Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 431
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Cell ; 185(12): 2148-2163.e27, 2022 06 09.
Artículo en Inglés | MEDLINE | ID: mdl-35584702

RESUMEN

Zinc (Zn) is an essential micronutrient and cofactor for up to 10% of proteins in living organisms. During Zn limitation, specialized enzymes called metallochaperones are predicted to allocate Zn to specific metalloproteins. This function has been putatively assigned to G3E GTPase COG0523 proteins, yet no Zn metallochaperone has been experimentally identified in any organism. Here, we functionally characterize a family of COG0523 proteins that is conserved across vertebrates. We identify Zn metalloprotease methionine aminopeptidase 1 (METAP1) as a COG0523 client, leading to the redesignation of this group of COG0523 proteins as the Zn-regulated GTPase metalloprotein activator (ZNG1) family. Using biochemical, structural, genetic, and pharmacological approaches across evolutionarily divergent models, including zebrafish and mice, we demonstrate a critical role for ZNG1 proteins in regulating cellular Zn homeostasis. Collectively, these data reveal the existence of a family of Zn metallochaperones and assign ZNG1 an important role for intracellular Zn trafficking.


Asunto(s)
Metaloendopeptidasas/metabolismo , Zinc , Animales , GTP Fosfohidrolasas/metabolismo , Homeostasis , Metalochaperonas/metabolismo , Metaloproteínas/genética , Ratones , Pez Cebra/metabolismo , Zinc/metabolismo
2.
Pflugers Arch ; 476(5): 755-767, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38305876

RESUMEN

It has been suggested that the novel selective phosphodiesterase 9 (PDE9) inhibitor may improve cardiac and renal function by blocking 3',5'-cyclic guanosine monophosphate (cGMP) degradation. 5/6 nephrectomized (5/6Nx) rats were used to investigate the effects of the PDE9 inhibitor (BAY 73-6691) on the heart and kidney. Two doses of BAY 73-6691 (1 mg/kg/day and 5 mg/kg/day) were given for 95 days. The 5/6Nx rats developed albuminuria, a decrease in serum creatinine clearance (Ccr), and elevated serum troponin T levels. Echocardiographic data showed that 5/6 nephrectomy resulted in increased fractional shortening (FS), stroke volume (SV), and left ventricular ejection fraction (EF). However, 95 days of PDE9 inhibitor treatment did not improve any cardiac and renal functional parameter. Histopathologically, 5/6 nephrectomy resulted in severe kidney and heart damage, such as renal interstitial fibrosis, glomerulosclerosis, and enlarged cardiomyocytes. Telmisartan attenuated renal interstitial fibrosis and glomerulosclerosis as well as improved cardiomyocyte size. However, except for cardiomyocyte size and renal perivascular fibrosis, BAY 73-6691 had no effect on other cardiac and renal histologic parameters. Pathway enrichment analysis using RNA sequencing data of kidney and heart tissue identified chronic kidney disease pathways, such as phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway, complement and coagulation cascades, and nuclear factor kappa B (NF-κB) signaling pathway. PDE9i did not affect any of these disease-related pathways. Two dosages of the PDE9 inhibitor BAY 73-6691 known to be effective in other rat models have only limited cardio-renal protective effects in 5/6 nephrectomized rats.


Asunto(s)
Corazón , Riñón , Nefrectomía , Animales , Masculino , Ratas , Corazón/efectos de los fármacos , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Miocardio/metabolismo , Miocardio/patología , Nefrectomía/métodos
3.
BMC Cancer ; 24(1): 491, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38632512

