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1.
J Nutr Biochem ; : 109765, 2024 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-39255902

RESUMO

Calorie restriction (CR) is known to confer health benefits, including longevity and disease prevention. Although CR is promising in preventing chronic kidney disease (CKD), its potential impact on the progression of kidney fibrosis from acute kidney injury (AKI) to CKD remains unclear. Here, we present evidence that CR exacerbates renal damage in a mouse model of folic acid (FA)-induced renal fibrosis by altering mitochondrial metabolism and inflammation. Mice subjected to CR (60% of ad libitum) for 3 days were subjected to high dose of FA (250 mg/kg) injection and maintained under CR for an additional week before being sacrificed. Biochemical analyses showed that CR mice exhibited increased kidney injury and fibrosis. RNA sequencing analysis demonstrated decreased electron transport and oxidative phosphorylation (OXPHOS) in CR kidneys with injury, heightened inflammatory, and fibrotic responses. Decreased CR significantly decreased OXPHOS gene and protein levels and reduced ß-oxidation-associated proteins in the kidney. To determine whether defects in mitochondrial metabolism is associated with inflammation in the kidney, further in vitro experiments were performed. NRK52E kidney epithelial cells were treated with antimycin A to induce mitochondrial damage. Antimycin A treatment significantly increased chemokine expression via a STING-dependent pathway. Serum restriction in NRK49F kidney fibroblasts was observed to enhance the fibrotic response induced by TGFß under in vitro conditions. In summary, our results indicate that CR exacerbates fibrosis and inflammatory responses in the kidney by altering mitochondrial metabolism, highlighting the importance of adequate energy supply for an effective response to AKI and fibrosis development.

2.
Biol Pharm Bull ; 47(9): 1557-1564, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39313392

RESUMO

Oxidative stress plays a crucial role in the development and progression of various kidney diseases. Nuclear factor erythroid 2-related factor 2 (NRF2) is the primary transcription factor that protects cells from oxidative stress by regulating cytoprotective genes including those involved in the antioxidant glutathione (GSH) pathway. GSH maintains cellular redox status and affects redox signaling, cell proliferation, and cell death. Antimycin A, an inhibitor of complex III of the electron transport chain, causes oxidative stress and reduces GSH levels. In this study, we induced mitochondrial damage in rat renal proximal tubular cells using antimycin A and investigated cellular viability and levels of NRF2 and GSH. Treatment with antimycin A altered the expression of antioxidant genes, including reduction in the transcription of glutathione-cysteine ligase subunits (Gclc and Gclm) and glutathione reductase (Gsr1), followed by a reduction in total GSH content with a concomitant decrease in NRF2 protein expression. AR-20007, previously described as an NRF2 activator, stabilizes and increases NRF2 protein expression in cells. By stimulating NRF2, AR-20007 increased the expression of antioxidant and detoxifying enzymes, thereby enhancing protection against oxidative stress induced by antimycin A. These data suggest that NRF2 activation effectively inhibits antimycin A-induced oxidative stress and that NRF2 may be a promising therapeutic target for preventing cell death during acute kidney injury.

3.
J Colloid Interface Sci ; 678(Pt A): 119-129, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39182386

RESUMO

Bismuth Vanadate (BiVO4) is a promising oxide-based photoanode for electrochemical applications, yet its practical use is constrained by poor charge transport properties, particularly under dark conditions. This study introduces a novel BiVO4 variant (Bi-BiVO4-10) that incorporates abundant oxygen vacancies and in-situ formed Bi metal, significantly enhancing its electrical conductivity and catalytic performance. Bi-BiVO4-10 demonstrates superior electrochemical performances compared to conventional BiVO4 (C-BiVO4), demonstrated by its most positive half-wave potential with the highest diffusion-limiting current in the oxygen reduction reaction (ORR) and earliest onset potential in the oxygen evolution reaction (OER). Notably, Bi-BiVO4-10 is explored for the first time as an electrocatalyst for lithium-oxygen (Li-O2) cells, showing reduced overcharge (610 mV) in the first cycle and extended cycle life (1050 h), outperforming carbon (320 h) and C-BiVO4 (450 h) references. The enhancement is attributed to the synergy of oxygen vacancies, Bi metal formation, increased surface area, and improved electrical conductivity, which collectively facilitate Li2O2 growth, enhance charge transport kinetics, and ensure stable cycling. Theoretical calculations reveal enhanced chemical interactions between intermediate molecules and the defect-rich surfaces of Bi-BiVO4-10, promoting efficient discharge and charge processes in Li-O2 batteries. This research highlights the potential of unconventional BiVO4-based materials as durable electrocatalysts and for broader electrochemical applications.

