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1.
JAMA Cardiol ; 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39167414

RESUMEN

A woman in her mid-20s presented with acute fever, chest pain, and exertional dyspnea. Electrocardiogram results showed sinus tachycardia, QRS widening, low-voltage complexes, and ST-segment elevation. What would you do next?

2.
Polymers (Basel) ; 16(13)2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-39000741

RESUMEN

With improvements in living standards, the demand for antibacterial self-cleaning coatings has significantly increased. In this work, self-cleaning coatings with antibacterial properties were fabricated by spray-coating a composite of fluorinated acrylic resin and Ag/SiO2 nanoparticles with quaternary ammonium salts. The synergistic action of the quaternary ammonium salts and silver nanostructures caused the coating to show a dual antibacterial effect. The Ag/SiO2 nanoparticles roughened the coating's surface and, in combination with the fluorinated chains, provided the surface a superhydrophobic self-cleaning property with a contact angle of 156° and a sliding angle of less than 2°. Notably, the composite coating withstood 100 abrasion cycles without losing its superhydrophobicity and the contact angle is still exceeded 150° after 60 h of immersion solutions with different pH values, demonstrating outstanding wear resistance and acid/alkali stability. The incorporation of nanostructured antibacterial agents was effective in improving the roughness and antibacterial properties of the low-surface-energy resin, resulting in a self-cleaning antibacterial composite coating. This method may pave a new route for the design of functional coating materials with excellent overall performance.

3.
Theor Appl Genet ; 137(8): 190, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39043952

RESUMEN

KEY MESSAGE: Extensive and comprehensive phenotypic data from a maize RIL population under both low- and normal-Pi treatments were used to conduct QTL mapping. Additionally, we integrated parental resequencing data from the RIL population, GWAS results, and transcriptome data to identify candidate genes associated with low-Pi stress in maize. Phosphorus (Pi) is one of the essential nutrients that greatly affect the maize yield. However, the genes underlying the QTL controlling maize low-Pi response remain largely unknown. In this study, a total of 38 traits at both seedling and maturity stages were evaluated under low- and normal-Pi conditions using a RIL population constructed from X178 (tolerant) and 9782 (sensitive), and most traits varied significantly between low- and normal-Pi treatments. Twenty-nine QTLs specific to low-Pi conditions were identified after excluding those with common intervals under both low- and normal-Pi conditions. Furthermore, 45 additional QTLs were identified based on the index value ((Trait_under_LowPi-Trait_under_NormalPi)/Trait_under_NormalPi) of each trait. These 74 QTLs collectively were classified as Pi-dependent QTLs. Additionally, 39 Pi-dependent QTLs were clustered in nine HotspotQTLs. The Pi-dependent QTL interval contained 19,613 unique genes, 6,999 of which exhibited sequence differences with non-synonymous mutation sites between X178 and 9782. Combined with in silico GWAS results, 277 consistent candidate genes were identified, with 124 genes located within the HotspotQTL intervals. The transcriptome analysis revealed that 21 genes, including the Pi transporter ZmPT7 and the strigolactones pathway-related gene ZmPDR1, exhibited consistent low-Pi stress response patterns across various maize inbred lines or tissues. It is noteworthy that ZmPDR1 in maize roots can be sharply up-regulated by low-Pi stress, suggesting its potential importance as a candidate gene for responding to low-Pi stress through the strigolactones pathway.


Asunto(s)
Mapeo Cromosómico , Fósforo , Sitios de Carácter Cuantitativo , Zea mays , Zea mays/genética , Zea mays/crecimiento & desarrollo , Mapeo Cromosómico/métodos , Fósforo/metabolismo , Fenotipo , Secuenciación de Nucleótidos de Alto Rendimiento , Genes de Plantas , Genoma de Planta , Regulación de la Expresión Génica de las Plantas , Simulación por Computador
4.
Medicine (Baltimore) ; 103(19): e37981, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38728508

