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1.
Ann Intensive Care ; 14(1): 74, 2024 May 12.
Article in English | MEDLINE | ID: mdl-38735891

ABSTRACT

BACKGROUND: Current data on post-discharge mortality and rehospitalization is still insufficient among in-hospital survivors of cardiogenic shock (CS), including acute myocardial infarction (AMI) and non-AMI survivors. METHODS: Patients with CS who survived after hospital discharge were selected from the Taiwan National Health Insurance Research Database. Each patient was followed up at 3-year intervals. Mortality and rehospitalization were analyzed using Kaplan-Meier curves and Cox regression models. RESULTS: There were 16,582 eligible patients. Of these, 42.4% and 57.6% were AMI-CS and non-AMI-CS survivors, respectively. The overall mortality and rehospitalization rates were considerably high, with reports of 7.0% and 22.1% at 30 days, 24.5% and 58.2% at 1 year, and 38.9% and 73.0% at 3 years, respectively, among in-hospital CS survivors. Cardiovascular (CV) problems caused approximately 40% mortality and 60% rehospitalization. Overall, the non-AMI-CS group had a higher mortality burden than the AMI-CS group owing to older age and a higher prevalence of comorbidities. In multivariable models, the non-AMI-CS group exhibited a lower risk of all-cause mortality (adjusted hazard ratio [aHR] 0.69, 95% confidence interval [CI] 0.60 to 0.78) and CV mortality (aHR 0.65, 95% CI 0.54 to 0.78) compared to the AMI-CS group. However, these risks diminished and even reversed after one year (aHR 1.13, 95% CI 1.03 to 1.25 for all-cause mortality; aHR 1.27, 95% CI 1.09 to 1.49 for CV mortality).This reversal was not observed in all-cause and CV rehospitalization. For rehospitalization, AMI-CS was associated with the risk of CV rehospitalization in the entire observation period (aHR:0.80, 95% CI:0.76-0.84). CONCLUSIONS: In-hospital AMI-CS survivors had an increased risk of CV rehospitalization and 30-day mortality, whereas those with non-AMI-CS had a greater mortality risk after 1-year follow-up.

3.
Biomed Environ Sci ; 37(3): 294-302, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38582993

ABSTRACT

Objective: Viral encephalitis is an infectious disease severely affecting human health. It is caused by a wide variety of viral pathogens, including herpes viruses, flaviviruses, enteroviruses, and other viruses. The laboratory diagnosis of viral encephalitis is a worldwide challenge. Recently, high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections. Thus, In this study, we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods: We designed nine pairs of specific polymerase chain reaction (PCR) primers for the 12 viruses by reviewing the relevant literature. The detection ability of the primers was verified by software simulation and the detection of known positive samples. Amplicon sequencing was used to validate the samples, and consistency was compared with Sanger sequencing. Results: The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×, and the sequence lengths were consistent with the sizes of the predicted amplicons. The sequences were verified using the National Center for Biotechnology Information BLAST, and all results were consistent with the results of Sanger sequencing. Conclusion: Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis. It is also a useful tool for the high-volume screening of clinical samples.


Subject(s)
Encephalitis, Viral , Viruses , Humans , Encephalitis, Viral/diagnosis , Viruses/genetics , High-Throughput Nucleotide Sequencing/methods , Polymerase Chain Reaction , DNA, Viral
4.
Anal Chem ; 96(17): 6523-6527, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38634570

ABSTRACT

Complete sample digestion is a prerequisite for acquiring high-quality analytical results for geological samples. Closed-vessel acid digestion (bomb) has typically been used for the total digestion of refractory geological samples. However, the long digestion time (4-5 days) and insoluble fluoride complexes still pose challenges for digesting refractory geological samples using this approach. In this study, an efficient and simplified digestion technique combining ultrafine powders from planetary ball milling with bomb digestion was developed for trace element analysis of refractory geological samples: peridotite and granitoid. The method shows two significant improvements compared with previous approaches. (1) By performing dry planetary ultrafine milling, the initial 200 mesh peridotite (<74 µm) could be reduced to 800 mesh (<20 µm) in 6 min at a ball-to-powder mass ratio of approximately 15 using 3 mm tungsten carbide milling balls. (2) Complete peridotite and granitoid dissolution were achieved in approximately 2 h, 60 times faster than what is achievable using previous methods (2 h vs 120 h). Moreover, ultrafine powders effectively suppressed insoluble fluoride formation during bomb digestion. A suite of peridotite and granitoid reference materials were measured to evaluate the stability of this method. This efficient, simple, and reliable sample digestion method could benefit geological, food, environmental, and other fields requiring solid sample decomposition via wet acid, fusion, combustion, or dry ashing.

