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1.
Sensors (Basel) ; 24(12)2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38931750

RESUMO

Fault diagnosis is one of the important applications of edge computing in the Industrial Internet of Things (IIoT). To address the issue that traditional fault diagnosis methods often struggle to effectively extract fault features, this paper proposes a novel rolling bearing fault diagnosis method that integrates Gramian Angular Field (GAF), Convolutional Neural Network (CNN), and Vision Transformer (ViT). First, GAF is used to convert one-dimensional vibration signals from sensors into two-dimensional images, effectively retaining the fault features of the vibration signal. Then, the CNN branch is used to extract the local features of the image, which are combined with the global features extracted by the ViT branch to diagnose the bearing fault. The effectiveness of this method is validated with two datasets. Experimental results show that the proposed method achieves average accuracies of 99.79% and 99.63% on the CWRU and XJTU-SY rolling bearing fault datasets, respectively. Compared with several widely used fault diagnosis methods, the proposed method achieves higher accuracy for different fault classifications, providing reliable technical support for performing complex fault diagnosis on edge devices.

2.
Food Chem ; 456: 140056, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38878546

RESUMO

In this study, carrageenan (CG), xanthan gum (XG) and locust bean gum (LBG), which can be used in infant formulas in China national standards, were selected to prepare LF-polysaccharide complexes to improve the stability of lactoferrin. The results showed that LF interacted more strongly with polysaccharides and did not affect the LF structure to a large extent when the pH and protein/polysaccharide mass ratio were 7 and 10:1 for LF-CG, 8 and 5:1 for LF-XG, 7 and 15:1 for LF-LBG. The zeta potential and fluorescence intensity of the LF-polysaccharide complexes displayed a decreasing trend with the increase in pH. When pH < 6, LF-CG and LF-XG exhibited precipitation and increased UV absorbance. Complexation between LF and CG/XG mainly attributed to electrostatic interactions, while LF and LBG form complexes based on hydrogen bonding or hydrophobic interactions. This study could provide a reference for the practical application of LF in infant formula.

3.
Front Plant Sci ; 15: 1406256, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38872890

RESUMO

Alfalfa (Medicago sativa L.) is one of the most important forage crops in the world. Drought is recognized as a major challenge limiting alfalfa production and threatening food security. Although some literature reviews have been conducted in this area, bibliometric reviews based on large amounts of published data are still lacking. In this paper, a bibliometric analysis of alfalfa drought stress from 1998-2023 was conducted using the Web of Science Core Collection database in order to assess global trends in alfalfa drought stress research and to provide new directions for future research. The results showed that the annual publication output maintained an increase in most years, with China and the United States contributing significantly to the field. Most of the journals published are specialized journals in botany, environmental science, soil science and crop science, as well as related agribusiness journals. "plant growth" and "yield" were the most frequently used keywords, reflecting the important purpose of research in this field. And two main research directions were identified: research on drought response mechanism of alfalfa and exploration of drought-resistant technology. In addition, physiological, biochemical, and molecular responses of drought tolerance and high yield in alfalfa, transgenics, and microbial fertilizer research have been hot research topics in recent years and may continue in the future. The ultimate goal of this paper is to provide a foundational reference for future research on alfalfa's drought resistance and yield optimization mechanisms, thereby enhancing the crop's application in agricultural production.

4.
J Cell Mol Med ; 28(12): e18407, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38894630

RESUMO

Chronic intermittent hypoxia (CIH) is associated with an increased risk of cardiovascular diseases. Previously, we have shown that berberine (BBR) is a potential cardioprotective agent. However, its effect and mechanism on CIH-induced cardiomyopathy remain uncovered. This study was designed to determine the effects of BBR against CIH-induced cardiac damage and to explore the molecular mechanisms. Mice were exposed to 5 weeks of CIH with or without the treatment of BBR and adeno-associated virus 9 (AAV9) carrying SIRT6 or SIRT6-specific short hairpin RNA. The effect of BBR was evaluated by echocardiography, histological analysis and western blot analysis. CIH caused the inactivation of myocardial SIRT6 and AMPK-FOXO3a signalling. BBR dose-dependently ameliorated cardiac injury in CIH-induced mice, as evidenced by increased cardiac function and decreased fibrosis. Notably, SIRT6 overexpression mimicked these beneficial effects, whereas infection with recombinant AAV9 carrying SIRT6-specific short hairpin RNA abrogated them. Mechanistically, BBR reduced oxidative stress damage and preserved mitochondrial function via activating SIRT6-AMPK-FOXO3a signalling, enhancing mitochondrial biogenesis as well as PINK1-Parkin-mediated mitophagy. Taken together, these data demonstrate that SIRT6 activation protects against the pathogenesis of CIH-induced cardiac dysfunction. BBR attenuates CIH-induced myocardial injury by improving mitochondrial biogenesis and PINK1-Parkin-dependent mitophagy via the SIRT6-AMPK-FOXO3a signalling pathway.


