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1.
J Adv Nurs ; 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38687803

RESUMEN

AIMS: To assess the level of mental workload (MWL) of intensive care unit (ICU) nurses in performing different human-machine tasks and examine the predictors of the MWL. DESIGN: A cross-sectional questionnaire study. METHODS: Between January and February 2021, data were collected from ICU nurses (n = 427) at nine tertiary hospitals selected from five (east, west, south, north, central) regions in China through an electronic questionnaire, including sociodemographic questions, the National Aeronautics and Space Administration Task Load Index, General Self-Efficacy Scale, Difficulty-assessing Index System of Nursing Operation Technique, and System Usability Scale. Descriptive statistics, t-tests, one-way ANOVA and multiple linear regression models were used. RESULTS: ICU nurses experienced a medium level of MWL (score 52.04 on a scale of 0-100) while performing human-machine tasks. ICU nurses' MWL was notably higher in conducting first aid and life support tasks (using defibrillators or ventilators). Predictors of MWL were task difficulty, system usability, professional title, age, self-efficacy, ICU category, and willingness to study emerging technology actively. Task difficulty and system usability were the strongest predictors of nearly all typical tasks. CONCLUSION: ICU nurses experience a medium MWL while performing human-machine tasks, but higher mental, temporal, and effort are perceived compared to physical demands. The MWL varied significantly across different human-machine tasks, among which are significantly higher: first aid and life support and information-based human-machine tasks. Task difficulty and system availability are decisive predictors of MWL. IMPACT: This is the first study to investigate the level of MWL of ICU nurses performing different representative human-machine tasks and to explore its predictors, which provides a reference for future research. These findings suggest that healthcare organizations should pay attention to the MWL of ICU nurses and develop customized management strategies based on task characteristics to maintain a moderate level of MWL, thus enabling ICU nurses to perform human-machine tasks better. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

2.
J Am Soc Nephrol ; 32(4): 866-885, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33627344

RESUMEN

BACKGROUND: Few therapies prevent venous neointimal hyperplasia (VNH) and venous stenosis (VS) formation in arteriovenous fistulas (AVF). Expression of the immediate early response gene X-1 (Iex-1), also known as Ier3, is associated with VNH and stenosis in murine AVFs. The study aimed to determine if local release of Ier3 long-acting inhibitor 1α,25(OH)2D3 from poly(lactic-co-glycolic acid) (PLGA) nanoparticles embedded in a thermosensitive Pluronic F127 hydrogel (1,25 NP) could affect VNH/VS formation in a large animal model. METHODS: Immediately after AVF creation in a porcine model of renal failure, 1,25 NP or vehicle control was injected into the adventitia space of AVF outflow veins. Scanning electron microscopy and dynamic light scattering characterized drug and control nanoparticles. Animals were sacrificed 3 and 28 days later for gene expression, immunohistologic, magnetic resonance imaging and angiography, and ultrasound analyses. Whole transcriptome RNA sequencing with differential gene expression analysis was performed on outflow veins of AVF. RESULTS: Encapsulation of 1α,25(OH)2D3 in PLGA nanoparticles formed nanoparticles of uniform size that were similar to nanoparticles without 1α,25(OH)2D3. The 1,25 NP-treated AVFs exhibited lower VNH/VS, Ier3 gene expression, and IER-3, MCP-1, CD68, HIF-1α, and VEGF-A immunostaining, fibrosis, and proliferation. Blood flow and lumen area increased significantly, whereas peak systolic velocity and wall shear stress decreased. Treatment increased Young's modulus and correlated with histologic assessment of fibrosis and with no evidence of vascular calcification. RNA sequencing analysis showed changes in the expression of genes associated with inflammatory, TGFß1, and apoptotic pathways. CONCLUSIONS: Local release of 1,25 NP improves AVF flow and hemodynamics, and reduces stenosis in association with reduction in inflammation, apoptosis, and fibrosis in a porcine model of arteriovenous fistula.

3.
J Am Soc Nephrol ; 31(8): 1781-1795, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32587073

RESUMEN

BACKGROUND: Percutaneous transluminal angioplasty (PTA) is the first line of treatment for stenosis in the arteriovenous fistula (AVF) created to provide access for hemodialysis, but resenosis still occurs. Transplants of adipose-derived mesenchymal stem cells (AMSCs) labeled with green fluorescent protein (GFP) to the adventitia could reduce pro-inflammatory gene expression, possibly restoring patency in a murine model of PTA for venous stenosis. METHODS: Partial nephrectomy of male C57BL/6J mice induced CKD. Placement of the AVF was 28 days later and, 14 days after that, PTA of the stenotic outflow vein was performed with delivery of either vehicle control or AMSCs (5×105) to the adventitia of the vein. Mice were euthanized 3 days later and gene expression for interleukin-1 beta (IL-1ß) and tumor necrosis factor-alpha TNF-α) analyzed, and histopathologic analysis performed on day 14 and 28. GFP (+) AMSCs were tracked after transplantation for up to 28 days and Doppler ultrasound performed weekly after AVF creation. RESULTS: Gene and protein expression of IL-1ß and TNF-α, fibrosis, proliferation, apoptosis and smooth muscle actin decreased, and the proportions of macrophage types (M2/M1) shifted in a manner consistent with less inflammation in AMSC-transplanted vessels compared to controls. After PTA, AMSC-treated vessels had significantly higher wall shear stress, average peak, and mean velocity, with increased lumen vessel area and decreased neointima/media area ratio compared to the control group. At 28 days after delivery, GFP (+) AMSC were present in the adventitia of the outflow vein. CONCLUSIONS: AMSC-treated vessels had improved vascular remodeling with decreased proinflammatory gene expression, inflammation, and fibrotic staining compared to untreated vessels.


