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1.
Clin Ophthalmol ; 18: 1851-1860, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38948340

RESUMEN

Background: To compare the efficacy of intravitreal injections of Conbercept combined with dexamethasone (DEX) for macular edema (ME) following central retinal vein occlusion (CRVO). Methods: This was a prospective, single-masked, randomised, controlled clinical trial. Patients with ME following CRVO were randomised into groups to receive intravitreal injections of 0.5 mg Conbercept plus 0.2 mg DEX or 0.5 mg Conbercept alone on day 0 followed by repeat injections as indicated. The primary outcome measure was the change in best-corrected visual acuity (BCVA) from baseline to month 12. Secondary outcome measures included decrease in central retinal thickness (CRT), injection frequency and interval and percentage of patients who gained more than 15 ETDRS letters or achieved a CRT of < 250 µm at month 12. Results: 33 males (51%) and 32 females (49%) were initially recruited with an average age of 56.64 ± 13.88 years. Patients in the Conbercept and Conbercept + DEX groups gained an average of 14.55 ± 19.19 and 14.88 ± 17.68 ETDRS letters, respectively, at months 12 (t = 4.221, P = 0.000; and t = 4.834, P = 0.000) with no significant difference between the two groups (t = 0.071, P = 0.943). In the Conbercept group, the mean reduction in CRT from baseline to month 12 was 435.26 ± 293.37 µm (t = 8.261, P = 0.000) compared to 431.36 ± 294.55 (t = 8.413, P = 0.000) in the Conbercept + DEX group. There was no significant difference between the two groups (t = 0.053, P = 0.958). The Conbercept + DEX group received fewer intravitreal injections. No major complications occurred. Conclusion: Conbercept, alone or with DEX, can improve BCVA and reduce CRT in ME following CRVO without serious adverse events. The treatment interval was longer in the Conbercept + DEX group. Trial Registration: The study was registered with the Chinese Clinical Trial Registry at 5 July 2017. (http://www.chictr.org.cn, 05/07/2017 Registration Number: ChiCTR-INR-17011877).

2.
Int Immunopharmacol ; 136: 112330, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-38823180

RESUMEN

An inflammatory response is one of the pathogeneses of depression. The anti-inflammatory and neuroprotective effects of auraptene have previously been confirmed. We established an inflammatory depression model by lipopolysaccharide (LPS) injection combined with unpredictable chronic mild stress (uCMS), aiming to explore the effects of auraptene on depressive-like behaviors in adult mice. Mice were divided into a control group, vehicle group, fluoxetine group, celecoxib group, and auraptene group. Then, behavioral tests were conducted to evaluate the effectiveness of auraptene in ameliorating depressive-like behavior. Cyclooxygenase-2 (COX-2), C-reactive protein (CRP), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) were examined by ELISA. Interleukin-10 (IL-10), interleukin-4 (IL-4), and transforming growth factor-ß (TGF-ß) were examined by protein chip technology. The morphology of microglia was observed by the immunohistochemical method. The data showed that, compared with the control group, the vehicle group mice exhibited a depressive-like behavioral phenotype, accompanied by an imbalance in inflammatory cytokines and the activation of microglia in the hippocampus. The depressive behaviors of the auraptene group's mice were significantly alleviated, along with the decrease in pro-inflammatory factors and increase in anti-inflammatory factors, while the activation of microglia was inhibited in the hippocampus. Subsequently, we investigated the role of auraptene in vitro-cultured BV-2 cells treated with LPS. The analysis showed that auraptene downregulated the expression of IL-6, TNF-α, and NO, and diminished the ratio of CD86/CD206. The results showed that auraptene reduced the excessive phagocytosis and ROS production of LPS-induced BV2 cells. In conclusion, auraptene relieved depressive-like behaviors in mice probably via modulating hippocampal neuroinflammation mediated by microglia.