RESUMEN

The incidence of chronic atrophic gastritis (CAG) is on the rise due to the growing pressure in modern social life, increasing bad living habits and emotional disorders (such as anxiety and depression), and the aging of the population. Of note, digestive system diseases are the dominant diseases in the field of traditional Chinese medicine (TCM). Therefore, this study evaluated the efficacy and safety of Piwei Peiyuan Prescription, a TCM prescription, in the treatment of CAG through a multicenter, double-blind, randomized, controlled design. This research was organized by the Second Affiliated Hospital of Anhui University of TCM and simultaneously performed in 6 centers. A total of 120 CAG patients were included and randomized into 2 groups: group A (treatment with Piwei Peiyuan granules plus Weifuchun Simulant) and Group B (treatment with Weifuchun Tablets plus Piwei Peiyuan Simulant). These 2 groups were compared in terms of gastroscopy scores, TCM syndrome scores, and serological indicators at baseline and within 12 weeks after treatment. According to endoscopic biopsy for pathological observation, atrophy (2.56 ±â€…1.08 vs 3.00 ±â€…1.00, P = .028) and intestinal epithelial hyperplasia (1.00 ±â€…1.43 vs 1.69 ±â€…1.80, P = .043) scores were lower in group A than in group B. For the more, group A had higher effective rates for inflammation, atrophy, and intestinal metaplasia (IM) in various regions of the stomach, especially for atrophy/IM of the gastric angle (64%, P = .034) and atrophy/IM of the lesser curvature of gastric antrum (63%, P = .042) than group B. According to TCM syndrome scores, Piwei Peiyuan Prescription improved the scores of gastric distension (2.30 ±â€…1.13 vs 2.80 ±â€…0.99, P = .022), preference for warmth and pressure (1.44 ±â€…1.06 vs 1.36 ±â€…1.10, P = .041), and poor appetite and indigestion (0.78 ±â€…0.66 vs 1.32 ±â€…0.72, P = .018). GAS, MTL, and PGE2 expression was significantly elevated after treatment with Piwei Peiyuan Prescription (P < .001). Piwei Peiyuan Prescription is effective for CAG treatment with high safety.


Asunto(s)
Medicamentos Herbarios Chinos , Gastritis Atrófica , Humanos , Gastritis Atrófica/tratamiento farmacológico , Femenino , Masculino , Método Doble Ciego , Persona de Mediana Edad , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/efectos adversos , Adulto , Resultado del Tratamiento , Enfermedad Crónica , Medicina Tradicional China/métodos , Anciano , Gastroscopía
5.
Postgrad Med ; 135(8): 831-841, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38032178

RESUMEN

OBJECTIVE: In this study, we evaluated the clinical utility of tracheal aspirates α-amylase (AM), pepsin, and lipid-laden macrophage index (LLMI) in the early diagnosis of ventilator-associated pneumonia (VAP) in elderly patients on mechanical ventilation. METHODS: Within 96 hours of tracheal intubation, tracheal aspirate specimens were collected from elderly patients on mechanical ventilation; AM, pepsin, and LLMI were detected, and we analyzed the potential of each index individually and in combination in diagnosing VAP. RESULTS: Patients with VAP had significantly higher levels of AM, pepsin, and LLMI compared to those without VAP (P < 0.001), and there was a positive correlation between the number of pre-intubation risk factors of aspiration and the detection value of each index in patients with VAP (P < 0.001). The area under a receiver operating characteristic (ROC) curve (AUC) of AM, pepsin, and LLMI in diagnosis of VAP were 0.821 (95% CI:0.713-0.904), 0.802 (95% CI:0.693-0.892), and 0.621 (95% CI:0.583-0.824), the sensitivities were 0.8815, 0.7632, and 0.6973, the specificities were 0.8495, 0.8602, and 0.6291, and the cutoff values were 4,321.5 U/L, 126.61 ng/ml, and 173.5, respectively. The AUC for the combination of indexes in diagnosing VAP was 0.905 (95% CI:0.812-0.934), and the sensitivity and specificity were 0.9211 and 0.9332, respectively. In the tracheal aspirate specimens, the detection rate of AM ≥ cutoff was the highest, while it was the lowest for LLMI (P < 0.001). The detection rates of AM ≥ cutoff and pepsin ≥ cutoff were higher within 48 hours after intubation than within 48-96 hours after intubation (P < 0.001). In contrast, the detection rate of LLMI ≥ cutoff was higher within 48-96 hours after intubation than within 48 hours after intubation (P < 0.001). The risk factors for VAP identified using logistic multivariate analysis included pre-intubation aspiration risk factors (≥3), MDR bacteria growth in tracheal aspirates, and tracheal aspirate AM ≥ 4,321.5 U/L, pepsin ≥ 126.61 ng/ml, and LLMI ≥ 173.5. CONCLUSION: The detection of AM, pepsin, and LLMI in tracheal aspirates has promising clinical utility as an early warning biomarker of VAP in elderly patients undergoing mechanical ventilation.