4.
Adv Mater ; : e2405650, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39169743

RESUMO

Plasmonic nanoparticles can be assembled into a superlattice, to form optical metamaterials, particularly targeting precise control of optical properties such as refractive index (RI). The superlattices exhibit enhanced near-field, given the sufficiently narrow gap between nanoparticles supporting multiple plasmonic resonance modes only realized in proximal environments. Herein, the planar superlattice of plasmonic Au nanohexagons (AuNHs) with precisely controlled geometries such as size, shape, and edge-gaps is reported. The proximal AuNHs superlattice realized over a large area with selective edge-to-edge assembly exhibited the highest-ever-recorded RI values in the near-infrared (NIR) band, surpassing the upper limit of the RI of the natural intrinsic materials (up to 10.04 at λ = 1.5 µm). The exceptionally enhanced RI is derived from intensified in-plane surface plasmon coupling across the superlattices. Precise control of the edge-gap of neighboring AuNHs systematically tuned the RI as confirmed by numerical analysis based on the plasmonic percolation model. Furthermore, a 1D photonic crystal, composed of alternating layers of AuNHs superlattices and low-index polymers, is constructed to enhance the selectivity of the reflectivity operating in the NIR band. It is expected that the proximal AuNHs superlattices can be used as new optical metamaterials that can be extended to the NIR range.

5.
Talanta ; 279: 126637, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39106648

RESUMO

The fabrication of ordered nanoarray electrode (NAE) using UV imprinting and their application as electrochemical (EC) immunosensor is described in this study. Especially, the influence of the array density factors on the performance of NAE was characterized electrochemically and compared with flat-electrode. Low-density (hole: 200 nm, hole space = 600 nm), medium-density (hole: 200 nm, hole space = 400 nm), and high-density NAE (hole: 200 nm, hole space = 200 nm) which have the same active area were fabricated and their redox cycling was compared with empirical results. We observed that the high-density is the optimum NAE exhibiting the lowest charge transfer resistance and the highest redox cycling performance among all NAEs. Finally, to observe the effect of their EC performance as biosensor, an EC immunoassay was performed using Interleukine-6 (IL-6), and high-density NAE has lowest a low limit of detection (LOD) of 0.45 pg/mL compared with other NAEs (medium-density: 3.91 pg/mL, low-density: 5.87 pg/mL).


Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas , Eletrodos , Técnicas Biossensoriais/métodos , Imunoensaio/métodos , Técnicas Eletroquímicas/métodos , Transporte de Elétrons , Limite de Detecção , Interleucina-6/análise , Humanos
6.
Int Immunopharmacol ; 141: 113018, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39216235

RESUMO

Turmeric (Curcuma longa L.) extract (CLE) has been shown to elicit several pharmacological properties and is widely used in Asian traditional medicine. Herein, we assessed the impact of CLE on airway inflammation in BALB/c mice and A549 cells to clarify the underlying mechanism. An asthmatic mouse model was established by administering ovalbumin (OVA). CLE (100 or 300 mg/kg/day) was orally administered daily from days 18 to 23, with dexamethasone (3 mg/kg/day) used as the positive control. Human airway epithelial cells, A549, were stimulated using recombinant tumor necrosis factor-α. The CLE100 and CLE400 groups exhibited a significant downregulation in eosinophil counts, cytokine levels, and immunoglobulin-E levels. Moreover, CLE administration dose-dependently suppressed oxidative stress and airway inflammation in the lung tissue. CLE administration inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) and the expression and activity of matrix metalloproteinase (MMP)-9. In vitro, CLE treatment reduced mRNA levels of proinflammatory cytokines, MAPK phosphorylation, and the expression and activity of MMP-2 and MMP-9. Additionally, 50 µg/mL CLE and 2.5 µg/mL curcumin showed similar anti-inflammatory effects. Collectively, our findings revealed that CLE could suppress airway inflammation in asthmatic mice and A549 cells via oxidative stress-driven MAPK/MMPs signaling, suggesting that CLE could be developed as a potential treatment option for patients with asthma.