Asunto(s)
Angioplastia/efectos adversos , Derivación Arteriovenosa Quirúrgica/efectos adversos , Oclusión de Injerto Vascular/prevención & control , Trasplante de Células Madre Mesenquimatosas , Animales , Antígenos CD/análisis , Antígenos de Diferenciación Mielomonocítica/análisis , Hemodinámica , Interleucina-1beta/fisiología , Antígeno Ki-67/análisis , Masculino , Ratones , Ratones Endogámicos C57BL , Óxido Nítrico Sintasa de Tipo II/análisis , RNA-Seq , Factor de Necrosis Tumoral alfa/fisiología
4.
Am J Physiol Renal Physiol ; 318(3): F565-F575, 2020 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-31813252

RESUMEN

Failure to mature and venous neointimal hyperplasia formation are the two major causes of hemodialysis arteriovenous fistula (AVF) vascular access failure. Percutaneous transluminal angioplasty (PTA) is the firstline treatment for both of these conditions, but, clinically, women have decreased patency rates compared with men. The hypothesis to be tested in the present study was that female mice after PTA of venous areas of higher intimal thickening have increased gene expression of transforming growth factor-ß1 (TGF-ß1) and TGF-ß receptor 1 (TGFß-R1) accompanied with histological changes of fibrosis compared with male mice. Seventeen male and eighteen female C57BL/6J mice were used in this study. Chronic kidney disease was induced by partial nephrectomy, and, 28 days later, an AVF was created to connect the left carotid artery to the right jugular vein. Two weeks later, the higher intimal thickening area was treated with PTA, and mice were euthanized 3 days later for gene expression analysis or 14 days later for histopathological analysis. Doppler ultrasound was performed weekly after AVF creation. At day 3, female AVF had significantly higher average gene expression of TGF-ß1 and TGFß-R1 compared with male AVF. At day 14, female outflow veins had a smaller venous diameter, lumen vessel area, decreased wall shear stress, lower average peak systolic velocity, and an increased neointima area-to-media area ratio. Moreover, female outflow veins showed a significant increase in α-smooth muscle actin and fibroblast-specific protein-1. There was a decrease in M1/M2 with an increase in CD68.


Asunto(s)
Angioplastia , Fístula Arteriovenosa/cirugía , Actinas/genética , Actinas/metabolismo , Animales , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/genética , Antígenos de Diferenciación Mielomonocítica/metabolismo , Arginasa/genética , Arginasa/metabolismo , Fístula Arteriovenosa/patología , Femenino , Regulación de la Expresión Génica , Masculino , Ratones Endogámicos C57BL , Cadenas Pesadas de Miosina/genética , Cadenas Pesadas de Miosina/metabolismo , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/genética , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Receptor Tipo I de Factor de Crecimiento Transformador beta/genética , Receptor Tipo I de Factor de Crecimiento Transformador beta/metabolismo , Proteína de Unión al Calcio S100A4/genética , Proteína de Unión al Calcio S100A4/metabolismo , Factores Sexuales , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismo , Regulación hacia Arriba
5.
Mol Ther ; 27(9): 1681-1693, 2019 09 04.
Artículo en Inglés | MEDLINE | ID: mdl-31326400

RESUMEN

The molecular mechanism of hemodialysis access arteriovenous fistula (AVF) failure due to venous neointimal hyperplasia (VNH) is not known. The role of microRNA-21 (miR-21) in VNH associated with AVF failure was investigated by performing in vivo and in vitro experiments. In situ hybridization results revealed that miR-21 expression increased and was associated with fibroblasts in failed AVFs from patients. In a murine AVF model, qRT-PCR gene expression results showed a significant increase in miR-21 and a decrease in miR-21 target genes in graft veins (GVs) compared to contralateral veins in mouse AVF. miR-21 knockdown in GVs was performed using a lentivirus-mediated small hairpin RNA (shRNA), and this improved AVF patency with a decrease in neointima compared to control GVs. Moreover, loss of miR-21 in GVs significantly decreased the Tgfß1, Col-Ia, and Col-Iva genes. Immunohistochemistry demonstrated a significant decrease in myofibroblasts and proliferation with an increase in terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining in miR-21-knockdown vessels, along with a decrease in hypoxia-inducible factor-1 alpha (HIF-1α) and phospho-SMAD2 (pSMAD-2) and phospho-SMAD3 (pSMAD-3) and an increase in phosphatase and tensin homolog (PTEN) staining. Hypoxic fibroblast knockdown for miR-21 showed a significant decrease in Tgfß-1 expression and pSMAD-2 and -3 levels and a decrease in myofibroblasts. These results indicate that miR-21 upregulation causes VNH formation by fibroblast-to-myofibroblast differentiation.