RESUMEN

BACKGROUND: This study aimed to systematically analyze the effect of a serine/threonine kinase (STK11) mutation (STK11mut) on therapeutic efficacy and prognosis in patients with non-small cell lung cancer (NSCLC). METHODS: Candidate articles were identified through a search of relevant literature published on or before April 1, 2023, in PubMed, Embase, Cochrane Library, CNKI and Wanfang databases. The extracted and analyzed data included the hazard ratios (HRs) of PFS and OS, the objective response rate (ORR) of immune checkpoint inhibitors (ICIs), and the positive rates of PD-L1 expression. The HR of PFS and OS and the merged ratios were calculated using a meta-analysis. The correlation between STK11mut and clinical characteristics was further analyzed in NSCLC datasets from public databases. RESULTS: Fourteen retrospective studies including 4317 patients with NSCLC of whom 605 had STK11mut were included. The meta-analysis revealed that the ORR of ICIs in patients with STK11mut was 10.1% (95%CI 0.9-25.2), and the positive rate of PD-L1 expression was 41.1% (95%CI 25.3-57.0). STK11mut was associated with poor PFS (HR = 1.49, 95%CI 1.28-1.74) and poor OS (HR = 1.44, 95%CI 1.24-1.67). In the bioinformatics analysis, PFS and OS in patients with STK11 alterations were worse than those in patients without alterations (p < 0.001, p = 0.002). Nutlin-3a, 5-fluorouracil, and vinorelbine may have better sensitivity in patients with STK11mut than in those with STK11wt. CONCLUSIONS: Patients with STK11-mutant NSCLC had low PD-L1 expression and ORR to ICIs, and their PFS and OS were worse than patients with STK11wt after comprehensive treatment. In the future, more reasonable systematic treatments should be explored for this subgroup of patients with STK11-mutant NSCLC.


Asunto(s)
Quinasas de la Proteína-Quinasa Activada por el AMP , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Quinasas de la Proteína-Quinasa Activada por el AMP/genética , Antígeno B7-H1 , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , Mutación , Pronóstico , Proteínas Serina-Treonina Quinasas/genética , Estudios Retrospectivos
4.
Bioorg Chem ; 148: 107478, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38788366

RESUMEN

The current standard treatment for ovarian cancer consists of surgery to reduce the size of the tumor, followed by treatment with chemotherapeutic drugs, which have major side effects. Therefore, finding a new natural product drug with fewer side effects is a strategy. Delphinium brunonianum (D. brunonianum) is a traditional Tibetan medicine, mainly from southern Tibet, China, whereas the chemical constituents in this plant remain elusive. The major metabolites in the dichloromethane fraction of D. brunonianum were analyzed and purified by HPLC and various column chromatography techniques. Nine diterpenoid alkaloids (1-9) and one amide alkaloid (10) were isolated from D. brunonianum, including three novel C19-type diterpenoid alkaloids (Brunonianines D-F) (1-3). Their structures were elucidated by 1D/2D NMR, HR-ESI-MS and single-crystal X-ray diffraction analyses. All compounds were evaluated for toxicity in four tumor cell lines. Most of the compounds exhibited potent inhibitory effects on Skov-3 cell lines, with IC50 values ranging from 2.57 to 8.05 µM. The western blotting experiment was used to further analyze the expression levels of molecules in the Bax/Bcl-2/Caspase-3 signaling pathway for compound 1. Molecular docking was performed to predict the binding modes of Brunonianine D with target proteins. In vivo experiments were also performed and evaluated in real time by monitoring the size of the Skov-3 tumor. Additionally, tumor H&E staining and the TUNEL assay used to evaluate anti-tumor effects.


Asunto(s)
Alcaloides , Antineoplásicos Fitogénicos , Apoptosis , Proliferación Celular , Delphinium , Diterpenos , Ensayos de Selección de Medicamentos Antitumorales , Neoplasias Ováricas , Femenino , Humanos , Delphinium/química , Alcaloides/farmacología , Alcaloides/química , Alcaloides/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Relación Estructura-Actividad , Animales , Estructura Molecular , Diterpenos/farmacología , Diterpenos/química , Diterpenos/aislamiento & purificación , Proliferación Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Ratones , Relación Dosis-Respuesta a Droga , Línea Celular Tumoral , Simulación del Acoplamiento Molecular
5.
J Sep Sci ; 47(1): e2300826, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38234028

RESUMEN

In traditional Chinese medicine, the two commodity forms of Cassiae Semen Raw and Prepared Cassiae Semen, exert different clinical applications, in which Prepared Cassiae Semen is commonly used to treat liver and eye diseases. However, the material basis of Raw and Prepared Cassiae Semen remains unclear due to the limited studies on their overall composition and metabolism in vivo. In this study, an integrated analysis strategy based on ultra-high-performance liquid chromatography coupled with quadrupole-Orbitrap high-resolution mass spectrometry was established to systematically screen the prototype and metabolite constituents of Raw and Prepared Cassiae Semen. Automatic matching analysis of metabolites was performed on Compound Discoverer software based on the function of predicting metabolites. Using this strategy, a total of 77 compounds in Raw Cassiae Semen and 71 compounds in Prepared Cassiae Semen were identified. Furthermore, in vivo study, 46 prototype components and 104 metabolites from the Raw Cassiae Semen group and 41 prototype components and 87 metabolites from the Prepared Cassiae Semen group were unambiguously or preliminarily identified in mice (plasma, urine, feces, eye, and liver). This is the first study of chemical component analysis and in vivo metabolite profiling of Raw and Prepared Cassiae Semen.