Assuntos
Anti-Inflamatórios , Asma , Curcuma , Metaloproteinase 9 da Matriz , Camundongos Endogâmicos BALB C , Estresse Oxidativo , Extratos Vegetais , Animais , Humanos , Estresse Oxidativo/efeitos dos fármacos , Asma/tratamento farmacológico , Asma/metabolismo , Asma/imunologia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Curcuma/química , Células A549 , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Camundongos , Citocinas/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Ovalbumina/imunologia , Modelos Animais de Doenças , Feminino , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , Pulmão/imunologia , Imunoglobulina E/sangue , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 2 da Matriz/genética , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos
7.
Chem Soc Rev ; 53(18): 9029-9058, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39158537

RESUMO

The integration of chirality, specifically through the chirality-induced spin selectivity (CISS) effect, into electrocatalytic processes represents a pioneering approach for enhancing the efficiency of energy conversion and storage systems. This review delves into the burgeoning field of chiral electrocatalysis, elucidating the fundamental principles, historical development, theoretical underpinnings, and practical applications of the CISS effect across a spectrum of electrocatalytic reactions, including the oxygen evolution reaction (OER), oxygen reduction reaction (ORR), and hydrogen evolution reaction (HER). We explore the methodological advancements in inducing the CISS effect through structural and surface engineering and discuss various techniques for its measurement, from magnetic conductive atomic force microscopy (mc-AFM) to hydrogen peroxide titration. Furthermore, this review highlights the transformative potential of the CISS effect in addressing the key challenges of the NRR and CO2RR processes and in mitigating singlet oxygen formation in metal-air batteries, thereby improving their performance and durability. Through this comprehensive overview, we aim to underscore the significant role of incorporating chirality and spin polarization in advancing electrocatalytic technologies for sustainable energy applications.

8.
Pharmaceuticals (Basel) ; 17(8)2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39204106

RESUMO

Fritillariae thunbergii Bulbus (FTB), a member of the Liliaceae family, has a long history of use in many herbal formulations for traditional and modern clinical applications to treat various infections and inflammation. To understand FTB's diverse physiochemical properties, it is important to determine the pharmacokinetic properties of its active constituents, the steroidal alkaloids. The aim of the present study was to investigate the pharmacokinetic alterations of the alkaloids, the active components of FTB, in the presence of colitis. A single oral dose of FTB (1 g/kg) was treated to a 2,4-dinitrobenzene sulfonic acid (DNBS)-induced colitis rat model to assess whether the colitis condition could influence the pharmacokinetics of the major alkaloids present in FTB. Among the four major alkaloids, peimisine exhibited a significantly increased systemic exposure, approximately five times higher, under the colitis condition compared with the normal state. Meanwhile, peimine, peiminine, and sipeimine exhibited shorter half-lives in the DNBS group without significant changes in systemic absorption. As herbal medicine may contain active substances with different or opposing efficacies, careful consideration of pharmacokinetic changes in individual components due to diseases is necessary. Further experiments on peimisine are required to ensure the effectiveness and safety of FTB's clinical application in the presence of colitis.

9.
Adv Sci (Weinh) ; : e2402029, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39075726

RESUMO

Recognition of signaling molecules for coordinated regulation of target genes is a fundamental process for biological systems. Cells often rely on transcription factors to accomplish these intricate tasks, yet the subtle conformational changes of protein structures, coupled with the complexity of intertwined protein interaction networks, pose challenges for repurposing these for bioengineering applications. This study introduces a novel platform for ligand-responsive gene regulation, termed START (Synthetic Trans-Acting Riboswitch with Triggering RNA). Inspired by the bacterial ligand sensing system, riboswitch, and the synthetic gene regulator, toehold switch, the START platform enables the implementation of synthetic biosensors for various ligands. Rational sequence design with targeted domain optimization yields high-performance STARTs with a dynamic range up to 67.29-fold and a tunable ligand sensitivity, providing a simple and intuitive strategy for sensor engineering. The START platform also exhibits modularity and composability to allow flexible genetic circuit construction, enabling seamless implementation of OR, AND, and NOT Boolean logic gates for multiple ligand inputs. The START design principle is capable of broadening the suite of synthetic biosensors for diverse chemical and protein ligands, providing a novel riboregulator chassis for synthetic biology and bioengineering applications.

