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1.
BMC Psychiatry ; 24(1): 269, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600448

RESUMO

OBJECTIVE: The purpose of this study was to investigate the effects of escitalopram on the peripheral expression of hypothalamic-pituitary-adrenal (HPA) axis-related genes (FKBP51, HSP90, NR3C1 and POMC) and HPA-axis hormones in patients with panic disorder (PD). METHODS: Seventy-seven patients with PD were treated with escitalopram for 12 weeks. All participants were assessed for the severity of panic symptoms using the Panic Disorder Severity Scale (PDSS). The expression of HPA-axis genes was measured using real-time quantitative fluorescent PCR, and ACTH and cortisol levels were measured using chemiluminescence at baseline and after 12 weeks of treatment. RESULTS: At baseline, patients with PD had elevated levels of ACTH and cortisol, and FKBP51 expression in comparison to healthy controls (all p < 0.01). Correlation analysis revealed that FKBP51 expression levels were significantly positively related to cortisol levels and the severity of PD (all p < 0.01). Furthermore, baseline ACTH and cortisol levels, and FKBP51 expression levels were significantly reduced after 12 weeks of treatment, and the change in the PDSS score from baseline to post-treatment was significantly and positively related to the change in cortisol (p < 0.01). CONCLUSIONS: The results suggest that PD may be associated with elevated levels of ACTH and cortisol, and FKBP51 expression, and that all three biomarkers are substantially decreased in patients who have received escitalopram treatment.


Assuntos
Transtorno de Pânico , Humanos , Transtorno de Pânico/tratamento farmacológico , Transtorno de Pânico/genética , Transtorno de Pânico/diagnóstico , Hormônio Adrenocorticotrópico/metabolismo , Hormônio Adrenocorticotrópico/farmacologia , Hidrocortisona/metabolismo , Escitalopram , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , RNA Mensageiro
2.
STAR Protoc ; 5(2): 103018, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38613778

RESUMO

The fatty acid-binding protein 5 (FABP5) is a key player in psoriasis development. Therefore, characterizing the expression profile of FABP5 in various cell types within both layers of psoriatic skin is important. Here, we present a protocol that describes steps for an imiquimod-induced psoriasis mouse model and preparation of epidermal and dermal single-cell suspensions. We then detail procedures to detect the FABP5 expression profile in skin keratinocytes and immune cells using intracellular flow cytometry staining. For complete details on the use and execution of this protocol, please refer to Hao et al.1.

3.
Appl Opt ; 63(8): 2101-2108, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38568654

RESUMO

This paper presents the test results for high-performance and high-uniformity waveguide silicon-based germanium (Ge) photodetectors (PDs) for the O band and C band. Both wafer-scale and chip-scale test results are provided. The fabricated lateral p-i-n (LPIN) PDs exhibit a responsivity of 0.97 A/W at a bias of -2V, a bandwidth of 60 GHz, and a no-return-to-zero (NRZ) eye diagram rate of 53.125 Gb/s. Additionally, an average dark current of 22.4 nA was obtained in the vertical p-i-n (VPIN) PDs at -2V by optimizing the doping process. The device can reach an average responsivity of 0.9 A/W in the O band. The standard deviation in a wafer with a dark current and responsivity is as low as 7.77 nA and 0.03 A/W at -2V, respectively.

4.
Nat Commun ; 15(1): 3129, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605050

RESUMO

The essence of difference between hemostasis and thrombosis is that the clotting reaction is a highly fine-tuned process. Vascular protein disulfide isomerase (PDI) represents a critical mechanism regulating the functions of hemostatic proteins. Herein we show that histidine-rich glycoprotein (HRG) is a substrate of PDI. Reduction of HRG by PDI enhances the procoagulant and anticoagulant activities of HRG by neutralization of endothelial heparan sulfate (HS) and inhibition of factor XII (FXIIa) activity, respectively. Murine HRG deficiency (Hrg-/-) leads to delayed onset but enhanced formation of thrombus compared to WT. However, in the combined FXII deficiency (F12-/-) and HRG deficiency (by siRNA or Hrg-/-), there is further thrombosis reduction compared to F12-/- alone, confirming HRG's procoagulant activity independent of FXIIa. Mutation of target disulfides of PDI leads to a gain-of-function mutant of HRG that promotes its activities during coagulation. Thus, PDI-HRG pathway fine-tunes thrombosis by promoting its rapid initiation via neutralization of HS and preventing excessive propagation via inhibition of FXIIa.