Asunto(s)
Neumonía Asociada al Ventilador , Respiración Artificial , Humanos , Anciano , Respiración Artificial/efectos adversos , Neumonía Asociada al Ventilador/etiología , Neumonía Asociada al Ventilador/microbiología , Pepsina A/análisis , Intubación Intratraqueal/efectos adversos , Biomarcadores/análisis , Unidades de Cuidados Intensivos
6.
Mol Biotechnol ; 2023 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-37566188

RESUMEN

Periodontitis is a leading chronic oral disorder and poses a serious burden on public health. O-GlcNAc glycosylation (O-GlcNAcylation) is regulated only by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) and participates in the regulation of human gingival fibroblasts (HGFs) function. Hence, the purpose of this study is to investigate whether HGFs cell function and periodontitis pathogenesis are regulated by O-GlcNAcylation. Herein, we first established cell model of periodontitis induced by lipopolysaccharide (LPS). The cell viability was measured with CCK-8 assay. Pyroptosis was measured by flow cytometry and western blot. The inflammatory factors levels were detected with ELISA kits. Afterward, our findings indicated that LPS elevated the O-GlcNAcylation level of HGFs and inhibition of O-GlcNAcylation improved LPS-induced pyroptosis of HGFs. Mechanistically, LPS heightened the expression of OGT to induce the O-GlcNAcylation of NLRP3. Subsequently, we certified that Thr542 was the O-GlcNAcylation site of NLRP3. More importantly, upregulation of NLRP3 reversed the effects of OGT knockdown on LPS-induced pyroptosis. In general, the current research demonstrated that LPS contributed to the pyroptosis of HGFs by enhancing the OGT expression to promote O-GlcNAcylation of NLRP3, which suggested that O-GlcNAcylation of NLRP3 was a driving factor for periodontitis and offered a novel insight into the treatment of this disease.

7.
Polymers (Basel) ; 15(5)2023 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-36904521

RESUMEN

Corrosion of structural parts not only reduces the service life of the equipment but also causes safety accidents, so building a long-lasting anti-corrosion coating on its surface is the key to solving this problem. Under the action of alkali catalysis, n-octyltriethoxysilane (OTES), dimethyldimethoxysilane (DMDMS), and perfluorodecyltrimethoxysilane (FTMS) hydrolyzed and polycondensed co-modified graphene oxide (GO), modified to synthesize a self-cleaning superhydrophobic material fluorosilane-modified graphene oxide (FGO). The structure, film morphology, and properties of FGO were systematically characterized. The results showed that the newly synthesized FGO was successfully modified by long-chain fluorocarbon groups and silanes. FGO presented an uneven and rough morphology on the substrate surface, the water contact angle was 151.3°, and the rolling angle was 3.9°, which caused the coating to exhibit excellent self-cleaning function. Meanwhile, the epoxy polymer/fluorosilane-modified graphene oxide (E-FGO) composite coating adhered to the carbon structural steel's surface, and its corrosion resistance was detected by the Tafel curve and EIS impedance. It was found that the current density of the 10 wt% E-FGO coating (Icorr) was the lowest (1.087 × 10-10 A/cm2), which was approximately 3 orders of magnitude lower than that of the unmodified epoxy coating. This was primarily due to the introduction of FGO, which formed a continuous physical barrier in the composite coating and gave the composite coating excellent hydrophobicity. This method might provide new ideas for advances in steel corrosion resistance in the marine sector.

8.
Diabetes Metab Syndr Obes ; 16: 653-662, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36923684

RESUMEN

Purpose: To investigate the association of visceral fat with arterial stiffness of heart failure patients with preserved ejection fraction (HFpEF) and to evaluate the extent to which this association is mediated by blood pressure (BP). Patients and Methods: This cross-sectional descriptive study (clinicaltrials.gov identifier: NCT04535726) recruited 94 patients with HFpEF totally from October to December 2020. The obesity-related measurements included visceral fat area (VFA), body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-hip ratio (WC/HC), abdominal circumference (AC), body fat mass and fat percentage. Brachial-ankle pulse wave velocity (baPWV) was used to estimate the degree of arterial stiffness. Mediation analysis was performed to reveal whether the effect of visceral fat area on arterial stiffness can be mediated by BP in patients with HFpEF and the extent to which this association was mediated by BP. Results: About 93.6% of HFpEF patients were accompanied with abdominal obesity. Patients in baPWV ≥1800cm/s group were older, with a higher incidence of type 2 diabetes mellitus (T2DM), hypertension and abdominal obesity. VFA, systolic BP (SBP), diastolic BP (DBP) and pulse pressure (PP) were correlated with baPWV in total group. Adjusted for age ≥75 years old, gender, smoking, T2DM, calcium channel blocker and statins, the mediation effect of systolic SBP and PP on the VFA-baPWV association were 53.3% (indirect effect was 2.28, 95% CI 0.62-4.73) and 48.4% (indirect effect was 2.07, 95% CI 0.51-4.38), respectively. DBP failed to mediate the association between VFA and baPWV (indirect effect was 0.50, 95% CI -0.41-2.14). Conclusion: The association of visceral fat with baPWV in HFpEF patients may be partly accounted for SBP or PP. Elevated SBP and PP might be important potential targets for preventing arterial stiffness in HFpEF patients.