5.
Bioorg Chem ; 146: 107290, 2024 May.
Article in English | MEDLINE | ID: mdl-38507999

ABSTRACT

Phenylpropanoids (PPs), a group of natural compounds characterized by one or more C6-C3 units, have exhibited considerable potential in addressing metabolic disease. However, the comprehensive investigation on the relationship of compound structures and involved activity, along with the action mechanisms on the drug target is absent. This study aimed to evaluate the antioxidant and inhibitory activities of 16 PPs against two digestive enzymes, including α-glucosidase and pancreatic lipase, explore the structure-activity relationships and elucidate the mechanisms underlying enzyme inhibition. The findings revealed the similarities in the rules governing antioxidant and enzyme inhibitory activities of PPs. Specifically, the introduction of hydroxyl groups generally exerted positive effects on the activities, while the further methoxylation and glycosylation were observed to be unfavorable. Among the studied PPs, esculetin exhibited the most potent antioxidant activity and dual enzymes inhibition potential, displaying IC50 values of 0.017 and 0.0428 mM for DPPH and ABTS radicals scavenging, as well as 1.36 and 6.67 mM for α-glucosidase and lipase inhibition, respectively. Quantification analysis indicated esculetin bound on both α-glucosidase and lipase successfully by a mixed-type mode. Further analyses by UV-Vis, FT-IR, fluorescence spectra, surface hydrophobicity, SEM, and molecular docking elucidated that esculetin could bind on the catalytic or non-catalytic sites of enzymes to form complex, impacting the normal spatial conformation for hydrolyzing the substrate, thus exhibiting the weakened activity. These results may shed light on the utilization value of natural PPs for the management of hyperglycemia and hyperlipemia, and afford the theoretical basis for designing drugs with stronger inhibition against the dual digestive enzymes based on esculetin.


Subject(s)
Antioxidants , Hypoglycemic Agents , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/chemistry , Antioxidants/pharmacology , Antioxidants/chemistry , alpha-Glucosidases/metabolism , Molecular Docking Simulation , Spectroscopy, Fourier Transform Infrared , Plant Extracts/chemistry , Lipase/metabolism , Structure-Activity Relationship
6.
J Food Prot ; 87(5): 100262, 2024 May.
Article in English | MEDLINE | ID: mdl-38484843

ABSTRACT

Adding an appropriate amount of copper to feed can promote the growth and development of livestock; however, a large amount of heavy metal copper can accumulate in livestock through the enrichment effect, which poses a serious threat to human health. Traditional Cu2+ detection relies heavily on complex and expensive instruments, such as inductively coupled plasma-optical emission spectrometry (ICP-OES) and inductively coupled plasma-mass spectrometry (ICP-MS); thus, convenient and simple rapid detection technologies are urgently needed. In this paper, synthesized copper antigens were used to immunize mice and highly specific anticopper monoclonal antibodies were obtained, which were verified to exhibit high affinity and specificity. Based on the above antibodies, an indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) was established for the rapid detection of copper content in pork. The standard inhibition curve of the method was obtained by antigen-antibody working concentration screening, in which the half inhibitory concentration (IC50) was 11.888 ng/mL, the limit of detection (LOD) was 0.841 ng/mL and the correlation coefficient R2 of the curve was 0.998. In the additive recovery experiment, the recovery rate ranged from 90% to 110%, and the coefficient of variation (CV) was less than 10%, indicating that the method achieved high accuracy and precision. Finally, the results of ic-ELISA combined with Bland-Altman analysis showed a high correlation with ICP-MS, and the correlation coefficient (R2) reached 0.990 when the copper concentration was less than 200 ng/mL. Thus, the ic-ELISA method exhibits high reliability.


