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2.
Sci Rep ; 14(1): 15735, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38977721

RESUMEN

The influence of precipitated nanophases on the mechanical properties of Fe-based amorphous nanocrystalline alloys is an urgent issue to be explored. Two amorphous nanocrystalline alloys, i.e., (Fe0.9Ni0.1)86B14 and (Fe0.7Ni0.3)86B14 containing nanophase of the body-centered cubic and face-centered cubic structures, respectively, were selected to investigate the effect of the structure and volume fraction of nanophase on their mechanical properties. The results of nanoindentation experiments and the calculation of the volume and size of the shear transition zone reveal that the two alloys show different mechanical properties. When the volume fraction of the nanophase in (Fe0.9Ni0.1)86B14 is larger than 50%, the elastic modulus is increased suddenly and the volume and size of the shear transition zone is decreased dramatically, while no dramatic change occurs in (Fe0.7Ni0.3)86B14. Moreover, it was found by using molecular dynamics simulations that the main reason for these abnormal mechanical properties is the change of cluster type in the system due to the incorporation of nanophases with different structures.

3.
Front Cardiovasc Med ; 11: 1409775, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39015680

RESUMEN

Background: Catastrophic Antiphospholipid Syndrome (CAPS), a severe systemic autoimmune disorder, predominantly causes life-threatening multi-organ failure, with a high mortality rate. It primarily affects small vessels, seldom impacting large vessels. Notably, acute massive pulmonary embolism (PE) with bilateral atrial thrombosis is an exceptional occurrence in CAPS. Acute pulmonary embolism (PE) is a common cardiovascular disease that progresses rapidly and has a high mortality rate. Acute massive PE combined with bilateral atrial thrombosis has an even higher mortality rate. PE treatments primarily include pharmaceuticals, catheter interventions, and surgical measures, with integrated treatment strategies demonstrating promising outcomes in clinical practice. Extracorporeal membrane oxygenation (ECMO) can provide cardiopulmonary support for the treatment of high-risk PE patients and is a proven therapeutic measure. Methods: This report presents the case of a 52-year-old male admitted due to fever and sudden onset of impaired consciousness, with cardiac ultrasound and pulmonary artery CT angiography revealing an acute large-scale pulmonary embolism accompanied by bilateral atrial thrombosis, with the condition rapidly worsening and manifesting severe respiratory and circulatory failure. With ECMO support, the patient underwent a thrombectomy using an AngioJet intervention. The diagnosis of CAPS was confirmed through clinical presentation and laboratory examination, and treatment was adjusted accordingly. Results: The patient made a successful recovery and was subsequently discharged from the hospital. Conclusion: In CAPS patients, the rare instance of acute massive PE accompanied by bilateral atrial thrombosis significantly risks severe respiratory and circulatory failure, adversely affecting prognosis. Early initiation of ECMO therapy is crucial, offering a vital opportunity to address the root cause. In this case report the patient was successfully treated with an AngioJet thrombectomy supported by ECMO.

4.
Signal Transduct Target Ther ; 9(1): 183, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38972904

RESUMEN

Helicobacter pylori (H. pylori) is currently recognized as the primary carcinogenic pathogen associated with gastric tumorigenesis, and its high prevalence and resistance make it difficult to tackle. A graph neural network-based deep learning model, employing different training sets of 13,638 molecules for pre-training and fine-tuning, was aided in predicting and exploring novel molecules against H. pylori. A positively predicted novel berberine derivative 8 with 3,13-disubstituted alkene exhibited a potency against all tested drug-susceptible and resistant H. pylori strains with minimum inhibitory concentrations (MICs) of 0.25-0.5 µg/mL. Pharmacokinetic studies demonstrated an ideal gastric retention of 8, with the stomach concentration significantly higher than its MIC at 24 h post dose. Oral administration of 8 and omeprazole (OPZ) showed a comparable gastric bacterial reduction (2.2-log reduction) to the triple-therapy, namely OPZ + amoxicillin (AMX) + clarithromycin (CLA) without obvious disturbance on the intestinal flora. A combination of OPZ, AMX, CLA, and 8 could further decrease the bacteria load (2.8-log reduction). More importantly, the mono-therapy of 8 exhibited comparable eradication to both triple-therapy (OPZ + AMX + CLA) and quadruple-therapy (OPZ + AMX + CLA + bismuth citrate) groups. SecA and BamD, playing a major role in outer membrane protein (OMP) transport and assembling, were identified and verified as the direct targets of 8 by employing the chemoproteomics technique. In summary, by targeting the relatively conserved OMPs transport and assembling system, 8 has the potential to be developed as a novel anti-H. pylori candidate, especially for the eradication of drug-resistant strains.