9.
Front Endocrinol (Lausanne) ; 14: 1143458, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36950688

RESUMEN

Background: Hyperuricemia and right ventricular dysfunction (RVD) are both widespread in heart failure with preserved ejection fraction (HFpEF) patients. RVD is associated with a poor prognosis in HFpEF. The correlation between serum uric acid (UA) levels and right ventricular function is unclear. The prognostic performance of UA in patients with HFpEF needs further validation. Methods and results: A total of 210 patients with HFpEF were included in the study and divided into two groups according to UA level: the normal UA group (≤7 mg/dl) and the high UA group (>7 mg/dl). The variables examined included clinical characteristics, echocardiography, and serum biochemical parameters. Right ventricular function was assessed by tricuspid annular plane systolic excursion (TAPSE) and tricuspid annular peak systolic velocity (TAPSV). Baseline characteristics were compared between the two groups, and the correlation between baseline UA and RVD was assessed using multifactorial binary logistic regression. Kaplan-Meier curves were used to describe all-cause mortality and heart failure readmission. Results showed that right ventricular function parameters were worse in the high UA group. After adjusting for UA, left ventricular posterior wall thickness (LVPWT), N-terminal B-type natriuretic peptide (NT-proBNP), atrial fibrillation (AF), and low-density lipoprotein cholesterol (LDL-C), UA (odds ratio = 2.028; p < 0.001) was independently associated with RVD, and UA >7 mg/dl (HR = 2.98; p < 0.001) was associated with heart failure readmission in patients with HFpEF. Conclusion: Elevated serum UA is closely associated with RVD and significantly associated with the heart failure readmission rate in patients with HFpEF.


Asunto(s)
Insuficiencia Cardíaca , Disfunción Ventricular Derecha , Humanos , Insuficiencia Cardíaca/complicaciones , Ácido Úrico , Volumen Sistólico , Disfunción Ventricular Derecha/complicaciones , Pronóstico , Factores de Riesgo
10.
Phytother Res ; 37(1): 342-357, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36089660

RESUMEN

Berberine, which is a potential antidepressant, exhibits definite efficiency in modulating the gut microbiota. Depressive behaviors in mice induced using chronic unpredictable mild stress (CUMS) stimulation were evaluated by behavioral experiments. The markers of neurons and synapses were measured using immunohistochemical staining. An enzyme-linked immunosorbent assay was adopted to analyze serum inflammatory cytokines levels and neurotransmitters were evaluated by LC-MS/MS. Untargeted metabolomics of tryptophan metabolism was further performed using LC-MS/MS. The target enzymes of berberine involved in tryptophan metabolism were assayed using AutoDock and GRMACS softwares. Then, antibiotics was utilized to induce intestinal flora disturbance. Berberine improved the depressive behaviors of mice in a microbiota-dependent manner. Increased neurons and synaptic plasticity were observed following berberine treatment. Meanwhile, berberine decreased serum levels of TNF-α, IL-1ß, and IL-4 and increased levels of IL-10. Moreover, berberine induced retraction of the abnormal neurotransmitters and metabolomics assays revealed that berberine promoted tryptophan biotransformation into serotonin and inhibited the kynurenine metabolism pathway, which was attributed to the potential agonist of tryptophan 5-hydroxylase 1 (TPH1) and inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1). In conclusion, berberine improves depressive symptoms in CUMS-stimulated mice by targeting both TPH1 and IDO1, which are involved in tryptophan metabolism.


Asunto(s)
Berberina , Triptófano , Ratones , Animales , Triptófano/metabolismo , Depresión/tratamiento farmacológico , Depresión/metabolismo , Berberina/farmacología , Cromatografía Liquida , Espectrometría de Masas en Tándem , Neurotransmisores , Estrés Psicológico/tratamiento farmacológico , Modelos Animales de Enfermedad , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Triptófano Hidroxilasa
11.
Front Plant Sci ; 13: 941764, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36275510

