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1.
Environ Res ; : 119621, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39019142

RESUMO

Atom-dispersed low-coordinated transition metal-Nx catalysts exhibit excellent efficiency in activating peroxydisulfate (PDS) for environmental remediation. However, their catalytic performance is limited due to metal-N coordination number and single-atom loading amount. In this study, low-coordinated nitrogen-doped graphene oxide (GO) confined single-atom Mn catalyst (Mn-SA/NGO) was synthesized by molten salt-assisted pyrolysis and coupled to PDS for degradation of tetracycline (TC) in water. Aberration-corrected high-angle annular dark-field scanning transmission electron microscopy (AC-HAADF-STEM) and X-ray absorption fine structure spectroscopy (XAFS) analysis showed the successful doping of single-atom Mn (weight percentage 1.6%) onto GO and the formation of low-coordinated Mn-N2 sites. The optimized parameters obtained by Box-Behnken Design achieved 100% TC removal in both prediction and experimental results. The Mn-SA/NGO+PDS system had strong anti-interference ability for TC removal in the presence of anions. Besides, Mn-SA/NGO possessed good reusability and stability. O2•-, •OH, and 1O2 were the main active species for TC degradation, and the TC mineralization reached 85.1%. Density functional theory (DFT) calculations confirmed that the introduction of single atoms Mn could effectively enhance adsorption and activation of PDS. The findings provide a reference for the synthesis of high-performance single-atom catalysts for effective removal of antibiotics.

2.
Front Physiol ; 15: 1402478, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38911325

RESUMO

Introduction: This study was undertaken to explore the potential therapeutic effects of Tongyang Huoxue Granules (TYHX) on sinoatrial node (SAN) dysfunction, a cardiac disorder characterized by impaired impulse generation or conduction. The research question addressed whether TYHX could positively influence SAN ion channel function, specifically targeting the sodium-calcium exchanger (I NCX) and L-type calcium channel (I CaL) of the SAN. Methods: Sinoatrial node cells (SANCs) were isolated and cultured from neonatal Japanese big-eared white rabbits within 24 h of birth. The study encompassed five groups: Control, H/R (hypoxia/reoxygenation), H/R+100 µg/mL TYHX, H/R+200 µg/mL TYHX, and H/R+400 µg/mL TYHX. The H/R model, simulating hypoxia/reoxygenation stress, was induced within 5 days of culture. Whole-cell patch clamp technique was employed to record currents following a 3-min perfusion and stabilization period with TYHX. Results: TYHX administration demonstrated improvements in the ignition phase of impaired SANCs. The half-maximal effective dose of TYHX, as determined by SANC beating frequency, was found to be 323.63 µg/mL. Inward current density of I NCX increased in response to TYHX (200 and 400 µg/mL), while TYHX enhanced I CaL current density in H/R SANCs, with 400 µg/mL exhibiting greater efficacy. Additionally, TYHX regulated the gating mechanisms of I CaL by right-shifting the steady-state inactivation curve and accelerating recovery from inactivation. Notably, TYHX increased the activation time constant under 200 and 400 µg/mL, prolonged the fast inactivation time constant τ1 with 400 µg/mL, and extended the slow inactivation time constant τ2 with 100 and 400 µg/mL. Discussion and conclusion: The findings suggest that TYHX may hold promise as a therapeutic intervention for sinus node dysfunction, offering potential avenues for drug development aimed at safeguarding SAN function.

3.
ACS Appl Mater Interfaces ; 16(25): 32702-32712, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38870327

RESUMO

Herein, we report a dual-functional flexible sensor (DFFS) using a magnetic conductive polymer composed of nickel (Ni), carbon black (CB), and polydimethylsiloxane (PDMS). The material selection for the DFFS utilizes the excellent elasticity of the PDMS matrix and the synergistic interaction between Ni and CB. The DFFS has a wide strain range of 0-170%, a high sensitivity of 74.13 (140-170%), and a low detection limit of 0.3% strain. The DFFS based on superior performance can accurately detect microstrain/microvibration, oncoming/contacting objects, and bicycle riding speed. Additionally, the DFFS can be used for comprehensive monitoring of human movements. Therefore, the DFFS of this work shows significant value for implementation in intelligent wearable devices and noncontact intelligent control.