Asunto(s)
MicroARNs/genética , Neointima/genética , Neointima/patología , Venas/metabolismo , Venas/patología , Animales , Apoptosis/genética , Fístula Arteriovenosa/genética , Fístula Arteriovenosa/patología , Biomarcadores , Diferenciación Celular/genética , Proliferación Celular , Modelos Animales de Enfermedad , Fibroblastos/metabolismo , Fibrosis/genética , Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Hiperplasia , Hipoxia/genética , Hipoxia/metabolismo , Inmunohistoquímica , Lentivirus/genética , Masculino , Ratones , Miofibroblastos/metabolismo , Neointima/terapia , Interferencia de ARN , ARN Interferente Pequeño/genética , Transducción Genética
6.
J Vasc Interv Radiol ; 30(9): 1512-1521.e3, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30902494

RESUMEN

PURPOSE: To develop a clinically relevant model of percutaneous transluminal angioplasty (PTA) of venous stenosis in mice with arteriovenous fistula (AVF); to test the hypothesis that there is increased wall shear stress (WSS) after PTA; and to histologically characterize the vessels. MATERIALS AND METHODS: Thirteen C57BL/6J male mice, 6-8 weeks old, underwent partial nephrectomy to create chronic kidney disease. Twenty-eight days later, an AVF was created from the right external jugular vein to the left carotid artery. Fourteen days later, an angioplasty or sham procedure was performed, and the mice were sacrificed 14 days later for histologic evaluation to identify the cells contributing to the vascular remodeling (α-SMA, FSP-1, CD31, and CD68), proliferation (Ki-67), cell death (TUNEL), and hypoxia staining (HIF-1α). Histomorphometric analysis was performed to assess lumen area, neointima+media area, and cellular density. Ultrasound was performed weekly after creation of the AVF. RESULTS: Venous stenosis occurred 14 days after the creation of an AVF. PTA-treated vessels had significantly higher WSS; average peak systolic velocity, with increased lumen vessel area; and decreased neointima + media area compared to sham controls. There was a significant decrease in the staining of smooth muscle cells, fibroblasts, macrophages, HIF-1α, proliferation, and apoptosis and an increase in CD31-(+) cells. CONCLUSIONS: A clinically relevant model of PTA of venous stenosis in mice was created. PTA-treated vessels had increased lumen vessel area and WSS. The alterations in tissue markers of vascular remodeling, tissue hypoxia, proliferation, and cell death may be implications for future design of drug and device development.


Asunto(s)
Angioplastia , Derivación Arteriovenosa Quirúrgica/efectos adversos , Oclusión de Injerto Vascular/terapia , Venas Yugulares/cirugía , Insuficiencia Renal Crónica/terapia , Animales , Biomarcadores/metabolismo , Arterias Carótidas/cirugía , Proliferación Celular , Modelos Animales de Enfermedad , Oclusión de Injerto Vascular/diagnóstico por imagen , Oclusión de Injerto Vascular/metabolismo , Oclusión de Injerto Vascular/patología , Venas Yugulares/diagnóstico por imagen , Venas Yugulares/metabolismo , Venas Yugulares/patología , Masculino , Ratones Endogámicos C57BL , Neointima , Factores de Tiempo , Remodelación Vascular
7.
Drug Dev Ind Pharm ; 44(4): 563-569, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29148846

RESUMEN

OBJECTIVE: Curcumin being used to treat various chronic diseases while its poor bioavailability issue limited its wide clinical application as a therapeutic agent. The aim of this work was to prepare curcumin-loaded self-assembled micelles using soluplus and solutol®HS15 (SSCMs) to enhance curcumin's solubility and thus oral bioavailability. METHODS: Optimum formulation was investigated and the optimized ratio of drugs and excipients was obtained and the SSCMs were prepared via ethanol solvent evaporation method. The optimal SSCMs were characterized by transmission electron microscopy, drug content analysis including loading efficiency (LE%) and entrapment efficiency (EE%), and the cumulative amount of curcumin released from the micelles were all calculated using HPLC method. The in vitro cytotoxicity and the permeability of SSCMs were measured by Caco-2 cell monolayers and the oral bioavailability was evaluated by SD rats. KEY FINDINGS: The solubility of curcumin in self-assembled micelles was dramatically increased by 4200 times as compared to free curcumin. Caco-2 cells transport experiment exhibited that while soluplus and solutol®HS15 were self-assembled into micelles, it could not only promote the permeability of curcumin across membrane for better absorption, but also could restrain the curcumin pumped outside due to the role of P-gp efflux mechanism of soluplus and solutol®HS15. Furthermore, the prepared SSCMs formulation was almost nontoxic and had safety performance on Caco-2 cells model. Moreover, curcumin's oral bioavailability of SSCMs formulation in SD rats had doubled than that of free curcumin. CONCLUSIONS: The prepared SSCMs were characterized by PS, PDI, LE%, EE% data analysis. After the soluplus and solutol®HS15 were self assembled into micelles, both the solubility and membrane permeability of curcumin were evaluated to have been enhanced, as well as the effect of efflux pump of curcumin was inhibited, hence to promote oral absorption and generate an increased bioavailability.