RESUMEN

As an interesting and important trait of some drought-tolerant species, heteromorphic leaves are distributed differentially along plant vertical heights. However, the underpinning mechanism for the formation of heteromorphic leaves remains unclear. We hypothesize that heteromorphic leaves are caused by the hydraulic constraints possibly due to the compensation of the changes in functional traits in response to water transport capacity or the reduction of ineffective water loss. In this study, differences in water transport capacity, morphological traits, anatomical structures, and cellular water relations among three typical types of heteromorphic leaves (i.e., lanceolate, ovate, and broad-ovate) of Populus euphratica Oliv. (a dominant species of desert riparian forest in Central and West Asia) and their relationships were analyzed in order to explore the forming mechanism of heteromorphic leaves. The results showed that the lanceolate, ovate, and broad-ovate leaves were growing in the lower, intermediate, and higher positions from the ground, respectively. Morphological traits, anatomical structures, cellular water relations, and water transport capacity significantly varied among the three types of heteromorphic leaves (P< 0.01). Drought stress in broad-ovate leaves was significantly higher than that in ovate and lanceolate leaves (P< 0.01). Water transport capacity has significant correlations with morphological traits, anatomical structures, and cellular water relations (R 2 ≥ 0.30; P< 0.01). Our results indicated that heteromorphic leaves were used as an important adaptive strategy for P. euphratica to alleviate the increase of hydraulic constraints along vertical heights.

12.
BMC Cardiovasc Disord ; 22(1): 434, 2022 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-36199038

RESUMEN

BACKGROUND: Neutrophils and high-density lipoprotein cholesterol (HDL-c) play critical roles in the pathogenesis of acute myocardial infarction. We aimed to investigate the value of neutrophils count to high-density lipoprotein cholesterol ratio (NHR) in predicting occurrence of in-hospital adverse events in ST-segment elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PPCI). METHODS: We retrospectively analyzed 532 patients who had been diagnosed with acute STEMI and treated with PPCI. Demographic and clinical data, admission laboratory parameters and NHR values were recorded. Major adverse cardiac events (MACE) were defined as stent thrombosis, cardiac rupture, cardiac arrest, ventricular aneurysm, malignant arrhythmia and cardiac death. Based on the receiver operating characteristic (ROC) analysis, all patients were divided into 2 groups based on the cut-off NHR value (NHR ≤ 11.28, NHR > 11.28). Cox regression analyses and the Kaplan-Meier survival curve were used to assess the prognostic ability of NHR in in-hospital MACE. RESULTS: MACE was observed in 72 patients (13.5%) during in-hospital follow-up. NHR was significantly higher in MACE group compared to MACE-free group (10.93 [6.26-13.97] vs. 8.13 [5.89-11.16]; P = 0.001). The incidence of in-hospital MACE was significantly higher in the NHR > 11.28 group than in NHR ≤ 11.28 group (24.8% vs. 9.6%; P < 0.001). In multivariable Cox regression analyses, ALT, Killip III-IV and increased NHR (hazard ratio, 2.211; 95% confidence interval,1.092-4.479; P = 0.027) were identified as independent predictive factors of occurrence of in-hospital MACE. Higher NHR group had worse cumulative survival compared with the lower group. CONCLUSIONS: NHR value on admission, which is an easily calculated and universally available maker, may be useful in in-hospital risk classification of STEMI patients undergoing PPCI.


Asunto(s)
Infarto del Miocardio , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , HDL-Colesterol , Humanos , Infarto del Miocardio/diagnóstico , Neutrófilos , Intervención Coronaria Percutánea/efectos adversos , Pronóstico , Estudios Retrospectivos , Infarto del Miocardio con Elevación del ST/diagnóstico , Infarto del Miocardio con Elevación del ST/etiología , Infarto del Miocardio con Elevación del ST/terapia , Resultado del Tratamiento
13.
Front Cardiovasc Med ; 9: 958426, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36211551

RESUMEN

Objective: As a new method of left ventricular-arterial coupling (VAC), the non-invasive myocardial work index (MWI) may provide more useful information than the classical methods of arterial elastance/left ventricular (LV) elastance index (the ratio of effective arterial elastance (Ea) over end-systolic elastance [Ea/Ees]). This research aims to investigate if MWI might be better associated with hypertension-mediated organ damage (HMOD) and diastolic dysfunction than Ea/Ees in hypertension. Methods: We prospectively enrolled 104 hypertensives and 69 normotensives. All subjects had speckle-tracking echocardiography for myocardial work, conventional echocardiography, and brachial-ankle pulse wave velocity (baPWV) measurements. The global work index (GWI) is a myocardial work component. The correlation between GWI and HMOD, as well as diastolic dysfunction, was analyzed. The receiver operating characteristic (ROC) curve was utilized for evaluating the GWI predicting efficacy. Results: The global work index was significantly higher in hypertensives than in normotensives (2,021.69 ± 348.02 vs. 1,757.45 ± 225.86 mmHg%, respectively, p < 0.001). Higher GWI was a risk factor on its own for increased baPWV, pulse pressure (PP), echocardiographic LV hypertrophy (LVH), and left atrial volume index (LAVI) (p = 0.030, p < 0.001, p = 0.018 p = 0.031, respectively), taking into account the sex, age, mean arterial pressure (MAP), body mass index (BMI), and antihypertensive therapy. However, no considerable associations were found between Ea/Ees and HMOD parameters and the diastolic dysfunction markers. The GWI area under the ROC curve for increased PP and baPWV, echocardiographic LVH, and increased LAVI were 0.799, 0.770, 0.674, and 0.679, respectively (p < 0.05). Conclusions: The global work index but not traditionally echocardiographic-derived Ea/Ees of VAC is independently related to HMOD and diastolic impairment in hypertensives with preserved LV ejection fraction. The GWI may be a potential marker for evaluating the VAC in hypertension.