Asunto(s)
Antibacterianos , Berberina , Aprendizaje Profundo , Helicobacter pylori , Helicobacter pylori/efectos de los fármacos , Berberina/farmacología , Berberina/química , Berberina/farmacocinética , Antibacterianos/farmacología , Antibacterianos/química , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Pruebas de Sensibilidad Microbiana , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple/genética , Animales , Omeprazol/farmacología , Claritromicina/farmacología , Amoxicilina/farmacología
5.
Artículo en Inglés | MEDLINE | ID: mdl-38974772

RESUMEN

Barth syndrome (BTHS) is a mitochondrial lipid disorder caused by mutations in TAFAZZIN (TAZ), required for cardiolipin (CL) remodeling. Cardiomyopathy is a major clinical feature, with no curative therapy. Linoleic acid (LA) supplementation is proposed to ameliorate BTHS cardiomyopathy by enhancing linoleoyl group incorporation into CL. While the beneficial effect of dietary LA supplementation in delaying the development of BTHS cardiomyopathy has been recently tested, its potential to reverse established BTHS cardiomyopathy remains unclear. Our study revealed that LA supplementation cannot rescue established BTHS cardiomyopathy in mice, highlighting the importance of early initiation of LA supplementation for maximum benefits.

6.
Adv Healthc Mater ; : e2400254, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38857027

RESUMEN

Lipid-lowering drugs, especially statins, are extensively utilized in clinical settings for the prevention of hyperlipidemia. Nevertheless, prolonged usage of current lipid-lowering medications is associated with significant adverse reactions. Therefore, it is imperative to develop novel therapeutic agents for lipid-lowering therapy. In this study, a chenodeoxycholic acid and lactobionic acid double-modified polyethyleneimine (PDL) nanocomposite as a gene delivery vehicle for lipid-lowering therapy by targeting the liver, are synthesized. Results from the in vitro experiments demonstrate that PDL exhibits superior transfection efficiency compared to polyethyleneimine in alpha mouse liver 12 (AML12) cells and effectively carries plasmids. Moreover, PDL can be internalized by AML12 cells and rapidly escape lysosomal entrapment. Intravenous administration of cyanine5.5 (Cy5.5)-conjugated PDL nanocomposites reveals their preferential accumulation in the liver compared to polyethyleneimine counterparts. Systemic delivery of low-density lipoprotein receptor plasmid-loaded PDL nanocomposites into mice leads to reduced levels of low-density lipoprotein cholesterol (LDL-C) and triglycerides (TC) in the bloodstream without any observed adverse effects on mouse health or well-being. Collectively, these findings suggest that low-density lipoprotein receptor plasmid-loaded PDL nanocomposites hold promise as potential therapeutics for lipid-lowering therapy.