Asunto(s)
Cumarinas , Citocinas , Depresión , Hipocampo , Lipopolisacáridos , Microglía , Estrés Psicológico , Animales , Microglía/efectos de los fármacos , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/patología , Masculino , Depresión/tratamiento farmacológico , Depresión/inmunología , Depresión/inducido químicamente , Ratones , Estrés Psicológico/tratamiento farmacológico , Estrés Psicológico/inmunología , Cumarinas/farmacología , Cumarinas/uso terapéutico , Citocinas/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Modelos Animales de Enfermedad , Conducta Animal/efectos de los fármacos , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/inmunología , Ratones Endogámicos C57BL , Mediadores de Inflamación/metabolismo
3.
Molecules ; 29(12)2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38930964

RESUMEN

Microemulsions are thermodynamically stable, optically isotropic, transparent, or semi-transparent mixed solutions composed of two immiscible solvents stabilized by amphiphilic solutes. This comprehensive review explores state-of-the-art techniques for characterizing microemulsions, which are versatile solutions essential across various industries, such as pharmaceuticals, food, and petroleum. This article delves into spectroscopic methods, nuclear magnetic resonance, small-angle scattering, dynamic light scattering, conductometry, zeta potential analysis, cryo-electron microscopy, refractive index measurement, and differential scanning calorimetry, examining each technique's strengths, limitations, and potential applications. Emphasizing the necessity of a multi-technique approach for a thorough understanding, it underscores the importance of integrating diverse analytical methods to unravel microemulsion structures from molecular to macroscopic scales. This synthesis provides a roadmap for researchers and practitioners, fostering advancements in microemulsion science and its wide-ranging industrial applications.

4.
Eur J Med Chem ; 275: 116577, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-38875809

RESUMEN

Sphingosine kinase 2 (SphK2) has emerged as a promising target for cancer therapy due to its critical role in tumor growth. However, the lack of potent and selective inhibitors has hindered its clinical application. Herein, we report the design and synthesis of a series of novel SphK2 inhibitors, culminating in the identification of compound 12q as a highly selective and potent inhibitor of SphK2. Molecular dynamics simulations suggest that the incorporation of larger substitution groups facilitates a more effective occupation of the binding site, thereby stabilizing the complex. Compared to the widely used inhibitor ABC294640, compound 12q exhibits superior anti-proliferative activity against various cancer cells, inducing G2 phase arrest and apoptosis in liver cancer cells HepG2. Notably, 12q inhibited migration and colony formation in HepG2 and altered intracellular sphingolipid content. Moreover, intraperitoneal administration of 12q in mice resulted in decreased levels of S1P. 12q provides a valuable tool compound for exploring the therapeutic potential of targeting SphK2 in cancer.


Asunto(s)
Acetamidas , Antineoplásicos , Proliferación Celular , Ensayos de Selección de Medicamentos Antitumorales , Fosfotransferasas (Aceptor de Grupo Alcohol) , Fosfotransferasas (Aceptor de Grupo Alcohol)/antagonistas & inhibidores , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Humanos , Animales , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Ratones , Proliferación Celular/efectos de los fármacos , Relación Estructura-Actividad , Acetamidas/farmacología , Acetamidas/síntesis química , Acetamidas/química , Estructura Molecular , Apoptosis/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Descubrimiento de Drogas , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/síntesis química
5.
Toxicol Lett ; 398: 127-139, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38914176

RESUMEN

Increasing epidemiological evidence has shown that PM2.5 exposure is significantly associated with the occurrence of osteoporosis. It has been well demonstrated that PM2.5 exposure enhanced the differentiation and function of osteoclasts by indirectly causing chronic inflammation, while the mechanism in osteoblasts remains unclear. In our study, toxic effects were evaluated by direct exposure of 20-80 µg/ml PM2.5 to MC3T3-E1 cells and BMSCs. The results showed that PM2.5 exposure did not affect cell viability via proliferation and apoptosis, but significantly inhibited osteoblast differentiation in a dose-dependent manner. Osteogenic transcription factors Runx2 and Sp7 and other biomarkers Alp and Ocn decreased after PM2.5 exposure. RNA-seq revealed TGF-ß signaling was involved in PM2.5 exposure inhibited osteoblast differentiation, which led to P-Smad1/5 and P-Smad2 reduction in the nucleus by increasing the ubiquitination and degradation of Smad4. At last, the inflammation response increased in MC3T3-E1 cells with PM2.5 exposure. Moreover, the mRNA levels of Mmp9 increased in bone marrow-derived macrophage cells treated with the conditional medium collected from MC3T3-E1 cells exposed to PM2.5. Overall, these results indicated that PM2.5 exposure inhibits osteoblast differentiation and concurrently increases the maturation of osteoclasts. Our study provides in-depth mechanistic insights into the direct impact of PM2.5 exposure on osteoblast, which would indicate the unrecognized role of PM2.5 on osteoporosis.