Subject(s)
Copper , Enzyme-Linked Immunosorbent Assay , Meat Products , Enzyme-Linked Immunosorbent Assay/methods , Animals , Meat Products/analysis , Mice , Food Contamination/analysis , Humans , Swine
7.
Intest Res ; 2024 Feb 21.
Article in English | MEDLINE | ID: mdl-38373704

ABSTRACT

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is a common disease with severe inflammatory processes associated with numerous gastrointestinal diseases, such as inflammatory bowel disease (IBD). Therefore, we investigated the relationship between NAFLD and IBD and the possible risk factors associated with the diagnosis of IBD. Methods: This longitudinal nationwide cohort study investigated the risk of IBD in patients with NAFLD alone. General characteristics, comorbidities, and incidence of IBD were also compared. Results: Patients diagnosed with NAFLD had a significant risk of developing IBD compared to control individuals, who were associated with a 2.245-fold risk of the diagnosis of IBD and a 2.260- and 2.231-fold of increased diagnosis of ulcerative colitis and Crohn's disease, respectively (P< 0.001). The cumulative risk of IBD increased annually during the follow-up of patients with NAFLD (P< 0.001). Conclusions: Our results emphasize that NAFLD significantly impacts its incidence in patients with NAFLD. If patients with NAFLD present with risk factors, such as diabetes mellitus and dyslipidemia, these conditions should be properly treated with regular follow-ups. Furthermore, we believe that these causes may be associated with the second peak of IBD.

9.
Hellenic J Cardiol ; 2024 Jan 12.
Article in English | MEDLINE | ID: mdl-38218375

ABSTRACT

BACKGROUND: Patients with high bleeding risk (HBR) may exhibit uncertain adherence to dual antiplatelet therapy (DAPT) following drug-eluting stent (DES) implantation. The current population-based cohort study aimed to investigate the sex-based differences in adverse outcomes among the HBR population by analyzing the National Health Insurance Research Database in Taiwan. METHODS: Patients who had HBR features defined by the Academic Research Consortium (ARC) and received DES implantation between January 1, 2007, and December 31, 2017, were enrolled. Propensity score matching was adopted to select 3,981 pairs with similar clinical cardiovascular risks but different sexes. A competing risk model was performed to evaluate the risk of adverse ischemic events (cardiac death, nonfatal myocardial infarction, and ischemic stroke) and any bleeding events in both sexes. Noncardiac death was considered a competing risk. RESULTS: Within a 5-year follow-up, the incidence rates (per 1,000 person-year (95% confidence interval (CI)) of composite ischemic events and any bleeding events in males were respectively 44.09 (40.25-48.30) and 42.55 (38.79-46.68), while those in females were respectively 40.18 (36.51-44.23) and 42.35 (38.57-46.51). After adjustment for clinical variables, male patients had a marginally increased risk in the composite ischemic events (adjusted subdistribution hazard ratio (SHR) = 1.15 (1.00-1.31), p = 0.045) and a similar risk of any bleeding events (adjusted SHR = 1.00 (0.88-1.15), p = 0.946) compared with female patients. CONCLUSIONS: Of the HBR population, males had an increased risk of ischemic outcomes but a similar risk of bleeding compared with females following DES implantation.

10.
Biomater Sci ; 12(5): 1281-1293, 2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38252410

ABSTRACT

Acute liver injury (ALI) is a highly fatal condition characterized by sudden massive necrosis of liver cells, inflammation, and impaired coagulation function. Currently, the primary clinical approach for managing ALI involves symptom management based on the underlying causes. The association between excessive reactive oxygen species originating from macrophages and acute liver injury is noteworthy. Therefore, we designed a novel nanoscale phase variant contrast agent, denoted as PFP@CeO2@Lips, which effectively scavenges reactive oxygen species, and enables visualization through low intensity pulsed ultrasound activation. The efficacy of the nanoparticles in scavenging excess reactive oxygen species from RAW264.7 and protective AML12 cells has been demonstrated through in vitro and in vivo experiments. Additionally, these nanoparticles have shown a protective effect against LPS/D-GalN attack in C57BL/6J mice. Furthermore, when exposed to LIPUS irritation, the nanoparticles undergo liquid-gas phase transition and enable ultrasound imaging.


Subject(s)
Liver , Nanoparticles , Mice , Animals , Reactive Oxygen Species , Mice, Inbred C57BL , Liver/diagnostic imaging , Inflammation , Ultrasonic Waves
11.
Microbiol Resour Announc ; 13(2): e0099323, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38206024

ABSTRACT

The complete genome sequence of Candidatus Phytoplasma australasiaticum strain WF_GM2021, which consists of one 633,005-bp circular chromosome, is presented in this work. This uncultivated plant-pathogenic bacterium is associated with soybean (Glycine max) witches' broom disease in Wufeng District, Taichung City, Taiwan.