Assuntos
Berberina , Proteína Forkhead Box O3 , Hipóxia , Transdução de Sinais , Sirtuínas , Berberina/farmacologia , Berberina/uso terapêutico , Animais , Sirtuínas/metabolismo , Sirtuínas/genética , Transdução de Sinais/efeitos dos fármacos , Hipóxia/metabolismo , Camundongos , Masculino , Proteína Forkhead Box O3/metabolismo , Proteína Forkhead Box O3/genética , Estresse Oxidativo/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por AMP/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitofagia/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Modelos Animais de Doenças
5.
Games Health J ; 13(3): 149-163, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38563785

RESUMO

Purpose: To investigate the effectiveness of virtual reality (VR)-based interventions for functional rehabilitation of the upper limb in breast cancer patients through a systematic review and meta-analysis. Methods: The PubMed, Cochrane, Web of Science, CINAHL, Scopus, CNKI, Wanfang, and VIP databases were systematically searched for relevant literature published from the establishment of the database to June 2023. Differences in the effectiveness of VR-based interventions and other intervention therapies were compared using random effects model meta-analysis and standard deviation (SMD). Results: Seven eligible articles were identified and included in the meta-analysis. The combined analysis found that VR-based interventions had a positive impact on patients' upper limb mobility in terms of flexion (SMD = 1.33, 95% confidence interval; CI [0.48-2.19], P = 0.002), abduction (SMD = 1.22, 95% CI [0.58-1.86], P = 0.0002), and external rotation (SMD = 0.94, 95% CI [0.48-1.40], P < 0.0001). In addition, VR-based interventions could significantly improve the postoperative pain of patients with breast cancer. However, in grip strength (SMD = 0.43, 95% CI [-3.05 to 3.92], P = 0.81), shoulder muscle strength in flexion strength (SMD = 0.05, 95% CI [-2.07 to 2.18], P = 0.96), abduction strength (SMD = -0.10, 95% CI [-1.32 to 1.12], P = 0.88), external rotation strength (SMD = 0.46, 95% CI [-1.96 to 2.88], P = 0.71), and lymphedema, VR was as effective as other intervention treatments. A subgroup analysis showed that patients younger than 55 years had more benefit with VR-based rehabilitation than with other interventions and showed improvements with the intervention within 2 weeks. The intervention effect of using auxiliary equipment such as robotic arms is better than VR exercise based solely on games. Conclusion: The results of meta-analysis show that the intervention measures based on VR have positive effects on the improvement of upper limb mobility and pain relief in breast cancer patients. However, considering the low quality of evidence and small sample size, more clinical studies should be conducted to improve the credibility of the results.


Assuntos
Neoplasias da Mama , Extremidade Superior , Realidade Virtual , Humanos , Neoplasias da Mama/psicologia , Neoplasias da Mama/reabilitação , Extremidade Superior/fisiopatologia , Extremidade Superior/fisiologia , Feminino
6.
Environ Monit Assess ; 196(5): 448, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38607467