10.
Front Pharmacol ; 15: 1415670, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39050759

RESUMO

Introduction: Cissus quadrangularis is a vining plant widely used as a traditional herbal remedy for various ailments. In this study, the therapeutic effects of C. quadrangularis extract (CQR-300) on type 2 diabetes mellitus (T2DM) were investigated in a leptin receptor-mutated db/db mouse model. Methods: CQR-300 was orally administered to db/db mice (n = 6/group) at different doses (50, 100, and 200 mg/kg) for 8 weeks. Blood glucose levels and oral glucose tolerance were assessed using the AccuCheck glucometer. Enzyme-linked immunosorbent assay was performed to evaluate insulin and hemoglobin A1c (HbA1c) levels in the blood of db/db mice. Liver and pancreatic tissues from db/db mice were examined by hematoxylin and eosin (H&E) and immunohistochemical staining. The protein levels of gluconeogenesis-, lipogenesis-, and oxidative stress-related factors were evaluated using western blotting. Results and discussion: CQR-300 treatment effectively reduced body weight, blood glucose, and insulin levels. HbA1c levels were increased by leptin receptor mutation. Additionally, in the oral glucose tolerance tests, the CQR-300 treated group had a faster blood glucose recovery rate than the db/db group. H&E and Oil red-O staining of the liver showed decreased lipid accumulation in the CQR-300 treated group than the db/db group. Western blot analysis confirmed that CQR-300 effectively inhibited gluconeogenesis, lipogenesis, and oxidative stress-related factors. Our findings suggest that CQR-300 has the potential to be used as a T2DM supplement.

11.
Nutrients ; 16(14)2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39064710

RESUMO

Ageratum conyzoides, an annual herbaceous plant that inhabits tropical and subtropical regions, has been traditionally used in Asia, Africa, and South America for phytotherapy to treat infectious and inflammatory conditions. However, the pharmacological effects of standardized ethanolic extract of Ageratum conyzoides (ACE) on benign prostatic hyperplasia (BPH) remain unexplored. The objective of this research is to examine the potential physiological impacts of ACE, a traditionally utilized remedy for inflammatory ailments, in a rat model with BPH induced by testosterone propionate (TP). Rats were subcutaneously administered TP (3 mg/kg) to induce BPH and concurrently orally administered ACE (20, 50, and 100 mg/kg) daily for 42 days. ACE markedly improved BPH characteristics, including prostate weight, prostate index, and epithelial thickness, while also suppressing androgens and related hormones. The findings were supported by a decrease in androgen receptor and downstream signals associated with BPH in the prostate tissues of the ACE groups. Furthermore, increased apoptotic signals were observed in the prostate tissue of the ACE groups, along with heightened detection of the apoptotic nucleus compared to the BPH alone group. These changes seen in the group that received finasteride were similar to those observed in this group. These findings suggest that ACE shows promise as an alternative phytotherapeutic agent for treating BPH.


Assuntos
Ageratum , Apoptose , Proliferação de Células , Extratos Vegetais , Próstata , Hiperplasia Prostática , Ratos Sprague-Dawley , Masculino , Animais , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/patologia , Extratos Vegetais/farmacologia , Apoptose/efeitos dos fármacos , Próstata/efeitos dos fármacos , Próstata/patologia , Ratos , Ageratum/química , Proliferação de Células/efeitos dos fármacos , Testosterona/sangue , Propionato de Testosterona , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Fitoterapia
12.
J Environ Manage ; 362: 121246, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38823298

RESUMO

Wind energy plays an important role in the sustainable energy transition towards a low-carbon society. Proper assessment of wind energy resources and accurate wind energy prediction are essential prerequisites for balancing electricity supply and demand. However, these remain challenging, especially for onshore wind farms over complex terrains, owing to the interplay between surface heterogeneities and intermittent turbulent flows in the planetary boundary layer. This study aimed to improve wind characteristic assessment and medium-term wind power forecasts over complex hilly terrain using a numerical weather prediction (NWP) model. The NWP model reproduced the wind speed distribution, duration, and spatio-temporal variabilities of the observed hub-height wind speed at 24 wind turbines in onshore wind farms when incorporating more realistic surface roughness effects, such as the subgrid-scale topography, roughness sublayer, and canopy height. This study also emphasizes the good features for machine learning that represent heterogeneities in the surface roughness elements in the atmospheric model. We showed that medium-term forecasting using the NWP model output and a simple artificial neural network (ANN) improved day-ahead wind power forecasts by 14% in terms of annual normalized mean absolute error. Our results suggest that better parameterizations of surface friction in atmospheric models are important for wind power forecasting and resource assessment using NWP models, especially when combined with machine learning techniques, and shed light on onshore wind power forecasting and wind energy assessment in mountainous regions.