7.
Acta Biomater ; 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38901753

RESUMEN

The treatment of sepsis caused by multidrug-resistant (MDR) Gram-negative bacterial infections remains challenging. With these pathogens exhibiting resistance to carbapenems and new generation cephalosporins, the traditional antibiotic polymyxin B (PMB) has reemerged as a critical treatment option. However, its severe neurotoxicity and nephrotoxicity greatly limit the clinical application. Therefore, we designed negatively charged high-density lipoprotein (HDL) mimicking nanodiscs as a PMB delivery system, which can simultaneously reduce toxicity and enhance drug efficacy. The negative charge prevented the PMB release in physiological conditions and binding to cell membranes, significantly reducing toxicity in mammalian cells and mice. Notably, nanodisc-PMB exhibits superior efficacy than free PMB in sepsis induced by carbapenem-resistant Acinetobacter baumannii (CRAB) strains. Nanodisc-PMB shows promise as a treatment for carbapenem-resistant Gram-negative bacterial sepsis, especially caused by Acinetobacter baumannii, and the nanodiscs could be repurposed for other toxic antibiotics as an innovative delivery system. STATEMENT OF SIGNIFICANCE: Multidrug-resistant Gram-negative bacteria, notably carbapenem-resistant Acinetobacter baumannii, currently pose a substantial challenge due to the scarcity of effective treatments, rendering Polymyxins a last-resort antibiotic option. However, their therapeutic application is significantly limited by severe neurotoxic and nephrotoxic side effects. Prevailing polymyxin delivery systems focus on either reducing toxicity or enhancing bioavailability yet fail to simultaneously achieve both. In this scenario, we have developed a distinctive HDL-mimicking nanodisc for polymyxin B, which not only significantly reduces toxicity but also improves efficacy against Gram-negative bacteria, especially in sepsis caused by CRAB. This research offers an innovative drug delivery system for polymyxin B. Such advancement could notably improve the therapeutic landscape and make a significant contribution to the arsenal against these notorious pathogens.

8.
Artículo en Inglés | MEDLINE | ID: mdl-38915260

RESUMEN

BACKGROUND: Homozygous phytosterolaemia, is a rare autosomal recessive disorder which lead to severely elevated plasma levels of plant phytosterols causing an increased risk of coronary artery disease (CAD) and mimics the clinical presentation of familial hypercholesterolaemia(FH). Integration of the genetic variants for homozygous phytosterolaemia into the genetic panel for FH in clinical practice likely increases the detection of milder genetic forms of phytosterolaemia, of which the implications to clinical practice including cascade testing remain unclear. RESULTS: We report three families with pathogenic loss-of-function variants in ABCG5 and/or ABCG8, in which probands were identified incidentally when genetically testing them for FH. The proband of the first family was a 35-year-old man with a homozygous ABCG5 loss-of-function variant (c.1336C > T, p.Arg446*) causing severe phytosterolaemia and premature CAD on cardiac imaging; his younger brother was heterozygous for the same variant with mildly elevated phytosterol levels. The second family included 2 sisters (31 and 29-year-old) with digenic variants in ABCG5 (c.1336C > T, p.Arg446*) and ABCG8 (c.1269G > T, p.Glu423Asp with uncertain significance) with moderately elevated plasma phytosterol levels and premature CAD on cardiac imaging. The third family referred to a 68-year-old man and his 44-year-old daughter who were both heterozygous for a pathogenic ABCG5 variant (c.1166G > A, p.Arg389His), had mild phytosterolaemia and CAD on cardiac imaging. Treatment with ezetimibe alone or in combination with colesevelam reduced elevated plasma sitosterol and campesterol concentrations by 30 to 80%. CONCLUSION: Phytosterolaemia is specific genetic disorder that can mimic FH, cause premature atherosclerosis, and require specific pharmacotherapy. Cascade testing for pathogenic ABCG5/G8 variants can lead to earlier detection and treatment of affected family members.