Asunto(s)
Diferenciación Celular , Osteoblastos , Material Particulado , Proteína Smad4 , Ubiquitinación , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Animales , Diferenciación Celular/efectos de los fármacos , Proteína Smad4/metabolismo , Proteína Smad4/genética , Ratones , Material Particulado/toxicidad , Ubiquitinación/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Contaminantes Atmosféricos/toxicidad , Línea Celular , Supervivencia Celular/efectos de los fármacos , Factor de Crecimiento Transformador beta/metabolismo , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/genética , Proteolisis/efectos de los fármacos
6.
ACS Omega ; 9(17): 19148-19157, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38708247

RESUMEN

The long-term prognosis of nonsmall cell lung cancer (NSCLC) remains unsatisfactory, which is a major challenge in lung cancer treatment. BIRC3 is an inhibitor of apoptosis (IAP) protein that contributes to tumor regulation. However, the underlying regulatory mechanisms of BIRC3 in NSCLC remains unknown. We initiated an analysis of BIRC3 expression data in NSCLC tumors and adjacent tissues using the TCGA and GEO databases and examined the variations in prognosis. Further, we conducted overexpression (OE) and knockdown (KD) studies on BIRC3 to evaluate its effects on NSCLC cell proliferation, migration, and invasion. Additionally, through utilization of a nude mouse model, the regulatory effects of BIRC3 on NSCLC were verified in vivo. Co-immunoprecipitation (Co-IP) assay served to pinpoint the proteins with which BIRC3 interacts. The results indicated that BIRC3 is down-regulated in NSCLC tissues and that patients with high BIRC3 expression demonstrate a better prognosis. BIRC3 is a tumor suppressor, inhibiting the proliferation and metastasis of NSCLC. Co-IP results revealed that BIRC3 interacts with HSP90B1, leading to a decrease in HSP90B1 expression and subsequent negative regulation of the ERK signaling pathway. BIRC3 may serve as a prognostic biomarker for NSCLC. It directly interacts with HSP90B1 to negatively regulate the ERK signaling pathway, thereby hindering the progression of NSCLC.

7.
J Am Chem Soc ; 146(19): 13546-13557, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38690842

RESUMEN

Glycidic esters represent pivotal constituents in synthetic chemistry, offering enhanced versatility for tailoring toward a diverse array of molecular targets in comparison with simple epoxides. While considerable progress has been made in the asymmetric synthesis of trans- and trisubstituted glycidic esters, achieving enantioselective preparation of cis-glycidic esters has remained a long-standing challenge. Here, we demonstrate a selectivity-predictable modular platform for the asymmetric synthesis of cis-glycidic esters via a novel dinuclear (salen)titanium(III)-catalyzed radical-type kinetic resolution (KR) approach. This radical KR protocol operates under mild conditions and demonstrates a wide substrate scope, facilitating the synthesis of alkyl- and aryl-substituted cis-glycidic esters with high levels of regioselectivity and enantioselectivity, along with hydroxy ester byproducts representing synthetically valuable motifs as well. This study presents a unique exploration of radical-type KR applied to epoxides, effectively overcoming the steric challenges inherent in conventional nucleophilic-type methodologies typically employed in epoxide chemistry.

8.
Int J Mol Sci ; 25(10)2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38791115

RESUMEN

Surface chemistry and bulk structure jointly play crucial roles in achieving high-performance supercapacitors. Here, the synergistic effect of surface chemistry properties (vacancy and phosphorization) and structure-derived properties (hollow hydrangea-like structure) on energy storage is explored by the surface treatment and architecture design of the nanostructures. The theoretical calculations and experiments prove that surface chemistry modulation is capable of improving electronic conductivity and electrolyte wettability. The structural engineering of both hollow and nanosheets produces a high specific surface area and an abundant pore structure, which is favorable in exposing more active sites and shortens the ion diffusion distance. Benefiting from its admirable physicochemical properties, the surface phosphorylated MnCo2O4.5 hollow hydrangea-like structure (P-MnCoO) delivers a high capacitance of 425 F g-1 at 1 A g-1, a superior capability rate of 63.9%, capacitance retention at 10 A g-1, and extremely long cyclic stability (91.1% after 10,000 cycles). The fabricated P-MnCoO/AC asymmetric supercapacitor achieved superior energy and power density. This work opens a new avenue to further improve the electrochemical performance of metal oxides for supercapacitors.