Assuntos
Previsões , Redes Neurais de Computação , Vento , Modelos Teóricos , Tempo (Meteorologia)
13.
Redox Biol ; 73: 103193, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38781728

RESUMO

Obesity is associated with an increased incidence of asthma. However, the mechanisms underlying this association are not fully understood. In this study, we investigated the role of thioredoxin-interacting protein (TXNIP) in obesity-induced asthma. Asthma was induced by intranasal injection of a protease from Aspergillus oryzae in normal diet (ND)- or high fat diet (HFD)-fed mice to investigate the symptoms. We measured TXNIP expression in the lungs of patients with asthma and in ND or HFD asthmatic mice. To explore the role of TXNIP in asthma pathogenesis, we induced asthma in the same manner in alveolar type 2 cell-specific TXNIP deficient (TXNIPCre) mice. In addition, the expression levels of pro-inflammatory cytokines were compared based on TXNIP gene expression in A549 cells stimulated with recombinant human tumor necrosis factor alpha. Compared to ND-fed mice, HFD-fed mice had elevated levels of free fatty acids and adipokines, resulting in high reactive oxygen species levels and more severe asthma symptoms. TXNIP expression was increased in both, asthmatic patients and HFD asthmatic mice. However, in experiments using TXNIPCre mice, despite being TXNIP deficient, TXNIPCre mice exhibited exacerbated asthma symptoms. Consistent with this, in vitro studies showed highest expression levels of pro-inflammatory cytokines in TXNIP-silenced cells. Overall, our findings suggest that increased TXNIP levels in obesity-induced asthma is compensatory to protect against inflammatory responses.


Assuntos
Asma , Proteínas de Transporte , Dieta Hiperlipídica , Obesidade , Tiorredoxinas , Animais , Asma/metabolismo , Asma/etiologia , Asma/patologia , Asma/genética , Camundongos , Humanos , Obesidade/metabolismo , Obesidade/genética , Obesidade/etiologia , Proteínas de Transporte/metabolismo , Proteínas de Transporte/genética , Dieta Hiperlipídica/efeitos adversos , Tiorredoxinas/metabolismo , Tiorredoxinas/genética , Células Epiteliais Alveolares/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Masculino , Células A549 , Camundongos Knockout
14.
Front Immunol ; 15: 1362404, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38745671

RESUMO

Introduction: The anti-inflammatory effect of green tea extract (GTE) has been confirmed in asthmatic mice, however, the pharmacological mechanism is not fully elucidated. Methods: To investigate the therapeutic efficacy of GTE in asthma and identify specific pathways, murine model of allergic asthma was established by ovalbumin (OVA) sensitization and the challenge for 4 weeks, with oral treatment using GTE and dexamethasone (DEX). Inflammatory cell counts, cytokines, OVA-specific IgE, airway hyperreactivity, and antioxidant markers in the lung were evaluated. Also, pulmonary histopathological analysis and western blotting were performed. In vitro, we established the model by stimulating the human airway epithelial cell line NCI-H292 using lipopolysaccharide, and treating with GTE and mitogen-activated protein kinases (MAPKs) inhibitors. Results: The GTE100 and GTE400 groups showed a decrease in airway hyperresponsiveness and the number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) compared to the OVA group. GTE treatment also reduced interleukin (IL)-13, IL-5, and IL-4 levels in the BALF, and OVA-specific immunoglobulin E levels in the serum compared to those in the OVA group. GTE treatment decreased OVA-induced mucus secretion and airway inflammation. In addition, GTE suppressed the oxidative stress, and phosphorylation of MAPKs, which generally occurs after exposure to OVA. GTE administration also reduced matrix metalloproteinase-9 activity and protein levels. Conclusion: GTE effectively inhibited asthmatic respiratory inflammation and mucus hyperproduction induced by OVA inhalation. These results suggest that GTE has the potential to be used for the treatment of asthma.