12.
J AOAC Int ; 107(1): 158-163, 2024 Jan 04.
Article in English | MEDLINE | ID: mdl-37531289

ABSTRACT

BACKGROUND: Dendrobium huoshanense (DHS) is a classic traditional Chinese medicine (TCM) with distinctive medicinal benefits and great economic worth; nevertheless, because of similar tastes and looks, it is simple to adulterate with less expensive substitutes (such as Dendrobium henanense [DHN]). OBJECTIVE: This work aimed to develop a reliable tool to detect and quantify the adulteration of DHS with DHN by using UV-Vis-shortwave near-infrared diffuse reflectance spectroscopy (UV-Vis-SWNIR DRS) combined with chemometrics. METHODS: Adulterated samples prepared in varying concentrations (0-100%, w/w) were analyzed with UV-Vis-SWNIR DRS methods. Partial least-square-discriminant analysis (PLS-DA) and partial least-squares (PLS) regression techniques were used for the differentiation of adulterated DHN from pure DHS and the prediction of adulteration levels. RESULTS: The PLS-DA classification models successfully differentiated adulterated and nonadulterated DHS with an over 100% correct classification rate. UV-Vis-SWNIR DRS data were also successfully used to predict adulteration levels with a high coefficient of determination for calibration (0.9924) and prediction (0.9906) models and low error values for calibration (3.863%) and prediction (5.067%). CONCLUSION: UV-Vis-SWNIR DRS, as a fast and environmentally friendly tool, has great potential for both the identification and quantification of adulteration practices involving herbal medicines and foods. HIGHLIGHTS: UV-Vis-SWNIR DRS combined with chemometrics can be applied to identify and quantify the adulteration of herbal medicines and foods.


Subject(s)
Dendrobium , Chemometrics , Spectroscopy, Near-Infrared/methods , Discriminant Analysis , Least-Squares Analysis , Plant Extracts , Food Contamination/analysis
13.
Plant Cell ; 36(3): 688-708, 2024 Feb 26.
Article in English | MEDLINE | ID: mdl-37936326

ABSTRACT

Aluminum (Al) stress triggers the accumulation of hydrogen peroxide (H2O2) in roots. However, whether H2O2 plays a regulatory role in aluminum resistance remains unclear. In this study, we show that H2O2 plays a crucial role in regulation of Al resistance, which is modulated by the mitochondrion-localized pentatricopeptide repeat protein REGULATION OF ALMT1 EXPRESSION 6 (RAE6). Mutation in RAE6 impairs the activity of complex I of the mitochondrial electron transport chain, resulting in the accumulation of H2O2 and increased sensitivity to Al. Our results suggest that higher H2O2 concentrations promote the oxidation of SENSITIVE TO PROTON RHIZOTOXICITY 1 (STOP1), an essential transcription factor that promotes Al resistance, thereby promoting its degradation by enhancing the interaction between STOP1 and the F-box protein RAE1. Conversely, decreasing H2O2 levels or blocking the oxidation of STOP1 leads to greater STOP1 stability and increased Al resistance. Moreover, we show that the thioredoxin TRX1 interacts with STOP1 to catalyze its chemical reduction. Thus, our results highlight the importance of H2O2 in Al resistance and regulation of STOP1 stability in Arabidopsis (Arabidopsis thaliana).


Subject(s)
Arabidopsis Proteins , Arabidopsis , Transcription Factors/genetics , Transcription Factors/metabolism , Hydrogen Peroxide/metabolism , Arabidopsis Proteins/metabolism , Aluminum/toxicity , Aluminum/metabolism , Gene Expression Regulation, Plant/genetics , Arabidopsis/metabolism , Plant Roots/genetics , Plant Roots/metabolism
14.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1013597

ABSTRACT

Aim To investigate the role of metabolites of eicosapentaenoic acid (EPA) in promoting the transdifferentiation of pancreatic α cells to β cells. Methods Male C57BL/6J mice were injected intraperitoneally with 60 mg/kg streptozocin (STZ) for five consecutive days to establish a type 1 diabetes (T1DM) mouse model. After two weeks, they were randomly divided into model groups and 97% EPA diet intervention group, 75% fish oil (50% EPA +25% DHA) diet intervention group, and random blood glucose was detected every week; after the model expired, the regeneration of pancreatic β cells in mouse pancreas was observed by immunofluorescence staining. The islets of mice (obtained by crossing GCG