9.
Int Immunopharmacol ; 137: 112355, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-38851158

RESUMEN

One major obstacle in the treatment of cancer is the presence of proteins resistant to cancer therapy, which can impede the effectiveness of traditional approaches such as radiation and chemotherapy. This resistance can lead to disease progression and cause treatment failure. Extensive research is currently focused on studying these proteins to create tailored treatments that can circumvent resistance mechanisms. CLU (Clusterin), a chaperone protein, has gained notoriety for its role in promoting resistance to a wide range of cancer treatments, including chemotherapy, radiation therapy, and targeted therapy. The protein has also been discovered to have a role in regulating the immunosuppressive environment within tumors. Its ability to influence oncogenic signaling and inhibit cell death bolster cancer cells resistant against treatments, which poses a significant challenge in the field of oncology. Researchers are actively investigating to the mechanisms by which CLU exerts its resistance-promoting effects, with the ultimate goal of developing strategies to circumvent its impact and enhance the effectiveness of cancer therapies. By exploring CLU's impact on cancer, resistance mechanisms, tumor microenvironment (TME), and therapeutic strategies, this review aims to contribute to the ongoing efforts to improve cancer treatment outcomes.


Asunto(s)
Clusterina , Resistencia a Antineoplásicos , Neoplasias , Microambiente Tumoral , Humanos , Clusterina/metabolismo , Neoplasias/inmunología , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Animales , Microambiente Tumoral/inmunología
10.
Exp Cell Res ; 440(1): 114117, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38848952

RESUMEN

PURPOSE: Membrane associated ubiquitin ligase MARCH2 majorly involves in inflammation response and protein trafficking. However, its comprehensive role in hepatocellular carcinoma (HCC) is largely unknown. METHODS: Firstly, multiple bioinformatic analyses were applied to determine MARCH2 mRNA level, its expression comparison in diverse molecular and immune subtypes, and diagnostic value in HCC. Subsequently, RNA-seq, real-time quantitative PCR, immunohistochemistry and cell proliferation assay are used to explore the epithelial-mesenchymal transition (EMT) and proliferation by gene-silencing or overexpressing in cultured HCC cells or in vivo xenograft. Moreover, dual luciferase reporter assay and immunoblotting are delved into verify the transcription factor that activating MARCH2 promoter. RESULTS: Multiple bioinformatic analyses demonstrate that MARCH2 is upregulated in multiple cancer types and exhibits startling diagnostic value as well as distinct molecular and immune subtypes in HCC. RNA-seq analysis reveals MARCH2 may promote EMT, cell proliferation and migration in HepG2 cells. Furthermore, overexpression of MARCH2 triggers EMT and significantly enhances HCC cell migration, proliferation and colony formation in a ligase activity-dependent manner. Additionally, above observations are validated in the HepG2 mice xenografts. For up-stream mechanism, transcription factor KLF15 is highly expressed in HCC and activates MARCH2 expression. CONCLUSION: KLF15 activated MARCH2 triggers EMT and serves as a fascinating biomarker for precise diagnosis of HCC. Consequently, MARCH2 emerges as a promising candidate for target therapy in cancer management.


Asunto(s)
Carcinoma Hepatocelular , Movimiento Celular , Proliferación Celular , Transición Epitelial-Mesenquimal , Regulación Neoplásica de la Expresión Génica , Factores de Transcripción de Tipo Kruppel , Neoplasias Hepáticas , Ubiquitina-Proteína Ligasas , Animales , Femenino , Humanos , Masculino , Ratones , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/metabolismo , Movimiento Celular/genética , Proliferación Celular/genética , Transición Epitelial-Mesenquimal/genética , Células Hep G2 , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/diagnóstico , Ratones Endogámicos BALB C , Ratones Desnudos , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo
11.
Eur J Pediatr ; 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38888644