Asunto(s)
Capacidad Eléctrica , Compuestos de Manganeso , Óxidos , Oxígeno , Compuestos de Manganeso/química , Óxidos/química , Oxígeno/química , Propiedades de Superficie , Nanoestructuras/química , Técnicas Electroquímicas/métodos
9.
Eur J Med Chem ; 271: 116408, 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38621327

RESUMEN

As an essential form of lipid modification for maintaining vital cellular functions, palmitoylation plays an important role in in the regulation of various physiological processes, serving as a promising therapeutic target for diseases like cancer and neurological disorders. Ongoing research has revealed that palmitoylation can be categorized into three distinct types: N-palmitoylation, O-palmitoylation and S-palmitoylation. Herein this paper provides an overview of the regulatory enzymes involved in palmitoylation, including palmitoyltransferases and depalmitoylases, and discusses the currently available broad-spectrum and selective inhibitors for these enzymes.


Asunto(s)
Aciltransferasas , Lipoilación , Bibliotecas de Moléculas Pequeñas , Humanos , Aciltransferasas/metabolismo , Aciltransferasas/antagonistas & inhibidores , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/farmacología , Animales , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Estructura Molecular , Proteínas/metabolismo , Proteínas/química
10.
MedComm (2020) ; 5(4): e540, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38606360

RESUMEN

Senile plaque, composed of amyloid ß protein (Aß) aggregates, is a critical pathological feature in Alzheimer's disease (AD), leading to cognitive dysfunction. However, how Aß aggregates exert age-dependent toxicity and temporal cognitive dysfunction in APP/PS1 mice remains incompletely understood. In this study, we investigated AD pathogenesis and dynamic alterations in lysosomal pathways within the hippocampus of age-gradient male mice using transcriptome sequencing, molecular biology assays, and histopathological analyses. We observed high levels of ß-amyloid precursor protein (APP) protein expression in the hippocampus at an early stage and age-dependent Aß deposition. Transcriptome sequencing revealed the enrichment of differential genes related to the lysosome pathway. Furthermore, the protein expression of ATP6V0d2 and CTSD associated with lysosomal functions exhibited dynamic changes with age, increasing in the early stage and decreasing later. Similar age-dependent patterns were observed for the endosome function, autophagy pathway, and SGK1/FOXO3a pathway. Nissl and Golgi staining in the hippocampal region showed age-dependent neuronal loss and synaptic damage, respectively. These findings clearly define the age-gradient changes in the autophagy-lysosome system, the endosome/lysosome system, and the SGK1/FOXO3a pathway in the hippocampus of APP/PS1 mice, providing new perspectives and clues for understanding the possible mechanisms of AD, especially the transition from compensatory to decompensated state.

11.
Nat Commun ; 15(1): 3399, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38649376

RESUMEN

The van der Waals antiferromagnetic topological insulator MnBi2Te4 represents a promising platform for exploring the layer-dependent magnetism and topological states of matter. Recently observed discrepancies between magnetic and transport properties have aroused controversies concerning the topological nature of MnBi2Te4 in the ground state. In this article, we demonstrate that fabrication can induce mismatched even-odd layer dependent magnetotransport in few-layer MnBi2Te4. We perform a comprehensive study of the magnetotransport properties in 6- and 7-septuple-layer MnBi2Te4, and reveal that both even- and odd-number-layer device can show zero Hall plateau phenomena in zero magnetic field. Importantly, a statistical survey of the optical contrast in more than 200 MnBi2Te4 flakes reveals that the zero Hall plateau in odd-number-layer devices arises from the reduction of the effective thickness during the fabrication, a factor that was rarely noticed in previous studies of 2D materials. Our finding not only provides an explanation to the controversies regarding the discrepancy of the even-odd layer dependent magnetotransport in MnBi2Te4, but also highlights the critical issues concerning the fabrication and characterization of 2D material devices.