RESUMO

Soil in mining wastelands is seriously polluted with heavy metals. Zero-valent iron (ZVI) is widely used for remediation of heavy metal-polluted soil because of its excellent adsorption properties; however, the remediation process is affected by complex environmental conditions, such as acid rain and freeze-thaw cycles. In this study, the effects of different pH values and freeze-thaw cycles on remediation of antimony (Sb)- and arsenic (As)-contaminated soil by ZVI were investigated in laboratory simulation experiments. The stability and potential human health risks associated with the remediated soil were evaluated. The results showed that ZVI has a significant stabilizing effect on Sb and As in both acidic and alkaline soils contaminated with dual levels of Sb and As, and the freeze-thaw process in different pH value solution systems further enhances the ability of ZVI to stabilize Sb and As, especially in acidic soils. However, it should be noted that apart from the pH=1.0 solution environment, ZVI's ability to stabilize As is attenuated under other circumstances, potentially leading to leaching of its unstable form and thereby increasing contamination risks. This indicates that the F1 (2% ZVI+pH=1 solution+freeze-thaw cycle) processing exhibits superior effectiveness. After F1 treatment, the bioavailability of Sb and As in both soils also significantly decreased during the gastric and intestinal stages (about 60.00%), the non-carcinogenic and carcinogenic risks of Sb and As in alkaline soils are eliminated for children and adults, with a decrease ranging from 60.00% to 70.00%, while in acidic soil, the non-carcinogenic and carcinogenic risks of As to adults and children is acceptable, but Sb still poses non-carcinogenic risks to children, despite reductions of about 65.00%. These findings demonstrate that soil pH is a crucial factor influencing the efficacy of ZVI in stabilizing Sb and As contaminants during freeze-thaw cycles. This provides a solid theoretical foundation for utilizing ZVI in the remediation of Sb- and As-contaminated soils, emphasizing the significance of considering both pH levels and freeze-thaw conditions to ensure effective and safe treatment.


Assuntos
Antimônio , Arsênio , Humanos , Adulto , Criança , Ferro , Monitoramento Ambiental , Medição de Risco , Solo , Concentração de Íons de Hidrogênio
7.
Sci Rep ; 14(1): 9167, 2024 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649770

RESUMO

Syndecan-binding protein (SDCBP) was reported to stimulate the advancement of esophageal squamous cell carcinoma (ESCC) and could potentially be a target for ESCC treatment. There is a growing corpus of research on the anti-tumor effects of iron chelators; however, very few studies have addressed the involvement of dexrazoxane in cancer. In this study, structure-based virtual screening was employed to select drugs targeting SDCBP from the Food and Drug Administration (FDA)-approved drug databases. The sepharose 4B beads pull-down assay revealed that dexrazoxane targeted SDCBP by interacting with its PDZ1 domain. Additionally, dexrazoxane inhibited ESCC cell proliferation and anchorage-independent colony formation via SDCBP. ESCC cell apoptosis and G2 phase arrest were induced as measured by the flow cytometry assay. Subsequent research revealed that dexrazoxane attenuated the binding ability between SDCBP and EGFR in an immunoprecipitation assay. Furthermore, dexrazoxane impaired EGFR membrane localization and inactivated the EGFR/PI3K/Akt pathway. In vivo, xenograft mouse experiments indicated that dexrazoxane suppressed ESCC tumor growth. These data indicate that dexrazoxane might be established as a potential anti-cancer agent in ESCC by targeting SDCBP.


Assuntos
Proliferação de Células , Receptores ErbB , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Sinteninas , Ensaios Antitumorais Modelo de Xenoenxerto , Humanos , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores ErbB/metabolismo , Animais , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Proliferação de Células/efeitos dos fármacos , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sinteninas/metabolismo , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Camundongos Nus , Antineoplásicos/farmacologia
8.
J Mol Med (Berl) ; 102(6): 773-785, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38668786

RESUMO

Autosomal dominant polycystic kidney disease is a genetic kidney disease caused by mutations in the genes PKD1 or PKD2. Its course is characterized by the formation of progressively enlarged cysts in the renal tubules bilaterally. The basic genetic explanation for autosomal dominant polycystic kidney disease is the double-hit theory, and many of its mechanistic issues can be explained by the cilia doctrine. However, the precise molecular mechanisms underpinning this condition's occurrence are still not completely understood. Experimental evidence suggests that aquaporins, a class of transmembrane channel proteins, including aquaporin-1, aquaporin-2, aquaporin-3, and aquaporin-11, are involved in the mechanism of autosomal dominant polycystic kidney disease. Aquaporins are either a potential new target for the treatment of autosomal dominant polycystic kidney disease, and further study into the physiopathological role of aquaporins in autosomal dominant polycystic kidney disease will assist to clarify the disease's pathophysiology and increase the pool of potential treatment options. We primarily cover pertinent findings on aquaporins in autosomal dominant polycystic kidney disease in this review.