Asunto(s)
Curcumina/administración & dosificación , Animales , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Disponibilidad Biológica , Células CACO-2 , Supervivencia Celular , Curcumina/química , Curcumina/farmacocinética , Composición de Medicamentos , Excipientes , Humanos , Micelas , Polietilenglicoles , Polivinilos , Ratas , Ratas Sprague-Dawley , Solubilidad , Solventes
8.
Echocardiography ; 34(10): 1495-1499, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28833419

RESUMEN

OBJECTIVE: To discuss the diagnostic value of multislice CT angiography (MSCTA) in acute aortic syndrome (AAS). MATERIALS AND METHODS: The clinical and imaging data of 36 cases diagnosed as AAS by MSCTA were collected. The manifestations of the MSCTA images were reviewed retrospectively, and the average x-ray dose was calculated. RESULTS: Among 36 AAS cases, 16 cases had aortic dissection (AD), 8 cases had penetrating atherosclerotic ulcer (PAU), 7 cases had intramural hematoma (IMH), and 5 cases had unstable thoracic aneurysm (UTA). Of 16 cases with AD, type A and type B accounted for 43.7% (7/16) and 56.3% (9/16), respectively. Of 7 cases with IMH, type A and type B accounted for 42.9% (3/7) and 57.1% (4/7), respectively. CONCLUSION: In spite of the x-ray radiation, MSCTA proves to be a rapid and noninvasive imaging technique for the diagnosis of AAS.


Asunto(s)
Aneurisma de la Aorta Torácica/diagnóstico por imagen , Enfermedades de la Aorta/diagnóstico por imagen , Disección Aórtica/diagnóstico por imagen , Hematoma/diagnóstico por imagen , Tomografía Computarizada Espiral/métodos , Úlcera/diagnóstico por imagen , Enfermedad Aguda , Adulto , Anciano , Anciano de 80 o más Años , Aorta/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dosis de Radiación , Reproducibilidad de los Resultados , Estudios Retrospectivos , Síndrome
9.
Echocardiography ; 34(2): 257-263, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27933648

RESUMEN

OBJECTIVE: To evaluate right ventricular function in patients with acute pulmonary embolism (APE) using electrocardiogram-gated CTA and to discuss the clinical value of pulmonary artery CTA PATIENTS AND METHODS: Based on death risk evaluation, 86 APE patients were divided into high-risk group (n=46) and non-high-risk group (n=40). The CT pulmonary embolism (PE) index and parameters of right ventricular function were analyzed from the CTPA images and compared between the two groups. Potential correlation between the two was also discussed. RESULT: CT PE index (median 24.69%) of the high-risk group was obviously higher than that of the non-high-risk group (median 8.58%) (P<.05). Except the diameter of superior vena cava, all other parameters of right ventricular function were significantly different between the two groups (P<.05). CT PE index was correlated with the parameters of right ventricular function. CONCLUSION: ECG-gated pulmonary artery CTA is suitable for assessing the severity of APE and right ventricular function.


Asunto(s)
Angiografía por Tomografía Computarizada/métodos , Electrocardiografía/métodos , Embolia Pulmonar/complicaciones , Disfunción Ventricular Derecha/complicaciones , Disfunción Ventricular Derecha/diagnóstico por imagen , Enfermedad Aguda , Adulto , Anciano , Femenino , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/fisiopatología , Curva ROC , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Disfunción Ventricular Derecha/fisiopatología , Adulto Joven
10.
Sports Med Health Sci ; 5(3): 196-204, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37753419

RESUMEN

During the Coronavirus disease (COVID-19), the physical activity of older adults is at a lower level. The study aimed to examine the effectiveness of aerobic dancing on physical fitness and cognitive function in older adults. We conducted a randomized controlled trial with 34 older adults who were assigned into an aerobic dancing group and a control group. Three dance sessions weekly for 60 â€‹min were scheduled for the aerobic dancing group for a total of 12 weeks. Physical fitness, blood pressure, lipids, glucose, cognitive function were assessed before and after the intervention. Baseline adjusted Analysis of Covariance (ANCOVA) was used to determine whether outcome variables varied between groups at pre-test and post-test. Effect size (Cohen's d) was calculated to determine the differences between groups from baseline to post-test. After 12 weeks, we found that the aerobic dancing group showed significant improvement in memory (portrait memory: F â€‹= â€‹10.45, p â€‹= â€‹0.003, d â€‹= â€‹1.18). The Limit of Stability (LOS) parameters in the aerobic dancing group displayed a significant increase after the intervention (right angle: F â€‹= â€‹5.90, p â€‹= â€‹0.022, d â€‹= â€‹0.60; right-anterior angle: F â€‹= â€‹4.23, p â€‹= â€‹0.049, d â€‹= â€‹0.12). Some beneficial effects were found on flexibility, grip strength, balance and subjective well-being (sit and reach: F â€‹= â€‹0.25, p â€‹= â€‹0.62, d â€‹= â€‹-0.40; grip strength: F â€‹= â€‹3.38, p â€‹= â€‹0.08, d â€‹= â€‹0.89; one-legged standing with eyes closed: F â€‹= â€‹1.26, p â€‹= â€‹0.27, d â€‹= â€‹0.50) in the aerobic dancing group. Aerobic dancing training was effective in improving memory and balance ability in older adults during the COVID-19 pandemic in China. In the future, aerobic dancing is a promising tool to encourage physical activity in older adults.

