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1.
Europace ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38646912

RESUMO

INTRODUCTION: Traditional AF recurrence after catheter ablation is reported as a binary outcome. However, a paradigm shift towards a more granular definition, considering arrhythmic or symptomatic burden, is emerging. HYPOTHESIS: We hypothesize that ablation reduces AF burden independently of conventional recurrence status in persistent AF patients, correlating with symptom burden reduction. METHODS: 98 patients with persistent AF from the DECAAFII trial with pre-ablation follow-up were included. Patients recorded daily single-lead ECG strips, defining AF burden as the proportion of AF days among total submitted ECG days. The primary outcome was atrial arrhythmia recurrence. The Atrial Fibrillation Severity Scale (AFSS) was administered pre-ablation and at 12-months post-ablation. RESULTS: At follow-up, 69 patients had atrial arrhythmia recurrence and 29 remained in sinus rhythm. These patients were categorized into a recurrence (n=69) and no-recurrence group (n=29). Both groups had similar baseline characteristics, but recurrence patients were older (p=0.005), had a higher prevalence of hyperlipidemia (p=0.007), and a larger LA volume (p=0.01). There was a reduction in AF burden in the recurrence group when compared to their pre-ablation burden (65% vs. 15%, p<0.0001). Utah Stage 4 fibrosis and diabetes predicted less improvement in AF burden. The symptom severity score at 12 months post-ablation was significantly reduced compared to the pre-ablation score in the recurrence group, and there was a significant correlation between the reduction in symptom severity score and AF burden reduction (R=0.39, p=0.001). CONCLUSION: Catheter ablation reduces AF burden irrespective of arrhythmia recurrence post-procedure. There's a strong correlation between AF burden reduction and symptom improvement post-ablation. Notably, elevated left atrial fibrosis impedes AF burden decrease following catheter ablation.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38625452

RESUMO

We examined the integrity of flash-frozen and cryo-sectioned cardiac muscle preparations (introduced by Feng and Jin, 2020) by assessing tension transients in response to sinusoidal length changes at varying frequencies (1-100 Hz) at 25 °C. Using 70-µm-thick sections, we isolated fiber preparations to study cross-bridge (CB) kinetics: preparations were activated by saturating Ca2+ as well as varying concentrations of ATP and phosphate (Pi). Our results showed that, compared to ordinary skinned fibers, in-series stiffness decreased to 1/2, which resulted in a decrease of isometric tension to 62%, but CB kinetics and Ca2+ sensitivity were little affected. The pCa study demonstrated that the rate constant of the force generation step (2πb) is proportionate to [Ca2+] at < 5 µM, suggesting that the activation mechanism can be described by a simple second order reaction. We also found that tension, stiffness, and magnitude parameters are related to [Ca2+] by the Hill equation, with a cooperativity coefficient of 4-5, which is consistent with the fact that Ca2+ activation mechanisms involve cooperative multimolecular interactions. Our results support the long-held hypothesis that Process C (Phase 2) represents the CB detachment step, and Process B (Phase 3) represents the force generation step. Moreover, we discovered that constant H may represent the work-performing step in cardiac preparations. Our experiments demonstrate excellent CB kinetics with two well-defined exponentials that can be more distinguished than those found using ordinary skinned fibers. Flash-frozen and cryo-sectioned preparations are especially suitable for multi-institutional collaborations nationally and internationally because of their ease of transportation.