14.
Phytother Res ; 36(7): 2964-2981, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35583808

RESUMEN

Amelioration of neuroinflammation via modulating microglia is a promising approach for cerebral ischemia therapy. The aim of the present study was to explore gut-brain axis signals in berberine-modulating microglia polarization following cerebral ischemia. The potential pathway was determined through analyzing the activation of the vagus nerve, hydrogen sulfide (H2 S) metabolism, and cysteine persulfides of transient receptor potential vanilloid 1 (TRPV1) receptor. The cerebral microenvironment feature was explored with a metabolomics assay. The data indicated that berberine ameliorated behavioral deficiency in transient middle cerebral artery occlusion rats through modulating microglia polarization and neuroinflammation depending on microbiota. Enhanced vagus nerve activity following berberine treatment was blocked by antibiotic cocktails, capsazepine, or sodium molybdate, respectively. Berberine-induced H2 S production was responsible for vagus nerve stimulation achieved through assimilatory and dissimilatory sulfate reduction with increased synthetic enzymes. Sulfation of the TRPV1 receptor resulted in vagus nerve activation and promoted the c-fos and ChAT in the nucleus tractus solitaries with berberine. Sphingolipid metabolism is the primary metabolic characteristic with berberine in the cerebral cortex, hippocampus, and cerebral spinal fluid disrupted by antibiotics. Berberine, in conclusion, modulates microglia polarization in a microbiota-dependent manner. H2 S stimulates the vagus nerve through TRPV1 is responsible for the berberine-induced gut-brain axis signal transmission. Sphingolipid metabolism might mediate the neuroinflammation amelioration following vagus afferent fiber activation.


Asunto(s)
Berberina , Isquemia Encefálica , Sulfuro de Hidrógeno , Microbiota , Animales , Berberina/farmacología , Sulfuro de Hidrógeno/metabolismo , Sulfuro de Hidrógeno/farmacología , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Microglía/metabolismo , Ratas , Esfingolípidos/metabolismo , Nervio Vago/metabolismo
15.
Front Cardiovasc Med ; 9: 888736, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35600476

RESUMEN

Background: Elevated blood urea nitrogen (BUN) and reduced albumin have been prominently correlated with unfavorable outcomes in patients with cardiovascular diseases. However, whether combination BUN and albumin levels could predict the adverse outcomes of cardiac surgery patients remains to be confirmed. Here, we investigated the prognostic effect of the preoperative BUN to serum albumin ratio (BAR) in cardiac surgery patients. Methods: Data were obtained from the Medical Information Mart for Intensive Care (MIMIC) III and eICU databases and classified into a training cohort and validation cohort. The BAR (mg/g) was calculated by initial BUN (mg/dl)/serum albumin (g/dl). The primary outcome was in-hospital mortality. Secondary outcomes were 1-year mortality, prolonged length at intensive care unit, and duration of hospital stay. The associations of BAR with outcomes were explored by multivariate regression analysis and subgroup analyses. Then, C statistics were performed to assess the added prognostic impact of BAR beyond a baseline risk model. Results: Patients with in-hospital death had significantly higher levels of BAR. Multivariate regression analysis identified BAR, as a categorical or continuous variable, as an independent factor for adverse outcomes of cardiac surgery (all p < 0.05). Subgroup analyses demonstrated a significant relationship between elevated BAR and in-hospital mortality in different subclasses. The addition of BAR to a baseline model provided additional prognostic information benefits for assessing primary outcome. Results were concordant in the external validation cohort. Conclusions: Increased preoperative BAR is a potent predictor of unfavorable outcomes in patients undergoing cardiac surgery.