Assuntos
Aquaporinas , Rim Policístico Autossômico Dominante , Humanos , Rim Policístico Autossômico Dominante/metabolismo , Rim Policístico Autossômico Dominante/genética , Aquaporinas/metabolismo , Aquaporinas/genética , Animais , Mutação
9.
Am J Cancer Res ; 14(3): 1353-1362, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590416

RESUMO

The challenge of methotrexate (MTX) resistance among low-risk gestational trophoblastic neoplasia (GTN) patients has always been prominent. Despite the International Federation of Gynaecology and Obstetrics (FIGO) score of 0-4 patients comprising the majority of low-risk GTN patients, a comprehensive exploration of the prevalence and risk factors associated with MTX resistance has been limited. Therefore, we aimed to identify associated risk factors in GTN patients with a FIGO score of 0-4. Between January 2005 and December 2020, 310 low-risk GTN patients received primary MTX chemotherapy in two hospitals, with 265 having a FIGO score of 0-4. In the FIGO 0-4 subgroup, 94 (35.5%) were resistant to MTX chemotherapy, and 34 (12.8%) needed multi-agent chemotherapy. Clinicopathologic diagnosis of postmolar choriocarcinoma (OR = 17.18, 95% CI: 4.64-63.70, P < 0.001) and higher pretreatment human chorionic gonadotropin concentration on a logarithmic scale (log-hCG concentration) (OR = 18.11, 95% CI: 3.72-88.15, P < 0.001) were identified as independent risk factors associated with MTX resistance according to multivariable logistic regression. The decision tree model and regression model were developed to predict the risk of MTX resistance in GTN patients with a FIGO score of 0-4. Evaluation of model discrimination, calibration and net benefit revealed the superiority of the decision tree model, which comprised clinicopathologic diagnosis and pretreatment hCG concentration. The patients in the high- and medium-risk groups of the decision tree model had a higher probability of MTX resistance. This study represents the investigation into MTX resistance in GTN patients with a FIGO score of 0-4 and disclosed a remission rate of approximately 65% with MTX chemotherapy. Higher pretreatment hCG concentration and clinicopathologic diagnosis of postmolar choriocarcinoma were independent risk factors associated with resistance to MTX chemotherapy. The decision tree model demonstrated enhanced predictive capabilities regarding the risk of MTX resistance and can serve as a valuable tool to guide the clinical treatment decisions for GTN patients with a FIGO score of 0-4.

10.
ACS Nano ; 18(12): 9019-9030, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38483200

RESUMO

Urinary tract infections (UTIs), common bacterial infections in communities and medical facilities, are mainly mediated by FimH. The glycan sites of the uromodulin protein play a crucial role in protecting against UTIs by interacting with FimH. A bioinspired approach using glycan-FimH interactions may effectively reduce bacteria through an antiadhesive mechanism, thereby curbing bacterial resistance. However, typical antiadhesive therapy alone fails to address the excessive reactive oxygen species and inflammatory response during UTIs. To bridge this gap, antioxidant nanozymes with antiadhesive ability were developed as nanodecoys to counter bacteria and inflammation. Specifically, ultrasmall dextran-coated ceria (DEC) was engineered to address UTIs, with dextran blocking FimH adhesion and ceria exhibiting anti-inflammatory properties. DECs, metabolizable by the kidneys, reduced bacterial content in the urinary tract, mitigating inflammation and tissue damage. In murine models, DECs successfully treated acute UTIs, repeated infections, and catheter-related UTIs. This dual approach not only highlights the potential of nanozymes for UTIs but also suggests applicability to other FimH-induced infections in the lungs and bowels, marking a significant advancement in nanozyme-based clinical approaches.