Assuntos
Dimetilpolisiloxanos , Microesferas , Níquel , Fuligem , Dispositivos Eletrônicos Vestíveis , Dimetilpolisiloxanos/química , Humanos , Níquel/química , Fuligem/química , Movimento , Condutividade Elétrica
4.
Gene ; 927: 148733, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38945310

RESUMO

The adeno-associated virus (AAV) is a defective single-stranded DNA virus with the simplest structure reported to date. It constitutes a capsid protein and single-stranded DNA. With its high transduction efficiency, low immunogenicity, and tissue specificity, it is the most widely used and promising gene therapy vector. The clustered regularly interspaced short palindromic sequence (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing system is an emerging technology that utilizes cas9 nuclease to specifically recognize and cleave target genes under the guidance of small guide RNA and realizes gene editing through homologous directional repair and non-homologous recombination repair. In recent years, an increasing number of animal experiments and clinical studies have revealed the great potential of AAV as a vector to deliver the CRISPR/cas9 system for treating genetic diseases and viral infections. However, the immunogenicity, toxicity, low transmission efficiency in brain and ear tissues, packaging size limitations of AAV, and immunogenicity and off-target effects of Cas9 protein pose several clinical challenges. This research reviews the role, challenges, and countermeasures of the AAV-CRISPR/cas9 system in gene therapy.

5.
Neurosurgery ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38860769

RESUMO

BACKGROUND AND OBJECTIVES: This study aimed to investigate the clinical, radiological, pathological features, treatment options, and outcomes of isocitrate dehydrogenase (IDH)-mutant brainstem gliomas (BSG-IDHmut). METHODS: A retrospective analysis of 22 patients diagnosed with BSG-IDHmut and treated at our institution from January 2011 to January 2017 was performed. Their clinical, radiological data, and long-term outcomes were collected and analyzed. RESULTS: The median age of patients was 38.5 years, with a male predominance (63.6%). All patients had IDH1 and TP53 mutations, with noncanonical IDH mutations in 59.1% of cases, 06-methylguanine-DNA methyltransferase promoter methylation in 55.6%, and alpha-thalassemia mental retardation X-linked loss in 63.2%, respectively. Tumors were primarily located in the pontine-medullary oblongata (54.5%) and frequently involved the pontine brachium (50%). Most tumors exhibited ill-defined boundaries (68.2%), no T2-FLAIR mismatch (100%), and no contrast enhancement (86.3%). Two radiological growth patterns were also identified: focal and extensively infiltrative, which were associated with the treatment strategy when tumor recurred. Seven patients (31.8%) received surgery only and 15 (68.2%) surgery plus other therapy. The median overall survival was 124.8 months, with 1-year, 2-year, 5-year, and 10-year survival rates of 81.8%, 68.2%, 54.5%, and 13.6%, respectively. Six patients experienced tumor recurrence, and all retained their radiological growth patterns, with 2 transformed into central nervous system World Health Organization grade 4. CONCLUSION: BSG-IDHmut represents a unique subgroup of brainstem gliomas with distinctive features and more favorable prognosis compared with other brainstem gliomas. Further research is required to better understand the molecular mechanisms and optimize treatment strategies for this rare and complex disease.