Assuntos
Isomerases de Dissulfetos de Proteínas , Trombose , Animais , Camundongos , Isomerases de Dissulfetos de Proteínas/genética , Dissulfetos , Proteínas/metabolismo , Trombose/genética , Trombose/metabolismo , Heparitina Sulfato , Fator XII/metabolismo
5.
J Colloid Interface Sci ; 666: 244-258, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38598997

RESUMO

Starvation therapy has shown promise as a cancer treatment, but its efficacy is often limited when used alone. In this work, a multifunctional nanoscale cascade enzyme system, named CaCO3@MnO2-NH2@GOx@PVP (CMGP), was fabricated for enhanced starvation/chemodynamic combination cancer therapy. CMGP is composed of CaCO3 nanoparticles wrapped in a MnO2 shell, with glucose oxidase (GOx) adsorbed and modified with polyvinylpyrrolidone (PVP). MnO2 decomposes H2O2 in cancer cells into O2, which enhances the efficiency of GOx-mediated starvation therapy. CaCO3 can be decomposed in the acidic cancer cell environment, causing Ca2+ overload in cancer cells and inhibiting mitochondrial metabolism. This synergizes with GOx to achieve more efficient starvation therapy. Additionally, the H2O2 and gluconic acid produced during glucose consumption by GOx are utilized by MnO2 with catalase-like activity to enhance O2 production and Mn2+ release. This process accelerates glucose consumption, reactive oxygen species (ROS) generation, and CaCO3 decomposition, promoting the Ca2+ release. CMGP can alleviate tumor hypoxia by cycling the enzymatic cascade reaction, which increases enzyme activity and combines with Ca2+ overload to achieve enhanced combined starvation/chemodynamic therapy. In vitro and in vivo studies demonstrate that CMGP has effective anticancer abilities and good biosafety. It represents a new strategy with great potential for combined cancer therapy.


Assuntos
Carbonato de Cálcio , Glucose Oxidase , Compostos de Manganês , Óxidos , Glucose Oxidase/metabolismo , Glucose Oxidase/química , Glucose Oxidase/farmacologia , Compostos de Manganês/química , Compostos de Manganês/farmacologia , Óxidos/química , Óxidos/farmacologia , Humanos , Animais , Carbonato de Cálcio/química , Carbonato de Cálcio/farmacologia , Carbonato de Cálcio/metabolismo , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/química , Nanopartículas/química , Povidona/química , Povidona/farmacologia , Hipóxia Tumoral/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Tamanho da Partícula , Linhagem Celular Tumoral , Peróxido de Hidrogênio/metabolismo , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Propriedades de Superfície , Camundongos Endogâmicos BALB C
6.
Ophthalmol Ther ; 13(5): 1103-1123, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38498280

RESUMO

INTRODUCTION: Immune checkpoint inhibitors have made tremendous progress over the last decade in the treatment of cutaneous melanoma, but their application in uveal melanoma treatment is less successful, owing in part to the immunological privilege of the eye and the liver, the most frequent site of metastasis. Nevertheless, the therapeutic outcomes reported currently are less pessimistic. METHODS: In this review, we provide an overview of recent studies of immune checkpoint inhibitors in uveal melanoma and its metastasis and classify studies in this field into three groups: monotherapy of immune checkpoint inhibitors, dual-agent immune checkpoint inhibitors, and immune checkpoint inhibitors combined with other systemic or regional therapies. RESULTS: Briefly, monotherapy with immune checkpoint inhibitors performed poorly. Dual-agent immune checkpoint inhibitors had slightly better outcomes than traditional treatments, especially in specific patient populations. As for the combination therapy, the combination with other systemic therapies did not show superiority over dual-agent immune checkpoint inhibitors, but combination with hepatic regional therapies was quite promising. Moreover, research on emerging checkpoints is currently limited to the stage of mechanistic studies. CONCLUSION: We propose that immune checkpoint inhibitors remain alternative treatments for patients with uveal melanoma, but factors such as cost-effectiveness should also be taken into account. The combination therapy with immune checkpoint inhibitors deserves to be further explored.

