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1.
Lasers Surg Med ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38738401

RESUMO

OBJECTIVES: The aim of this study is to investigate the safety and efficacy of excimer laser coronary angioplasty (ELCA) combined with drug-coated balloons (DCBs) in the treatment of in-stent restenosis (ISR), and to explore whether the contrast injection technique would improve the neointimal tissue ablation of ELCA. METHODS: We studied patients diagnosed with ISR between January 2019 and October 2022 at two medical centers. These patients underwent DCB angioplasty guided by optical coherence tomography (OCT). Based on whether ELCA was performed before DCB treatment, patients were categorized into two groups: the ELCA + DCB group and the DCB group. All patients underwent clinical follow-up 1 year after the procedure. The primary endpoint was the 1-year rate of target lesion revascularization (TLR), which was defined as any repeat percutaneous intervention or bypass surgery on the target vessel conducted to address restenosis or other complications related to the target lesion. The secondary endpoints including immediate luminal gain (ΔMLA, defined as the difference in minimum lumen area before and after the intervention). RESULTS: A total of 85 lesions in 75 patients were included. The mean age of the study population was 64.2 ± 12.0 years, with 81.3% male. Baseline clinical characteristics were well-balanced, and procedural success was 100% in both groups. The ELCA + DCB group (n = 24) exhibited a greater ΔMLA compared to the DCB group (n = 61) (3.57 ± 0.79 mm² vs. 2.50 ± 1.06 mm², [95% confidence interval, CI: 0.57-1.69], p < 0.001), The reduction in 1-year TLR was more frequently observed in patients from the ELCA + DCB group compared to the DCB group (hazard ratio 0.33 [95% CI: 0.11-0.99]; log-rank p = 0.048). The exploratory analysis showed that ELCA with contrast infusion is associated with greater acute lumen gain compared to ELCA with saline infusion (p < 0.001). CONCLUSIONS: The combination of ELCA and DCB is a safe and effective treatment strategy for in-stent stenosis. Additionally, compared with saline injection, ELCA with contrast injection is associated with greater acute lumen gain. However, the optimal contrast agent concentration and long-term outcome of the contrast injection technique need confirmation through larger sample sizes and prospective studies.

2.
Sci Rep ; 14(1): 3454, 2024 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-38342930

RESUMO

With the advancement of technology, the demand for increased production efficiency has gradually risen, leading to the emergence of new trends in agricultural automation and intelligence. Precision classification models play a crucial role in helping farmers accurately identify, classify, and process various agricultural products, thereby enhancing production efficiency and maximizing the economic value of agricultural products. The current MobileNetV2 network model is capable of performing the aforementioned tasks. However, it tends to exhibit recognition biases when identifying different subcategories within agricultural product varieties. To address this challenge, this paper introduces an improved MobileNetV2 convolutional neural network model. Firstly, inspired by the Inception module in GoogLeNet, we combine the improved Inception module with the original residual module, innovatively proposing a new Res-Inception module. Additionally, to further enhance the model's accuracy in detection tasks, we introduce an efficient multi-scale cross-space learning module (EMA) and embed it into the backbone structure of the network. Experimental results on the Fruit-360 dataset demonstrate that the improved MobileNetV2 outperforms the original MobileNetV2 in agricultural product classification tasks, with an accuracy increase of 1.86%.

3.
J Cell Mol Med ; 28(2): e18048, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37986543

RESUMO

Intervertebral disc degeneration (IVDD) is a common chronic musculoskeletal disease that causes chronic low back pain and imposes an immense financial strain on patients. The pathological mechanisms underlying IVDD have not been fully elucidated. The development of IVDD is closely associated with abnormal epigenetic changes, suggesting that IVDD progression may be controlled by epigenetic mechanisms. Consequently, this study aimed to investigate the role of epigenetic regulation, including DNA methyltransferase 3a (DNMT3a)-mediated methylation and peroxisome proliferator-activated receptor γ (PPARγ) inhibition, in IVDD development. The expression of DNMT3a and PPARγ in early and late IVDD of nucleus pulposus (NP) tissues was detected using immunohistochemistry and western blotting analyses. Cellularly, DNMT3a inhibition significantly inhibited IL-1ß-induced apoptosis and extracellular matrix (ECM) degradation in rat NP cells. Pretreatment with T0070907, a specific inhibitor of PPARγ, significantly reversed the anti-apoptotic and ECM degradation effects of DNMT3a inhibition. Mechanistically, DNMT3a modified PPARγ promoter hypermethylation to activate the nuclear factor-κB (NF-κB) pathway. DNMT3a inhibition alleviated IVDD progression. Conclusively, the results of this study show that DNMT3a activates the NF-κB pathway by modifying PPARγ promoter hypermethylation to promote apoptosis and ECM degradation. Therefore, we believe that the ability of DNMT3a to mediate the PPARγ/NF-κB axis may provide new ideas for the potential pathogenesis of IVDD and may become an attractive target for the treatment of IVDD.


Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Núcleo Pulposo , Animais , Humanos , Ratos , DNA Metiltransferase 3A , Epigênese Genética , Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/patologia , Metilação , NF-kappa B/metabolismo , Núcleo Pulposo/patologia , PPAR gama/genética , PPAR gama/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais
4.
Int J Mol Sci ; 24(23)2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-38068915

RESUMO

The dysregulation of intracellular and extracellular environments as well as the aberrant expression of ion channels on the cell membrane are intricately linked to a diverse array of degenerative disorders, including intervertebral disc degeneration. This condition is a significant contributor to low back pain, which poses a substantial burden on both personal quality of life and societal economics. Changes in the number and function of ion channels can disrupt the water and ion balance both inside and outside cells, thereby impacting the physiological functions of tissues and organs. Therefore, maintaining ion homeostasis and stable expression of ion channels within the cellular microenvironment may prove beneficial in the treatment of disc degeneration. Aquaporin (AQP), calcium ion channels, and acid-sensitive ion channels (ASIC) play crucial roles in regulating water, calcium ions, and hydrogen ions levels. These channels have significant effects on physiological and pathological processes such as cellular aging, inflammatory response, stromal decomposition, endoplasmic reticulum stress, and accumulation of cell metabolites. Additionally, Piezo 1, transient receptor potential vanilloid type 4 (TRPV4), tension response enhancer binding protein (TonEBP), potassium ions, zinc ions, and tungsten all play a role in the process of intervertebral disc degeneration. This review endeavors to elucidate alterations in the microenvironment of the nucleus pulposus during intervertebral disc degeneration (IVDD), with a view to offer novel insights and approaches for exploring therapeutic interventions against disc degeneration.


Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Núcleo Pulposo , Humanos , Núcleo Pulposo/metabolismo , Degeneração do Disco Intervertebral/metabolismo , Qualidade de Vida , Disco Intervertebral/metabolismo , Canais Iônicos/metabolismo , Homeostase/fisiologia , Íons/metabolismo , Água/metabolismo
5.
Opt Lett ; 48(22): 5951-5954, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37966760

RESUMO

Spatiotemporal vortices (STOVs) are a new, to the best of our knowledge, type of structured light in which the optical phase circulates in space-time. In this work, we propose to generate STOVs via second harmonic generation in lithium niobate nonlinear photonic crystals (NPCs) with a linearly chirped Gaussian pulse as the fundamental wave. The structural function of the NPC is derived by the inverse design method. Numerical simulations of the intensity and phase profiles of the generated second harmonic waves are performed with both the amplitude-phase-modulated and the simplified binary-phase-modulated NPCs. We anticipate our study will be valuable for the experimental generation and manipulation of STOVs in NPCs.

6.
Sensors (Basel) ; 23(20)2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37896479

RESUMO

Accurately detecting student classroom behaviors in classroom videos is beneficial for analyzing students' classroom performance and consequently enhancing teaching effectiveness. To address challenges such as object density, occlusion, and multi-scale scenarios in classroom video images, this paper introduces an improved YOLOv8 classroom detection model. Firstly, by combining modules from the Res2Net and YOLOv8 network models, a novel C2f_Res2block module is proposed. This module, along with MHSA and EMA, is integrated into the YOLOv8 model. Experimental results on a classroom detection dataset demonstrate that the improved model in this paper exhibits better detection performance compared to the original YOLOv8, with an average precision (mAP@0.5) increase of 4.2%.