15.
Neurosci Lett ; 820: 137612, 2024 Jan 18.
Article in English | MEDLINE | ID: mdl-38142924

ABSTRACT

In Alzheimer's disease (AD), microglia are involved in synaptic pruning and mediate synapse loss. LINGO-1 is a negative regulator of nerve growth, and whether antagonizing LINGO-1 can attenuate synaptic pruning by microglia and rescue dendritic spines in the hippocampus in AD is still unclear. On this basis, the anti-LINGO-1 antibody, which binds to LINGO-1 protein and antagonizes the effects of LINGO-1, was administered to 10-month-old APP/PS1 transgenic mice for 2 months. The Morris water maze test, immunohistochemical and stereological methods, immunofluorescence and 3D reconstruction were used. Compared to wild-type mice, APP/PS1 transgenic mice had worse performance on behavioral tests, fewer dendritic spines but more microglia in the hippocampus. Meanwhile, the microglia in APP/PS1 transgenic mice had more branches of medium length (4-6 µm) and a cell body area with greater variability. Moreover, APP/PS1 transgenic mice had more postsynaptic termini colocalized with microglia in the hippocampus than wild-type mice. The anti-LINGO-1 antibody significantly reversed these changes in AD, indicating that the anti-LINGO-1 antibody can improve hippocampus-dependent learning and memory abilities and effectively rescue dendritic spines in the hippocampus of AD mice and that microglia might participate in this progression in AD. These results provide a scientific basis for further studying the mechanism of the anti-LINGO-1 antibody in AD and help to elucidate the role of LINGO-1 in the treatment of AD.


Subject(s)
Alzheimer Disease , Amyloid beta-Protein Precursor , Animals , Mice , Alzheimer Disease/metabolism , Amyloid beta-Protein Precursor/genetics , Amyloid beta-Protein Precursor/metabolism , Dendritic Spines/metabolism , Disease Models, Animal , Hippocampus/metabolism , Maze Learning , Mice, Transgenic , Microglia/metabolism , Presenilin-1/genetics , Presenilin-1/metabolism
16.
J Am Heart Assoc ; 13(1): e032268, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38156549

ABSTRACT

BACKGROUND: Aging of the proximal aorta can lead to increased pressure and flow pulsatility in the cerebral microcirculation, which may cause cognitive impairment. This study investigated the association between aortic characteristic impedance (Zc), an indicator of regional stiffness of the proximal aorta, and suspected mild cognitive impairment (MCI), compared with carotid-femoral pulse wave velocity (CFPWV). METHODS AND RESULTS: A total of 1461 healthy community residents (46.4% men; age range, 35-96 years [mean±SD, 59.9±11.8 years]) without a history of cardiovascular events or stroke were included in the study. Zc was estimated using applanation tonometry and echocardiography. Cognitive function was assessed using the Mini-Mental State Examination. Education-adjusted cut points were used to define suspected MCI. Subjects with suspected MCI (n=493 [33.7%]) had significantly higher Zc and CFPWV than those without. In multivariable analysis, both Zc and CFPWV were inversely associated with Mini-Mental State Examination score. Zc (odds ratio per 1 SD, 1.22 [95% CI, 1.09-1.37] and CFPWV (odds ratio per 1 SD, 1.18 [95% CI, 1.01-1.38]) was also significantly associated with suspected MCI, after adjusting for age, sex, education level, mean arterial pressure, hypertension, diabetes, low-density lipoprotein cholesterol, and smoking status. In joint analysis, Zc was significantly associated with suspected MCI, but CFPWV was not. In the age subgroups of <50 years and 50 to 70 years, only Zc was significantly associated with suspected MCI. CONCLUSIONS: This study found that Zc was significantly associated with Mini-Mental State Examination score and suspected MCI, especially in younger and middle-aged adults. These findings suggest that Zc may be a useful biomarker for identifying individuals at risk for MCI.