7.
Micromachines (Basel) ; 15(3)2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38542569

RESUMO

Light detection and ranging (LiDAR) is widely used in scenarios such as autonomous driving, imaging, remote sensing surveying, and space communication due to its advantages of high ranging accuracy and large scanning angle. Optical phased array (OPA) has been studied as an important solution for achieving all-solid-state scanning. In this work, the recent research progress in improving the beam steering performance of the OPA based on silicon photonic integrated chips was reviewed. An optimization scheme for aperiodic OPA is proposed.

8.
Mater Horiz ; 11(7): 1668-1678, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38476075

RESUMO

Although stimuli-responsive microemulsions (MEMs) consisting of water, oil and surfactants have found extensive potential applications in industrial fields, a responsive MEM exhibiting either macroscale superlubricity or two friction states where its coefficient of friction (CoF) can be switched by more than one order of magnitude has not yet been reported. Moreover, although traditional liquid superlubricants can provide ultralow friction and wear, effective control over the friction between two contacting surfaces is crucial for both achieving accurate control of the operation of an instrument and fabricating smart devices. Here we create a thermo- and magneto-responsive MEM capable of providing superlubrication for metallic materials in a broad temperature range from -30 to 20 °C using n-hexane, water, surfactant DDACe ((C12H25)2N+(CH3)2[CeCl4]-) and ethylene glycol. The MEM can abruptly and dramatically switch its CoF by approximately 25 fold based on a thermally reversible MEM-emulsion (EM) transition. Its anti-freezing performance allows it to provide effective lubrication even when the surrounding temperature attains as low as -60 °C. Together with its facile preparation, ultrahigh colloidal stability and magnetically controlled migration, such a novel smart MEM is envisioned to find widespread applications in materials science.

9.
Front Bioeng Biotechnol ; 12: 1327172, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38532881

RESUMO

Corynebacterium glutamicum plays a crucial role as a significant industrial producer of metabolites. Despite the successful development of CRISPR-Cas9 and CRISPR-Cas12a-assisted genome editing technologies in C. glutamicum, their editing resolution and efficiency are hampered by the diverse on-target activities of guide RNAs (gRNAs). To address this problem, a hybrid CRISPR-Cas9-Cas12a genome editing platform (HyCas9-12aGEP) was developed in C. glutamicum in this study to co-express sgRNA (corresponding to SpCas9 guide RNA), crRNA (corresponding to FnCas12a guide RNA), or hfgRNA (formed by the fusion of sgRNA and crRNA). HyCas9-12aGEP improves the efficiency of mapping active gRNAs and outperforms both CRISPR-Cas9 and CRISPR-Cas12a in genome editing resolution and efficiency. In the experiment involving the deletion of the cg0697-0740 gene segment, an unexpected phenotype was observed, and HyCas9-12aGEP efficiently identified the responsible genotype from more than 40 genes. Here, HyCas9-12aGEP greatly improve our capability in terms of genome reprogramming in C. glutamicum.

10.
Opt Express ; 32(3): 4498-4510, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38297650

RESUMO

A phase retrieval method based on deep learning with bandpass filtering in holographic data storage is proposed. The relationship between the known encoded data pages and their near-field diffraction intensity patterns is established by an end-to-end convolutional neural network, which is used to predict the unknown phase data page. We found the training efficiency of phase retrieval by deep learning is mainly determined by the edge details of the adjacent phase codes, which are the high-frequency components of the phase code. Therefore, we can attenuate the low-frequency components to reduce material consumption. Besides, we also filter out the high-order frequency over twice Nyquist size, which is redundant information with poor anti-noise performance. Compared with full-frequency recording, the consumption of storage media is reduced by 2.94 times, thus improving the storage density.