RESUMEN

PURPOSE: Familial hypercholesterolemia (FH) leads to elevated low-density lipoprotein cholesterol levels, which increases the risk of premature atherosclerotic cardiovascular disease (ASCVD). Since the first functional and morphologic changes of the arterial wall occur in childhood, treatment should start early in childhood to mitigate the elevated risk of ASCVD. Pediatricians play an important role in the detection and care of children with FH. In this study, we aim to explore potential gaps in FH care amongst Dutch pediatricians, in order to enhance their knowledge and awareness of detecting and treating children with FH. METHODS: An anonymous online survey, deployed using Google Forms, including 26 closed and semi-closed questions on FH care in children was distributed by the Dutch Association of Pediatrics via a newsletter to which the majority of the practicing Dutch pediatricians subscribe. In addition, we requested that the pediatric departments of all Dutch hospitals in the Netherlands distribute this survey personally among their employed pediatricians. Respondents were instructed to answer the questions without any help or use of online resources. RESULTS: Between September 1st, 2023 and November 1st, 2023, 158 (an estimated 11% response rate) Dutch pediatricians completed the survey. They reported a median (IQR) of 15.0 (6.0-22.0) years of experience as a pediatrician, and 34 (21.5%) were working in academic hospitals. The majority (76.6%) of pediatricians correctly identified a typical FH lipid profile but 68 (43.0%) underestimated the true prevalence of FH (1:300). Underestimation and unawareness of the increased risk of FH patients for ASCVD were reported by 37.3% and 25.9% of pediatricians, respectively. Although 70.9% of the pediatricians correctly defined FH, only 67 (42.4%) selected statins and ezetimibe to treat severe hypercholesterolemia. CONCLUSIONS: The results of this study suggest significant gaps in knowledge and awareness of FH in children among Dutch pediatricians. FH care in children needs improvement through educational and training initiatives to mitigate the life-long risk of ASCVD from early life. WHAT IS KNOWN: • Familial hypercholesterolemia (FH) leads to elevated LDL-cholesterol levels, which increases the risk of premature atherosclerotic cardiovascular disease (ASCVD). • The process of atherosclerosis starts in childhood • Pediatricians play an important role in the detection and treatment of children with FH. WHAT IS NEW: • Our results highlight significant gaps in care for children with FH amongst pediatricians and this may lead to suboptimal detection and treatment. • FH care in children needs improvement by educational initiatives to ultimately prevent ASCVD in adulthood.

12.
Artículo en Inglés | MEDLINE | ID: mdl-38804624

RESUMEN

BACKGROUND: The aim of this study was using bioinformatic tools to identify hub genes in the relationship between septic cardiomyopathy (SCM) and cuproptosis and predict potential Chinese herbal drug candidates. METHODS: SCM datasets were downloaded from the gene expression omnibus. Cuproptosis related genes were collected from a research published on Science in March, 2022. The expression profiles of genes related to cuproptosis in SCM were extracted. Differentially expressed genes (DEGs) were analyzed using R package limma. A single-sample gene set enrichment analysis was conducted to measure the correlation between DEGs and immune cell infiltration. Hub genes were screened out by random forest model. Finally, HERB database and COREMINE database were used to predict Chinese herbal drugs for hub genes and carry out molecular docking. RESULTS: A total of 9 DEGs were identified. Cuproptosis differential genes PDHB, DLAT, DLD, FDX1, GCSH, LIAS were significantly correlated with one or more cells and their functions in immune infiltration. The random forest model screened pyruvate dehydrogenase E1 beta subunit (PDHB) as the hub gene. PDHB was negatively correlated with Plasmacytoid dendritic cell infiltration. Pyruvic acid, rhodioloside and adenosine were predicted with PDHB as the target, and all three components are able to bind to PDHB. CONCLUSIONS: Cuproptosis related gene PDHB is associated with the occurrence and immune infiltration of septic cardiomyopathy. Rhodioloside and other Chinese herbal drugs may play a role in the treatment of SCM by regulating the expression of PDHB.