11.
J Ethnopharmacol ; 314: 116624, 2023 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-37182676

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Inflammation plays pivotal role in the development of chronic diseases. Reducing chronic inflammation is an important strategy for preventing and managing many chronic diseases. In traditional Chinese medicine, the processed Buthus martensii Karsch (BmK) scorpion (also called "Quanxie") has been used to treat chronic inflammatory arthritis and spondylitis for hundreds of years suggests that "Quanxie" could potentially be utilized as a resource for identifying new anti-inflammatory compounds. However, the molecular basis and the underline mechanism for the anti-inflammatory effect of processed BmK scorpion are still unclear. AIM OF THE STUDY: The study aims to determine the potential involvement of macrophage-expressed Kv1.3 in the anti-inflammatory effect of processed BmK scorpion venom, as well as to identify new Kv1.3 blockers derived from processed BmK scorpion. MATERIALS AND METHODS: In this study, the in vivo and in vitro anti-inflammatory activities were determined using carrageenan-induced paw edema, LPS-induced sepsis mouse models and LPS-induced macrophage activation model respectively. The effect of processed BmK scorpion water extract, processed BmK venom and BmKK2 on different potassium channels were detected by whole-cell voltage-clamp recordings on transfected HEK293 cells or mouse BMDMs. The cytokines were detected using Q-PCR and competitive enzyme-linked immunosorbent assay. High performance liquid chromatography, SDS-PAGE and peptide Mass Spectrometry analysis were used to isolate and identify the BmKK2. SiRNA, western blotting and flow cytometry were used to analysis the anti-inflammatory mechanism of BmKK2. RESULTS: Here we demonstrate that BmKK2, a thermostable toxin targeting Kv1.3 is the critical anti-inflammatory component in the processed BmK scorpion. BmKK2 inhibits inflammation by targeting and inhibiting the activity of macrophage Kv1.3, thereby inhibiting the activation of NF-κB-NLRP3 pathway and the subsequent release of inflammatory factors. CONCLUSIONS: These findings provide new insights into the molecular basis of the anti-inflammatory effects of "Quanxie" and highlight the importance of targeting Kv1.3 expressed on macrophages as an anti-inflammatory approach.


Asunto(s)
FN-kappa B , Venenos de Escorpión , Ratones , Humanos , Animales , Escorpiones/química , Escorpiones/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR , Lipopolisacáridos , Células HEK293 , Macrófagos/metabolismo , Inflamación , Venenos de Escorpión/farmacología , Venenos de Escorpión/química
12.
Virus Res ; 331: 199126, 2023 07 02.
Artículo en Inglés | MEDLINE | ID: mdl-37105436

RESUMEN

The emergence of Carbapenem-resistant Klebsiella pneumoniae (CRKP) represents a threat to public health. Polymyxin-B is generally considered a last-resort antibiotic. In this study, we isolated a carbapenem- and polymyxin-B resistant K. pneumoniae phage BL02 for the first time in Southwestern China and evaluated its biological characteristics and whole-genome sequence. Polymyxin-B resistant K. pneumoniae, (CK02), was isolated from the blood of a male with severe septic shock, and phage BL02 was screened and purified from the hospital sewage. BL02 could lyse 40 out of 46 CRKP isolates (86.96%) and has high activity in the pH range of 6-10 and the temperature range of 4-55 °C. The latency period of BL02 was about 10 min and the lysis period was about 50 min. The genome results showed that BL02 was a linear dsDNA with a total length of 175,595 bp and a GC content of 41.83%. A total of 275 ORFs were predicted and no tRNA, rRNA, drug resistance genes, or virulence genes were found in the genome. Phylogenetic analysis showed that BL02 belongs to the family Straboviridae. Treatment of infected mice with two antibiotics (tigecycline or ceftazidime/avibactam) resulted in 7-day survival rates of 28.57% and 42.86%, respectively. In contrast, the survival rate of mice in the single-dose BL02-treated group was 71.43%. In summary, this preclinical study isolated a phage capable of lysing polymyxin-B resistant K. pneumoniae and validated its safety and efficacy in an in vivo model, which provides a reference for further research on controlling MDR pathogens.


Asunto(s)
Bacteriófagos , Infecciones por Klebsiella , Masculino , Animales , Ratones , Polimixina B/farmacología , Polimixina B/uso terapéutico , Carbapenémicos/farmacología , Carbapenémicos/uso terapéutico , Klebsiella pneumoniae/genética , Aguas del Alcantarillado , Bacteriófagos/genética , Filogenia , Infecciones por Klebsiella/tratamiento farmacológico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Pruebas de Sensibilidad Microbiana
13.
J Clin Med ; 11(14)2022 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-35887748