6.
Nanomaterials (Basel) ; 14(10)2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38786798

RESUMO

Micro-arc oxidation (MAO) is a promising technology for enhancing the wear resistance of engine cylinders by growing a high hardness alumina ceramic film on the surface of light aluminum engine cylinders. However, the positive and negative pulse coordination, voltage characteristic signal, hardness distribution characteristics of the ceramic film, and their internal mechanism during the growth process are still unclear. This paper investigates the synergistic effect mechanism of cathodic and anodic current on the growth behaviour of alumina, dynamic voltage signal, and hardness distribution of micro-arc oxidation film. Ceramic film samples were fabricated under various conditions, including current densities of 10, 12, 14, and 16 A/dm2, and current density ratios of cathode and anode of 1.1, 1.2, and 1.3, respectively. Based on the observed characteristics of the process voltage curve and the spark signal changes, the growth of the ceramic film can be divided into five stages. The influence of positive and negative current density parameters on the segmented growth process of the ceramic film is mainly reflected in the transition time, voltage variation rate, and the voltage value of different growth stages. Enhancing the cathode pulse effect or increasing the current density level can effectively shorten the transition time and accelerate the voltage drop rate. The microhardness of the ceramic film cross-section presents a discontinuous soft-hard-soft regional distribution. Multiple thermal cycles lead to a gradient differentiation of the Al2O3 crystal phase transition ratio along the thickness direction of the layer. The layer grown on the outer surface of the initial substrate exhibits the highest hardness, with a small gradient change in hardness, forming a high hardness zone approximately 20-30 µm wide. This high hardness zone extends to both sides, with hardness decreasing rapidly.

7.
Cell Stress Chaperones ; 29(3): 510-518, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38821173

RESUMO

Heart failure (HF) refers to a group of clinical syndromes in which various heart diseases lead to the inability of cardiac output to meet the metabolic needs of the body's tissues. Cardiac metabolism requires enormous amounts of energy; thus, impaired myocardial energy metabolism is considered a key factor in the occurrence and development of HF. Mitochondria serve as the primary energy source for cardiomyocytes, and their regular functionality underpins healthy cardiac function. The mitochondrial quality control system is a crucial mechanism for regulating the functionality of cardiomyocytes, and any abnormality in this system can potentially impact the morphology and structure of mitochondria, as well as the energy metabolism of cardiomyocytes. Phosphoglycerate mutase 5 (PGAM5), a multifunctional protein, plays a key role in the regulation of mitochondrial quality control through multiple pathways. Therefore, abnormal PGAM5 function is closely related to mitochondrial damage. This article reviews the mechanism of PGAM5's involvement in the regulation of the mitochondrial quality control system in the occurrence and development of HF, thereby providing a theoretical basis for future in-depth research.


Assuntos
Insuficiência Cardíaca , Mitocôndrias Cardíacas , Humanos , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/patologia , Animais , Mitocôndrias Cardíacas/metabolismo , Fosfoproteínas Fosfatases/metabolismo , Proteínas Mitocondriais/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Mitocôndrias/metabolismo , Metabolismo Energético
8.
J Mater Chem B ; 12(24): 5974-5981, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38809058

RESUMO

Rapid and sensitive detection of food-borne bacteria has remained challenging over the past few decades. We propose a surface-enhanced Raman scattering sensing strategy based on a novel bioinspired surface-enhanced Raman scattering substrate, which can directly detect dye molecular residues and food-borne pathogen microorganisms in the environment. The surface-enhanced Raman scattering platform consists of a natural diatomite microporous array decorated with a metal-phenolic network that enables the in situ reduction of gold nanoparticles. The as-prepared nanocomposites display excellent surface-enhanced Raman scattering activity with the lowest limit of detection and the maximum Raman enhancement factor of dye molecules up to 10-11 M and 1.18 × 107, respectively. For food-borne bacterial detection, a diatomite microporous array decorated with a metal polyphenol network and gold nanoparticle-based surface-enhanced Raman scattering analysis is capable of distinguishing the biochemical fingerprint information of Staphylococcus aureus and Escherichia coli, indicating the great potential for strain identification.