12.
J Med Chem ; 67(9): 7033-7047, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38634331

RESUMEN

A brand-new enhanced starvation is put forward to trigger sensitized chemotherapy: blocking tumor-relation blood vessel formation and accelerating nutrient degradation and efflux. Following this concept, two cisplatin-like gemfibrozil-derived Pt(IV) prodrugs, GP and GPG, are synthesized. GP and GPG had nanomolar IC50 against A2780 cells and higher selectivity against normal cells than cisplatin. Bioactivity results confirmed that GP and GPG highly accumulated in cells and induced DNA damage, G2-phase arrest, and p53 expression. Besides, they could increase ROS and MDA levels and reduce mitochondrial membrane potential and Bcl-2 expression to promote cell apoptosis. In vivo, GP showed superior antitumor activity in A2780 tumor-bearing mice with no observable tissue damage. Mechanistic studies suggested that highly selective chemotherapy could be due to the new enhanced starvation effect: blocking vasculature formation via inhibiting the CYP2C8/EETs pathway and VEGFR2, NF-κB, and COX-2 expression and cholesterol efflux and degradation acceleration via increasing ABCA1 and PPARα.


Asunto(s)
Antineoplásicos , Gemfibrozilo , Animales , Humanos , Ratones , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Gemfibrozilo/farmacología , Ratones Endogámicos BALB C , Compuestos Organoplatinos/farmacología , Compuestos Organoplatinos/química , Profármacos/farmacología , Profármacos/química , Profármacos/síntesis química
13.
ACS Org Inorg Au ; 4(2): 258-267, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38585511

RESUMEN

The industrial production of methanol through CO hydrogenation using the Cu/ZnO/Al2O3 catalyst requires harsh conditions, and the development of new catalysts with low operating temperatures is highly desirable. In this study, organic biomimetic FLP catalysts with good tolerance to CO poison are theoretically designed. The base-free catalytic reaction contains the 1,1-addition of CO into a formic acid intermediate and the hydrogenation of the formic acid intermediate into methanol. Low-energy spans (25.6, 22.1, and 20.6 kcal/mol) are achieved, indicating that CO can be hydrogenated into methanol at low temperatures. The new extended aromatization-dearomatization effect involving multiple rings is proposed to effectively facilitate the rate-determining CO 1,1-addition step, and a new CO activation model is proposed for organic catalysts.

14.
Sci Rep ; 14(1): 7991, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38580792

RESUMEN

In sustaining arch locked-segment-type slopes, natural soil arches play a key anti-sliding role in the slope's evolution. In this study, a self-developed model test device was used to simulate the whole process of deformation evolution of sustaining arch locked-segment-type slopes, and the formation of natural sustaining arch and its locking control effect on slope stability were studied. The test results show that the continuous formation and progressive destruction of the sustaining arch were observed. The sustaining arch formed in the second time has the best locking effect, and the anti-sliding force reaches its stress peak point. However, the slope is not in a critically unstable state, instead, the stress is continuously adjusted to form a larger range of soil arch to resist the slope thrust. Consequently, the slope destabilizes until the ultimate shear strength of arch foots is exceeded, at which point the critical arch height of the arch is reached. The critical arch height mechanical model for slope stability analysis was developed based on the soil arching effect and limit equilibrium theory. The applicability of the model was demonstrated by the physical test and Xintan slope data, which can provide some guidance for early warning of landslides.

15.
Bioresour Technol ; 399: 130595, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38493936

RESUMEN

Poplar is widely used in the paper industry and accompanied by abundant branches waste, which is potential feedstock for bioethanol production. Acid-chlorite pretreatment can selectively remove lignin, thereby significantly increasing enzymatic efficiency. Moreover, lignin residues valorization via gasification-syngas fermentation can achieve higher fuel yield. Herein, environmental and economic aspects were conducted to assess technological routes, which guides further process optimization. Life cycle assessment results show that wood-based biorefineries especially coupling scenarios have significant advantages in reducing global warming potential in contrast to fossil-based automotive fuels. Normalization results indicate that acidification potential surpasses other indicators as the primary impact category. In terms of economic feasibility, coupling scenarios present better investment prospects. Bioethanol yield is the most critical factor affecting market competitiveness. Minimum ethanol selling price below ethanol international market price is promising with higher-levels technology. Further work should be focused on technological breakthrough, consumable reduction or replacement.