RESUMEN

BACKGROUND: Aging and physical inactivity are associated with declines in physical fitness and cognitive function. Active video games have proven to be beneficial for the physical health of older adults, but the exact effect of active video games on physical fitness and cognitive function was still unclear. Based on self-determination theory (SDT), which is a widely used theory of healthy behavior change, this study aimed to explore the effects of an active video game intervention on fitness and cognitive function in older adults. METHODS: A total of 38 participants (mean age = 65.68 ± 3.78 years, 24 female) were randomly assigned to either an intervention group (active video game training) or a control group (no additional intervention). The participants in the intervention group trained for a total of 36 sessions (3 times per week for 50-55 min each) for 12 weeks. The control group continued with their normal daily living. The pre- and posttest measurements included: IPAQ-C score and physical fitness (BMI, body fat percent, blood pressure, reaction time, sit and reach, vital capacity, grip strength, static balance, blood biochemical tests for liver function, kidney function, blood lipids, glucose and insulin levels) and cognitive functions (processing speed, spatial ability, working memory, language ability, associative memory). RESULT: The intervention group showed a significantly smaller decrease in total average physical activity relative to the control group. BMI, vital capacity, systolic blood pressure, diastolic blood pressure, and spatial cognition significantly improved after training in the intervention group (BMI: F = 9.814, p = 0.004, d = -0.93, vital capacity: F = 4.708, p = 0.038, d = 0.67, systolic blood pressure: F = 5.28, p = 0.028, d = -0.68, diastolic blood pressure: F = 6.418, p = 0.016, d = -0.86, spatial cognition: F = 8.261, p = 0.007, d = 0.72). Three measures of static balance (closed eyes) also showed improvements after training (total length of swing: F = 3.728, d = -0.62, total velocity of swing: F = 3.740, d = -0.62, total area of swing: F = 2.920, d = -0.70). No significant training effects were evident in the results from the blood biochemical tests. CONCLUSION: This study indicates a positive influence of active video game training on physical fitness and cognitive function. The use of SDT-based active video game exercise as a feasible, safe, and effective training method for improving community older adults' healthy, promoting group cohesion, and increasing motivation to exercise.

14.
J Ethnopharmacol ; 288: 114998, 2022 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-35063590

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Chronic pain management represents a serious healthcare problem worldwide. The use of opioid analgesics for pain has always been hampered by their side effects; in particular, the addictive liability associated with chronic use. Finding a morphine replacement has been a long-standing goal in the field of analgesia. In traditional Chinese medicine, processed Buthus martensii Karsch (BmK) scorpion has been used as a painkiller to treat chronic inflammatory arthritis and spondylitis, so called "Scorpio-analgesia". However, the molecular basis and the underline mechanism for the Scorpio-analgesia are still unclear. AIM OF THE STUDY: The study aims to investigate the molecular basis of "Scorpio analgesia" and identify novel analgesics from BmK scorpion. MATERIALS AND METHODS: In this study, the analgesic abilities were determined using formalin-, acetic acid- and complete Freund's adjuvant-induced pain models. The effect of BmK venom and processed BmK venom on Nav1.7 were detected by whole-cell voltage-clamp recordings on HEK293-hNav1.7 stable cell line. Action potentials in Dorsal root ganglion (DRG) neurons induced by Makatoxin-3-R58A were recorded in current-clamp mode. The content of Makatoxin-3 was detected using competitive enzyme-linked immunosorbent assay based on the Makatoxin-3 antibody. High performance liquid chromatography, western blot and circular dichroism spectroscopy were used to analysis the stability of Makatoxin-3. RESULTS: Here we demonstrate that Makatoxin-3, an α-like toxin in BmK scorpion venom targeting Nav1.7 is the critical component in Scorpio-analgesia. The analgesic effect of Makatoxin-3 could not be reversed by naloxone and is more potent than Nav1.7-selective inhibitors and non-steroidal anti-inflammatory drugs in inflammatory models. Moreover, a R58A mutant of Makatoxin-3 is capable of eliciting analgesia effect without inducing pain response. CONCLUSIONS: This study advances ion channel biology and proposes Nav1.7 agonists, rather than the presumed Nav1.7-only blockers, for non-narcotic relief of chronic pain.


Asunto(s)
Analgésicos/farmacología , Inflamación/tratamiento farmacológico , Dolor/tratamiento farmacológico , Venenos de Escorpión/farmacología , Potenciales de Acción/efectos de los fármacos , Analgésicos/aislamiento & purificación , Animales , Modelos Animales de Enfermedad , Adyuvante de Freund , Ganglios Espinales/efectos de los fármacos , Células HEK293 , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Canal de Sodio Activado por Voltaje NAV1.7/efectos de los fármacos , Neuronas/efectos de los fármacos , Dolor/patología , Agonistas del Canal de Sodio Activado por Voltaje/aislamiento & purificación , Agonistas del Canal de Sodio Activado por Voltaje/farmacología
15.
Contrast Media Mol Imaging ; 2022: 2146343, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35069041

RESUMEN

Background: This study aims to evaluate the application of dual-energy computed tomography (DECT) for multiparameter quantitative measurement in early-stage hepatocellular carcinoma (HCC). Methods: The study retrospectively enrolled 30 patients with early-stage HCC and 43 patients with early-stage HCC who received radiofrequency ablation (RFA) and underwent abdomen enhanced CT scans in GSI mode. The GSI viewer was used for image display and data analysis. The regions of interest (ROIs) were delineated in the arterial phase and the venous phase. The optimal single energy value, CT values on different energy levels (40 keV, 70 keV, 100 keV, and 140 keV), the optimal energy level, the slope of the spectral attenuation curve, the effective atomic number (Z eff), iodine concentration (IC), water concentration (WC), normalized iodine concentration (NIC), and normalized water concentration (NWC) are measured and quantitatively analyzed. Results: The CT values of early-stage HCC at different single energy levels in dual phases were significantly different, and the single energy values were negatively correlated with the CT values. In the arterial phase and the venous phase, the optimal energy values for the best contrast-to-noise ratio were (68.34 ± 3.20) keV and (70.14 ± 2.01) keV, respectively. The slope of the spectral attenuation curve showed a downward trend at 40 keV, 70 keV, 100 keV, and 140 keV, but there was no statistically significant difference (P > 0.05). Z eff was positively correlated with IC and standardized IC, but has no significant correlation with WC and NWC in dual phases. Conclusion: DECT imaging contains multiparameter information and has different application values for early-stage HCC, and it is necessary to select the parameters reasonably for personalized and comprehensive evaluation.