Assuntos
Asma , Células Epiteliais , Metaloproteinase 9 da Matriz , Estresse Oxidativo , Extratos Vegetais , Animais , Feminino , Humanos , Camundongos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Asma/tratamento farmacológico , Asma/imunologia , Asma/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Células Epiteliais/efeitos dos fármacos , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Endogâmicos BALB C , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Ovalbumina/imunologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Mucosa Respiratória/metabolismo , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/imunologia , Mucosa Respiratória/patologia , Transdução de Sinais/efeitos dos fármacos
15.
Aging Cell ; 23(8): e14184, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38687090

RESUMO

Cellular senescence contributes to inflammatory kidney disease via the secretion of inflammatory and profibrotic factors. Protease-activating receptor 2 (PAR2) is a key regulator of inflammation in kidney diseases. However, the relationship between PAR2 and cellular senescence in kidney disease has not yet been described. In this study, we found that PAR2-mediated metabolic changes in renal tubular epithelial cells induced cellular senescence and increased inflammatory responses. Using an aging and renal injury model, PAR2 expression was shown to be associated with cellular senescence. Under in vitro conditions in NRK52E cells, PAR2 activation induces tubular epithelial cell senescence and senescent cells showed defective fatty acid oxidation (FAO). Cpt1α inhibition showed similar senescent phenotype in the cells, implicating the important role of defective FAO in senescence. Finally, we subjected mice lacking PAR2 to aging and renal injury. PAR2-deficient kidneys are protected from adenine- and cisplatin-induced renal fibrosis and injury, respectively, by reducing senescence and inflammation. Moreover, kidneys lacking PAR2 exhibited reduced numbers of senescent cells and inflammation during aging. These findings offer fresh insights into the mechanisms underlying renal senescence and indicate that targeting PAR2 or FAO may be a promising therapeutic approach for managing kidney injury.


Assuntos
Envelhecimento , Senescência Celular , Fibrose , Inflamação , Receptor PAR-2 , Insuficiência Renal Crônica , Animais , Receptor PAR-2/metabolismo , Receptor PAR-2/genética , Inflamação/metabolismo , Inflamação/patologia , Camundongos , Envelhecimento/metabolismo , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia , Humanos , Camundongos Endogâmicos C57BL , Camundongos Knockout
16.
J Ginseng Res ; 48(2): 181-189, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38465217

RESUMO

Background: Cigarette smoke is generally accepted as a major contributor to chronic obstructive pulmonary disease (COPD), which is characterized by emphysematous lesions. In this study, we investigated the protective effects of Korean Red Ginseng (KRG) against cigarette smoke condensate (CSC)-induced emphysema. Methods: Mice were instilled with 50 mg/kg of CSC intranasally once a week for 4 weeks, KRG was administered to the mice once daily for 4 weeks at doses of 100 or 300 mg/kg, and dexamethasone (DEX, positive control) was administered to the mice once daily for 2 weeks at 3 mg/kg. Results: KRG markedly decreased the macrophage population in bronchoalveolar lavage fluid and reduced emphysematous lesions in the lung tissues. KRG suppressed CSC-induced apoptosis as revealed by terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling staining and Caspase 3 immunohistochemistry. Additionally, KRG effectively inhibited CSC-mediated activation of Bcl-2-associated X protein/Caspase 3 signaling, followed by the induction of cell survival signaling, including vascular endothelial growth factor/phosphoinositide 3-kinase/protein kinase B in vivo and in vitro. The DEX group also showed similar improved results in vivo and in vitro. Conclusion: Taken together, KRG effectively inhibits macrophage-mediated emphysema induced by CSC exposure, possibly via the suppression of pro-apoptotic signaling, which results in cell survival pathway activation. These findings suggest that KRG has therapeutic potential for the prevention of emphysema in COPD patients.

17.
ACS Nano ; 18(10): 7402-7410, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38411049

RESUMO

In this research, we designed a stepwise synthetic method for Au@Pt hexapods where six elongated Au pods are arranged in a pairwise perpendicular fashion, sharing a common point (the central origin in a Cartesian-coordinate-like hexapod shape), featured with tip-selectively decorated Pt square nanoplates. Au@Pt hexapods were successfully synthesized by applying three distinctive chemical reactions in a stepwise manner. The Pt adatoms formed discontinuous thin nanoplates that selectively covered six concave facets of a Au truncated octahedron and served as etching masks in the succeeding etching process, which prevented underlying Au atoms from being oxidized. The subsequent isotropic etching proceeded radially, starting from the bare Au surface, carving the central nanocrystal in a concave manner. By controlling the etching conditions, Au@Pt hexapods were successfully fabricated, wherein the core Au domain is connected to six protruding arms, which hold Pt nanoplates at the ends. Due to their morphology, Au@Pt hexapods feature distinctive optical properties in the near-infrared region, as a proof of concept, allowing for surface-enhanced Raman spectroscopy (SERS)-based monitoring of in situ CO electrooxidation. We further extended our synthetic library by tailoring the size of the Pt nanoplates and neck widths of Au branches, demonstrating the validity of selective blocking and etching-based colloidal synthesis.