Assuntos
Terra de Diatomáceas , Escherichia coli , Ouro , Análise Espectral Raman , Staphylococcus aureus , Análise Espectral Raman/métodos , Staphylococcus aureus/isolamento & purificação , Terra de Diatomáceas/química , Escherichia coli/isolamento & purificação , Ouro/química , Nanopartículas Metálicas/química , Microbiologia de Alimentos , Propriedades de Superfície , Tamanho da Partícula
9.
Chem Sci ; 15(19): 7010-7033, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38756795

RESUMO

The research interest in aqueous zinc-ion batteries (AZIBs) has been surging due to the advantages of safety, abundance, and high electrochemical performance. However, some technique issues, such as dendrites, hydrogen evolution reaction, and corrosion, severely prohibit the development of AZIBs in practical utilizations. The underlying mechanisms regarding electrochemical performance deterioration and structure degradation are too complex to understand, especially when it comes to zinc metal anode-electrolyte interface. Recently, theoretical simulations and in situ characterizations have played a crucial role in AZIBs and are exploited to guide the research on electrolyte engineering and solid electrolyte interphase. Herein, we present a comprehensive review of the current state of the fundamental mechanisms involved in the zinc plating/stripping process and underscore the importance of theoretical simulations and in situ characterizations in mechanism research. Finally, we summarize the challenges and opportunities for AZIBs in practical applications, especially as a stationary energy storage and conversion device in a smart grid.

10.
J Colloid Interface Sci ; 668: 678-690, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38710124

RESUMO

Aerogels, as a unique porous material, are expected to be used as insulation materials to solve the global environmental and energy crisis. Using chitosan, citric acid, pectin and phytic acid as raw materials, an all-biomass-based aerogel with high modulus was prepared by the triple strategy of ionic, physical and chemical cross-linking through directional freezing technique. Based on this three-dimensional network, the aerogel exhibited excellent compressive modulus (24.89 ± 1.76 MPa) over a wide temperature range and thermal insulation properties. In the presence of chitosan, citric acid and phytic acid, the aerogel obtained excellent fire safety (LOI value up to 31.2%) and antibacterial properties (antibacterial activity against Staphylococcus aureus and Escherichia coli reached 81.98% and 67.43%). In addition, the modified aerogel exhibited excellent hydrophobicity (hydrophobic angle of 146°) and oil-water separation properties. More importantly, the aerogel exhibited a biodegradation rate of up to 40.31% for 35 days due to its all-biomass nature. This work provides a green and sustainable strategy for the production of highly environmentally friendly thermal insulation materials with high strength, flame retardant, antibacterial and hydrophobic properties.


Assuntos
Antibacterianos , Quitosana , Ácido Cítrico , Escherichia coli , Géis , Staphylococcus aureus , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Géis/química , Quitosana/química , Ácido Cítrico/química , Biomassa , Interações Hidrofóbicas e Hidrofílicas , Porosidade , Ácido Fítico/química , Pectinas/química , Reagentes de Ligações Cruzadas/química , Testes de Sensibilidade Microbiana , Propriedades de Superfície , Tamanho da Partícula , Temperatura
11.
Biol Pharm Bull ; 47(5): 955-964, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38644204

RESUMO

The occurrence of in-stent restenosis (ISR) poses a significant challenge for percutaneous coronary intervention (PCI). Thus, the promotion of vascular reendothelialization is essential to inhibit endothelial proliferation. In this study, we clarified the mechanism by which Detoxification and Activating Blood Circulation Decoction (DABCD) promotes vascular reendothelialization to avoid ISR by miRNA-126-mediated modulation of the vascular endothelial growth factor (VEGF) signaling pathway. A rat model of post-PCI restenosis was established by balloon injury. The injured aortic segment was collected 14 and 28 d after model establishment. Our findings indicate that on the 14th and 28th days following balloon injury, DABCD reduced intimal hyperplasia and inflammation and promoted vascular reendothelialization. Additionally, DABCD markedly increased nitric oxide (NO) expression and significantly decreased ET-1 production in rat serum. DABCD also increased the mRNA level of endothelial nitric oxide synthase (eNOS) and the protein expression of VEGF, p-Akt, and p-extracellular signal-regulated kinase (ERK)1/2 in vascular tissue. Unexpectedly, the expression of miR-126a-5p mRNA was significantly lower in the aortic tissue of balloon-injured rats than in the aortic tissue of control rats, and higher miR-126a-5p levels were observed in the DABCD groups. The results of this study indicated that the vascular reendothelialization effect of DABCD on arterial intimal injury is associated with the inhibition of neointimal formation and the enhancement of vascular endothelial activity. More specifically, the effects of DABCD were mediated, at least in part, through miR-126-mediated VEGF signaling pathway activation.