13.
Neth Heart J ; 32(5): 213-220, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38573436

RESUMEN

BACKGROUND: Familial hypercholesterolaemia (FH) warrants early diagnosis to prevent premature atherosclerotic cardiovascular disease (CVD). However, underdiagnosis and undertreatment of FH persist. This study aimed to assess the knowledge and practice of FH care among general practitioners (GPs) in the Netherlands. METHODS: An internationally standardised, online questionnaire was sent to Dutch GPs between February 2021 and July 2022. The survey assessed knowledge and awareness of FH, encompassing general familiarity, awareness of management guidelines, inheritance, prevalence, CVD risk, and clinical practice related to FH. Comparative analysis was performed using data on primary care physicians from Western Australia, the Asia-Pacific region and the United Kingdom. RESULTS: Of the 221 participating GPs, 62.4% rated their familiarity with FH as above average (score > 4 on a 1-7 scale), with 91.4% considering themselves familiar with FH treatment and referral guidelines. Correct identification of the FH definition, typical lipid profile, inheritance pattern, prevalence and CVD risk was reported by 83.7%, 87.8%, 55.7%, 19.5%, and 13.6% of the respondents, respectively. Of the participants, 58.4% answered fewer than half of the 8 knowledge questions correctly. Dutch GPs reported greater FH familiarity and guideline awareness compared with their international counterparts but exhibited similar low performance on FH knowledge questions. CONCLUSION: Despite the Netherlands' relatively high FH detection rate, substantial knowledge gaps regarding FH persist among Dutch GPs, mirroring global trends. Enhanced FH education and awareness in primary care are imperative to improve FH detection and ensure adequate treatment. Targeting the global suboptimal understanding of FH might require international efforts.

14.
Cancer Imaging ; 24(1): 50, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38605380

RESUMEN

OBJECTIVE: The preoperative identification of tumor grade in chondrosarcoma (CS) is crucial for devising effective treatment strategies and predicting outcomes. The study aims to build and validate a CT-based radiomics nomogram (RN) for the preoperative identification of tumor grade in CS, and to evaluate the correlation between the RN-predicted tumor grade and postoperative outcome. METHODS: A total of 196 patients (139 in the training cohort and 57 in the external validation cohort) were derived from three different centers. A clinical model, radiomics signature (RS) and RN (which combines significant clinical factors and RS) were developed and validated to assess their ability to distinguish low-grade from high-grade CS with area under the curve (AUC). Additionally, Kaplan-Meier survival analysis was applied to examine the association between RN-predicted tumor grade and recurrence-free survival (RFS) of CS. The predictive accuracy of the RN was evaluated using Harrell's concordance index (C-index), hazard ratio (HR) and AUC. RESULTS: Size, endosteal scalloping and active periostitis were selected to build the clinical model. Three radiomics features, based on CT images, were selected to construct the RS. Both the RN (AUC, 0.842) and RS (AUC, 0.835) were superior to the clinical model (AUC, 0.776) in the validation set (P = 0.003, 0.040, respectively). A correlation between Nomogram score (Nomo-score, derived from RN) and RFS was observed through Kaplan-Meier survival analysis in the training and test cohorts (log-rank P < 0.050). Patients with high Nomo-score tumors were 2.669 times more likely to suffer recurrence than those with low Nomo-score tumors (HR, 2.669, P < 0.001). CONCLUSIONS: The CT-based RN performed well in predicting both the histologic grade and outcome of CS.


Asunto(s)
Neoplasias Óseas , Condrosarcoma , Humanos , Nomogramas , Radiómica , Condrosarcoma/diagnóstico por imagen , Neoplasias Óseas/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Estudios Retrospectivos
15.
Liver Int ; 44(7): 1668-1679, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38554044