Subject(s)
Cognitive Dysfunction , Vascular Stiffness , Adult , Male , Middle Aged , Humans , Aged , Aged, 80 and over , Female , Blood Pressure , Pulse Wave Analysis , Electric Impedance , Aorta/diagnostic imaging , Cognitive Dysfunction/diagnosis
17.
Front Microbiol ; 14: 1326253, 2023.
Article in English | MEDLINE | ID: mdl-38143868

ABSTRACT

Tropical Asian collections of Inosperma are usually poisonous mushrooms that have caused many poisoning incidents. However, the species diversity and the toxic mechanisms of these Inosperma species are still unclear. In this study, we describe the discovery of Inosperma wuzhishanense sp. nov. from Wuzhishan City, Hainan Province, tropical China. The new species was identified based on morphological and multi-locus (ITS, nrLSU, and RPB2) phylogenetic analyses. The new species is characterized by its reddish-brown pileus, fibrillose stipes with finely protruding fibrils, rather crowded lamellae, smooth and ellipsoid basidiospores, and mostly clavate, thin-walled cheilocystidia. The new species is phylogenetically nested in the Old World tropical clade 2 and is sister to the tropical Indian taxa I. akirnum. Detailed descriptions, color photos of the new species, and comparisons with its closely related species are provided. Additionally, the muscarine content of the new species was analyzed by ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS). The muscarine contents ranged from 4,359.79 ± 83.87 mg/kg to 7,114.03 ± 76.55 mg/kg, 2,748.37 ± 106.85 mg/kg to 4,491.35 ± 467.21 mg/kg, and 2,301.36 ± 83.52 mg/kg to 2,775.90 ± 205.624 mg/kg in the stipe, pileus, and lamellae, respectively. The elemental composition and concentration were determined using inductively coupled plasma-mass spectrometry (ICP-MS). A total of 24 elements were detected. Among the heavy metals detected, arsenic showed the highest level of toxicity with a concentration of 36.76 ± 0.43 mg/kg.

18.
iScience ; 26(12): 108347, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-38125021

ABSTRACT

It is imperative to optimally utilize virtues and obviate defects of fully automated analysis and expert knowledge in new paradigms of healthcare. We present a deep learning-based semiautomated workflow (RAINMAN) with 12,809 follow-up scans among 2,172 patients with treated nasopharyngeal carcinoma from three centers (ChiCTR.org.cn, Chi-CTR2200056595). A boost of diagnostic performance and reduced workload was observed in RAINMAN compared with the original manual interpretations (internal vs. external: sensitivity, 2.5% [p = 0.500] vs. 3.2% [p = 0.031]; specificity, 2.9% [p < 0.001] vs. 0.3% [p = 0.302]; workload reduction, 79.3% vs. 76.2%). The workflow also yielded a triaging performance of 83.6%, with increases of 1.5% in sensitivity (p = 1.000) and 0.6%-1.3% (all p < 0.05) in specificity compared to three radiologists in the reader study. The semiautomated workflow shows its unique superiority in reducing radiologist's workload by eliminating negative scans while retaining the diagnostic performance of radiologists.

19.
Stud Health Technol Inform ; 308: 130-136, 2023 Nov 23.
Article in English | MEDLINE | ID: mdl-38007734

ABSTRACT

OBJECTIVES: To study the effects of grape seed proanthocyanidins (GSP) combined with allicin on serum lipids level and vascular damage in a rat model of hyperlipidemia. MATERIALS AND METHODS: SD rats(male, 170-220 gn= 40) were randomized into five groups (n = 8/group): modelhigh fat and cholesterol diet; controlnormal diet; model+low-dose (GSP+allicin )(GSP 45mg/kg, allicin 30mg/kg, orally); model+high-dose (GSP+allicin) (GSP180mg/kg, allicin 90mg/kg, orally) and positive control (model+simvastatin (4 mg/kg)). Normal control group was fed conventionally, and remaining four groups were fed high cholesterol and fat food to replicate the high fat model. After 9 weeks, the normal control group continued to receive regular feeding, while the other groups continued to receive high-fat feeding. At the same time, model and normal control groups were given equal volume of physiological saline by gavage, and the other treatment groups began to receive corresponding drugs by gavage once a day. After 4 weeks, serum levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) as well as high-density lipoprotein cholesterol (HDL-C) in rats were determined. And the body weight of rat, total antioxidant capacity (T-AOC), superoxide dismutase (SOD) and malondialdehyde (MDA)in serum were identified. The level of endothelin-1(ET-1) was quantitative analysis by ELISA assay. RESULTS: In comparison to normal controls, the model group displayed a marked rise in body weight, an increment in serum concentrations of LDL-C, TG and TC, as well as a decline in HDL (P<0.01), demonstrating successful model replication; All doses of GSP in combination with allicin resulted in a reduction in TG, LDL-C, and TC and an enhancement in HDL-C in contrast to the model control (all P<0.05). High-dose (GSP+allicin ) decreased MDA, and increased T-AOC and SOD activity(all P<0.01). All doses of GSP combined with allicin decreased ET-1 (all P<0.05). In addition, the protective effect of GSP combined with allicin was dose-dependent. CONCLUSIONS: Studies have shown that GSP combined with allicin can significantly improve blood lipids in hyperlipidemic rats, and this mechanism may be related to antioxidants and reduced endothelial damage.