Assuntos
MicroRNAs , Óxido Nítrico Sintase Tipo III , Ratos Sprague-Dawley , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular , Animais , MicroRNAs/metabolismo , MicroRNAs/genética , Masculino , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Transdução de Sinais/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/metabolismo , Óxido Nítrico/metabolismo , Ratos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Reestenose Coronária/metabolismo , Aorta/efeitos dos fármacos , Aorta/patologia , Aorta/metabolismo
12.
Water Res ; 255: 121483, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38508039

RESUMO

Fly ash (FA) and eggshells (ES) are common solid wastes with significant potential for the recovery of phosphorus from water. This study focuses on synthesizing a low-cost and environmental-friendly phosphate adsorbent called eggshell-fly ash geopolymer composite (EFG) using eggshells instead of chemicals. The CaO obtained from the high-temperature pyrolysis of eggshells provides active sites for phosphate adsorption, and CO2 serves as a pore-forming agent. The phosphate adsorption performance of EFG varied with the eggshell-fly ash ratios and achieved a maximum of 49.92 mg P/g at an eggshell-fly ash ratio of 40 %. The adsorption process was well described by the pseudo-second-order model and the Langmuir model. EFG also exhibited a good regeneration performance through six-cycle experiments and achieved the highest phosphate desorption at pH 4.0. The results of the column experiment showed that EFG can be used as a filter media for phosphorus removal in a real-scale application with low cost. Soil burial test indicated saturated EFG has a good phosphate slow-release performance (maintained for up to 60 days). Overall, EFG has demonstrated to be a promising adsorbent for phosphorus recovery.

13.
Connect Tissue Res ; 65(2): 102-116, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38493368

RESUMO

PURPOSE: Traditionally, the epidural fat (EF) is known as a physical buffer for the dural sac against the force and a lubricant facilitating the relative motion of the latter on the osseous spine. Along with the development of the studies on EF, controversies still exist on vital questions, such as the underlying mechanism of the spinal epidural lipomatosis. Meanwhile, the scattered and fragmented researches hinder the global insight into the seemingly dispensable tissue. METHODS: Herein, we reviewed literature on the EF and its derivatives to elucidate the dynamic change and complex function of EF in the local milieu, especially at the pathophysiological conditions. We start with an introduction to EF and the current pathogenic landscape, emphasizing the interlink between the EF and adjacent structures. We generally categorize the major pathological changes of the EF into hypertrophy, atrophy, and inflammation. RESULTS AND CONCLUSIONS: It is acknowledged that not only the EF (or its cellular components) may be influenced by various endogenic/exogenic and focal/systematic stimuli, but the adjacent structures can also in turn be affected by the EF, which may be a hidden pathogenic clue for specific spinal disease. Meanwhile, the unrevealed sections, which are also the directions the future research, are proposed according to the objective result and rational inference. Further effort should be taken to reveal the underlying mechanism and develop novel therapeutic pathways for the relevant diseases.


Assuntos
Espaço Epidural , Lipomatose , Humanos , Espaço Epidural/patologia , Imageamento por Ressonância Magnética/métodos , Lipomatose/patologia , Osso e Ossos/patologia
14.
Phytother Res ; 38(5): 2496-2517, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38447978