Asunto(s)
Carcinoma Hepatocelular , Yodo , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagen , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos
16.
Front Plant Sci ; 13: 1043757, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36699859

RESUMEN

Oryza Sativa is one of the most important food crops in China, which is easily affected by drought during its growth and development. As a member of the calcium signaling pathway, CBL-interacting protein kinase (CIPK) plays an important role in plant growth and development as well as environmental stress. However, there is no report on the function and mechanism of OsCIPK17 in rice drought resistance. We combined transcriptional and metabonomic analysis to clarify the specific mechanism of OsCIPK17 in response to rice drought tolerance. The results showed that OsCIPK17 improved drought resistance of rice by regulating deep roots under drought stress; Response to drought by regulating the energy metabolism pathway and controlling the accumulation of citric acid in the tricarboxylic acid (TCA) cycle; Our exogenous experiments also proved that OsCIPK17 responds to citric acid, and this process involves the auxin metabolism pathway; Exogenous citric acid can improve the drought resistance of overexpression plants. Our research reveals that OsCIPK17 positively regulates rice drought resistance and participates in the accumulation of citric acid in the TCA cycle, providing new insights for rice drought resistance.

17.
World J Clin Cases ; 9(34): 10652-10658, 2021 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-35004997

RESUMEN

BACKGROUND: The treatment of small-cell lung cancer (SCLC) has progressed little in recent years because of its unique biological activities and complex genomic alterations. Chemotherapy combined with radiotherapy has been widely accepted as the first-line treatment for SCLC. CASE SUMMARY: Here, we present a 68-year-old male smoker who was diagnosed with SCLC of the right lung. After several cycles of concurrent chemoradiotherapy, the tumor progressed with broad metastasis to liver and bone. Histopathological examination showed an obvious transformation to adenocarcinoma, probably a partial recurrence mediated by the chemotherapy-based regimen. A mixed tumor as the primary lesion and transformation from SCLC or/and tumor stem cells may have accounted for the pathology conversion. We adjusted the treatment schedule in accord with the change in phenotype. CONCLUSION: Although diffuse skeletal and hepatic metastases were seen on a recent computed tomography scan, the patient is alive, with intervals of progression and shrinkage of his cancer.

18.
Front Physiol ; 12: 708651, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34489729

RESUMEN

Background: Acute type B aortic dissection is a highly serious aortic pathology. Aortic geometric parameters may be useful variables related to the occurrence of acute type B aortic dissection (aTBAD). The aim of the study is to delineate the alteration in aortic geometric parameters and analyze the specific geometric factors associated with aTBAD. Methods: The propensity score matching method was applied to control confounding factors. The aortic diameter, length, angulation, tortuosity, and type of aortic arch of the aTBAD and control group were retrospectively analyzed via three-dimensional computed tomography imaging created by the 3mensio software (version 10.0, Maastricht, The Netherlands). The geometric variables of true lumen and false lumen in the descending aorta were measured to estimate the severity of aortic dissection. Multivariable logistic regression models were used to investigate the significant and specific factors associated with aTBAD occurrence. The area under the receiver operating characteristic curve (AUC) was used to estimate the performance of the model. Results: After propensity score matching, 168 matched pairs of patients were selected. The ascending aorta and aortic arch diameters were dilated, and the ascending aorta and total aorta lengths were elongated in aTBAD group significantly (P < 0.001). The ascending aorta and aortic arch angulations in the aTBAD group were sharper than those of the controls (P = 0.01, P < 0.001, respectively). The aortic arch and total aorta tortuosities were significantly higher in the aTBAD group (P = 0.001, P < 0.001, respectively). There were more type III arch patients in the aTBAD group than the controls (67.9 vs. 22.6%). The true lumen angulation was sharper than that in the false lumen (P < 0.01). The true lumen tortuosity was significantly lower than that in the false lumen (P < 0.001). The multivariable models identified that aortic arch angulation, tortuosity, and type III arch were independent and specific geometric factors associated with aTBAD occurrence. The AUC of the multivariable models 1, 2, 3 were 0.945, 0.953, and 0.96, respectively. Conclusions: The sharper angulation and higher tortuosity of aortic arch and type III arch were the geometric factors associated with aTBAD in addition to the ascending aorta elongation and aortic arch dilation. The angulation and tortuosity of the true and false lumens may carry significant clinical implications for the treatment and prognosis of aTBAD.