7.
J Back Musculoskelet Rehabil ; 36(6): 1345-1354, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37458019

RESUMO

BACKGROUND: Adolescent idiopathic scoliosis (AIS) is a common structural disorder of the spine in adolescents, often associated with structural deformities in both coronal and axial positions. Apical vertex rotation (AVR) is one of the main indicators of axial deformity in patients with scoliosis. Currently, there are few studies on the impact of AVR in the treatment of AIS. OBJECTIVE: This study examined the influence of different AVR on AIS after brace treatment. METHODS: Data were collected from 106 AIS participants aged 11-16 years from the orthopedic outpatient clinic of the Second Hospital of Lanzhou University. Two orthopaedic professionals measured the Cobb angle, AVR and spinal mid-line offset before and after brace treatment, and descriptive and linear correlation analyses were used to determine the correlation between AVR and AIS measured parameters. RESULTS: (1) In AIS volunteers with the same AVR, the treatment effect of AIS with lumbar predominant curvature was higher than that of AIS with thoracic predominant curvature. The treatment effect tended to decrease with increasing AVR. (2) Spinal mid-line deviation was associated with AVR. For patients with AIS with I and II degrees of AVR, the treatment effect of spinal mid-line offset after bracing is better. For AIS patients with AVR III degrees and above, the degree of correction of spinal mid-line offset decreases with the continuous correction of Cobb angle. CONCLUSIONS: The efficacy of AIS was found to be related to the severity of AVR. The efficacy of AIS with predominantly lumbar curvature was significantly higher than that of AIS with predominantly thoracic curvature. The efficacy of treatment of mid-line spinal deviation also decreased with increasing AVR.


Assuntos
Cifose , Escoliose , Humanos , Adolescente , Escoliose/terapia , Rotação , Vértebras Torácicas , Estudos Retrospectivos , Resultado do Tratamento
8.
Cell ; 186(14): 3095-3110.e19, 2023 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-37321219

RESUMO

The human body contains thousands of metabolites derived from mammalian cells, the microbiota, food, and medical drugs. Many bioactive metabolites act through the engagement of G-protein-coupled receptors (GPCRs); however, technological limitations constrain current explorations of metabolite-GPCR interactions. Here, we developed a highly multiplexed screening technology called PRESTO-Salsa that enables simultaneous assessment of nearly all conventional GPCRs (>300 receptors) in a single well of a 96-well plate. Using PRESTO-Salsa, we screened 1,041 human-associated metabolites against the GPCRome and uncovered previously unreported endogenous, exogenous, and microbial GPCR agonists. Next, we leveraged PRESTO-Salsa to generate an atlas of microbiome-GPCR interactions across 435 human microbiome strains from multiple body sites, revealing conserved patterns of cross-tissue GPCR engagement and activation of CD97/ADGRE5 by the Porphyromonas gingivalis protease gingipain K. These studies thus establish a highly multiplexed bioactivity screening technology and expose a diverse landscape of human, diet, drug, and microbiota metabolome-GPCRome interactions.


Assuntos
Microbiota , Receptores Acoplados a Proteínas G , Animais , Humanos , Receptores Acoplados a Proteínas G/metabolismo , Metaboloma , Mamíferos/metabolismo
10.
Clin Rehabil ; 37(9): 1178-1188, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36991565

RESUMO

OBJECTIVE: To evaluate the effect of telerehabilitation on oral function of oral and maxillofacial tumor patients. DESIGN: Unicentral, single-blind, randomized controlled trial. SETTING: Community. SUBJECTS: Patients with primary oral and maxillofacial tumor receiving surgical treatment. INTERVENTIONS: Telerehabilitation guidance from therapists. MAIN MEASURES: At the beginning of training (T0) and 1 month (T1), 3 months (T2) and 6 months (T3) after training, patients' masticatory ability (mastication efficiency-masticatory performance evaluating gum, maximum bite force and mouth opening) and swallowing ability (water swallowing test) was measured. Modified Sato questionnaire and MD Anderson dysphagia inventory (MDADI) were used for self-evaluation of masticatory and swallowing ability. RESULTS: A total of 64 participants (intervention: 33; control: 31) were included. The masticatory efficiency scores of the intervention group were significantly better than those of the control group at T2 (intervention: 3.67 (0.48); control: 3.03 (0.85)) and T3 (intervention: 4.20 (0.30); control: 3.50 (0.79)); and maximum mouth opening was better at T2 (intervention: 3.18 (0.59); control: 2.77 (0.54)) and T3 (intervention: 3.54 (0.58); control: 3.09 (0.41)). In water swallowing test, the intervention group had better scores at T2 and T3. The scores of MDADI scale in intervention group were better than those in the control group after 3 months of training. In subgroup analysis, the intervention group of oral cancer patients had better swallowing function at T2 and T3, but no significant difference was found in the subgroup of oropharyngeal cancer. CONCLUSIONS: Telerehabilitation could greatly improve the long-term (3-6 months) training effect under the condition of greatly saving medical resources and reducing personnel contact.