18.
J Cardiothorac Surg ; 19(1): 34, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38297348

RESUMO

BACKGROUND: Surgical resection remains the mainstay of treatment for cardiac sarcoma, a rare but lethal disease. Achieving complete removal of a large-sized left ventricular sarcoma remains a challenge even with various surgical approaches that have been employed. CASE PRESENTATION: We present a case of a 74-year-old woman with shortness of breath who underwent surgical removal of a primary cardiac sarcoma, measuring 6 × 3.5 × 3 cm, attached to the septum of the left ventricle and caused sub-aortic valve obstruction. Transaortic approach was chosen and the access to this entire huge mass was enabled by using interim partial resection which created a space for further dissection and subsequent deeper endoscopic views. The further dissection was finally able to be advanced on the apex, and the residual mass was completely resected with gross tumor-free margins. CONCLUSION: Interim partial resection and endoscopic guidance can highly facilitate the transaortic removal of even large left ventricular sarcomas.


Assuntos
Neoplasias Cardíacas , Sarcoma , Feminino , Humanos , Idoso , Ventrículos do Coração/cirurgia , Endoscopia , Sarcoma/cirurgia , Coração , Neoplasias Cardíacas/diagnóstico por imagem , Neoplasias Cardíacas/cirurgia
19.
J Ginseng Res ; 48(1): 52-58, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38223821

RESUMO

Background: Skeletal muscle denervation leads to motor neuron degeneration, which in turn reduces muscle fiber volumes. Recent studies have revealed that apoptosis plays a role in regulating denervation-associated pathologic muscle wasting. Korean red ginseng (KRG) has various biological activities and is currently widely consumed as a medicinal product worldwide. Among them, ginseng has protective effects against muscle atrophy in in vivo and in vitro. However, the effects of KRG on denervation-induced muscle damage have not been fully elucidated. Methods: We induced skeletal muscle atrophy in mice by dissecting the sciatic nerves, administered KRG, and then analyzed the muscles. KRG was administered to the mice once daily for 3 weeks at 100 and 400 mg/kg/day doses after operation. Results: KRG treatment significantly increased skeletal muscle weight and tibialis anterior (TA) muscle fiber volume in injured areas and reduced histological alterations in TA muscle. In addition, KRG treatment reduced denervation-induced apoptotic changes in TA muscle. KRG attenuated p53/Bax/cytochrome c/Caspase 3 signaling induced by nerve injury in a dose-dependent manner. Also, KRG decreases protein kinase B/mammalian target of rapamycin pathway, reducing restorative myogenesis. Conclusion: Thus, KRG has potential protective role against denervation-induced muscle atrophy. The effect of KRG treatment was accompanied by reduced levels of mitochondria-associated apoptosis.

20.
ACS Nano ; 18(1): 909-918, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-37991339

RESUMO

Chiral perovskites have garnered significant attention, owing to their chiroptical properties and emerging applications. Current fabrication methods often involve complex chemical synthesis routes. Herein, an alternative approach for introducing chirality into nonchiral hybrid organic-inorganic perovskites (HOIPs) using nanotemplates composed of cholesteric polymeric networks is proposed. This method eliminates the need for additional molecular design. In this process, HOIP precursors are incorporated into a porous cholesteric polymer film, and two-dimensional (2D) HOIPs grow inside the nanopores. Circularly polarized light emission (CPLE) was observed even though the selective reflection band of the cholesteric polymer films containing a representative HOIP deviated from the emission wavelength of the 2D HOIP. This effect was confirmed by the induced circular dichroism (CD) observed in the absorbance band of the HOIP. The observed CPLE and CD are attributed to the chirality induced by the template in the originally nonchiral 2D HOIP. Additionally, the developed 2D HOIP exhibited a long exciton lifetime and good stability under harsh conditions. These findings provide valuable insights into the development and design of innovative optoelectronic materials.

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