntos
Levofloxacino , Poluentes Químicos da Água , Levofloxacino/análise , Areia , Porosidade , Polímeros , Adsorção , Poluentes Químicos da Água/química
16.
Phytomedicine ; 111: 154662, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36681054

RESUMO

BACKGROUND: Postoperative abdominal adhesion (PAA) is the most common complication after abdominal surgeries, which can lead to intestinal obstruction, chronic abdominal pain or female infertility. Jiawei Xiaochengqi decoction (JWXCQ) is a hospital preparation widely used for PAA treatment in Nanfang Hospital of Southern Medical University for more than twenty years. PURPOSE: This study aimed to investigate the therapeutic effects and potential mechanism of JWXCQ against PAA and provide beneficial information for its clinical application. METHODS: The main active components of JWXCQ were identified using ultra high performance liquid chromatography (UHPLC) combined with standard substance comparison. The efficacy and underlying mechanism of JWXCQ were evaluated through in vivo experiments with a postsurgical-induced peritoneal adhesion rat model, and in vitro studies with LPS-stimulated Raw 264.7 macrophages and primary fibroblasts. H&E and Masson staining were performed to assess histopathological changes. The levels of cytokines/proteins-associated with inflammation and degradation of extracellular matrix as well as CXCL2-CXCR2 pathway-related proteins were determined by ELISA, qRT-PCR, western blot assays or immunohistochemistry, respectively. Furthermore, siCXCR2 transfection was used to validate the mechanism of action of JWXCQ. RESULTS: JWXCQ treatment significantly reduced the formation of PAA, inhibited the inflammation and collagen deposition, and facilitated the secretion of MMP9, decreased the levels of IL-1ß, IL-6, TIMP1, COL-1, and suppressed the CXCL2-CXCR2 pathway in PAA rats. Furthermore, JWXCQ inhibited its downstream pathways, the JAK2-STAT3 and PI3K-AKT signaling, as indicated by the suppression of the phosphorylation levels of STAT3 and AKT. In vitro cell experiments revealed that JWXCQ reduced IL-1ß and IL-6 secretion in Raw 264.7 macrophages and COL-1 in primary fibroblasts. The CXCL2-CXCR2, JAK2-STAT3 and PI3K-AKT pathways were also inhibited after JWXCQ treatment, which were consistent with the in vivo results. More importantly, silence of CXCR2 eliminated the regulatory effects of JWXCQ. CONCLUSION: JWXCQ could effectively prevent the PAA formation by alleviating inflammation and collagen deposition, which was associated with the inhibition of CXCL2-CXCR2 pathway. This study investigated the relevant pharmacological mechanisms of JWXCQ, providing further evidence for the application of JWXCQ in clinical PAA treatment.


Assuntos
Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Animais , Feminino , Ratos , Quimiocina CXCL2/metabolismo , Citocinas/metabolismo , Inflamação/tratamento farmacológico , Interleucina-6
17.
Front Pharmacol ; 14: 1252146, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37964876

RESUMO

Hyperlipidemia is a disorder of lipid metabolism resulting from abnormal blood lipid metabolism and is one of the most frequent metabolic diseases that endanger people's health. Yinlan Tiaozhi capsule (YL) is a formulated TCM widely used to treat hyperlipidemia. The purpose of this study was to discover biomarkers utilizing untargeted metabolomics techniques, as well as to analyze the mechanisms underlying the changes in metabolic pathways linked to lipid-lowering, anti-inflammation, and regulation of angiogenesis in hyperlipidemia mice. To assess the efficacy of YL, serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) levels were measured. Biochemical examinations showed that YL significantly reduced the levels of TC, TG, LDL-c, Il6, Tnf-α, and Vegfa in hyperlipidemia mice (p < 0.01). YL also significantly increased the levels of HDL-c and Alb (p < 0.01). Twenty-seven potential serum biomarkers associated with hyperlipidemia were determined. These differential metabolites were related to the reduction of serum lipid levels in hyperlipidemia mice, probably through metabolic pathways such as linoleic acid metabolism, glycerophospholipid metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and D-glutamine and D-glutamate metabolism. Further correlation analysis showed that the serum lipid reduction through YL was related to the metabolites (amino acid metabolites, phospholipids metabolites, and fatty acids metabolites). The present study reveals that YL has a profound effect on alleviating triton WR-1339-induced hyperlipidemia, inflammation, and angiogenesis and that the positive effects of YL were primarily associated with the correction of metabolic abnormalities and the maintenance of metabolite dynamic balance.