Assuntos
Transtornos de Deglutição , Neoplasias Orofaríngeas , Telerreabilitação , Humanos , Deglutição , Método Simples-Cego , Neoplasias Orofaríngeas/patologia , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/etiologia
11.
Chem Commun (Camb) ; 59(6): 712-715, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36541014

RESUMO

To achieve stable Li anode cycling with a high-voltage cathode and high efficiency, a novel ester diluent-based localized high-concentration electrolyte (LHCE) was successfully applied. The oxidation resistance of the high-concentration electrolyte is retained after dilution. More than 99.5% Coulombic efficiency is achieved in Li||Cu cells owing to the optimized physical properties, and the robust SEI film enables superior long-term operation with a high-voltage cathode. This strategy verifies the effectiveness of developing ester diluents for LHCEs applied in lithium metal batteries.

12.
Cell Prolif ; 56(1): e13338, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36193577

RESUMO

Intervertebral disc degeneration (IDD), an important cause of chronic low back pain (LBP), is considered the pathological basis for various spinal degenerative diseases. A series of factors, including inflammatory response, oxidative stress, autophagy, abnormal mechanical stress, nutritional deficiency, and genetics, lead to reduced extracellular matrix (ECM) synthesis by intervertebral disc (IVD) cells and accelerate IDD progression. Mammalian target of rapamycin (mTOR) is an evolutionarily conserved serine/threonine kinase that plays a vital role in diverse degenerative diseases. Recent studies have shown that mTOR signalling is involved in the regulation of autophagy, oxidative stress, inflammatory responses, ECM homeostasis, cellular senescence, and apoptosis in IVD cells. Accordingly, we reviewed the mechanism of mTOR signalling in the pathogenesis of IDD to provide innovative ideas for future research and IDD treatment.


Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Núcleo Pulposo , Animais , Humanos , Degeneração do Disco Intervertebral/patologia , Sirolimo , Disco Intervertebral/patologia , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Mamíferos/metabolismo , Núcleo Pulposo/metabolismo
13.
IEEE Trans Cybern ; 53(4): 2558-2571, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34851846

RESUMO

Block compressive sensing (CS) is a well-known signal acquisition and reconstruction paradigm with widespread application prospects in science, engineering, and cybernetic systems. However, state-of-the-art block-based image CS (BCS) methods generally suffer from two issues. The sparsifying domain and the sensing matrices widely used for image acquisition are not data driven and, thus, both the features of the image and the relationships among subblock images are ignored. Moreover, it requires to address a high-dimensional optimization problem with extensive computational complexity for image reconstruction. In this article, we provide a deep learning (DL) strategy for BCS, called AutoBCS, which automatically takes the prior knowledge of images into account in the acquisition step and establishes a reconstruction model for performing fast image reconstruction. More precisely, we present a learning-based sensing matrix to accomplish image acquisition, thereby capturing and preserving more image characteristics than those captured by the existing methods. In addition, we build a noniterative reconstruction network, which provides an end-to-end BCS reconstruction framework to maximize image reconstruction efficiency. Furthermore, we investigate comprehensive comparison studies with both traditional BCS approaches and newly developed DL methods. Compared with these approaches, our proposed AutoBCS can not only provide superior performance in terms of image quality metrics (SSIM and PSNR) and visual perception but also automatically benefit reconstruction speed.