3.
Nat Commun ; 15(1): 3200, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38615014

RESUMO

Histone lysine crotonylation (Kcr), as a posttranslational modification, is widespread as acetylation (Kac); however, its roles are largely unknown in kidney fibrosis. In this study, we report that histone Kcr of tubular epithelial cells is abnormally elevated in fibrotic kidneys. By screening these crotonylated/acetylated factors, a crotonyl-CoA-producing enzyme ACSS2 (acyl-CoA synthetase short chain family member 2) is found to remarkably increase histone 3 lysine 9 crotonylation (H3K9cr) level without influencing H3K9ac in kidneys and tubular epithelial cells. The integrated analysis of ChIP-seq and RNA-seq of fibrotic kidneys reveal that the hub proinflammatory cytokine IL-1ß, which is regulated by H3K9cr, play crucial roles in fibrogenesis. Furthermore, genetic and pharmacologic inhibition of ACSS2 both suppress H3K9cr-mediated IL-1ß expression, which thereby alleviate IL-1ß-dependent macrophage activation and tubular cell senescence to delay renal fibrosis. Collectively, our findings uncover that H3K9cr exerts a critical, previously unrecognized role in kidney fibrosis, where ACSS2 represents an attractive drug target to slow fibrotic kidney disease progression.


Assuntos
Histonas , Nefropatias , Humanos , Lisina , Ativação de Macrófagos , Rim , Senescência Celular , Células Epiteliais , Interleucina-1beta , Acetato-CoA Ligase
4.
J Biomed Opt ; 29(4): 046008, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38659998

RESUMO

Significance: Optical imaging is a non-invasive imaging technology that utilizes near-infrared light, allows for the image reconstruction of optical properties like diffuse and absorption coefficients within the tissue. A recent trend is to use signal processing techniques or new light sources and expanding its application. Aim: We aim to develop the reflective optical imaging using the chaotic correlation technology with chaotic laser and optimize the quality and spatial resolution of reflective optical imaging. Approach: Scattering medium was measured using reflective configuration in different inhomogeneous regions to evaluate the performance of the imaging system. The accuracy of the recovered optical properties was investigated. The reconstruction errors of absorption coefficients and geometric centers were analyzed, and the feature metrics of the reconstructed images were evaluated. Results: We showed how chaotic correlation technology can be utilized for information extraction and image reconstruction. This means that a higher signal-to-noise ratio and image reconstruction of inhomogeneous phantoms under different scenarios successfully were achieved. Conclusions: This work highlights that the peak values of correlation of chaotic exhibit smaller reconstruction error and better reconstruction performance in optical imaging compared with reflective optical imaging with the continuous wave laser.


Assuntos
Processamento de Imagem Assistida por Computador , Lasers , Imagem Óptica , Imagens de Fantasmas , Espalhamento de Radiação , Imagem Óptica/métodos , Processamento de Imagem Assistida por Computador/métodos , Razão Sinal-Ruído , Dinâmica não Linear , Algoritmos , Desenho de Equipamento
5.
J Agric Food Chem ; 72(12): 6236-6249, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38484389

RESUMO

Hypercholesterolemia poses a significant cardiovascular risk, particularly in postmenopausal women. The anti-hypercholesterolemic properties of Lactiplantibacillus plantarum ATCC8014 (LP) are well recognized; however, its improving symptoms on postmenopausal hypercholesterolemia and the possible mechanisms have yet to be elucidated. Here, we utilized female ApoE-deficient (ApoE-/-) mice undergoing bilateral ovariectomy, fed a high-fat diet, and administered 109 colony-forming units (CFU) of LP for 13 consecutive weeks. LP intervention reduces total cholesterol (TC) and triglyceride (TG) accumulation in the serum and liver and accelerates their fecal excretion, which is mainly accomplished by increasing the excretion of fecal secondary bile acids (BAs), thereby facilitating cholesterol conversion. Correlation analysis revealed that lithocholic acid (LCA) is an important regulator of postmenopausal lipid abnormalities. LP can reduce LCA accumulation in the liver and serum while enhancing its fecal excretion, accomplished by elevating the relative abundances of Allobaculum and Olsenella in the ileum. Our findings demonstrate that postmenopausal lipid dysfunction is accompanied by abnormalities in BA metabolism and dysbiosis of the intestinal microbiota. LP holds therapeutic potential for postmenopausal hypercholesterolemia. Its effectiveness in ameliorating lipid dysregulation is primarily achieved through reshaping the diversity and abundance of the intestinal microbiota to correct BA abnormalities.