RESUMO

We investigated the mechanism by which quercetin preserves mitochondrial quality control (MQC) in cardiomyocytes subjected to ischemia-reperfusion stress. An enzyme-linked immunosorbent assay was employed in the in vivo experiments to assess myocardial injury markers, measure the transcript levels of SIRT5/DNAPK-cs/MLKL during various time intervals of ischemia-reperfusion, and observe structural changes in cardiomyocytes using transmission electron microscopy. In in vitro investigations, adenovirus transfection was employed to establish a gene-modified model of DNA-PKcs, and primary cardiomyocytes were obtained from a mouse model with modified SIRT5 gene. Reverse transcription polymerase chain reaction, laser confocal microscopy, immunofluorescence localization, JC-1 fluorescence assay, Seahorse energy analysis, and various other assays were applied to corroborate the regulatory influence of quercetin on the MQC network in cardiomyocytes after ischemia-reperfusion. In vitro experiments demonstrated that ischemia-reperfusion injury caused changes in the structure of the myocardium. It was seen that quercetin had a beneficial effect on the myocardial tissue, providing protection. As the ischemia-reperfusion process continued, the levels of DNA-PKcs/SIRT5/MLKL transcripts were also found to change. In vitro investigations revealed that quercetin mitigated cardiomyocyte injury caused by mitochondrial oxidative stress through DNA-PKcs, and regulated mitophagy and mitochondrial kinetics to sustain optimal mitochondrial energy metabolism levels. Quercetin, through SIRT5 desuccinylation, modulated the stability of DNA-PKcs, and together they regulated the "mitophagy-unfolded protein response." This preserved the integrity of mitochondrial membrane and genome, mitochondrial dynamics, and mitochondrial energy metabolism. Quercetin may operate synergistically to oversee the regulation of mitophagy and the unfolded protein response through DNA-PKcs-SIRT5 interaction.


Assuntos
Miócitos Cardíacos , Quercetina , Sirtuínas , Quercetina/farmacologia , Animais , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Camundongos , Sirtuínas/metabolismo , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteína Quinase Ativada por DNA/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Mitofagia/efeitos dos fármacos
15.
Oncogene ; 43(18): 1386-1396, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38467852

RESUMO

Clear cell renal cell carcinoma (ccRCC) presents a unique profile characterized by high levels of angiogenesis and robust vascularization. Understanding the underlying mechanisms driving this heterogeneity is essential for developing effective therapeutic strategies. This study revealed that ubiquitin B (UBB) is downregulated in ccRCC, which adversely affects the survival of ccRCC patients. UBB exerts regulatory control over vascular endothelial growth factor A (VEGFA) by directly interacting with specificity protein 1 (SP1), consequently exerting significant influence on angiogenic processes. Subsequently, we validated that DNA methyltransferase 3 alpha (DNMT3A) is located in the promoter of UBB to epigenetically inhibit UBB transcription. Additionally, we found that an unharmonious UBB/VEGFA ratio mediates pazopanib resistance in ccRCC. These findings underscore the critical involvement of UBB in antiangiogenic therapy and unveil a novel therapeutic strategy for ccRCC.


Assuntos
Carcinoma de Células Renais , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais , Neovascularização Patológica , Fator de Transcrição Sp1 , Fator A de Crescimento do Endotélio Vascular , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/irrigação sanguínea , Carcinoma de Células Renais/tratamento farmacológico , Humanos , Neoplasias Renais/patologia , Neoplasias Renais/genética , Neoplasias Renais/irrigação sanguínea , Neoplasias Renais/metabolismo , Neoplasias Renais/tratamento farmacológico , Fator de Transcrição Sp1/metabolismo , Fator de Transcrição Sp1/genética , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Linhagem Celular Tumoral , Animais , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Indazóis/farmacologia , Indazóis/uso terapêutico , DNA Metiltransferase 3A/metabolismo , Sulfonamidas/farmacologia , Camundongos , Ubiquitina/metabolismo , DNA (Citosina-5-)-Metiltransferases/metabolismo , DNA (Citosina-5-)-Metiltransferases/genética , Resistencia a Medicamentos Antineoplásicos/genética , Regiões Promotoras Genéticas , Feminino , Masculino , Angiogênese
16.
Int J Mol Sci ; 25(6)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38542316