Assuntos
Adesinas de Escherichia coli , Infecções Urinárias , Camundongos , Humanos , Animais , Adesinas de Escherichia coli/metabolismo , Proteínas de Fímbrias/metabolismo , Dextranos , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia , Inflamação , Antibacterianos
11.
Sci Rep ; 14(1): 3211, 2024 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-38332001

RESUMO

Type 2 diabetic kidney disease (T2DKD) is a common microvascular complication of type 2 diabetes mellitus (T2DM), and its incidence is significantly increasing. Microinflammation plays an important role in the development of T2DKD. Based on this, this study investigated the value of inflammatory markers including neutrophil-lymphocyte ratio (NLR), high-sensitivity C-reactive protein (hs-CRP), monocyte chemoattractant protein-1 (MCP-1) in the prediction of T2DKD. This was a cross-sectional survey study. A total of 90 patients with T2DM, who were hospitalized in the nephrology and endocrinology departments of the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from June 2021 to January 2022, were included and divided into three groups (A1, A2, A3) according to the urinary albumin-to-creatinine ratio (UACR). Observe and compare the basic information, clinical and laboratory data, and the inflammatory markers NLR, hs-CRP, MCP-1. Results revealed that high levels of NLR (OR = 6.562, 95% CI 2.060-20.902, P = 0.001) and MCP-1 (OR = 1.060, 95% CI 1.026-1.095, P < 0.001) were risk factors in the development of T2DKD. Receiver operating characteristic curve analysis showed that the area under curve of NLR and MCP-1 in diagnosing T2DKD were 0.760 (95% CI 0.6577-0.863, P < 0.001) and 0.862 (95% CI 0.7787-0.937, P < 0.001). Therefore, the inflammatory markers NLR and MCP-1 are risk factors affecting the development of T2DKD, which of clinical value may be used as novel markers of T2DKD.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Humanos , Proteína C-Reativa/análise , Quimiocina CCL2/urina , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/urina , Linfócitos/química , Neutrófilos/química , Estudos Retrospectivos , Curva ROC
13.
Nano Lett ; 24(7): 2289-2298, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38341876

RESUMO

Antibiotic therapeutics to combat intestinal pathogen infections often exacerbate microbiota dysbiosis and impair mucosal barrier functions. Probiotics are promising strategies, because they inhibit pathogen colonization and improve intestinal microbiota imbalance. Nevertheless, their limited targeting ability and susceptibility to oxidative stress have hindered their therapeutic potential. To tackle these challenges, Ces3 is synthesized by in situ growth of CeO2 nanozymes with positive charges on probiotic spores, facilitating electrostatic interactions with negatively charged pathogens and possessing a high reactive oxygen species (ROS) scavenging activity. Importantly, Ces3 can resist the harsh environment of the gastrointestinal tract. In mice with S. Typhimurium-infected acute gastroenteritis, Ces3 shows potent anti-S. Typhimurium activity, thereby alleviating the dissemination of S. Typhimurium into other organs. Additionally, owing to its O2 deprivation capacity, Ces3 promotes the proliferation of anaerobic probiotics, reshaping a healthy intestinal microbiota. This work demonstrates the promise of combining antibacterial, anti-inflammatory, and O2 content regulation properties for acute gastroenteritis therapy.


Assuntos
Gastroenterite , Probióticos , Animais , Camundongos , Intestinos , Gastroenterite/tratamento farmacológico , Gastroenterite/microbiologia , Antibacterianos/uso terapêutico , Probióticos/uso terapêutico , Esporos
14.
BMC Anesthesiol ; 24(1): 25, 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38218762

RESUMO

BACKGROUND: This meta-analysis aimed to explore the correlation between the different doses of remifentanil-based anaesthesia and postoperative pain in randomised trials. METHODS: The electronic databases including PubMed, Cochrane, clinical trial registries, and Google Scholar were searched up to November 2022 for randomised controlled trials (RCTs) that assessed the dose dependent efficacy of remifentanil for postoperative pain intensity and hyperalgesia. RESULTS: 31 studies involving 2019 patients were included for analysis. Compared with the high remifentanil dose administration, patients in low doses showed less postoperative pain intensity at 1-2 h (weighted mean differences (WMD): 0.60, 95% CI, 0.05 to 1.15), 3-8 h (WMD: 0.38, 95% CI, 0.00 to 0.75), 24 h (WMD: 0.26, 95% CI, 0.04 to 0.48) and 48 h (WMD: 0.32, 95% CI, 0.09 to 0.55). Remifentanil-free regimen failed to decrease the pain score at 24 h (WMD: 0.10, 95% CI, -0.10 to 0.30) and 48 h (WMD: 0.15, 95% CI, -0.22 to 0.52) in comparison with remifentanil-based anaesthesia. After excluding trials with high heterogeneity, the dose of the remifentanil regimen was closely correlated with the postoperative pain score (P=0.03). In addition, the dose of the remifentanil regimen was not associated with the incidence of postoperative nausea and vomiting (PONV) (P=0.37). CONCLUSIONS: Our meta-analysis reveals that the low dose of remifentanil infusion is recommendable for general anaesthesia maintenance. No evidence suggests that remifentanil-free regimen has superiority in reducing postoperative pain. Moreover, remifentanil doesn't have a dose dependent effect in initiating PONV. TRIAL REGISTRATION: The protocol of present study was registered with PROSPERO (CRD42022378360).