11.
Heliyon ; 10(2): e24183, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38298679

RESUMO

Electric load forecasting is a vital task for energy management and policy-making. However, it is also a challenging problem due to the complex and dynamic nature of electric load data. In this paper, a novel technique, called LSV/MOPA, has been proposed for electric load forecasting. The technique is a hybrid model that combines the advantages of Long Short-Term Memory (LSTM) and Support Vector Regression (SVR), two powerful artificial intelligence algorithms. The hybrid model is further optimized by a newly Modified Orca Predation Algorithm (MOPA), which enhances the forecasting accuracy and efficiency. The LSV/MOPA model has been applied to historical electric load data from South Korea, covering four regions and 20 years. The LSV/MOPA model has been compared with other state-of-the-art forecasting techniques, including SVR/FFA, LSTM/BO, LSTM-SVR, and CNN-LSTM. The results show that the LSV/MOPA model with minimum average mean absolute percentage deviation error, including 365 in northern region, 12.8 in southern region, 8.6 in central region, and 30.8 in eastern region, provides the best fitting and outperforms the other techniques in terms of the Mean Absolute Percentage Deviation (MAPD) index, achieving lower values for all regions and years. The LSV/MOPA model also exhibits faster convergence and better generalization than the other techniques. This study demonstrates the effectiveness and superiority of the LSV/MOPA model for electric load forecasting and suggests its potential applications in other sectors where accurate forecasting is crucial.

12.
Elife ; 122024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38372724

RESUMO

Epigenetic regulators present novel opportunities for both ischemic stroke research and therapeutic interventions. While previous work has implicated that they may provide neuroprotection by potentially influencing coordinated sets of genes and pathways, most of them remain largely uncharacterized in ischemic conditions. In this study, we used the oxygen-glucose deprivation (OGD) model in the immortalized mouse hippocampal neuronal cell line HT-22 and carried out an RNAi screen on epigenetic regulators. PRMT5 was identified as a novel negative regulator of neuronal cell survival after OGD, which presented a phenotype of translocation from the cytosol to the nucleus upon oxygen and energy depletion both in vitro and in vivo. PRMT5 bound to the chromatin and a large number of promoter regions to repress downstream gene expression. Silencing Prmt5 significantly dampened the OGD-induced changes for a large-scale of genes, and gene ontology analysis showed that PRMT5-target genes were highly enriched for Hedgehog signaling. Encouraged by the above observation, mice were treated with middle cerebral artery occlusion with the PRMT5 inhibitor EPZ015666 and found that PRMT5 inhibition sustains protection against neuronal death in vivo. Together, these findings revealed a novel epigenetic mechanism of PRMT5 in cerebral ischemia and uncovered a potential target for neuroprotection.


Assuntos
Isquemia Encefálica , Proteínas Hedgehog , Proteína-Arginina N-Metiltransferases , Animais , Camundongos , Isquemia Encefálica/genética , Glucose , Neuroproteção/genética , Oxigênio , Fenótipo , Proteína-Arginina N-Metiltransferases/genética
13.
World J Microbiol Biotechnol ; 40(4): 116, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38418617

RESUMO

In this study, we devised a diagnostic platform harnessing a combination of recombinase polymerase amplification (RPA) and the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a system. Notably, this platform obviates the need for intricate equipment and finds utility in diverse settings. Two result display methods were incorporated in this investigation: the RPA-Cas12a-fluorescence method and the RPA-Cas12a-LFS (lateral flow strip). Upon validation, both display platforms exhibited no instances of cross-reactivity, with seven additional types of fungal pathogens responsible for respiratory infections. The established detection limit was ascertained to be as low as 102 copies/µL. In comparison to fluorescence quantitative PCR, the platform demonstrated a sensitivity of 96.7%, a specificity of 100%, and a consistency rate of 98.0%.This platform provides expeditious, precise, and on-site detection capabilities, thereby rendering it a pivotal diagnostic instrument amenable for deployment in primary healthcare facilities and point-of-care settings.


Assuntos
Pneumonia , Recombinases , Aspergillus fumigatus/genética , Sistemas CRISPR-Cas , Coloração e Rotulagem
14.
Angew Chem Int Ed Engl ; 63(11): e202319698, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38190301

RESUMO

Liquid crystal elastomers (LCEs) are stimulus-responsive materials with intrinsic anisotropy. However, it is still challenging to in situ program the mesogen alignment to realize three-dimensional (3D) deformations with high-resolution patterned structures. This work presents a feasible strategy to program the anisotropy of LCEs by using chalcone mesogens that can undergo a photoinduced cycloaddition reaction under linear polarized light. It is shown that by controlling the polarization director and the irradiation region, patterned alignment distribution in a freestanding LCE film can be created, which leads to complex and reversible 3D shape-morphing behaviors. The work demonstrates an in situ light-writing method to achieve sophisticated topography changes in LCEs, which has potential applications in encryption, sensors, and beyond.

15.
J Clin Neurol ; 20(2): 194-200, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38171500

RESUMO

BACKGROUND AND PURPOSE: Performing the differential diagnosis of Parkinson's disease (PD) and multiple-system atrophy of parkinsonian type (MSA-P) is challenging. The oculomotor performances of patients with PD and MSA-P were investigated to explore their potential role as a biomarker for this differentiation. METHODS: Reflexive saccades and smooth pursuit were examined in 56 patients with PD and 34 with MSA-P in the off-medication state. RESULTS: Patients with PD and MSA-P had similar oculomotor abnormalities of prolonged and hypometric reflexive saccades. The incidence rates of decreased reflexive saccadic velocity and saccadic smooth pursuit were significantly higher in MSA-P than in PD (p<0.05 for both). Multiple logistic regression analysis indicated that slowed reflexive saccades (odds ratio [OR]=8.14, 95% confidence interval [CI]=1.45-45.5) and saccadic smooth pursuit (OR=5.27, 95% CI=1.24-22.43) were significantly related to MSA-P. CONCLUSIONS: The distinctive oculomotor abnormalities of saccadic smooth pursuit and slowed reflexive saccades in MSA-P may serve as useful biomarkers for discriminating MSA-P from PD.

16.
J Virol ; 98(2): e0134523, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38226815

RESUMO

Chronic hepatitis B virus (HBV) infection (CHB) is a risk factor for the development of liver fibrosis, cirrhosis, and hepatocellular carcinoma. Covalently closed circular DNA serves as the sole transcription template for all viral RNAs and viral transcription is driven and enhanced by viral promoter and enhancer elements, respectively. Interactions between transcription factors and these cis-elements regulate their activities and change the production levels of viral RNAs. Here, we report the identification of homeobox protein MSX-1 (MSX1) as a novel host restriction factor of HBV in liver. In both HBV-transfected and HBV-infected cells, MSX1 suppresses viral gene expression and genome replication. Mechanistically, MSX1 downregulates enhancer II/core promoter (EnII/Cp) activity via direct binding to an MSX1 responsive element within EnII/Cp, and such binding competes with hepatocyte nuclear factor 4α binding to EnII/Cp due to partial overlap between their respective binding sites. Furthermore, CHB patients in immune active phase express higher levels of intrahepatic MSX1 but relatively lower levels of serum and intrahepatic HBV markers compared to those in immune tolerant phase. Finally, MSX1 was demonstrated to induce viral clearance in two mouse models of HBV persistence, suggesting possible therapeutic potential for CHB.IMPORTANCECovalently closed circular DNA plays a key role for the persistence of hepatitis B virus (HBV) since it serves as the template for viral transcription. Identification of transcription factors that regulate HBV transcription not only provides insights into molecular mechanisms of viral life cycle regulation but may also provide potential antiviral targets. In this work, we identified host MSX1 as a novel restriction factor of HBV transcription. Meanwhile, we observed higher intrahepatic MSX1 expression in chronic hepatitis B virus (CHB) patients in immune active phase compared to those in immune tolerant phase, suggesting possible involvement of MSX1 in the regulation of HBV activity by the host. Lastly, intrahepatic overexpression of MSX1 delivered by recombinant adenoviruses into two mouse models of HBV persistence demonstrated MSX1-mediated repression of HBV in vivo, and MSX1-induced clearance of intrahepatic HBV DNA in treated mice suggested its potential as a therapeutic target for the treatment of CHB.


Assuntos
Hepatite B Crônica , Hepatite B , Fator de Transcrição MSX1 , Animais , Humanos , Camundongos , DNA Circular , DNA Viral/genética , Hepatite B/metabolismo , Vírus da Hepatite B/fisiologia , RNA Viral , Fatores de Transcrição/genética , Replicação Viral/genética , Fator de Transcrição MSX1/metabolismo
17.
Artigo em Inglês | MEDLINE | ID: mdl-38261016

RESUMO

BACKGROUND: Short-term personalized vestibular rehabilitation (ST-PVR) can establish stable vestibular compensation. However, there is a lack of a clear definition for clinical indicators that can dynamically reflect the progress of vestibular rehabilitation (VR). OBJECTIVE: To explore the clinical indicators suitable for evaluating the effectiveness of ST-PVR in treating benign recurrent vertigo (BRV). METHODS: In total, 50 patients diagnosed with BRV were enrolled. All patients received the ST-PVR treatment program. At 2 and 4 weeks after rehabilitation, subjective scales, including the visual analogue scale (VAS), dizziness handicap inventory scale (DHI), activities-specific balance confidence scale (ABC) and generalized anxiety disorder (GAD-7) were assessed. Objective vestibular function tests were performed. VR grading was determined. RESULTS: At 2 weeks after rehabilitation, significant enhancements were observed in VAS, DHI, ABC, GAD-7, UW, vHIT results, and VR grading scores (p < 0.05). The sensory organization test (SOT) results demonstrated statistically significant improvements at 2 weeks and 4 weeks after rehabilitation (p < 0.05). CONCLUSION AND SIGNIFICANCE: Both subjective scales and partial examination results in objective assessment can serve as indicators to dynamically monitor the compensatory process of vestibular function in patients with BRV. The VR efficacy grading score, which incorporates the above indicators, allows for quantification of the changes that occur during the vestibular rehabilitation process.

18.
Arterioscler Thromb Vasc Biol ; 44(3): e82-e98, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38205640

RESUMO

BACKGROUND: Integrins mediate the adhesion, crawling, and migration of neutrophils during vascular inflammation. Thiol exchange is important in the regulation of integrin functions. ERp72 (endoplasmic reticulum-resident protein 72) is a member of the thiol isomerase family responsible for the catalysis of disulfide rearrangement. However, the role of ERp72 in the regulation of Mac-1 (integrin αMß2) on neutrophils remains elusive. METHODS: Intravital microscopy of the cremaster microcirculation was performed to determine in vivo neutrophil movement. Static adhesion, flow chamber, and flow cytometry were used to evaluate in vitro integrin functions. Confocal fluorescent microscopy and coimmunoprecipitation were utilized to characterize the interactions between ERp72 and Mac-1 on neutrophil surface. Cell-impermeable probes and mass spectrometry were used to label reactive thiols and identify target disulfide bonds during redox exchange. Biomembrane force probe was performed to quantitatively measure the binding affinity of Mac-1. A murine model of acute lung injury induced by lipopolysaccharide was utilized to evaluate neutrophil-associated vasculopathy. RESULTS: ERp72-deficient neutrophils exhibited increased rolling but decreased adhesion/crawling on inflamed venules in vivo and defective static adhesion in vitro. The defect was due to defective activation of integrin Mac-1 but not LFA-1 (lymphocyte function-associated antigen-1) using blocking or epitope-specific antibodies. ERp72 interacted with Mac-1 in lipid rafts on neutrophil surface leading to the reduction of the C654-C711 disulfide bond in the αM subunit that is critical for Mac-1 activation. Recombinant ERp72, via its catalytic motifs, increased the binding affinity of Mac-1 with ICAM-1 (intercellular adhesion molecule-1) and rescued the defective adhesion of ERp72-deficient neutrophils both in vitro and in vivo. Deletion of ERp72 in the bone marrow inhibited neutrophil infiltration, ameliorated tissue damage, and increased survival during murine acute lung injury. CONCLUSIONS: Extracellular ERp72 regulates integrin Mac-1 activity by catalyzing disulfide rearrangement on the αM subunit and may be a novel target for the treatment of neutrophil-associated vasculopathy.


Assuntos
Lesão Pulmonar Aguda , Antígeno de Macrófago 1 , Animais , Camundongos , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/metabolismo , Adesão Celular , Dissulfetos , Molécula 1 de Adesão Intercelular/metabolismo , Antígeno-1 Associado à Função Linfocitária/metabolismo , Antígeno de Macrófago 1/genética , Antígeno de Macrófago 1/metabolismo , Infiltração de Neutrófilos , Neutrófilos/metabolismo , Compostos de Sulfidrila/metabolismo
19.
J Pharm Biomed Anal ; 241: 115980, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38266455

RESUMO

Ovariectomy (OVX) is usually accompanied by the occurrence of metabolic syndrome. Previous studies have shown that Geng-Nian-Shu (GNS) plays an important regulatory role in perimenopausal syndrome (PMS) rats. GNS is a traditional Chinese medicine (TCM) prescription which composed of Suanzaoren Decoction and Ganmai Dazao Decoction in "Jingui Yaolue" and Siwu Decoction in "Heji Jufang". Recently, metabolomics analysis has been used to identify slight changes in the metabolic profile and to help understand disease progression and therapeutic interventions in PMS. However, the mechanism of GNS in the treatment of PMS is still unknown. We purposed to study the metabolic characteristics of PMS by serum and fecal metabolomics, and revealed the internal mechanism of GNS regulating ferroptosis against PMS. The PMS model was established by surgical removal of 4/5 ovaries of rats. HPLC-Q-TOF/MS was used to analyze the metabolomics of rat plasma and feces to explore the potential mechanism of GNS in PMS. The expression of ferroptosis-related proteins in rat ovaries was detected by tissue Prussian blue staining, Elisa kit and Western blotting. Cluster analysis of differential metabolites in plasma and feces between the control group and the model group showed that organic acids and their derivatives, lipids and lipid molecules were mainly disturbed during PMS in rats. After GNS administration, 17 differential metabolites were adjusted, involving several major pathways, such as the tricarboxylic acid (TCA) cycle, biosynthesis of amino acids and biosynthesis of unsaturated fatty acids. Further, we found that GNS affected ferroptosis in ovarian cells by regulating endogenous substances in OVX rats. Our study provides new insights into the mechanism of OVX-induced metabolic syndrome based on non-targeted metabolomics. It provides new ideas for the development and application of GNS and the diagnosis and treatment of PMS.


Assuntos
Medicamentos de Ervas Chinesas , Ferroptose , Síndrome Metabólica , Feminino , Ratos , Animais , Perimenopausa , Metabolômica , Metaboloma , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico
20.
Adv Healthc Mater ; 13(6): e2303405, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37949452

RESUMO

Stem cell therapy serves as an effective treatment for bone regeneration. Nevertheless, stem cells from bone marrow and peripheral blood are still lacking homologous properties. Dental pulp stem cells (DPSCs) are derived from neural crest, in coincidence with maxillofacial tissues, thus attracting great interest in in situ maxillofacial regenerative medicine. However, insufficient number and heterogenous alteration of seed cells retard further exploration of DPSC-based tissue engineering. Electric stimulation has recently attracted great interest in tissue regeneration. In this study, a novel DPSC-loaded conductive hydrogel microspheres integrated with wireless electric generator is fabricated. Application of exogenous electric cues can promote stemness maintaining and heterogeneity suppression for unpredictable differentiation of encapsulated DPSCs. Further investigations observe that electric signal fine-tunes regenerative niche by improvement on DPSC-mediated paracrine pattern, evidenced by enhanced angiogenic behavior and upregulated anti-inflammatory macrophage polarization. By wireless electric stimulation on implanted conductive hydrogel microspheres, loaded DPSCs facilitates the construction of immuno-angiogenic niche at early stage of tissue repair, and further contributes to advanced autologous mandibular bone defect regeneration. This novel strategy of DPSC-based tissue engineering exhibits promising translational and therapeutic potential for autologous maxillofacial tissue regeneration.


Assuntos
Sinais (Psicologia) , Hidrogéis , Microesferas , Condutividade Elétrica , Regeneração Óssea
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