RESUMO

Nardostachys jatamansi is widely used as a traditional medicine in Asian countries. Numerous recent studies have reported the biological activities of its secondary metabolites and extracts. In this study, a total of 14 components were isolated, including cycloolivil and 2-(3'-hydroxy-5'-ethoxyphenyl)-3-hydroxylmethyl-7-methoxy-2,3-dihydrobenzofuran-5-carboxylic acid, which were first discovered in N. jatamansi. The isolated compounds were investigated for their anti-inflammatory effects on HaCaT keratinocytes and their potential to alleviate skin inflammation. The results of the screening revealed that cycloolivil and 4ß-hydroxy-8ß-methoxy-10-methylene-2,9-dioxatricyclo[4.3.1.03,7]decane reduced the production of inflammatory cytokines induced by TNF-α/IFN-γ, such as IL-6, IL-8, and RANTES, in keratinocytes. This study focused on exploring the biological effects of cycloolivil, and the results suggested that cycloolivil inhibits the expression of COX-2 proteins. Further mechanistic evaluations confirmed that the anti-inflammatory effects of cycloolivil were mediated by blockage of the NF-κB and JAK/STAT signaling pathways. These results suggest that cycloolivil isolated from N. jatamansi could be used to treat skin inflammatory diseases.


Assuntos
NF-kappa B , Nardostachys , Fenóis , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Nardostachys/metabolismo , Interferon gama/metabolismo , Queratinócitos/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/metabolismo
17.
J Bone Miner Metab ; 42(2): 242-252, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38498197

RESUMO

INTRODUCTION: This study was to investigate the correlations between pyrethroid exposure and bone mineral density (BMD) and osteopenia. MATERIALS AND METHODS: This cross-sectional study included 1389 participants over 50 years of age drawn from the 2007-2010 and 2013-2014 National Health and Nutrition Examination Survey (NHANES). Three pyrethroid metabolites, 3-phenoxybenzoic acid (3-PBA), trans-3-(2,2-dichlorovinyl)-2,2-dimethyl-cyclopropane-1-carboxylic acid (trans-DCCA), and 4-fluoro-3-phenoxybenzoic acid (4-F-3PBA) were used as indicators of pyrethroid exposure. Low BMD was defined as T-score < - 1.0, including osteopenia. Weighted multivariable linear regression analysis or logistic regression analysis was utilized to evaluate the correlation between pyrethroid exposure and BMD and low BMD. Bayesian kernel machine regression (BKMR) model was utilized to analyze the correlation between pyrethroids mixed exposure and low BMD. RESULTS: There were 648 (48.41%) patients with low BMD. In individual pyrethroid metabolite analysis, both tertile 2 and tertile 3 of trans-DCCA were negatively related to total femur, femur neck, and total spine BMD [coefficient (ß) = - 0.041 to - 0.028; all P < 0.05]. Both tertile 2 and tertile 3 of 4-F-3PBA were negatively related to total femur BMD (P < 0.05). Only tertile 2 [odds ratio (OR) = 1.63; 95% CI = 1.07, 2.48] and tertile 3 (OR = 1.65; 95% CI = 1.10, 2.50) of trans-DCCA was correlated with an increased risk of low BMD. The BKMR analysis indicated that there was a positive tendency between mixed pyrethroids exposure and low BMD. CONCLUSION: In conclusion, pyrethroids exposure was negatively correlated with BMD levels, and the associations of pyrethroids with BMD and low BMD varied by specific pyrethroids, pyrethroid concentrations, and bone sites.


Assuntos
Benzoatos , Doenças Ósseas Metabólicas , Inseticidas , Éteres Fenílicos , Piretrinas , Adulto , Humanos , Pessoa de Meia-Idade , Piretrinas/efeitos adversos , Piretrinas/análise , Piretrinas/metabolismo , Inseticidas/efeitos adversos , Inseticidas/análise , Inseticidas/metabolismo , Inquéritos Nutricionais , Estudos Transversais , Densidade Óssea , Teorema de Bayes , Exposição Ambiental/efeitos adversos , Doenças Ósseas Metabólicas/induzido quimicamente , Doenças Ósseas Metabólicas/epidemiologia
18.
Clin Ophthalmol ; 18: 799-807, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38495679