Assuntos
Dor Pós-Operatória , Náusea e Vômito Pós-Operatórios , Humanos , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/uso terapêutico , Anestesia Geral , Hiperalgesia , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/induzido quimicamente , Náusea e Vômito Pós-Operatórios/induzido quimicamente , Remifentanil/administração & dosagem , Remifentanil/efeitos adversos , Remifentanil/uso terapêutico
15.
Free Radic Biol Med ; 210: 25-41, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37956909

RESUMO

Metabolic reprogramming of vascular smooth muscle cell (VSMC) plays a critical role in the pathogenesis of thoracic aortic dissection (TAD). Previous researches have mainly focused on dysregulation of fatty acid or glucose metabolism, while the impact of amino acids catabolic disorder in VSMCs during the development of TAD remains elusive. Here, we identified branched-chain amino acid (BCAA) catabolic defect as a metabolic hallmark of TAD. The bioinformatics analysis and data from human aorta revealed impaired BCAA catabolism in TAD individuals. This was accompanied by upregulated branched-chain α-ketoacid dehydrogenase kinase (BCKDK) expression and BCKD E1 subunit alpha (BCKDHA) phosphorylation, enhanced vascular inflammation, and hyperactivation of mTOR signaling. Further in vivo experiments demonstrated that inhibition of BCKDK with BT2 (a BCKDK allosteric inhibitor) treatment dephosphorylated BCKDHA and re-activated BCAA catabolism, attenuated VSMCs phenotypic switching, alleviated aortic remodeling, mitochondrial reactive oxygen species (ROS) damage and vascular inflammation. Additionally, the beneficial actions of BT2 were validated in a TNF-α challenged murine VSMC cell line. Meanwhile, rapamycin conferred similar beneficial effects against VSMC phenotypic switching, cellular ROS damage as well as inflammatory response. However, co-treatment with MHY1485 (a classic mTOR activator) reversed the beneficial effects of BT2 by reactivating mTOR signaling. Taken together, the in vivo and in vitro evidence showed that impairment of BCAA catabolism resulted in aortic accumulation of BCAA and further caused VSMC phenotypic switching, mitochondrial ROS damage and inflammatory response via mTOR hyperactivation. BCKDK and mTOR signaling may serve as the potential drug targets for the prevention and treatment of TAD.


Assuntos
Dissecção da Aorta Torácica , Músculo Liso Vascular , Animais , Humanos , Camundongos , Aminoácidos de Cadeia Ramificada/metabolismo , Inflamação/patologia , Músculo Liso Vascular/metabolismo , Espécies Reativas de Oxigênio , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
16.
Drug Des Devel Ther ; 17: 3151-3167, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37876500

RESUMO

Objective: Traditional Chinese medicine Polygonum cuspidatum (PC) has significant effects on reducing pain. In this study, we investigated the analgesic effects of the alcohol extract of PC on three types of inflammatory pain and explored its mechanism. Methods: Potential targets for the analgesic effects of the main active components of PC alcohol extract were screened by network pharmacology and molecular docking. Three different inflammatory pain mouse models (acetic acid twisting, formalin foot swelling, and xylene ear swelling) were used to study the analgesic effects of PC. The expression of latent signaling pathways in L4-6 spinal cord tissues in formalin foot swelling mice was evaluated using real-time qPCR (RT-qPCR), Western blot (WB), and immunohistochemistry (IHC) analyses. Results: Network pharmacology analysis shows that PC analgesic mechanism is related to the MAPK/ERK signaling pathway. The five main active components of PC have good docking ability with JNK and p38. PC alcohol extract significantly reduced the pain behavior and alleviated inflammatory reactions in three mouse models, inhibited the mRNA and protein phosphorylation levels of JNK, ERK, p38, and CREB in spinal cord tissues. Conclusion: PC alcohol extract can inhibit inflammation and alleviate pain, which is related to its inhibition of the MAPK/ERK signaling pathway in spinal cord. Thus, PC alcohol extract is a promising candidate for pain treatment.