16.
Drug Des Devel Ther ; 16: 931-950, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35391788

RESUMEN

Background: Abnormal sphingolipid metabolism is closely related to the occurrence and development of Alzheimer's disease (AD). With heat-clearing and detoxifying effects, Huanglian Jiedu decoction (HLJDD) has been used to treat dementia and improve learning and memory impairments. Purpose: To study the therapeutic effect of HLJDD on AD as it relates to sphingolipid metabolism. Methods: The level of sphingolipids in the brains of APP/PS1 mice and in the supernatant of ß-amyloid (Aß)25-35-induced BV2 microglia was detected by HPLC-QTOF-MS and HPLC-QTRAP-MS techniques, respectively. The co-expression of ionized calcium-binding adapter molecule 1 (Iba1) and Aß as well as four enzymes related to sphingolipid metabolism, including serine palmitoyltransferase 2 (SPTLC2), cer synthase 2 (CERS2), sphingomyelin phosphodiesterase 1 (SMPD1), and sphingomyelin synthase 1 (SGMS1), in the brains of APP/PS1 mice were evaluated by immunofluorescence double labelling. In addition, real-time quantitative reverse transcription-polymerase chain reaction was conducted to determine the mRNA expression of SPTLC2, CERS2, SMPD1, SGMS1, galactosylceramidase (GALC), and sphingosine kinase 2 (SPHK2) in Aß25-35-stimulated BV2 microglia. Results: Abnormal sphingolipid metabolism was observed both in APP/PS1 mouse brain tissues and Aß25-35-stimulated BV2 cells. The levels of sphingosine, sphinganine, sphingosine-1-phosphate, sphinganine-1-phosphate and sphingomyelin were significantly reduced, while the levels of ceramide-1-phosphate, ceramide, lactosylceramide and hexosylceramide significantly increased in Aß25-35-stimulated BV2 cells. In AD mice, more microglia were clustered in the Aß-positive region. The decreased level of SGMS1 and increased levels of CERS2, SPTLC and SMPD1 were also found. In addition, the expressions of SPTLC2, CERS2, and SMPD1 in Aß25-35-stimulated BV2 cells were increased significantly, while the expressions of GALC, SPHK2, and SGMS1 were decreased. These changes all showed a significant correction after HLJDD treatment. Conclusion: HLJDD is a good candidate for treating AD. This study provides a novel perspective on the potential roles of the sphingolipid metabolism in AD.


Asunto(s)
Enfermedad de Alzheimer , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Animales , Ceramidas/metabolismo , Ceramidas/uso terapéutico , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Ratones , Ratones Transgénicos , Microglía/metabolismo , Fosfatos/uso terapéutico , Esfingolípidos
17.
Front Cardiovasc Med ; 9: 814326, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35224047

RESUMEN

OBJECTIVE: Data regarding the influence of arterial stiffness on myocardial work (MW) has been scarce. This study was performed to investigate the association between brachial-ankle pulse wave velocity (baPWV) and MW by non-invasive left ventricular pressure-strain in a population of non-hypertensive and hypertensive individuals. METHODS: Two hundred and eight participants (104 hypertensive and 104 non-hypertensive individuals) were prospectively enrolled into the study. All participants underwent conventional echocardiography, as well as 2D speckle-tracking echocardiography to assess MW by non-invasive left ventricular pressure-strain and global longitudinal strain (GLS). baPWV measurements were made at the same day as the echocardiography. Then, participants were categorized according to baPWV tertiles. Correlation between baPWV and MW were analyzed. Predicting ability of baPWV for abnormal WM was analyzed using receiver operating characteristic (ROC) curve. RESULTS: The median baPWV from the low to high tertile groups were 1286.5 (1197.5-1343.5), 1490.0 (1444.5-1544.0), and 1803.8(1708.3-1972.0) cm/s, respectively. In simple linear regression analysis, baPWV had a significant positive association with global work index (GWI), global constructed work (GCW), and global wasted work (GWW), and a negative association with global work efficiency (GWE). The association remained significant after adjusting for major confounding factors in multiple linear regression analysis. The areas under the ROC curve of baPWV for predicting abnormal GWI, GCW, GWW, and GWE were 0.653, 0.666, 0.725, and 0.688, respectively (all p < 0.05). CONCLUSIONS: BaPWV is significantly associated with all four components of MW using non-invasive left ventricular pressure-strain method in a mixed population of non-hypertensive and hypertensive individuals.