Asunto(s)
Medicamentos Herbarios Chinos , Ratones , Animales , Medicamentos Herbarios Chinos/análisis , Cromatografía Líquida de Alta Presión/métodos , Cromatografía de Gases y Espectrometría de Masas , Espectrometría de Masas , Semillas/química
6.
BMC Pediatr ; 24(1): 272, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38664650

RESUMEN

INTRODUCTION: Neonatal respiratory failure (NRF) is a serious condition that often has high mortality and morbidity, effective interventions can be delivered in the future by identifying the risk factors associated with morbidity and mortality. However, recent advances in respiratory support have improved neonatal intensive care units (NICUs) care in China. We aimed to provide an updated review of the clinical profile and outcomes of NRF in the Jiangsu province. METHODS: Infants treated for NRF in the NICUs of 28 hospitals between March 2019 and March 2022 were retrospectively reviewed. Data collected included baseline perinatal and neonatal parameters, NICU admission- and treatment-related data, and patient outcomes in terms of mortality, major morbidity, and survival without major morbidities. RESULTS: A total of 5548 infants with NRF were included in the study. The most common primary respiratory disorder was respiratory distress syndrome (78.5%). NRF was managed with non-invasive and invasive respiratory support in 59.8% and 14.5% of patients, respectively. The application rate of surfactant therapy was 38.5%, while that of neonatal extracorporeal membrane oxygenation therapy was 0.2%. Mortality and major morbidity rates of 8.5% and 23.2% were observed, respectively. Congenital anomalies, hypoxic-ischemic encephalopathy, invasive respiratory support only and inhaled nitric oxide therapy were found to be significantly associated with the risk of death. Among surviving infants born at < 32 weeks of gestation or with a birth weight < 1500 g, caffeine therapy and repeat mechanical ventilation were demonstrated to significantly associate with increased major morbidity risk. CONCLUSION: Our study demonstrates the current clinical landscape of infants with NRF treated in the NICU, and, by proxy, highlights the ongoing advancements in the field of perinatal and neonatal intensive care in China.


Asunto(s)
Unidades de Cuidado Intensivo Neonatal , Síndrome de Dificultad Respiratoria del Recién Nacido , Humanos , Recién Nacido , China/epidemiología , Estudios Retrospectivos , Femenino , Masculino , Síndrome de Dificultad Respiratoria del Recién Nacido/terapia , Insuficiencia Respiratoria/terapia , Surfactantes Pulmonares/uso terapéutico , Surfactantes Pulmonares/administración & dosificación , Oxigenación por Membrana Extracorpórea , Respiración Artificial/estadística & datos numéricos , Resultado del Tratamiento
7.
Sensors (Basel) ; 24(3)2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38339677

RESUMEN

Guided-mode resonance (GMR) gratings have emerged as a promising sensing technology, with a growing number of applications in diverse fields. This study aimed to identify the optimal design parameters of a simple-to-fabricate and high-performance one-dimensional GMR grating. The structural parameters of the GMR grating were optimized, and a high-refractive-index thin film was simulated on the grating surface, resulting in efficient confinement of the electric field energy within the waveguide. Numerical simulations demonstrated that the optimized GMR grating exhibited remarkable sensitivity (252 nm/RIU) and an extremely narrow full width at half maximum (2 × 10-4 nm), resulting in an ultra-high figure of merit (839,666) at an incident angle of 50°. This performance is several orders of magnitude higher than that of conventional GMR sensors. To broaden the scope of the study and to make it more relevant to practical applications, simulations were also conducted at incident angles of 60° and 70°. This holistic approach sought to develop a comprehensive understanding of the performance of the GMR-based sensor under diverse operational conditions.