14.
Mediators Inflamm ; 2022: 2579003, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35966334

RESUMO

Spinal cord injury (SCI) is a highly disabling disorder for which few effective treatments are available. Grape seed proanthocyanidins (GSPs) are polyphenolic compounds with various biological activities. In our preliminary experiment, GSP promoted functional recovery in rats with SCI, but the mechanism remains unclear. Therefore, we explored the protective effects of GSP on SCI and its possible underlying mechanisms. We found that GSP promoted locomotor recovery, reduced neuronal apoptosis, increased neuronal preservation, and regulated microglial polarisation in vivo. We also performed in vitro studies to verify the effects of GSP on neuronal protection and microglial polarisation and their potential mechanisms. We found that GSP regulated microglial polarisation and inhibited apoptosis in PC12 cells induced by M1-BV2 cells through the Toll-like receptor 4- (TLR4-) mediated nuclear factor kappa B (NF-κB) and phosphatidylinositol 3-kinase/serine threonine kinase (PI3K/AKT) signaling pathways. This suggests that GSP regulates microglial polarisation and prevents neuronal apoptosis, possibly by the TLR4-mediated NF-κB and PI3K/AKT signaling pathways.


Assuntos
Fármacos Neuroprotetores , Traumatismos da Medula Espinal , Animais , Extrato de Sementes de Uva , Microglia/metabolismo , NF-kappa B/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Fosfatidilinositol 3-Quinases/metabolismo , Proantocianidinas , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/metabolismo , Receptor 4 Toll-Like/metabolismo
15.
Biomolecules ; 12(8)2022 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-36008968

RESUMO

Intervertebral disc degeneration (IVDD) is a common musculoskeletal degenerative disease worldwide, of which the main clinical manifestation is low back pain (LBP); approximately, 80% of people suffer from it in their lifetime. Currently, the pathogenesis of IVDD is unclear, and modern treatments can only alleviate its symptoms but cannot inhibit or reverse its progression. However, in recent years, targeted therapy has led to new therapeutic strategies. Cysteine-containing aspartate proteolytic enzymes (caspases) are a family of proteases present in the cytoplasm. They are evolutionarily conserved and are involved in cell growth, differentiation, and apoptotic death of eukaryotic cells. In recent years, it has been confirmed to be involved in the pathogenesis of various diseases, mainly by regulating cell apoptosis and inflammatory response. With continuous research on the pathogenesis and pathological process of IVDD, an increasing number of studies have shown that caspases are closely related to the IVDD process, especially in the intervertebral disc (IVD) cell apoptosis and inflammatory response. Therefore, herein we study the role of caspases in IVDD with respect to the structure of caspases and the related signaling pathways involved. This would help explore the strategy of regulating the activity of the caspases involved and develop caspase inhibitors to prevent and treat IVDD. The aim of this review was to identify the caspases involved in IVDD which could be potential targets for the treatment of IVDD.


Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Apoptose/fisiologia , Inibidores de Caspase , Caspases/metabolismo , Humanos , Disco Intervertebral/metabolismo , Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/tratamento farmacológico , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/patologia
16.
Nature ; 607(7919): 563-570, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35831502

RESUMO

Gut commensal bacteria with the ability to translocate across the intestinal barrier can drive the development of diverse immune-mediated diseases1-4. However, the key factors that dictate bacterial translocation remain unclear. Recent studies have revealed that gut microbiota strains can adapt and evolve throughout the lifetime of the host5-9, raising the possibility that changes in individual commensal bacteria themselves over time may affect their propensity to elicit inflammatory disease. Here we show that within-host evolution of the model gut pathobiont Enterococcus gallinarum facilitates bacterial translocation and initiation of inflammation. Using a combination of in vivo experimental evolution and comparative genomics, we found that E. gallinarum diverges into independent lineages adapted to colonize either luminal or mucosal niches in the gut. Compared with ancestral and luminal E. gallinarum, mucosally adapted strains evade detection and clearance by the immune system, exhibit increased translocation to and survival within the mesenteric lymph nodes and liver, and induce increased intestinal and hepatic inflammation. Mechanistically, these changes in bacterial behaviour are associated with non-synonymous mutations or insertion-deletions in defined regulatory genes in E. gallinarum, altered microbial gene expression programs and remodelled cell wall structures. Lactobacillus reuteri also exhibited broadly similar patterns of divergent evolution and enhanced immune evasion in a monocolonization-based model of within-host evolution. Overall, these studies define within-host evolution as a critical regulator of commensal pathogenicity that provides a unique source of stochasticity in the development and progression of microbiota-driven disease.