18.
Eur J Clin Nutr ; 76(4): 557-563, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34404932

RESUMEN

BACKGROUND: Malnutrition is a common occurrence in critically ill patients, and has been related to poor prognosis in various diseases. Here, we assess the prognostic value of malnutrition using nutritional indices in intensive care units (ICU) patients. METHODS: We retrieved information on 2060 patients from the Medical Information Mart for Intensive Care III, and randomized the patients into training and validation cohorts, at a ratio of 7:3. We estimated their nutritional indices using prognostic nutritional index (PNI), geriatric nutritional risk index (GNRI), and controlling nutritional status (CONUT) score. Both multivariate regression analysis and the Kaplan-Meier (KM) survival curve were used to examine the prognostic role of nutritional indices in ICU mortality. Then we evaluated the additional predictive significance of each nutritional index beyond the baseline model including conventional risk factors. RESULTS: Multivariate regression analysis revealed that PNI, GNRI, and CONUT were independent predictors of in-hospital and 1-year mortality (all P < 0.001). KM curves showed higher 1-year mortality rates in having nutritional risk patients (PNI ≤ 38 or GNRI ≤ 98 or CONUT ≥ 2). Moreover, subgroup analyses revealed a significant association between each nutritional index and 1-year mortality in patients with different comorbidities. We also observed a pronounced additional impact on the predictive value of 1-year mortality when PNI, GNRI, and CONUT were separately added to the baseline model. The additional role of each nutritional index was further verified in the validation cohort. CONCLUSIONS: Our results revealed that the nutritional indices at admission are significantly correlated with increased mortality rates in ICU adult patients.


Asunto(s)
Desnutrición , Evaluación Nutricional , Adulto , Anciano , Evaluación Geriátrica , Humanos , Unidades de Cuidados Intensivos , Estado Nutricional , Pronóstico , Estudios Retrospectivos , Factores de Riesgo
19.
Annu Int Conf IEEE Eng Med Biol Soc ; 2021: 7288-7291, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34892781

RESUMEN

Recent studies have demonstrated that home-based rehabilitation for stroke patients has excellent potential in reducing the cost and enhancing rehabilitation efficiency. Nonetheless, a timely and accurate rehabilitation assessment is required to attain efficacy and provide feedback to both clinicians and patients. In this paper, a lower limb motor function assessment approach based on limb kinematic data has been presented. The kinematic characteristics of lower limbs were quantified into specific evaluation parameters, which were calculated during a set of selected rehabilitation exercises. A body area network composed of two triaxial accelerometers was used to acquire the limb kinematic data of twenty stroke patients and six healthy subjects. While a referenced template was developed using the data from healthy subjects, an empirical score was obtained to evaluate the lower-limb motor function of stroke patients from the calculated parameters. The results have demonstrated that the scoring has a statistically significant strong correlation with the Brunnstrom stage classification, which provides a practical quantitative evaluation approach for home-based rehabilitation for lower limbs of stroke patients.Clinical Relevance- The proposed quality assessment method provides practical technical support for performing early support discharge rehabilitation.


Asunto(s)
Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Fenómenos Biomecánicos , Humanos , Extremidad Inferior , Extremidad Superior
20.
BMC Pulm Med ; 21(1): 208, 2021 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-34210314

RESUMEN

BACKGROUND: Molecular targeted therapy for non-small cell lung carcinoma (NSCLC) is restricted due to resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). This study evaluated the effects of dual targeting of MEK and PI3K in human EGFR-TKI resistant NSCLC cell lines. METHODS: EGFR-TKI resistant NSCLC cell lines H1975, H460, and A549, with different mutation and amplification status in EGFR, K-RAS, PIK3CA, and MET genes, were treated with a MEK162 (MEK inhibitor) and BKM120 (PI3K inhibitor) combination or a BIBW2992 (EGFR inhibitor) and ARQ197 (MET inhibitor) combination and assayed for cell proliferation, apoptosis, and cell cycle distribution. RESULTS: Dual targeting of MEK and PI3K efficiently inhibited the cell proliferation, induced apoptosis and the G0/G1 cell cycle, and decreased the phosphorylation of ERK1/2, AKT, S6, and 4E-BP1. H460 cells with K-RAS and PIK3CA mutation were most sensitive to MEK162 and BKM120 combinations. H1975 cells with EGFR and PIK3CA mutation and MET amplification were sensitive to BIBW2992 and ARQ197 combinations. CONCLUSION: Dual targeting regulated the proliferation of EGFR-TKI-resistant NSCLC cells, especially mutants in K-RAS and PIK3CA that are promising for EGFR-TKI-resistant NSCLC therapeutics.


Asunto(s)
Afatinib/farmacología , Aminopiridinas/farmacología , Carcinoma de Pulmón de Células no Pequeñas/patología , Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias Pulmonares/patología , Quinasas de Proteína Quinasa Activadas por Mitógenos/antagonistas & inhibidores , Morfolinas/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica , Apoptosis/efectos de los fármacos , Carcinoma de Pulmón de Células no Pequeñas/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/genética , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Mutación , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Pirrolidinonas/farmacología , Quinolinas/farmacología
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