8.
Fish Physiol Biochem ; 50(3): 941-954, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38381278

RESUMEN

Gastrin is an important intragastrointestinal hormone, but reports on its regulation of feeding behavior in fish are still scarce. This study aimed to determine the feeding regulatory function of gastrin in sturgeon. In this study, a gastrin/cholecystokinin-like peptide was identified in the genomes of sturgeon and proved to be gastrin by evolutionary tree analysis. Tissue distribution of gastrin and its receptor, cholecystokinin receptor B (CCKRB), showed that both had high mRNA abundance in the hypothalamus and gastrointestinal tract. In the duodenum, gastrin and CCKRB mRNAs were reduced at 1 h of fasting, and both were also observed in the stomach and hypothalamus in response to changes in feeding status. Sulfated gastrin 17 is the major form of gastrin in vivo. Therefore, we investigated the effect of sulfated gastrin 17 on feeding by intraperitoneal injection into Siberian sturgeon using sulfated gastrin 17. The results showed that gastrin 17 significantly reduced the cumulative feeding of Siberian sturgeon in the short term (1, 3 and 6 h) and long term (1, 2, 3, 4, 5 and 7 days). Finally, we explored the potential mechanism of feeding inhibition after intraperitoneal injection of gastrin 17 for 7 consecutive days. The results showed that gastrin 17 treatment significantly increased the mRNA levels of anorexigenic peptides (cart, cck and pyy), while it had no significant effect on the mRNA abundance of orexigenic peptides (npy and agrp). In addition, gastrin 17 treatment significantly affected the expression of appetite signaling pathways in the hypothalamus, such that the mRNA expression of ampkα1 was significantly reduced, whereas the mRNA abundance of stat3, mtor and s6k was significantly increased. In conclusion, the present study confirmed the anorectic effect of gastrin on Siberian sturgeon.


Asunto(s)
Peces , Gastrinas , Receptor de Colecistoquinina B , Animales , Gastrinas/metabolismo , Peces/fisiología , Peces/metabolismo , Receptor de Colecistoquinina B/metabolismo , Receptor de Colecistoquinina B/genética , Conducta Alimentaria/efectos de los fármacos , ARN Mensajero/metabolismo , ARN Mensajero/genética , Hipotálamo/metabolismo
9.
Zhongguo Zhong Yao Za Zhi ; 49(5): 1154-1163, 2024 Mar.
Artículo en Zh | MEDLINE | ID: mdl-38621962

RESUMEN

Ischemic stroke is divided into acute phase, subacute phase, and recovery phase, with different pathological and physiological characteristics manifested at each stage. Among them, immune and inflammatory reactions persist for several days and weeks after ischemia. Ischemic stroke not only triggers local inflammation in damaged brain regions but also induces a disorder in the immune system, thereby promoting neuroinflammation and exacerbating brain damage. Therefore, conducting an in-depth analysis of the interaction between the central nervous system and the immune system after ischemic stroke, intervening in the main factors of the interaction between them, blocking pathological cascades, and thereby reducing brain inflammation have become the treatment strategies for ischemic stroke. This study summarizes and sorts out the interaction pathways between the central nervous system and the immune system. The impact of the central nervous system on the immune system can be analyzed from the perspective of the autonomic nervous system, the hypothalamic-pituitary-adrenal axis(HPA), and local inflammatory stimulation. The impact of the immune system on the central nervous system can be analyzed from the dynamic changes of immune cells. At the same time, the relevant progress in the prevention and treatment of traditional Chinese medicine(TCM) is summarized, so as to provide new insights for the analysis of complex mechanisms of TCM in preventing and treating ischemic stroke.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Medicina Tradicional China , Sistema Hipotálamo-Hipofisario/patología , Sistema Hipófiso-Suprarrenal/patología , Sistema Nervioso Central , Isquemia Encefálica/terapia , Sistema Inmunológico , Inflamación
10.
Zhongguo Zhong Yao Za Zhi ; 49(7): 1865-1871, 2024 Apr.
Artículo en Zh | MEDLINE | ID: mdl-38812198