Asunto(s)
Etanol , Lignina , Animales , Lignina/química , Etanol/química , Madera/metabolismo , Biotecnología/métodos , Fermentación , Estadios del Ciclo de Vida
16.
ACS Appl Mater Interfaces ; 16(14): 17506-17516, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38538567

RESUMEN

Although the conversion of O2 and H2O to H2O2 over graphite carbon nitride (g-C3N4) has been realized by means of the photocatalytic process, the catalytic activity of pristine g-C3N4 is still restricted by the rapid charge recombination and inadequate exposure of the active site. In this work, we propose a straightforward strategy to solve these limitations by decreasing the thickness and improving the crystallinity of g-C3N4, resulting in the preparation of few-layered crystalline carbon nitride (FL-CCN). Benefiting from the minimal thickness and highly ordered in-plane triangular cavities within the structure, FL-CCN processes an extended π-conjugated system with a reduced charge transfer resistance and expanded specific surface area. These features accelerate the efficiency of photogenerated charge separation in FL-CCN and contribute to explore of its surface active sites. Consequently, FL-CCN exhibits a significantly improved H2O2 evolution rate (63.95 µmol g-1 h-1), which is 7.8 times higher than that of pristine g-C3N4 (8.15 µmol g-1 h-1), during the photocatalytic conversion of O2 and H2O. This systematic investigation offers valuable insights into the mechanism of photocatalytic H2O2 generation and the development of efficient catalysts.

17.
J Hazard Mater ; 469: 133919, 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38432093

RESUMEN

Chlorinated polyfluorinated ether sulfonate (Cl-PFESA), a substitute for perfluorooctane sulfonate (PFOS), has been widely used in the Chinese electroplating industry under the trade name F-53B. The production and use of F-53B is keep increasing in recent years, consequently causing more emissions into the environment. Thus, there is a growing concern about the adverse effects of F-53B on human health. However, related research is very limited, particularly in terms of its toxicity to the vascular system. In this study, C57BL/6 J mice were exposed to 0.04, 0.2, and 1 mg/kg F-53B for 12 weeks to assess its impact on the vascular system. We found that F-53B exposure caused aortic wall thickening, collagen deposition, and reduced elasticity in mice. In addition, F-53B exposure led to a loss of vascular endothelial integrity and a vascular inflammatory response. Intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were found to be indispensable for this process. Furthermore, RNA sequencing analysis revealed that F-53B can decrease the repair capacity of endothelial cells by inhibiting their proliferation and migration. Collectively, our findings demonstrate that F-53B exposure induces vascular inflammation and loss of endothelial integrity as well as suppresses the repair capacity of endothelial cells, which ultimately results in vascular injury, highlighting the need for a more thorough risk assessment of F-53B to human health.


Asunto(s)
Ácidos Alcanesulfónicos , Fluorocarburos , Contaminantes Químicos del Agua , Humanos , Animales , Ratones , Éter/metabolismo , Células Endoteliales , Pez Cebra/metabolismo , Ratones Endogámicos C57BL , Contaminantes Químicos del Agua/análisis , Alcanosulfonatos/toxicidad , Ácidos Alcanesulfónicos/toxicidad , Ácidos Alcanesulfónicos/metabolismo , Fluorocarburos/análisis
18.
J Orthop Surg Res ; 19(1): 198, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38528538

RESUMEN

PURPOSE: This study aimed to evaluate the protective effects of gentiopicroside against lipopolysaccharide-induced chondrocyte inflammation. METHODS: SW 1353 chondrosarcoma cells were stimulated with LPS (5 µg/ml) for 24 h and treated with different concentrations of gentiopicroside (GPS) for 24 h. The toxic effects of GPS on chondrocytes were determined using a CCK-8 assay and EdU staining. Western blotting, qPCR, and immunofluorescence analysis were used to examine the protective effect of GPS against the inflammatory response in chondrocytes induced by lipopolysaccharide (LPS). One-way ANOVA was used to compare the differences between the groups (significance level of 0.05). RESULTS: The CCK-8 results showed that 10, 20 and 40 µM GPS had no significant toxic effects on chondrocytes; GPS effectively reduced the production of IL-1ß and PGE2, reversed LPS-induced extracellular matrix degradation in cartilage by inhibiting the Stat3/Runx2 signaling pathway, and suppressed the hypertrophic transformation of SW 1353 chondrosarcoma cells. CONCLUSION: Our study demonstrated that GPS significantly inhibited the LPS-induced inflammatory response and hypertrophic cellular degeneration in SW 1353 chondrosarcoma cells and is a valuable traditional Chinese medicine for the treatment of knee osteoarthritis.