RESUMEN

BACKGROUND: Liver ischaemia/reperfusion (I/R) injury, which is an inevitable clinical problem of liver resection, liver transplantation and haemorrhagic shock. Fibroblast growth factor 21 (FGF21) was intimately coupled with multiple metabolic processes and proved to protect against apoptosis and inflammatory response in hepatocytes during hepatic I/R injury. However, the regulatory mechanisms of FGF21 in hepatic I/R injury remains unknown. Therefore, we hypothesize that FGF21 protects hepatic tissues from I/R injury. METHODS: Blood samples were available from haemangiomas patients undergoing hepatectomy and murine liver I/R model and used to further evaluate the serum levels of FGF21 both in humans and mice. We further explored the regulatory mechanisms of FGF21 in murine liver I/R model by using FGF21-knockout mice (FGF21-KO mice) and FGF21-overexpression transgenic mice (FGF21-OE mice) fed a high-fat or ketogenic diet. RESULTS: Our results show that the circulating levels of FGF21 were robustly decreased after liver I/R in both humans and mice. Silencing FGF21 expression with FGF21-KO mice aggravates liver injury at 6 h after 75 min of partial liver ischaemia, while FGF21-OE mice display alleviated hepatic I/R injury and inflammatory response. Compared with chow diet mice, exogenous FGF21 decreases the levels of aminotransferase, histological changes, apoptosis and inflammatory response in hepatic I/R injury treatment mice with a high-fat diet. Meanwhile, ketogenic diet mice are not sensitive to hepatic I/R injury. CONCLUSIONS: The circulating contents of FGF21 are decreased during liver warm I/R injury and exogenous FGF21 exerts hepatoprotective effects on hepatic I/R injury. Thus, FGF21 regulates hepatic I/R injury and may be a key therapeutic target.


Asunto(s)
Modelos Animales de Enfermedad , Factores de Crecimiento de Fibroblastos , Hígado , Ratones Noqueados , Daño por Reperfusión , Factores de Crecimiento de Fibroblastos/metabolismo , Factores de Crecimiento de Fibroblastos/genética , Animales , Daño por Reperfusión/prevención & control , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Humanos , Ratones , Hígado/patología , Hígado/metabolismo , Masculino , Ratones Endogámicos C57BL , Apoptosis , Hígado Graso/patología , Hígado Graso/genética , Hepatocitos/metabolismo , Hepatocitos/patología , Ratones Transgénicos , Femenino , Hepatectomía
17.
Phytomedicine ; 128: 155400, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38518641

RESUMEN

BACKGROUND: The emergence and spread of vancomycin-resistant enterococci (VRE) have posed a significant challenge to clinical treatment, underscoring the need to develop novel strategies. As therapeutic options for VRE are limited, discovering vancomycin enhancer is a feasible way of combating VRE. Gambogic acid (GA) is a natural product derived from the resin of Garcinia hanburyi Hook.f. (Clusiaceae), which possesses antibacterial activity. PURPOSE: This study aimed to investigate the potential of GA as an adjuvant to restore the susceptibility of VRE to vancomycin. METHODS: In vitro antibacterial and synergistic activities were evaluated against vancomycin-susceptible and resistant strains by the broth microdilution method for the Minimal Inhibitory Concentrations (MICs) determination, and checkerboard assay and time-kill curve analysis for synergy evaluation. In vivo study was conducted on a mouse multi-organ infection model. The underlying antibacterial mechanism of GA was also explored. RESULTS: GA showed a potent in vitro activity against all tested strains, with MICs ranging from 2 to 4 µg/ml. The combination of GA and vancomycin exhibited a synergistic effect against 18 out of 23 tested VRE strains, with a median fractional inhibitory concentration index (FICI) of 0.254, and demonstrated a synergistic effect in the time-kill assay. The combination therapy exhibited a significant reduction in tissue bacterial load compared with either compound used alone. GA strongly binds to the ParE subunit of topoisomerase IV, a bacterial type II DNA topoisomerase, and suppresses its activity. CONCLUSIONS: The study suggests that GA has a significant antibacterial activity against enterococci, and sub-MIC concentrations of GA can restore the activity of vancomycin against VRE in vitro and in vivo. These findings indicate that GA has the potential to be a new antibacterial adjuvant to vancomycin in the treatment of infections caused by VRE.