RESUMEN

This study aims to reveal the dynamics of the HPLC fingerprint, chromaticity values, and main chemical components of Mori Cortex during the stir-frying process. The fingerprints of raw and processed products of Mori Cortex were established. The content of mulberroside A, oxyresveratrol, kuwanon G, and kuwanon H in the samples and the chromaticity values of the samples were determined. Furthermore, the similarity evaluation of fingerprints and the correlation analysis between fingerprints and chromaticity values were carried out. The results showed that the fingerprints of raw and processed products of Mori Cortex had high similarity, and the overall changes in the content of the main chemical components in the stir-frying process were similar. According to the experience, when the stir-frying is moderate, the total chromaticity value difference |ΔE~*_(ab)| is above 1.5. With the extension of stir-frying time, the L~* and E~*_(ab) values keep decreasing, and the a~* value keeps increasing. The results of the correlation analysis between fingerprints and chromaticity values showed that peaks 1(5-hydroxy maltol), 2(mulberroside A), 3, 4, 6, 7, 11(oxyresveratrol), 14, 17(kuwanon G), and 18(kuwanon H) had significant correlations with the chromaticity values. Quantitative analysis of the four components with higher content showed that the content of the four components decreased to varying degrees when the stir-frying was excessive. In addition, 5-hydroxy maltol was produced after stir-frying of Mori Cortex, and the fingerprint and chromaticity values showed regular changes during the stir-frying process. The chromaticity can be included in the evaluation of the stir-frying process of Mori Cortex, which provides a reference for standardizing the quality of stir-fried Mori Cortex.


Asunto(s)
Medicamentos Herbarios Chinos , Morus , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/análisis , Morus/química , Disacáridos , Estilbenos
11.
Angew Chem Int Ed Engl ; 63(8): e202318497, 2024 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-38179852

RESUMEN

Utilizing water molecules to regulate the luminescence properties of solid materials is highly challenging. Herein, we develop a strategy to produce water-triggered luminescence-switching cocrystals by coassembling hydrophilic donors with electron-deficient acceptors, where 1,2,4,5-Tetracyanobenzene (TCNB) was used as the electron acceptor and pyridyl benzimidazole derivatives were used as the electron donors enabling multiple hydrogen-bonds. Two cocrystals, namely 2PYTC and 4PYTC were obtained and showed heat-activated emission, and such emission could be quenched or weakened by adding water molecules. The cocrystal structure exhibited the donor molecule that can form multiple hydro bonds with water and acceptor molecules due to the many nitrogen atoms of them. The analyses of the photophysical data, powder X-ray diffraction, and other data confirmed the reversible fluorescence "on-off" effects were caused by eliminating and adding water molecules in the crystal lattice. The density functional theory calculations indicate that the vibration of the O-H bond of water molecules in the cocrystal can absorb the excitation energy and suppress fluorescence. Furthermore, the obtained cocrystals also showed temperature, humidity, and H+ /NH4 + responsive emission behavior, which allows their applications as thermal and humidity sensors, and multiple information encryptions. This research paves the way for preparing intelligent hydrophilic organic cocrystal luminescent materials.

12.
BMC Bioinformatics ; 24(1): 129, 2023 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-37016308

RESUMEN

BACKGROUND: Identification of hot spots in protein-DNA binding interfaces is extremely important for understanding the underlying mechanisms of protein-DNA interactions and drug design. Since experimental methods for identifying hot spots are time-consuming and expensive, and most of the existing computational methods are based on traditional protein-DNA features to predict hot spots, unable to make full use of the effective information in the features. RESULTS: In this work, a method named WTL-PDH is proposed for hot spots prediction. To deal with the unbalanced dataset, we used the Synthetic Minority Over-sampling Technique to generate minority class samples to achieve the balance of dataset. First, we extracted the solvent accessible surface area features and structural features, and then processed the traditional features using discrete wavelet transform and wavelet packet transform to extract the wavelet energy information and wavelet entropy information, and obtained a total of 175 dimensional features. In order to obtain the best feature subset, we systematically evaluate these features in various feature selection strategies. Finally, light gradient boosting machine (LightGBM) was used to establish the model. CONCLUSIONS: Our method achieved good results on independent test set with AUC, MCC and F1 scores of 0.838, 0.533 and 0.750, respectively. WTL-PDH can achieve generally better performance in predicting hot spots when compared with state-of-the-art methods. The dataset and source code are available at https://github.com/chase2555/WTL-PDH .