Assuntos
Fallopia japonica , Ratos , Camundongos , Animais , Fallopia japonica/química , Ratos Sprague-Dawley , Simulação de Acoplamento Molecular , Dor/tratamento farmacológico , Transdução de Sinais , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Etanol , Inflamação/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Modelos Animais de Doenças , Formaldeído/farmacologia
17.
BMC Anesthesiol ; 23(1): 333, 2023 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-37798734

RESUMO

BACKGROUND: Postoperative sore throat (POST) is a common complaint after supraglottic airway device (SAD) application. Internal branch of the superior laryngeal nerve (iSLN) block has the potential to alleviate POST. The aim of this trial was to explore the effect of iSLN block in alleviating sore throat, as well as to identify the potential risk factors for POST after SAD insertion. METHODS: One hundred thirty-four patients scheduled for elective gynecological surgery were randomized to either group T: tetracaine syrup (1%) for local lubrication on i-gel supraglottic device (n = 67) or group B: i-gel insertion with water based lubricant on it and followed by bilateral iSLN block (ropivacaine, 0.375%, 2 ml for each side) (n = 67). Under ultrasound guidance, iSLN was exposed below thyrohyoid membrane. The primary outcome was the intensity of sore throat at 6 h after surgery. In addition, POST score at 0.5 h and 24 h, the severity of postoperative swallowing discomfort, acoustic analysis and complications were measured. RESULTS: Compared with tetracaine syrup for local lubrication, iSLN block resulted in a reduced intensity of POST at 0.5 h (P = 0.044, OR = 1.99, 95%CI 1.02 to 3.88) and 6 h (P < 0.001, OR = 5.07, 95%CI 2.53 to 10.14) after surgery, as well as less severity of swallowing discomfort (P < 0.001, OR = 2.21, 95%CI 1.63 to 2.99) and cough (P = 0.039, OR = 1.97, 95%CI 1.04 to 3.73). The patients after iSLN block presented lower jitter and shimmer value in acoustic analysis at 6 h after surgery (P < 0.001). CONCLUSIONS: iSLN block was effective in alleviating POST, improving voice function, as well as reducing postoperative swallowing discomfort and coughing. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2000037974) on 8th Sept 2020.


Assuntos
Anestesia por Condução , Nervos Laríngeos , Faringite , Humanos , Intubação Intratraqueal/métodos , Nervos Laríngeos/efeitos dos fármacos , Faringite/etiologia , Faringite/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Tetracaína/administração & dosagem , Bloqueio Nervoso , Resultado do Tratamento
18.
Planta ; 258(5): 99, 2023 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-37837470

RESUMO

MAIN CONCLUSION: Integrated root phenotypes and transcriptome analysis have revealed key candidate genes responsible for maize root growth and development in potassium deficiency. Potassium (K) is a vital macronutrient for plant growth, but our understanding of its regulatory mechanisms in maize root system architecture (RSA) and K+ uptake remains limited. To address this, we conducted hydroponic and field trials at different growth stages. K+ deficiency significantly inhibited maize root growth, with metrics like total root length, primary root length, width and maximum root number reduced by 50% to 80% during early seedling stages. In the field, RSA traits exhibited maximum values at the silking stage but continued to decline thereafter. Furthermore, K deprivation had a pronounced negative impact on root morphology and RSA growth and grain yield. RNA-Seq analysis identified 5972 differentially expressed genes (DEGs), including 17 associated with K+ signaling, transcription factors, and transporters. Weighted gene co-expression network analysis revealed 23 co-expressed modules, with enrichment of transcription factors at different developmental stages under K deficiency. Several DEGs and transcription factors were predicted as potential candidate genes responsible for maize root growth and development. Interestingly, some of these genes exhibited homology to well-known regulators of root architecture or development in Arabidopsis, such as Zm00001d014467 (AtRCI3), Zm00001d011237 (AtWRKY9), and Zm00001d030862 (AtAP2/ERF). Identifying these key genes helps to provide a deeper understanding of the molecular mechanisms governing maize root growth and development under nutrient deficient conditions offering potential benefits for enhancing maize production and improving stress resistance through targeted manipulation of RSA traits in modern breeding efforts.