19.
Front Immunol ; 12: 615859, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34220794

RESUMEN

Purpose: Systemic lupus erythematosus (SLE) is a serious autoimmune disease. Its molecular pathogenesis, especially the long non-coding RNA (lncRNA) function, remains unclear. We want to investigate the lncRNA dysregulation profile and their molecular mechanisms in SLE. Methods: In this study, we analyzed the transcriptome profiles (RNA-seq) of peripheral blood mononuclear cells (PBMCs) from SLE patients and two published transcriptome datasets to explore lncRNA profiles. The differentially expressed lncRNAs were confirmed by quantitative real-time PCR in another set of female patients. We constructed the lncRNA-mRNA regulatory networks by performing weighted gene co-expression network analysis (WGCNA). Dysregulated lncRNA AC007278.2 was repressed by short hairpin RNA (shRNA) in Jurkat cells. Dual-luciferase reporter gene assay was performed to investigate the regulatory mechanism of AC007278.2 on target gene CCR7. Results: We observed dominant up-regulation of transcripts, including mRNAs and lncRNAs, in SLE patients. By WGCNA method, we identified three modules that were highly related to SLE. We then focused on one lncRNA, AC007278.2, with a T-helper 1 lineage-specific expression pattern. We observed consistently higher AC007278.2 expression in SLE patients. Co-expression network revealed that AC007278.2 participated in the innate immune response and inflammatory bowel disease pathways. By knocking down AC007278.2 expression, we found that AC007278.2 could regulate the expression of inflammatory and cytokine stimulus response-related genes, including CCR7, AZU1, and TNIP3. AC007278.2 inhibits the functional CCR7 promoter to repress its transcription, thereby regulating autoimmunity and follicular T-helper cell differentiation. Conclusion: In summary, our study indicated the important regulatory role of lncRNAs in SLE. AC007278.2 may be treated as a novel biomarker for SLE diagnosis and treatment.


Asunto(s)
Centro Germinal/inmunología , Lupus Eritematoso Sistémico/genética , ARN Largo no Codificante/genética , Receptores CCR7/metabolismo , Células TH1/fisiología , Autoinmunidad/genética , Diferenciación Celular , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Marcadores Genéticos/genética , Humanos , Células Jurkat , Lupus Eritematoso Sistémico/diagnóstico , ARN Interferente Pequeño/genética , Receptores CCR7/genética , Transcriptoma , Regulación hacia Arriba
20.
Sci Rep ; 11(1): 4772, 2021 02 26.
Artículo en Inglés | MEDLINE | ID: mdl-33637886

RESUMEN

Percutaneous transluminal angioplasty (PTA) of stenotic arteriovenous fistulas (AVFs) is performed to maintain optimal function and patency. The one-year patency rate is 60% because of venous neointimal hyperplasia (VNH) and venous stenosis (VS) formation. Immediate early response gene X-1 (Iex-1) also known as Ier3 increases in response to wall shear stress (WSS), and can cause VNH/VS formation in murine AVF. In human stenotic samples from AVFs, we demonstrated increased gene expression of Ier3. We hypothesized that 1α, 25-dihydroxyvitamin D3, an inhibitor of IER3 delivered as 1α, 25-dihydroxyvitamin D3 encapsulated in poly lactic-co-glycolic acid (PLGA) nanoparticles loaded in Pluronic F127 hydrogel (1,25 NP) to the adventitia of the stenotic outflow vein after PTA would decrease VNH/VS formation by reducing Ier3 and chemokine (C-C motif) ligand 2 (Ccl2) expression. In our murine model of AVF stenosis treated with PTA, increased expression of Ier3 and Ccl2 was observed. Using this model, PTA was performed and 10-µL of 1,25 NP or control vehicle (PLGA in hydrogel) was administered by adventitial delivery. Animals were sacrificed at day 3 for unbiased whole genome transcriptomic analysis and at day 21 for immunohistochemical analysis. Doppler US was performed weekly after AVF creation. At day 3, significantly lower gene expression of Ier3 and Ccl2 was noted in 1,25 NP treated vessels. Twenty-one days after PTA, 1,25 NP treated vessels had increased lumen vessel area, with decreased neointima area/media area ratio and cell density compared to vehicle controls. There was a significant increase in apoptosis, with a reduction in CD68, F4/80, CD45, pro-inflammatory macrophages, fibroblasts, Picrosirius red, Masson's trichrome, collagen IV, and proliferation accompanied with higher wall shear stress (WSS) and average peak velocity. IER3 staining was localized to CD68 and FSP-1 (+) cells. After 1,25 NP delivery, there was a decrease in the proliferation of α-SMA (+) and CD68 (+) cells with increase in the apoptosis of FSP-1 (+) and CD68 (+) cells compared to vehicle controls. RNA sequencing revealed a decrease in inflammatory and apoptosis pathways following 1,25 NP delivery. These data suggest that adventitial delivery of 1,25 NP reduces VNH and venous stenosis formation after PTA.


Asunto(s)
Angioplastia , Fístula Arteriovenosa/terapia , Calcitriol/administración & dosificación , Constricción Patológica/tratamiento farmacológico , Vitaminas/administración & dosificación , Adulto , Adventicia/metabolismo , Anciano , Angioplastia/efectos adversos , Animales , Proteínas Reguladoras de la Apoptosis/antagonistas & inhibidores , Proteínas Reguladoras de la Apoptosis/genética , Fístula Arteriovenosa/genética , Calcitriol/uso terapéutico , Constricción Patológica/genética , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Femenino , Humanos , Masculino , Proteínas de la Membrana/antagonistas & inhibidores , Proteínas de la Membrana/genética , Ratones , Persona de Mediana Edad , Nanopartículas/química , Vitaminas/uso terapéutico
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