RESUMO

Purpose: To investigate the impact of vergence dysfunction on myopia progression in children with Defocus incorporated multiple segments (DIMS) spectacle lenses. Patients and Methods: We retrospectively enrolled children prescribed DIMS spectacle lenses to slow myopic progression. Baseline vergence dysfunction was determined according to phoria at distance and near. Axial length (AL) measurement and cycloplegic subjective refraction were performed before fitting the lenses and at six-month and one-year follow-ups. The six-month and one-year AL and spherical equivalent (SE) change from baseline were calculated and compared in subgroups stratified with the type of vergence dysfunction. Results: Two hundred and ninety-two myopic children were included. Significant AL elongation and SE progression were observed at six months and one year (P < 0.05 for all comparisons). Multiple regression demonstrated that AL elongation at six months (P < 0.001) and one year (P < 0.001) was negatively correlated with age, and SE progression at six months was associated with age (P = 0.002). The AL elongation at six months in children with convergence excess was significantly greater than in normal myopic subjects (P = 0.011) and subjects with convergence insufficiency (P = 0.008), divergence excess (P = 0.007), divergence insufficiency (P = 0.024) and basic esophoria (P = 0.048) at six months. Conclusion: The present research demonstrated that vergence dysfunction influences myopia progression for myopic children with DIMS, and the children with convergence excess suffer from the greatest myopia progression among different types of vergence dysfunction.

19.
RSC Adv ; 14(12): 8445-8453, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38476179

RESUMO

Fenton catalytic medicine that catalyzes the production of ·OH without external energy input or oxygen as a substrate has reshaped the landscape of conventional cancer therapy in recent decades, yet potential biosafety concerns caused by non-safety-approved components restrict their clinical translation from the bench to the bedside. Herein, to overcome this dilemma, we elaborately utilizate safety-approved hetastarch, which has been extensively employed in the clinic as a plasma substitute, as a stabilizer participating in the copper chloride-initiated polymerization of pyrrole monomer before loading it with DOX. The constructed DOX-loaded hetastarch-doped Cu-based polypyrrole (HES@CuP-D) catalyzes the excess H2O2 in tumor cells to ·OH through a Cu+-mediated Fenton-like reaction, which not only causes oxidative damage to tumor cells but also leads to the structural collapse and DOX release. Additionally, HES@CuP-D together with laser irradiation reinforces tumor killing efficiency by hyperthermia-enhanced catalytic activity and -accelerated drug release. As a result, the developed HES@CuP-D provides a promising strategy for Fenton catalytic therapy with negligible toxicity to the body.

20.
Int J Mol Sci ; 25(5)2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38473792

RESUMO

Lindera erythrocarpa, a flowering plant native to eastern Asia, has been reported to have neuroprotective activity. However, reports on the specific bioactive compounds in L. erythrocarpa are finite. The aim of this study was to investigate the anti-neuroinflammatory and neuroprotective effects of the compounds isolated from L. erythrocarpa. Dihydropashanone, a compound isolated from L. erythrocarpa extract, was found to have protected mouse hippocampus HT22 cells from glutamate-induced cell death. The antioxidant and anti-inflammatory properties of dihydropashanone in mouse microglial BV2 and HT22 cells were explored in this study. The results reveal that dihydropashanone inhibits lipopolysaccharide-induced inflammatory response and suppresses the activation of nuclear factor (NF)-κB in BV2 cells. In addition, dihydropashanone reduced the buildup of reactive oxygen species in HT22 cells and induced activation of the nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase (HO)-1 signaling pathway in BV2 and HT22 cells. Our results suggest that dihydropashanone reduces neuroinflammation by decreasing NF-κB activation in microglia cells and protects neurons from oxidative stress via the activation of the Nrf2/HO-1 pathway. Thus, our data suggest that dihydropashanone offers a broad range of applications in the treatment of neurodegenerative illnesses.


Assuntos
Lindera , Doenças Neurodegenerativas , Camundongos , Animais , Lindera/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais , Anti-Inflamatórios/farmacologia , NF-kappa B/metabolismo
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