Assuntos
Deficiência de Potássio , Zea mays , Zea mays/metabolismo , Deficiência de Potássio/genética , Transcriptoma/genética , Melhoramento Vegetal , Perfilação da Expressão Gênica , Fatores de Transcrição/genética , Genes Reguladores , Crescimento e Desenvolvimento , Regulação da Expressão Gênica de Plantas
19.
Medicine (Baltimore) ; 102(31): e34517, 2023 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-37543799

RESUMO

BACKGROUND: The transversus abdominis plane (TAP) block is commonly used in surgical practice for postoperative analgesia in abdominal surgery. However, numerous studies have demonstrated that TAP block is also suitable for intraoperative anesthesia of peritoneal dialysis catheter (PDC) insertion, although its efficacy and safety are still controversial. Local anesthetic infiltration (LAI) is currently the most general anesthesia strategy for PDC insertion. Consequently, we conducted this systematic review and meta-analysis to identify which anesthesia strategy is better between TAP block and LAI. METHODS: A systematic and comprehensive search was conducted on 5 databases, retrieving published and registered randomized controlled trials as of March 10, 2022, comparing the anesthesia effects of TAP block and LAI. The primary outcomes are the visual analogue scale (VAS) pain score of patients at various time points in the surgery. The secondary outcomes are the VAS pain score at rest at 2 and 24 hours postoperatively, intraoperative rescue anesthesia, general anesthesia switching rate, and PD-related complications. RESULTS: There were 9 trials with 432 patients identified. TAP block was more effective than LAI at reducing intraoperative and postoperative VAS pain scores in patients. Compared to LAI, TAP block significantly reduces the dosage of anesthetics used to rescue anesthesia during surgery, the general anesthesia switching rate, and the incidence of postoperative PD-related complications in patients. CONCLUSIONS: Our systematic review and meta-analysis proved that TAP block could be used as the primary anesthetic technique for PDC insertion, with superior anesthetic effects to LAI.


Assuntos
Bloqueio Nervoso , Diálise Peritoneal , Humanos , Anestésicos Locais , Músculos Abdominais , Bloqueio Nervoso/métodos , Diálise Peritoneal/efeitos adversos , Catéteres/efeitos adversos , Dor/complicações , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/etiologia , Analgésicos Opioides
20.
Angew Chem Int Ed Engl ; 62(33): e202304465, 2023 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-37338457

RESUMO

Senescent cells are the critical drivers of atherosclerosis formation and maturation. Mitigating senescent cells holds promise for the treatment of atherosclerosis. In an atherosclerotic plaque microenvironment, senescent cells interact with reactive oxygen species (ROS), promoting the disease development. Here, we hypothesize that a cascade nanozyme with antisenescence and antioxidant activities can serve as an effective therapeutic for atherosclerosis. An integrated cascade nanozyme with superoxide dismutase- and glutathione peroxidase-like activities, named MSe1 , is developed in this work. The obtained cascade nanozyme can attenuate human umbilical vein endothelial cell (HUVEC) senescence by protecting DNA from damage. It significantly weakens inflammation in macrophages and HUVECs by eliminating overproduced intracellular ROS. Additionally, the MSe1 nanozyme effectively inhibits foam cell formation in macrophages and HUVECs by decreasing the internalization of oxidized low-density lipoprotein. After intravenous administration, the MSe1 nanozyme significantly inhibits the formation of atherosclerosis in apolipoprotein E-deficient (ApoE-/- ) mice by reducing oxidative stress and inflammation and then decreases the infiltration of inflammatory cells and senescent cells in atherosclerotic plaques. This study not only provides a cascade nanozyme but also suggests that the combination of antisenescence and antioxidative stress holds considerable promise for treating atherosclerosis.


Assuntos
Aterosclerose , Placa Aterosclerótica , Humanos , Camundongos , Animais , Espécies Reativas de Oxigênio , Aterosclerose/tratamento farmacológico , Macrófagos , Células Endoteliais da Veia Umbilical Humana , Inflamação
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