18.
Adv Mater ; 35(49): e2306626, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37788420

RESUMO

Pressure-driven membrane separation promises a sustainable energy-water nexus but is hindered by ubiquitous fouling. Natural systems evolved from prebiotic chemistry offer a glimpse of creative solutions. Herein, a prebiotic-chemistry-inspired aminomalononitrile (AMN)/Mn2+ -mediated mineralization method is reported for universally engineering a superhydrophilic hierarchical MnO2 nanocoating to endow hydrophobic polymeric membranes with exceptional catalytic cleaning ability. Green hydrogen peroxide catalytically triggered in-situ cleaning of the mineralized membrane and enabled operando flux recovery to reach 99.8%. The mineralized membrane exhibited a 9-fold higher recovery compared to the unmineralized membrane, which is attributed to active catalytic antifouling coupled with passive hydration antifouling. Electron density differences derived from the precursor interaction during mediated mineralization unveiled an electron-rich bell-like structure with an inner electron-deficient Mn core. This work paves the way to construct multifunctional engineered materials for energy-efficient water treatment as well as for diverse promising applications in catalysis, solar steam generation, biomedicine, and beyond.

19.
Sci Rep ; 13(1): 6424, 2023 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-37076581

RESUMO

Yinlan Tiaozhi capsule (YLTZC) has been widely used to treat hyperlipidemia (HLP). However, its material basis and underlying pharmacological effects remain unclean. The current study aimed to explore the mechanisms involved in the treatment of YLTZC on HLP based on network pharmacology, molecular docking, and experimental verification. Firstly, UPLC-Q-TOF-MS/MS was used to comprehensively analyze and identify the chemical constituents in YLTZC. A total of 66 compounds, mainly including flavonoids, saponins, coumarins, lactones, organic acids, and limonin were characterized and classified. Simultaneously, the mass fragmentation pattern of different types of representative compounds was further explored. By network pharmacology analysis, naringenin and ferulic acid may be the core constituents. The 52 potential targets of YLTZC, including ALB, IL-6, TNF, and VEGFA, were considered potential therapeutic targets. Molecular docking results showed that the core active constituents of YLTZC (naringenin and ferulic acid) have a strong affinity with the core targets of HLP. Lastly, animal experiments confirmed that naringenin and ferulic acid significantly upregulated the mRNA expression of ALB and downregulated the mRNA expression of IL-6, TNF, and VEGFA. In sum, the constituents of YLTZC, such as naringenin and ferulic acid, might treat HLP by regulating the mechanism of angiogenesis and inhibiting inflammatory responses. Furthermore, our data fills the gap in the material basis of YLTZC.


Assuntos
Medicamentos de Ervas Chinesas , Hiperlipidemias , Animais , Hiperlipidemias/tratamento farmacológico , Interleucina-6 , Simulação de Acoplamento Molecular , Farmacologia em Rede , Espectrometria de Massas em Tandem , RNA Mensageiro , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico
20.
J Hazard Mater ; 422: 126829, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34399228

RESUMO

Levofloxacin (LEV) infiltrated in groundwater has threatened the safety of drinking water. For in-situ remediation of LEV-contaminated groundwater, there exists a main challenge of exploiting proper high efficient backfill medium in utilizing charming permeable reactive barriers (PRBs). Herein, three porous shapeable three-component hydrogen-bonded covalent organic aerogels (HCOA-1, HCOA-2 and HCOA-3) were fabricated based on a multiple-linking-site strategy to evaluate for adsorptive removal of LEV. The three HCOAs exhibited satisfactory performance in LEV adsorption that could integrate high adsorption capacity, good antiion interference, excellent recyclability and wide pH tolerance. The different regularity of kinetics and isotherms of three HCOAs signified that electrostatic effect, pore preservation, hydrogen bonding probably govern the adsorption process in combination, coupling with π-π electron-donor-acceptor (EDA), dipole-dipole and hydrophobic-hydrophobic interaction besides. In addition, the response surface methodology (RSM) was employed for studying the single and synergetic effects of selected variables and optimizing operation conditions. Furthermore, a laboratory PRB column packed with processable HCOA-2 was set up to investigate the LEV removal, and the breakthrough data was explained by Adams-Bohart, Thomas, BDST and Yoon-Nelson models. We believe could hopefully bring HCOAs into the real in-situ remediation of such challenging and persistent LEV-polluted groundwater with further massive-scale efficiently.


Assuntos
Recuperação e Remediação Ambiental , Água Subterrânea , Poluentes Químicos da Água , Adsorção , Hidrogênio , Levofloxacino , Porosidade , Poluentes Químicos da Água/análise
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