Subject(s)
Hyperlipidemias , Proanthocyanidins , Vitis , Rats , Male , Animals , Rats, Sprague-Dawley , Proanthocyanidins/pharmacology , Proanthocyanidins/therapeutic use , Cholesterol, LDL/therapeutic use , Lipids , Hyperlipidemias/drug therapy , Triglycerides/therapeutic use , Antioxidants/pharmacology , Antioxidants/therapeutic use , Cholesterol/therapeutic use , Superoxide Dismutase/therapeutic use , Cholesterol, HDL/therapeutic use , Body Weight , Seeds
20.
BMC Cancer ; 23(1): 1108, 2023 Nov 14.
Article in English | MEDLINE | ID: mdl-37964204

ABSTRACT

BACKGROUND: Ankyrin repeat domain 49 (ANKRD49) has been found to be highly expressed in multiple cancer including lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC). However, the function of ANKRD49 in the pathogenesis of NSCLC still remains elusive. Previously, ANKRD49 has been demonstrated to promote the invasion and metastasis of A549 cells, a LUAD cell line, via activating the p38-ATF-2-MMP2/MMP9 pathways. Considering the heterogeneity of tumor cells, the function and mechanism of ANKRD49 in NSCLC need more NSCLC-originated cells to clarify. METHODS: Real-time qPCR was employed to test ANKRD49 expression levels in nine pairs of fresh NSCLC tissues and the corresponding adjacent normal tissues. The function of ANKRD49 was investigated using overexpression and RNA interference assays in lung adenocarcinoma cell line (NCI-H1299) and lung squamous carcinoma cell line (NCI-H1703) through gelatin zymography, cell counting kit-8, colony formation, wound healing, migration and invasion assays mmunoprecipitation was performed to in vitro. Immunoprecipitation was performed to test the interaction of c-Jun and ATF2. Chromatin immunoprecipitation was conducted to assess the transcriptional regulation of ATF2/c-Jun on MMP-2/9. Moreover, the tumorigenicity of ANKRD49 was evaluated in nude mice models and the involved signal molecular was also measured by immunohistochemical method. RESULTS: We found that the levels of ANKRD49 in cancerous tissues were higher than those in adjacent normal tissues. in vitro assay showed that ANKRD49 promoted the migration and invasion of NCI-H1299 and NCI-H1703 cells via enhancing the levels of MMP-2 and MMP-9. Furthermore, ANKRD49 elevated phosphorylation of JNK and then activated c-Jun and ATF2 which interact in nucleus to promote the binding of ATF2:c-Jun with the promoter MMP-2 or MMP-9. In vivo assay showed that ANKRD49 promoted lung metastasis of injected-NSCLC cells and the high metastatic rate was positively correlated with the high expression of ANKRD49, MMP-2, MMP-9, p-JNK, p-c-Jun and p-ATF2. CONCLUSION: The present study indicated that ANKRD49 accelerated the invasion and metastasis of NSCLC cells via JNK-mediated transcription activation of c-Jun and ATF2 which regulated the expression of MMP-2/MMP-9. The molecular mechanisms of ANKRD49's function is different from those found in A549 cells. The current study is a supplement and improvement to the previous research.


Subject(s)
Adenocarcinoma of Lung , Carcinoma, Non-Small-Cell Lung , Carcinoma, Squamous Cell , Lung Neoplasms , Animals , Mice , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Mice, Nude , Cell Proliferation/genetics , Cell Line, Tumor , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology
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