Asunto(s)
Programas Informáticos , Análisis de Ondículas , Modelos Moleculares , Bases de Datos de Proteínas , Unión Proteica , Algoritmos
13.
Am J Physiol Cell Physiol ; 324(4): C951-C962, 2023 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-36779666

RESUMEN

The mechanisms of nephroprotection in nondiabetic chronic kidney disease (CKD) models by sodium-glucose cotransporter 2 (SGLT2) inhibitors are not well defined. Five groups were established: sham-operated rats, placebo-treated rats with 5/6 nephrectomy (5/6Nx), 5/6Nx + telmisartan (5 mg/kg/day), 5/6Nx + empagliflozin (3 mg/kg/day), and 5/6Nx + empagliflozin (15 mg/kg/day). Treatment duration was 95 days. Empagliflozin showed a dose-dependent beneficial effect on the change from baseline of creatinine clearance (Ccr). The urinary albumin-to-creatinine ratio likewise improved in a dose-dependent manner. Both dosages of empagliflozin improved morphological kidney damage parameters such as renal interstitial fibrosis and glomerulosclerosis. 5/6 nephrectomy led to a substantial reduction of urinary adenosine excretion, a surrogate parameter of the tubuloglomerular feedback (TGF) mechanism. Empagliflozin caused a dose-dependent increase in urinary adenosine excretion. The urinary adenosine excretion was negatively correlated with renal interstitial fibrosis and positively correlated with Ccr. Immunofluorescence analysis revealed that empagliflozin had no effect on CD8+ and CD4+ T cells as well as on CD68+ cells (macrophages). To further explore potential mechanisms, a nonhypothesis-driven approach was used. RNA sequencing followed by quantitative real-time polymerase chain reaction revealed that complement component 1Q subcomponent A chain (C1QA) as well as complement component 1Q subcomponent C chain (C1QC) gene expression were upregulated in the placebo-treated 5/6Nx rats and this upregulation was blunted by treatment with empagliflozin. In conclusion, empagliflozin-mediated nephroprotection in nondiabetic CKD is due to a dose-dependent activation of the TGF as well as empagliflozin-mediated effects on the complement system.


Asunto(s)
Diabetes Mellitus Tipo 2 , Insuficiencia Renal Crónica , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Ratas , Animales , Complemento C1q , Creatinina , Retroalimentación , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Fibrosis
14.
Ann Rheum Dis ; 82(3): 393-402, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36261249

RESUMEN

OBJECTIVES: This study investigated the stage-specific and location-specific deposition and characteristics of minerals in human osteoarthritis (OA) cartilages via multiple nano-analytical technologies. METHODS: Normal and OA cartilages were serially sectioned for micro-CT, scanning electron microscopy with energy dispersive X-ray spectroscopy, micro-Raman spectroscopy, focused ion beam scanning electron microscopy, high-resolution electron energy loss spectrometry with transmission electron microscopy, nanoindentation and atomic force microscopy to analyse the structural, compositional and mechanical properties of cartilage in OA progression. RESULTS: We found that OA progressed by both top-down calcification at the joint surface and bottom-up calcification at the osteochondral interface. The top-down calcification process started with spherical mineral particle formation in the joint surface during early-stage OA (OA-E), followed by fibre formation and densely packed material transformation deep into the cartilage during advanced-stage OA (OA-A). The bottom-up calcification in OA-E started when an excessive layer of calcified tissue formed above the original calcified cartilage, exhibiting a calcified sandwich structure. Over time, the original and upper layers of calcified cartilage fused, which thickened the calcified cartilage region and disrupted the cartilage structure. During OA-E, the calcified cartilage was hypermineralised, containing stiffer carbonated hydroxyapatite (HAp). During OA-A, it was hypomineralised and contained softer HAp. This discrepancy may be attributed to matrix vesicle nucleation during OA-E and carbonate cores during OA-A. CONCLUSIONS: This work refines our current understanding of the mechanism underlying OA progression and provides the foothold for potential therapeutic targeting strategies once the location-specific cartilage calcification features in OA are established.


Asunto(s)
Calcinosis , Cartílago Articular , Osteoartritis , Humanos , Cartílago Articular/diagnóstico por imagen , Osteoartritis/diagnóstico por imagen , Calcinosis/diagnóstico por imagen , Calcinosis/etiología
15.
Opt Express ; 31(20): 32900-32908, 2023 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-37859082

RESUMEN

In this paper, we use a pair of self-resonating subwavelength spoof plasmonic structures to achieve remote non-radiative terahertz wireless power transfer, while nearly without affecting the electromagnetic environment of free space around the structure. The resonating frequency and quality factor of the magnetic dipole mode supported by the spoof plasmonic structures can be freely tuned by tailoring the geometric structure. By putting the weak source and detector into the self-resonating structures, we can find that the effective non-radiative terahertz power transferring distance can reach several hundred times the radius of the structures. Finally, we also demonstrate the efficient wireless power transfer capability for the multi-target receiving system. These results may provide a novel approach to the design of non-radiative terahertz wireless power transfer and communications.