Asunto(s)
Condrosarcoma , Glucósidos Iridoides , Osteoartritis , Humanos , Condrocitos/metabolismo , Lipopolisacáridos/toxicidad , Osteoartritis/metabolismo , Sincalida/metabolismo , Sincalida/farmacología , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Hipertrofia , Condrosarcoma/tratamiento farmacológico , Interleucina-1beta/metabolismo , FN-kappa B/metabolismo
19.
ACS Pharmacol Transl Sci ; 7(3): 797-808, 2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38481693

RESUMEN

Chronic pain is a common condition that causes negative emotions as the disease progresses. The anterior cingulate cortex (ACC) is a key region in the integration of nociceptive perception and emotional response in chronic pain. Linderane (LDR) is an active ingredient from Linderae radix, a traditional Chinese medicine with anti-inflammatory, analgesic, and antibacterial properties. In this study, the analgesic and antianxiety effects of LDR were evaluated using a complete Freund's adjuvant (CFA)-induced inflammatory pain model in C57BL/6 male mice. Mechanical and thermal pain sensitivity were measured through plantar mechanical analgesia and hot plate apparatus, and anxiety-like behavior was evaluated by open field and elevated plus maze tests. The results showed that LDR-alleviated CFA-induced pain and anxiety, reduced the release of inflammatory cytokines, and inhibited ACC microglial activation. Target prediction, molecular docking, and cellular thermal shift assay demonstrated that LDR could bind to the cannabinoid 2 receptor (CB2R), a key component of the endocannabinoid system with an important role in regulating pain and related emotions. Moreover, both the analgesic effect of LDR and its regulation of microglia polarization were reversed by a CB2R antagonist (SR144528) treatment. Therefore, our results suggested that LDR exerted analgesic effects by regulating microglial polarization in ACC via CB2R activation.

20.
Environ Res ; 249: 118497, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38365054

RESUMEN

Developing a photoelectric cathode capable of efficiently activating molecular oxygen to degrade pollutants is a coveted yet challenging goal. In pursuit of this, we synthesize a Fe doped porous carbon nitride catalyst (Fe-CN) using an ionothermal strategy and subsequently loaded it on the hydrophobic carbon felt (CF) to fabricate the Fe-CN/CF photoelectric cathode. This cathode benefits from the synergistic effects between the porous CN support and the highly dispersed Fe species, which enhance O2 absorption and activation. Additionally, the hydrophobic CF serves as a gas diffusion layer, accelerating O2 mass transfer. These features enable the Fe-CN/CF cathode to demonstrate notable photoelectrocatalytic (PEC) degradation efficiency. Specifically, under optimal conditions (cathodic bias of -0.3 VAg/AgCl, pH 7, and a catalyst loading of 3 mg/cm2), the system achieves a 76.4% removal rate of tetracycline (TC) within 60 min. The general application potential of this system is further underscored by its ability to remove approximately 98% of 4-chlorophenol (4-CP) and phenol under identical conditions. Subsequent investigations into the active species and degradation pathways reveal that 1O2 and h+ play dominant role during the PEC degradation process, leading to gradually breakdown of TC into less toxicity, smaller molecular intermediates. This work presents a straightforward yet effective strategy for constructing efficient PEC systems that leverage molecular oxygen activation to degrade pollutants.


Asunto(s)
Carbono , Hierro , Nitrilos , Oxígeno , Nitrilos/química , Oxígeno/química , Carbono/química , Hierro/química , Catálisis , Contaminantes Químicos del Agua/química , Porosidad , Interacciones Hidrofóbicas e Hidrofílicas , Electrodos , Técnicas Electroquímicas/métodos
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