Asunto(s)
Antibacterianos , Sinergismo Farmacológico , Pruebas de Sensibilidad Microbiana , Enterococos Resistentes a la Vancomicina , Vancomicina , Xantonas , Xantonas/farmacología , Animales , Enterococos Resistentes a la Vancomicina/efectos de los fármacos , Antibacterianos/farmacología , Vancomicina/farmacología , Ratones , Garcinia/química , Femenino , Infecciones por Bacterias Grampositivas/tratamiento farmacológico
18.
Laryngoscope ; 134(7): 3220-3225, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38409660

RESUMEN

OBJECTIVE: This study aimed to compare the selective absorption of the 445-nm Blue laser (BL) and the 532-nm pulsed potassium-titanyl-phosphate (KTP) laser by blood vessels. METHODS: Thirty-six chicken eggs at day 14 of incubation were dissected to expose the chick chorioallantoic membrane (CAM). Third-order vessels of the CAM were identified and irradiated using BL and KTP lasers using various settings at a laser-to-vessel distance of 3 mm using 0.4 mm fiber size. In total, 494 vessels segments were irradiated. Mean (standard deviation) number of irradiations for each setting was 26.0 (4.6), range from 15 to 39. Outcome measures included ablation rate (AR) and rupture rate (RR). RESULTS: The two lasers were compared for AR and RR at long and medium pulse width (PW) associated with different power levels. At long PW (above 100 ms), BL showed significantly higher AR than KTP at high energy (600 mJ/pulse) and low energy (400 mJ/pulse); they did not show different AR and RR at medium energy levels (500 mJ/pulse). Using medium PW settings plus high and medium energy levels, BL and KTP showed relatively high AR and did not significantly differ in performance. However, at medium PW plus low energy (400-450 mJ/pulse), KTP showed significantly higher AR compared to BL. CONCLUSION: At long PW, BL appeared to show higher AR than KTP at high or low energy levels, but they showed equivalent performance at medium energy. At medium PW, both performed similarly from high to medium energy, but KTP appeared to perform better than BL at lower energy settings. LEVEL OF EVIDENCE: NA Laryngoscope, 134:3220-3225, 2024.


Asunto(s)
Membrana Corioalantoides , Láseres de Estado Sólido , Animales , Láseres de Estado Sólido/uso terapéutico , Membrana Corioalantoides/efectos de la radiación , Embrión de Pollo , Vasos Sanguíneos/efectos de la radiación
20.
J Thorac Dis ; 16(1): 12-25, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38410544

RESUMEN

Background: This study aims to visually assess the bibliometric status, current hotspots, and development trends in the field of extracorporeal membrane oxygenation (ECMO)-assisted support for respiratory failure through an examination of articles pertaining to ECMO-assisted support for respiratory failure. Methods: A search was conducted on pertinent literature in the domain of ECMO-assisted support for respiratory failure published from 2003 to 2023, utilizing the Web of Science Core Collection (WOSCC) database. A bibliometric analysis was conducted using CiteSpace and VOSviewer visualization software to identify and assess associations between keywords, countries, institutions, authors, journals, and references. Results: The present study incorporated a compilation of 1,901 pertinent articles. The United States published the maximum number of research articles in this field, and was closely followed by Germany and China. Furthermore, the University of Michigan was the leading institution in ECMO research. In this context, Daniel Brodie, an American expert, significantly contributed to this field and had published 107 related articles on the subject. Concurrently, active collaboration among ECMO researchers was also observed. Asaio Journal was the most prolific contributor, and Giles J. Peek, 2009, published in Lancet, comprised the most cited article in the field. Additionally, the analysis of keywords could be divided into three categories: (I) neonatal ECMO; (II) complications of ECMO; (III) ECMO application in coronavirus disease 2019 (COVID-19); (IV) application of point-of-care ultra sound in ECMO. Conclusions: This study employed CiteSpace and VOSviewer to conduct a systematic literature review on ECMO-assisted support for respiratory failure from 2003 to 2023 in the Web of Science core database. The research outcomes in this domain were presented, offering researchers references for them to gain an accurate understanding of the current state of research and emerging trends in this field.

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