16.
FASEB J ; 36(4): e22259, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35294083

RESUMEN

Effects of feeding male rats during spermatogenesis a high-fat, high-sucrose and high-salt diet (HFSSD) over two generations (F0 and F1) on renal outcomes are unknown. Male F0 and F1 rats were fed either control diet (F0CD+F1CD) or HFSSD (F0HD+F1HD). The outcomes were glomerular filtration rate and urinary albumin excretion in F1 and F2 offspring. If both outcomes were altered a morphological and molecular assessment was done. F2 offspring of both sexes had a decreased GFR. However, increased urinary albumin excretion was only observed in female F2 F0HD+F1HD offspring compared with controls. F0HD+F1HD female F2 offspring developed glomerulosclerosis (+31%; p < .01) and increased renal interstitial fibrosis (+52%; p < .05). RNA sequencing followed by qRT-PCR validation showed that four genes (Enpp6, Tmem144, Cd300lf, and Actr3b) were differentially regulated in the kidneys of female F2 offspring. lncRNA XR-146683.1 expression decreased in female F0HD+F1HD F2 offspring and its expression was (r = 0.44, p = .027) correlated with the expression of Tmem144. Methylation of CpG islands in the promoter region of the Cd300lf gene was increased (p = .001) in female F2 F0HD+F1HD offspring compared to controls. Promoter CpG island methylation rate of Cd300lf was inversely correlated with Cd300lf mRNA expression in F2 female offspring (r = -0.483, p = .012). Cd300lf mRNA expression was inversely correlated with the urinary albumin-to-creatinine ratio in female F2 offspring (r = -0.588, p = .005). Paternal pre-conceptional unhealthy diet given for two generations predispose female F2 offspring to chronic kidney disease due to epigenetic alterations of renal gene expression. Particularly, Cd300lf gene promotor methylation was inversely associated with Cd300lf mRNA expression and Cd300lf mRNA expression itself was inversely associated with urinary albumin excretion in F2 female offspring whose fathers and grandfathers got a pre-conceptional unhealthy diet.


Asunto(s)
Efectos Tardíos de la Exposición Prenatal , Insuficiencia Renal Crónica , Albúminas , Animales , Dieta , Dieta Alta en Grasa/efectos adversos , Femenino , Humanos , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal/metabolismo , ARN Mensajero , Ratas , Cloruro de Sodio , Cloruro de Sodio Dietético , Espermatogénesis , Sacarosa/efectos adversos
17.
Molecules ; 28(14)2023 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-37513364

RESUMEN

Rosmarinus officinalis leaves (ROLs) are widely used in the food and cosmetics industries due to their high antioxidant activity and fascinating flavor properties. Carnosic acid (CA) and rosmarinic acid (RA) are regarded as the characteristic antioxidant components of ROLs, and the selective separation of CA and RA remains a significant challenge. In this work, the feasibility of achieving the selective separation of CA and RA from ROLs by solid-phase extraction (SPE) and liquid-liquid extraction (LLE) was studied and compared. The experiments suggested that SPE with CAD-40 macroporous resin as the adsorbent was a good choice for selectively isolating CA from the extracts of ROLs and could produce raw CA with purity levels as high as 76.5%. The LLE with ethyl acetate (EA) as the extraction solvent was more suitable for extracting RA from the diluted extracts of ROLs and could produce raw RA with a purity level of 56.3%. Compared with the reported column chromatography and LLE techniques, the developed SPE-LLE method not only exhibited higher extraction efficiency for CA and RA, but can also produce CA and RA with higher purity.