Assuntos
Bactérias , Translocação Bacteriana , Evolução Biológica , Microbioma Gastrointestinal , Fígado , Bactérias/genética , Bactérias/imunologia , Bactérias/patogenicidade , Translocação Bacteriana/genética , Parede Celular/genética , Enterococcus/genética , Enterococcus/imunologia , Microbioma Gastrointestinal/genética , Genômica , Interações Hospedeiro-Patógeno/imunologia , Humanos , Inflamação/microbiologia , Inflamação/patologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Limosilactobacillus reuteri/genética , Limosilactobacillus reuteri/imunologia , Fígado/microbiologia , Fígado/patologia , Linfonodos/microbiologia , Mutação , Processos Estocásticos , Simbiose/genética , Simbiose/imunologia
17.
Cell Cycle ; 21(21): 2268-2282, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35758219

RESUMO

N-acetylserotonin (NAS) exerts neuroprotective, antioxidant, and anti-apoptotic effects. Oxidative stress and apoptosis are the primary causes of spinal cord injury (SCI). Herein, we explored potential protective effects and mechanisms of NAS in a neuron oxidative damage model in vitro. We established an oxidative damage model in PC12 cells induced by hydrogen peroxide (H2O2) and treated these cells with NAS. NAS enhanced the activity of superoxide dismutase and halted the increase in reactive oxygen species (ROS) and the expression of inducible nitric oxide synthase. Additionally, NAS promoted protein expression of Bcl-2, but inhibited protein expressions of Fas, FADD, cytochrome c, Bax, cleaved caspase-9, and cleaved caspase-3, namely, decreasing protein expression of the Fas and mitochondrial pathways. Furthermore, it reduced the rate of apoptosis and necroptosis-related protein expressions of MLKL and p-MLKL. Moreover, NAS promoted the protein expression of p-PI3K and p-AKT, and the addition of the PI3K inhibitor LY294002 partially attenuated the antioxidant stress and anti-apoptotic effects of NAS in H2O2 stimulated PC12 cells. In conclusion, NAS protected PC12 cells from apoptosis and oxidative stress induced by H2O2 by inhibiting ROS activity and activating the PI3K/AKT signaling pathway.


Assuntos
Peróxido de Hidrogênio , Fosfatidilinositol 3-Quinases , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Apoptose , Caspase 3/metabolismo , Caspase 9/metabolismo , Citocromos c/metabolismo , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/toxicidade , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo , Células PC12 , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Serotonina/análogos & derivados , Superóxido Dismutase/metabolismo , Proteína X Associada a bcl-2/metabolismo
18.
Connect Tissue Res ; 63(6): 559-576, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35736364

RESUMO

Intervertebral disc degeneration (IDD) is a common age-related disease with clinical manifestations of lumbar and leg pain and limited mobility. The pathogenesis of IDD is mainly mediated by the death of intervertebral disc (IVD) cells and the imbalance of extracellular matrix (ECM) synthesis and degradation. Oxidative stress and inflammatory reactions are the important factors causing this pathological change. Therefore, the regulation of reactive oxygen species and production of inflammatory factors may be an effective strategy to delay the progression of IDD. In recent years, nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream regulated protein heme oxygenase-1 (HO-1) have received special attention due to their antioxidant, anti-inflammatory and anti-apoptotic protective effects. Recent studies have elucidated the important role of these two proteins in the treatment of IDD disease. However, Nrf2 and HO-1 have not been systematically reported in IDD-related diseases. Therefore, this review describes the biological characteristics of Nrf2 and HO-1, the relationship between Nrf2- and HO-1-regulated oxidative stress and the inflammatory response and IDD, and the progress in research on some extracts targeting Nrf2 and HO-1 to improve IDD. Understanding the role and mechanism of Nrf2 and HO-1 in IDD may provide novel ideas for the clinical treatment and development of Nrf2- and HO-1-targeted drugs.


Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Núcleo Pulposo , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/uso terapêutico , Antioxidantes/metabolismo , Antioxidantes/uso terapêutico , Heme Oxigenase-1/metabolismo , Heme Oxigenase-1/uso terapêutico , Humanos , Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/patologia , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/uso terapêutico , Núcleo Pulposo/patologia , Espécies Reativas de Oxigênio/metabolismo
19.
FASEB J ; 36(7): e22369, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35747912

RESUMO

Intervertebral disc (IVD) degeneration (IVDD) is closely linked to degenerative spinal disease, resulting in disability, poor quality of life, and financial burden. Apoptosis of nucleus pulposus (NP) cells (NPCs) is a key pathological basis of IVDD. Periostin (POSTN), an extracellular matrix protein, is expressed in many tissues, whereas its abnormal expression is associated with IVDD. The conventional Wnt/ß-catenin pathway is also involved in IVDD and contributes to NPCs apoptosis. However, research on the mechanisms of POSTN in IVDD is lacking. This study investigated the relationship between POSTN and ß-catenin expression in degenerated IVDs. We detected the expression of POSTN, ß-catenin, and cleaved-caspase-3 (C-caspase3) in degenerated and non-degenerated IVD tissues of different grades (n = 8) using RT-qPCR, immunohistochemical staining, and western blotting analysis. Next, we explored the effects of recombinant periostin (rPOSTN) and isoquercitrin (Iso), an inhibitor of the Wnt/ß-catenin pathway, on NPCs apoptosis. Finally, we inhibited the expression of POSTN in degenerated NPCs in vivo and investigated the anti-apoptotic effect. The expression of ß-catenin, POSTN, and C-caspase3 in severe degenerative IVDs was significantly higher than that in mild degenerative IVDs. These findings were confirmed in rat and cell-based degenerative models. When treated with rPOSTN, the Wnt/ß-catenin pathway activity and cell apoptosis were time- and dose-dependent. However, rPOSTN-induced NPCs apoptosis decreased after iso-induced inhibition of the Wnt/ß-catenin pathway. POSTN inhibition reduced apoptosis but was restored by rPOSTN re-addition. Lastly, POSTN inhibition ameliorated puncture-induced IVDD in vivo. Overall, our study demonstrated that POSTN promotes NPCs apoptosis and aggravates degeneration by activating the Wnt/ß-catenin pathway.


Assuntos
Degeneração do Disco Intervertebral , Núcleo Pulposo , Animais , Apoptose , Degeneração do Disco Intervertebral/metabolismo , Núcleo Pulposo/metabolismo , Qualidade de Vida , Ratos , Via de Sinalização Wnt , beta Catenina/metabolismo
20.
Connect Tissue Res ; 63(6): 650-662, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35491814

RESUMO

BACKGROUND: Low back pain is a common symptom of intervertebral disc degeneration (IDD), which seriously affects the quality of life of patients. The abnormal apoptosis and senescence of nucleus pulposus (NP) cells play important roles in the pathogenesis of IDD. Proanthocyanidins (PACs) are polyphenolic compounds with anti-apoptosis and anti-aging effects. However, their functions in NP cells are not yet clear. Therefore, this study was performed to explore the effects of PACs on NP cell apoptosis and aging and the underlying mechanisms of action. METHODS: Cell viability was evaluated by cell counting kit-8 (CCK-8) assay. The apoptosis rate was determined TUNEL assays. Levels of apoptosis-associated molecules (Bcl-2, Bax, C-caspase-3 and Caspase-9) were evaluated via western blot. The senescence was observed through SA-ß-gal staining and western blotting analysis was performed to observe the expression of senescence-related molecules (p-P53, P53, P21 and P16). RESULTS: Pretreatment with PACs exhibited protective effects against IL-1ß-induced NP cell apoptosis including apoptosis rate, expressions of proapoptosis and antiapoptosis related genes and protein. PACs could also alleviate the increase of p-p53, P21, and P16 in IL-1ß-treated NP cells. SA-ß-gal staining showed that IL-1ß-induced senescence of NP cells was prevented by PACs pertreatment. In addition, PACs activated PI3K/Akt pathway in IL-1ß-stimulated NP cells. However, these protected effects were inhibited after LY294002 treatment. CONCLUSION: The results of the present study showed that PACs inhibit IL-1ß-induced apoptosis and aging of NP cells by activating the PI3K/Akt pathway, and suggested that PACs have therapeutic potential for IDD.


Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Núcleo Pulposo , Proantocianidinas , Envelhecimento , Caspase 3/metabolismo , Caspase 9/metabolismo , Caspase 9/farmacologia , Células Cultivadas , Humanos , Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/patologia , Núcleo Pulposo/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proantocianidinas/metabolismo , Proantocianidinas/farmacologia , Proantocianidinas/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Qualidade de Vida , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/farmacologia , Proteína Supressora de Tumor p53/uso terapêutico , Proteína X Associada a bcl-2/metabolismo , Proteína X Associada a bcl-2/farmacologia
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