Assuntos
Microbioma Gastrointestinal , Hipercolesterolemia , Lactobacillus plantarum , Humanos , Feminino , Camundongos , Animais , Hipercolesterolemia/metabolismo , Ácidos e Sais Biliares/metabolismo , Pós-Menopausa , Colesterol/metabolismo , Lactobacillus plantarum/metabolismo , Fígado/metabolismo , Apolipoproteínas E/metabolismo , Camundongos Endogâmicos C57BL , Dieta Hiperlipídica
6.
Artigo em Inglês | MEDLINE | ID: mdl-38466605

RESUMO

The nature of heterophilous graphs is significantly different from that of homophilous graphs, which causes difficulties in early graph neural network (GNN) models and suggests aggregations beyond the one-hop neighborhood. In this article, we develop a new way to implement multiscale extraction via constructing Haar-type graph framelets with desired properties of permutation equivariance, efficiency, and sparsity, for deep learning tasks on graphs. We further design a graph framelet neural network model permutation equivariant graph framelet augmented network (PEGFAN) based on our constructed graph framelets. The experiments are conducted on a synthetic dataset and nine benchmark datasets to compare the performance with other state-of-the-art models. The result shows that our model can achieve the best performance on certain datasets of heterophilous graphs (including the majority of heterophilous datasets with relatively larger sizes and denser connections) and competitive performance on the remaining.

8.
Pest Manag Sci ; 80(3): 1348-1360, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37915287

RESUMO

BACKGROUND: During unmanned aerial vehicles (UAVs) spraying, downwash and crosswind generate back pressure in comprehensive, which changes in spatial atomization characteristics of spraying droplets. However, the process of such atomization characteristics needs to be clarified. This study focuses on the effect of rotor speed and crosswind speed on spatial atomization characteristics. The computational fluid dynamics (CFD) models of the distributions of airflow, back pressure and atomization characteristics were established, and verification was conducted by developing a validation platform. RESULTS: The CFD results indicated that small droplets of 65-130 µm atomized by negative pressure would be coalesced near the nozzle, while large droplets of 390-520 µm atomized by positive pressure would be aggregated further away. Crosswind caused atomization stratification with droplet sizes of approximately 90 µm, 320 µm and 390 µm. When crosswind speed increased from 3 m/s to 6 m/s, the spraying drifted from 0.5 m to 1 m. When rotor speed increased from 2000 RPM to 3000 RPM, droplet distribution was expanded and droplet particle size was more uniform. Verification results demonstrated that the spraying distribution and the droplet size variation were consistent with the CFD. CONCLUSIONS: Spatial atomization characteristics were highly correlated with airflow and back pressure. Moreover, as crosswind generated droplet drift and atomization stratification and downwash could improve the uniformity of droplet distribution, spraying performance was superior by enhancing downwash to restrain the adverse effect of crosswind in real applications. © 2023 Society of Chemical Industry.


Assuntos
Hidrodinâmica , Tamanho da Partícula
9.
Stat Med ; 43(4): 674-688, 2024 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-38043523

RESUMO

Measures of substance concentration in urine, serum or other biological matrices often have an assay limit of detection. When concentration levels fall below the limit, exact measures cannot be obtained, and thus are left censored. The problem becomes more challenging when the censored data come from heterogeneous populations consisting of exposed and non-exposed subjects. If the censored data come from non-exposed subjects, their measures are always zero and hence censored, forming a latent class governed by a distinct censoring mechanism compared with the exposed subjects. The exposed group's censored measurements are always greater than zero, but less than the detection limit. It is very often that the exposed and non-exposed subjects may have different disease traits or different relationships with outcomes of interest, so we need to disentangle the two different populations for valid inference. In this article, we aim to fill the methodological gaps in the literature by developing a novel joint modeling approach to not only address the censoring issue in predictors, but also untangle different relationships of exposed and non-exposed subjects with the outcome. Simulation studies are performed to assess the numerical performance of our proposed approach when the sample size is small to moderate. The joint modeling approach is also applied to examine associations between plasma metabolites and blood pressure in Bogalusa Heart Study, and identify new metabolites that are highly associated with blood pressure.


Assuntos
Modelos Estatísticos , Humanos , Limite de Detecção , Simulação por Computador , Estudos Longitudinais
10.
Mol Ther ; 32(1): 218-226, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-37974399

RESUMO

Human recombinant ACE2 (hrACE2) has been highly anticipated as a successful COVID-19 treatment; however, its potential to cause cardiac side effects has given rise to many concerns. Here, we developed a cardiotoxicity-eliminated hrACE2 variant, which had four mutation sites within hrACE2 (H345L, H374L, H378L, H505L) and was named as hrACE2-4mu. hrACE2-4mu has a consistent binding affinity with the variant SARS-CoV-2 spike proteins (SPs) and an efficient ability to block SP-induced SARS-CoV-2 entry into cells. In golden hamsters, injection of purified wild-type (WT) hrACE2 rescues the early stages of pneumonia caused by the SPs of the WT, delta, and omicron variants with reduced inflammatory cell infiltration. However, long-term injection of WT hrACE2 induces undesired cardiac fibrosis, as demonstrated by upregulated fibronectin and collagen expression. Our newly developed hrACE2-4mu showed similar protective abilities against a series of coronavirus cell invasions as WT hrACE2, meanwhile it did not cause apparent cardiac side effects. Thus, we generated a cardiotoxicity-eliminated variant of hrACE2 as a pan-inhibitor against coronavirus cell invasion, providing a potential novel strategy for the treatment of COVID-19 and other coronaviruses.


Assuntos
Enzima de Conversão de Angiotensina 2 , COVID-19 , Animais , Cricetinae , Humanos , Enzima de Conversão de Angiotensina 2/genética , Cardiotoxicidade/etiologia , Tratamento Farmacológico da COVID-19 , Coração , Mesocricetus
11.
J Interv Card Electrophysiol ; 67(2): 263-271, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36973597

RESUMO

BACKGROUND: The low-voltage area detected by electroanatomic mapping (EAM) is a surrogate marker of left atrial fibrosis. However, the correlation between the EAM and late gadolinium enhancement magnetic resonance imaging (LGE-MRI) has been inconsistent among studies. This study aimed to investigate how LA size affects the correlation between EAM and LGE-MRI. METHODS: High-density EAMs of the LA during sinus rhythm were collected in 22 patients undergoing AF ablation. The EAMs were co-registered with pre-ablation LGE-MRI models. Voltages in the areas with and without LGE were recorded. Left atrial volume index (LAVI) was calculated from MRI, and LAVI > 62 ml/m2 was defined as significant LA enlargement (LAE). RESULTS: Atrial bipolar voltage negatively correlates with the left atrial volume index. The median voltages in areas without LGE were 1.1 mV vs 2.0 mV in patients with vs without significant LAE (p = 0.002). In areas of LGE, median voltages were 0.4 mV vs 0.8 mV in patients with vs without significant LAE (p = 0.02). A voltage threshold of 1.7 mV predicted atrial LGE in patients with normal or mildly enlarged LA (sensitivity and specificity of 74% and 59%, respectively). In contrast, areas of voltage less than 0.75 mV correlated with LGE in patients with significant LA enlargement (sensitivity 68% and specificity 66%). CONCLUSIONS: LAVI affects left atrial bipolar voltage, and the correlation between low-voltage areas and LGE-MRI. Distinct voltage thresholds according to the LAVI value might be considered to identify atrial scar by EAM.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Humanos , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/cirurgia , Meios de Contraste , Gadolínio , Átrios do Coração/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Fibrose , Ablação por Cateter/métodos
12.
Inorg Chem ; 63(1): 677-688, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38109074

RESUMO

The abuse of antibiotics leads to an increasing emergence of drug-resistant bacteria, which not only causes a waste of medical resources but also seriously endangers people's health and life safety. Therefore, it is highly desirable to develop an efficient antibacterial strategy to reduce the reliance on traditional antibiotics. Antibacterial photodynamic therapy (aPDT) is regarded as an intriguing antimicrobial method that is less likely to generate drug resistance, but its efficiency still needs to be further improved. Herein, a robust titanium-based metal-organic framework ACM-1 was adopted to support Ag nanoparticles (NPs) to obtain Ag NPs@ACM-1 for boosting antibacterial efficiency via synergistic chemical-photodynamic therapy. Apart from the intrinsic antibacterial nature, Ag NPs largely boost ROS production and thus improve aPDT efficacy. As a consequence, Ag NPs@ACM-1 shows excellent antibacterial activity under visible light illumination, and its minimum bactericidal concentrations (MBCs) against E. coli, S. aureus, and MRSA are as low as 39.1, 39.1, and 62.5 µg mL-1, respectively. Moreover, to expand the practicability of Ag NPs@ACM-1, two (a dense and a loose) Ag NPs@ACM-1 films were readily fabricated by simply dispersing Ag NPs@ACM-1 into heated aqueous solutions of edible agar and sequentially cooling through heating or freeze-drying, respectively. Notably, these two films are mechanically flexible and exhibit excellent antibacterial activities, and their antimicrobial performances can be well retained in their recyclable and remade films. As agar is nontoxic, degradable, inexpensive, and ecosustainable, the dense and loose Ag NPs@ACM-1 films are potent to serve as recyclable and degradable antibacterial plastics and antibacterial dressings, respectively.


Assuntos
Anti-Infecciosos , Nanopartículas Metálicas , Estruturas Metalorgânicas , Fotoquimioterapia , Humanos , Prata/farmacologia , Titânio/farmacologia , Estruturas Metalorgânicas/farmacologia , Staphylococcus aureus , Escherichia coli , Ágar , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana
13.
Animal Model Exp Med ; 6(6): 518-525, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38064180

RESUMO

MicroRNAs (miRNAs) are small noncoding RNA molecules ubiquitously distributed across diverse organisms, serving as pivotal regulators of genetic expression. Notably, plant-derived miRNAs have been demonstrated to have unique bioactivity and certain stability in mammalian systems, thereby facilitating their capacity for cross-kingdom modulation of gene expression. While there is substantial evidence supporting the regulation of mammalian cells by plant-derived miRNAs, several questions remain unanswered. Specifically, a comprehensive investigation of the mechanisms underlying the stability and transport of plant miRNAs and their cross-kingdom regulation of gene expression in mammals remains to be done. In this review, we summarized the origin, processing, and functional mechanisms of plant miRNAs in mammalian tissues and circulation, emphasizing their greater resistance to mammalian digestion and circulation systems compared to animal miRNAs. Additionally, we introduce four well-known plant miRNAs that have been extensively studied for their functions and mechanisms in mammalian systems. By delving into these aspects, we aim to offer a fundamental understanding of this intriguing field and shed light on the complex interactions between plant miRNAs and mammalian biology.


Assuntos
MicroRNAs , Animais , MicroRNAs/genética , Plantas/genética , Plantas/metabolismo , Mamíferos/genética , Mamíferos/metabolismo
14.
JBI Evid Implement ; 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37982206

RESUMO

INTRODUCTION AND OBJECTIVES: A central venous catheter (CVC)-a type of central venous access device (CVAD)-is the most common intervention for critical illnesses. Obstruction of the CVC can lead to fatal consequences. Thus, it is critical to maintain catheter lumen patency. The CVC occlusion rate in a hospital in Taiwan was 33%. This project aimed to decrease the CVC occlusion rate in acute care. METHODS: This project was conceptually informed by the JBI Evidence-Based Model of Healthcare, in particular, the conceptualization of evidence implementation as inclusive of context analysis, implementation, and evaluation of outcomes using evidence-based quality indicators. As part of the seven-phase implementation process, we used audit and feedback in a pre- and post-test design to measure baseline compliance. Based on the initial audit, we developed an implementation strategy responsive to the identified gaps in compliance. We then undertook a final audit to measure changes in compliance to evaluate our implementation effects. The JBI software, PACES, and the situational analysis software, GRiP, were used for data collection and implementation planning. There were six evidence-based criteria, with a sample size of 30 nurses for each criterion. The team carried out the project from September 2022 to January 2023. RESULTS: Post-implementation audit compliance rates increased to 100% for the following criteria: the organization had a standardized flushing and locking solution protocol (0%), the CVAD lumen was locked upon completion of the final flush (10%), a single-dose system was used for flushing and locking the CVAD (60%), and preservative-free 0.9% sodium chloride was used to flush the CVAD (60%). Furthermore, the CVC occlusion rate decreased from 33% to 5%. CONCLUSIONS: The project successfully decreased the rate of CVC occlusion and increased the competence of nurses in acute care settings. The implementation of best practices in clinical care should focus on leadership, cross-department coordination, education, and innovation.

15.
Res Sq ; 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37961283

RESUMO

The use of frozen and cryo-sectioned cardiac muscle preparations, introduced recently by (Feng & Jin, 2020), offers promising advantages of easy transport and exchange of muscle samples among collaborating laboratories. In this report, we examined integrity of such preparation by studying tension transients in response to sinusoidal length changes and following concomitant amplitude and phase shift in tension time courses at varying frequencies. We used sections with 70 µm thickness, isolated fiber preparations, and studied cross-bridge (CB) kinetics: we activated the preparations with saturating Ca2+, and varying concentrations of ATP and phosphate (Pi). Our experiments have demonstrated that this preparation has the normal active tension and elementary steps of the CB cycle. Furthermore, we investigated the effect of Ca2+ on the rate constants and found that the rate constant r4 of the force generation step is proportionate to [Ca2+] when it is <5 µM. This observation suggests that the activation mechanism can be described by a simple second order reaction. As expected, we found that magnitude parameters including tension and stiffness are related to [Ca2+] by the Hill equation with cooperativity of 4-5, consistent to the fact that Ca2+ activation mechanisms involve cooperative multimolecular interactions. Our results are consistent with a long-held hypothesis that process C (phase 2 of step analysis) represents the CB detachment step, and process B (phase 3) represents the force generation step. In this report, we further found that constant H may also represent work performance step. Our experiments have demonstrated excellent CB kinetics with reduced noise and well-defined two exponentials, which are better than skinned fibers, and easier to handle and study than single myofibrils.

16.
Materials (Basel) ; 16(22)2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-38005056

RESUMO

Duplex stainless steel (DSS) exhibits good mechanical properties and corrosion resistance, and has attracted more and more attention within the fields of both science and technology. However, the increasing levels of N and of Cr, Mo, etc., as alloying elements in DSS increase production difficulty. In particular, the N element increases the risk of Cr2N precipitation, which can seriously deteriorate the thermal plasticity of DSS, while increasing its strength. For this reason, a low-N-content 25Cr-type DSS was designed in order to adapt additive manufacturing processes. With regard to the nano-inclusions of oxide precipitation and effective grain refinement, and considering the benefits of selective laser melting fabrication, a low-N 25Cr-type duplex stainless steel with a 0.09 wt.% N content achieved high mechanical properties, with a yield strength of 712 MPa and an elongation of 27.5%, while the V-notch impact toughness was 160 J/cm2. The microstructure evolution and the reasons behind the improvement in mechanical properties will be discussed in detail.

17.
Mol Brain ; 16(1): 80, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-37986006

RESUMO

Cognitive dysfunction increases as menopause progresses. We previously found that estrogen receptors (ERs) contribute to dyslipidemia, but the specific relationship between ERs, dyslipidemia and cognitive dysfunction remains poorly understood. In the present study, we analyzed sequencing data from female hippocampus and normal breast aspirate samples from normal and Alzheimer's disease (AD) women, and the results suggest that abnormal ERs signaling is associated with dyslipidemia and cognitive dysfunction. We replicated a mouse model of dyslipidemia and postmenopausal status in LDLR-/- mice and treated them with ß-estradiol or simvastatin, and found that ovariectomy in LDLR-/- mice led to an exacerbation of dyslipidemia and increased hippocampal apoptosis and cognitive impairment, which were associated with reduced estradiol levels and ERα, ERß and GPER expression. In vitro, a lipid overload model of SH-SY-5Y cells was established and treated with inhibitors of ERs. ß-estradiol or simvastatin effectively attenuated dyslipidemia-induced neuronal apoptosis via upregulation of ERs, whereas ERα, ERß and GPER inhibitors together abolished the protective effect of simvastatin on lipid-induced neuronal apoptosis. We conclude that decreased estrogen and its receptor function in the postmenopausal stage promote neuronal damage and cognitive impairment by exacerbating dyslipidemia, and that estrogen supplementation or lipid lowering is an effective way to ameliorate hippocampal damage and cognitive dysfunction via upregulation of ERs.


Assuntos
Disfunção Cognitiva , Receptor alfa de Estrogênio , Humanos , Camundongos , Feminino , Animais , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Pós-Menopausa , Estrogênios/farmacologia , Estradiol/farmacologia , Disfunção Cognitiva/complicações , Sinvastatina/farmacologia , Sinvastatina/uso terapêutico , Lipídeos
18.
Biomol Biomed ; 2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37838928

RESUMO

Parathyroid hormone-related protein (PTHrP) plays a significant role in various tumor types, including prostate cancer. However, its specific role and underlying mechanisms in prostate cancer remain unclear. This study investigates the role of PTHrP and its interaction with the mesenchymal-epithelial transition factor (c-Met) in prostate cancer. PTHrP was overexpressed and knocked down in prostate cancer cell lines to determine its effect on cell functions. Xenograft tumor models were employed to assess the impact of PTHrP overexpression on tumor growth. To delve into the interaction between PTHrP and c-Met, rescue experiments were conducted. Clinical data and tissue samples from prostate cancer patients were gathered and analyzed for PTHrP and c-Met expression. PTHrP overexpression in prostate cancer cells upregulates c-Met expression and augments cell functions. In contrast, PTHrP knockdown diminishes c-Met expression and inhibites cell functions. In vivo experiments further demonstrated that PTHrP overexpression promoted tumor growth in xenograft models. Moreover, modulating c-Met expression in rescue experiments led to concurrent alterations in prostate cancer cell functions. Immunohistochemical analysis of clinical samples displayed a significant positive correlation between PTHrP and c-Met expression. Additionally, PTHrP expression correlated with clinical parameters like prostate-specific antigen (PSA) levels, tumor stage, lymph node involvement, distant metastasis, and Gleason score. PTHrP plays a crucial role in prostate cancer progression by upregulating c-Met expression. These insights point to PTHrP as a promising potential biomarker for prostate cancer.

19.
J Hazard Mater ; 460: 132512, 2023 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-37703740

RESUMO

Pseudomonas aeruginosa, a versatile bacterium, has dual significance because of its beneficial roles in environmental soil processes and its detrimental effects as a nosocomial pathogen that causes clinical infections. Understanding adaptability to environmental stress is essential. This investigation delves into the complex interplay of two-component system (TCS), specifically ParRS and CprRS, as P. aeruginosa interprets host signals and navigates stress challenges. In this study, through phenotypic and proteomic analyses, the nuanced contributions of ParRS and CprRS to the pathogenesis and resilience mechanisms were elucidated. Furthermore, the indispensable roles of the ParS and CprS extracellular sensor domains in orchestrating signal perception remain unknown. Structural revelations imply a remarkable convergence of TCS sensors in interacting with host peptides, suggesting evolutionary strategies for bacterial adaptation. This pioneering work not only established links between cationic antimicrobial peptide (CAMP) resistance-associated TCSs and virulence modulation in nosocomial bacteria, but also transcended conventional boundaries. These implications extend beyond clinical resistance, permeating into the realm of soil revitalization and environmental guardianship. As it unveils P. aeruginosa intricacies, this study assumes a mantle of guiding strategies to mitigate clinical hazards, harness environmental advantages, and propel sustainable solutions forward.


Assuntos
Infecção Hospitalar , Pseudomonas aeruginosa , Humanos , Virulência , Proteômica , Peptídeos , Solo
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