Asunto(s)
Extractos Vegetales , Rosmarinus , Extractos Vegetales/química , Extracción en Fase Sólida/métodos , Cinamatos/química , Extracción Líquido-Líquido/métodos , Rosmarinus/química , Antioxidantes/análisis , Cromatografía Líquida de Alta Presión , Ácido Rosmarínico
18.
Zhongguo Zhong Yao Za Zhi ; 48(9): 2471-2479, 2023 May.
Artículo en Zh | MEDLINE | ID: mdl-37282876

RESUMEN

In order to comprehensively evaluate the quality of Viticis Fructus, this study established HPLC fingerprints and evaluated the quality of 24 batches of Viticis Fructus samples from different species by similarity evaluation and multivariate statistical analysis(PCA, HCA, PLS-DA). On this basis, an HPLC method was established to compare the content differences of the main components, including casticin, agnuside, homoorientin, and p-hydroxybenzoic acid. The analysis was performed on the chromatographic column(Waters Symmetry C_(18)) with a gradient mobile phase of acetonitrile(A)-0.05% phosphoric acid solution(B) at the flow rate of 1 mL·min~(-1) and detection wavelength of 258 nm. The column temperature was 30 ℃ and the injection volume was 10 µL. The HPLC fingerprint of 24 batches of Viticis Fructus samples was established with 21 common peaks, and nine peaks were identified. Similarity analysis was carried out based on chromatographic data of 24 batches of chromatographic data of Viticis Fructus, and the results showed that except for DYMJ-16, the similarity of Vitex trifolia var. simplicifolia was ≥0.900, while that of V. trifolia was ≤0.864. In addition, the similarity analysis of two different species showed that the similarity of 16 batches of V. trifolia var. simplicifolia was 0.894-0.997 and that of the eight batches of V. trifolia was between 0.990 and 0.997. The results showed that the similarity of fingerprints of these two species was different, but the similarity between the same species was good. The results of the three multivariate statistical analyses were consistent, which could distinguish the two different species. The VIP analysis results of PLS-DA showed that casticin and agnuside contributed the most to the distinction. The content determination results showed that there was no significant difference in the content of homoorientin and p-hydroxybenzoic acid in Viticis Fructus from different species, but the content of casticin and agnuside was significantly different in different species(P<0.01). The content of casticin was higher in V. trifolia var. simplicifolia, while agnuside was higher in V. trifolia. The findings of this study show that there are differences in fingerprint similarity and component content of Viticis Fructus from different species, which can provide references for the in-depth study of the quality and clinical application of Viticis Fructus.


Asunto(s)
Medicamentos Herbarios Chinos , Vitex , Medicamentos Herbarios Chinos/química , Cromatografía Líquida de Alta Presión/métodos , Frutas/química , Vitex/química
19.
Angew Chem Int Ed Engl ; 62(4): e202215652, 2023 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-36399135

RESUMEN

A design strategy that combines molecular conformation, alkyl chain length, and charge-transfer effects has been developed to obtain conformational and stacking-adaptable donor-acceptor-π type molecules for precisely regulating the monomer and excimer emission in a single luminous platform under different environments. These fluorophores can exhibit bright monomer emissions when they are in the dispersed state based on their planar conformation. However, when the luminous molecules with short alkyl side chains are in the crystalline state, their molecular conformation can become distorted, further inducing strong intermolecular interactions and staggered π-π stacking for bright excimer emission. More importantly, their dispersed and aggregated states can be reversibly regulated in a phase-change fatty acid matrix, to achieve temperature-responsive fluorescence for temperature monitoring and advanced information encryption.

20.
Angew Chem Int Ed Engl ; 62(32): e202305925, 2023 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-37264744

RESUMEN

It is challenging to achieve stable and efficient radical emissions under ambient conditions. Herein, we present a rational design strategy to protect photoinduced carbonyl free radical emission through electrostatic interaction and spin delocalization effects. The host-guest system is constructed from tricarbonyl-substituted benzene molecules and a series of imidazolium ionic liquids as the guest and host, respectively, whereby the carbonyl anion radical emission can be in situ generated under the light irradiation and further stabilized by electrostatic interaction. More importantly, the anion species and the alkyl chain length of imidazolium ionic liquids show a noticeable effect on luminescence efficiency, with the highest radical emission efficiency is as high as 53.3 % after optimizing the imidazole ionic liquid's structure, which is about four times higher than the polymer-protected radical system. Theoretical calculations confirm the synergistic effect of strong electrostatic interactions and that the spin delocalization effect significantly stabilizes the radical emission. Moreover, such a radical emission system also could be integrated with a fluorescent dye to induce multi-color or even white light emission with reversible temperature-responsive characteristics. The radical emission system can also be used to detect different amine compounds on the basis of the emission changes and photoactivation time.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA