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1.
Phys Rev Lett ; 129(8): 084301, 2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-36053695

RESUMO

Weyl points-topological monopoles of quantized Berry flux-are predicted to spread to Weyl exceptional rings in the presence of non-Hermiticity. Here, we use a one-dimensional Aubry-Andre-Harper model to construct a Weyl semimetal in a three-dimensional parameter space comprising one reciprocal dimension and two synthetic dimensions. The inclusion of non-Hermiticity in the form of gain and loss produces a synthetic Weyl exceptional ring (SWER). The topology of the SWER is characterized by both its topological charge and non-Hermitian winding numbers. We experimentally observe the SWER and synthetic Fermi arc in a one-dimensional phononic crystal with the non-Hermiticity introduced by active acoustic components. Our findings pave the way for studying the high-dimensional non-Hermitian topological physics in acoustics.

2.
Nat Commun ; 13(1): 5171, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36055988

RESUMO

Speeding up the transmission of information carried by waves is of fundamental interest for wave physics, with pivotal significance for underwater communications. To overcome the current limitations in information transfer capacity, here we propose and experimentally validate a mechanism using multipath sound twisting to realize real-time high-capacity communication free of signal-processing or sensor-scanning. The undesired channel crosstalk, conventionally reduced via time-consuming postprocessing, is virtually suppressed by using a metamaterial layer as purely-passive demultiplexer with high spatial selectivity. Furthermore, the compactness of system ensures high information density crucial for acoustics-based applications. A distinct example of complicated image transmission is experimentally demonstrated, showing as many independent channels as the path number multiplied by vortex mode number and an extremely-low bit error rate nearly 1/10 of the forward error correction limit. Our strategy opens an avenue to metamaterial-based high-capacity communication paradigm compatible with the conventional multiplexing mechanisms, with far-reaching impact on acoustics and other domains.

3.
Front Pharmacol ; 13: 905564, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091797

RESUMO

Background: Irritable bowel syndrome (IBS) reduces patients' quality of life and causes great burdens due to its unclear pathogenesis and criteria for diagnosis. This study aimed to explore the differences in prevalence and the influencing factors for IBS and its subtypes. Methods: The UK Biobank surveyed 174,771 adult participants who completed the Digestive Health Questionnaire (DHQ) through emails and websites. DHQ included the Rome III criteria, IBS symptom severity score, and Patient Health Questionnaire 12 Somatic Symptom score. The UK Biobank also asked regarding previous IBS diagnosis, diagnosis for post-infectious IBS (PI-IBS), and environmental exposures and associated conditions (including anxiety or depression, based on treatment sought or offered). Pearson's Chi-squared test or Wilcoxon's rank-sum test was used for potential associations. Binary logic regression based on sex stratification was used to examine associations between selected factors and IBS and its subtypes. Results: This study included 31,918 participants who met the Rome III criteria for IBS. The pooled prevalence of IBS in the UK Biobank was 18.3%, with mixed IBS as the predominant subtype (59.0%), followed by diarrhea-predominant IBS (25.1%), constipation-predominant IBS (14.7%), and untyped IBS (1.1%). IBS was significantly associated with somatization (male: OR = 5.326, 95% CI = 4.863-5.832; female: OR = 4.738, 95% CI = 4.498-4.992) and coeliac disease (male: OR = 4.107, 95% CI = 3.132-5.385; female: OR = 3.783, 95% CI = 3.310-4.323). Differences in antibiotics and mental status were presented among subtypes and sex. Furthermore, 1,787 individuals were diagnosed with PI-IBS in the group of patients with IBS. The prevalence of PI-IBS in IBS was 16.6% in the UK Biobank, and it was characterized by diarrhea, fever, bloody diarrhea, and vomiting. Conclusion: Somatization and coeliac disease are primary risk factors for IBS. Distinguishing differential risk factors is critical for the precise diagnosis and treatment of IBS subtypes, particularly sex-specific differences in mental health status. General practitioners should focus on the treatment according to IBS subtypes.

4.
Front Oncol ; 12: 973357, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059634

RESUMO

Background: Hepatocellular carcinoma (HCC) patients with main portal vein tumor thrombus (MPVTT) may be able to have TACE through stent implantation into the portal vein with thrombosis to recover portal blood flow. Purpose: The goal of this study was to compare clinical results of conventional transcatheter arterial chemoembolization (C-TACE) and doxorubicin-eluting bead transcatheter arterial chemoembolization (D-TACE) combined with endovascular brachytherapy in HCC patients with MPVTT. Methods: This study was a retrospective controlled study with follow-up dates spanning from Mar 2015 to Feb 2020. Patients with both HCC and MPVTT were divided into two groups. Portal vein stents with iodine-125 seed strands were implanted first; then, C-TACE or D-TACE was administered to all patients. Objective response rates were assessed. Results: A total of 26 patients were enrolled, with 13 in each group. During follow-up, the portal stent patency times were 112.3 ± 98.2 days in the C-TACE group and 101.7 ± 90.4 days in the D-TACE group. The time to disease progression was 42 days in the C-TACE group and 120 days in the D-TACE group (p=0.03). The overall survival time from the first intervention procedure was 216 days in the C-TACE group and 239 days in the D-TACE group (p=0.047). The D-TACE group was superior to the C-TACE group in terms of progression-free survival (PFS) and overall survival (OS) times. Conclusion: Endovascular implantation of brachytherapy combined with TACE is safe and effective in HCC patients with MPVTT. This combination therapy may be helpful for survival benefits to patients with stage BCLC-C HCC.

5.
J Asthma Allergy ; 15: 1179-1194, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059920

RESUMO

Background: Allergic asthma is the most common type of asthma and often occurs in early life with increasing comorbidities, including atopic dermatitis and allergic rhinitis. MicroRNAs (miRNAs) are involved in the pathogenesis of numerous immune and inflammatory disorders, particularly allergic inflammation. The specific miRNA profiles of children with allergic asthma have not been fully delineated and still require in-depth study. Objective: This study aimed to identify the expression profile of miRNAs and constructed a network of the interactions between differentially expressed miRNAs and target mRNAs to provide novel insights into understanding the pathogenesis of allergic asthma. Materials and Methods: In this study, we performed high-throughput sequencing of peripheral blood mononuclear cells (PBMCs) from children in the acute phase of asthma. Bioinformatics approaches, including miRanda, Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, were employed to predict novel therapeutic and diagnostic targets for allergic asthma. Real-time quantitative PCR was conducted to detect the expression of aberrantly expressed miRNAs. Results: One hundred and sixty-one differentially expressed miRNAs were identified in children with allergic asthma, including 140 conserved miRNAs and 21 novel miRNAs. A total of 8929 targeted mRNAs (44,186 transcripts) associated with differentially expressed miRNAs were predicted and significantly enriched in the cGMP-PKG signalling pathway, cholinergic synapse, and salivary secretion. We also found that miRNA-370-3p targeted PKG and MLCP molecules in the cGMP-PKG signalling pathway and was involved in the pathogenesis of allergic asthma. Conclusion: We identified the miRNA profile of PBMCs in children with allergic asthma and also found that miRNA-370-3p targeted PKG and MLCP molecules in the cGMP-PKG signalling pathway, which provides a novel insight into understanding the pathogenesis of allergic asthma and investigating new targets for the treatment of allergic asthma in children.

6.
Oxid Med Cell Longev ; 2022: 2297268, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36120597

RESUMO

Objective: Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2DM) commonly coexist and act synergistically to drive adverse clinical outcomes. This study is aimed at investigating the effects of exercise intervention and oral hypoglycaemic drug of metformin (MET) alone or combined on hepatic lipid accumulation. To investigate if oxidative stress and endoplasmic reticulum stress (ERS) are involved in lipotoxicity-induced hepatocyte apoptosis in diabetic mice and whether exercise and/or MET alleviated oxidative stress or ERS-apoptosis by AMPK-Nrf2-HO-1 signaling pathway. Methods: Forty db/db mice with diabetes (random blood glucose ≥ 250 mg/dL) were randomly allocated into four groups: control (CON), exercise training alone (EX), metformin treatment alone (MET), and exercise combined with metformin (EM) groups. Hematoxylin-eosin and oil red O staining were carried out to observe hepatic lipid accumulation. Immunohistochemical and TUNEL methods were used to detect the protein expression of the binding immunoglobulin protein (BiP) and superoxide dismutase-1 (SOD1) and the apoptosis level of hepatocytes. ERS-related gene expression and the AMPK-Nrf2-HO-1 signaling pathway were tested by western blotting. Results: Our data showed that db/db mice exhibited increased liver lipid accumulation, which induced oxidative and ER stress of the PERK-eIF2α-ATF4 pathway, and hepatocyte apoptosis. MET combined with exercise training significantly alleviated hepatic lipid accumulation by suppressing BiP expression, the central regulator of ER homeostasis, and its downstream PERK-eIF2α-ATF4 pathway, as well as upregulated the AMPK-Nrf2-HO-1 signaling pathway. Moreover, the combination of exercise and MET displayed protective effects on hepatocyte apoptosis by downregulating Bax expression and TUNEL-positive staining, restoring the balance of cleaved-caspase-3 and caspase-3, and improving the antioxidant defense system to prevent oxidative damage in db/db mice. Conclusion: Compared to MET or exercise intervention alone, the combined exercise and metformin exhibited significant effect on ameliorating hepatic steatosis, inhibiting oxidative and ER stress-induced hepatocyte apoptosis via improving the capacity of the antioxidant defense system and suppression of the PERK-eIF2α-ATF4 pathway. Furthermore, upregulation of AMPK-Nrf2-HO-1 signaling pathway might be a key crosstalk between MET and exercise, which may have additive effects on alleviating hepatic lipid accumulation.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Metformina , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Antioxidantes/farmacologia , Apoptose , Glicemia , Caspase 3/metabolismo , Diabetes Mellitus Experimental/metabolismo , Estresse do Retículo Endoplasmático , Amarelo de Eosina-(YS)/farmacologia , Hematoxilina/farmacologia , Hepatócitos/metabolismo , Hipoglicemiantes/farmacologia , Lipídeos , Metformina/farmacologia , Metformina/uso terapêutico , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Transdução de Sinais , Superóxido Dismutase-1/metabolismo , Proteína X Associada a bcl-2/metabolismo
7.
BMJ Open ; 12(9): e065780, 2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36171045

RESUMO

OBJECTIVES: Over the past decade, the incidence and global burden of coronary heart disease (CHD) have increased in the young population. We aimed to identify patient characteristics and risk factors for premature CHD, including single-vessel disease (SVD) and multivessel disease (MVD). DESIGN: Retrospective, cross-sectional study. SETTING: Demographic and clinical data of patients with CHD were collected from the patient medical records of a tertiary hospital in Tianjin, China, between 2014 and 2017. PARTICIPANTS: A total of 2846 patients were enrolled in the study. PRIMARY AND SECONDARY OUTCOME MEASURES: Premature CHD, which is the primary outcome, was defined as men<45 years and women<55 years. MVD, which is the secondary outcome, was defined as at least two vessels with ≥50% stenosis. Logistic regression models were applied to analyse the characteristics and risk factors of premature CHD and MVD. RESULTS: Most of the characteristics between patients with premature and mature CHD were not statistically significant. A significantly higher dyslipidaemia prevalence was found in female patients with premature CHD (OR=1.412, 95% CI: 1.029 to 1.936). In the crude model, instead of premature SVD, premature (OR=2.065, 95% CI: 1.426 to 2.991) or mature (OR=1.837, 95% CI: 1.104 to 3.056) MVD was more common in female patients with the highest triglyceride-glucose (TyG) index quartile than those with the lowest TyG index quartile. In male patients, the same trend was observed for mature MVD (OR=2.272, 95% CI: 1.312 to 3.937). The significance of the TyG index was not revealed in multivariate analyses; however, hypertension, diabetes, obesity, smoking, old myocardial infarction and lipoprotein (a) showed a positive association with MVD. CONCLUSIONS: Dyslipidaemia should be considered as an effective factor for the prediction and prevention of premature CHD in women. The TyG index can be a simple auxiliary indicator that can be used in population-based cardiovascular disease screening for the early identification of vascular disease severity.


Assuntos
Doença da Artéria Coronariana , Dislipidemias , Biomarcadores , Glicemia , China/epidemiologia , Doença da Artéria Coronariana/epidemiologia , Estudos Transversais , Dislipidemias/epidemiologia , Feminino , Glucose , Humanos , Lipoproteína(a) , Masculino , Estudos Retrospectivos , Fatores de Risco , Triglicerídeos
8.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 34(8): 802-807, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-36177921

RESUMO

OBJECTIVE: To explore the relationship between the pulse pressure/central venous pressure (PP/CVP) ratio and the cardiac output (CO) of patients after cardiac surgery from the basic principles of hemodynamics, and to further evaluate the predictive value of PP/CVP ratio in patients with secondary low cardiac output syndrome (LCOS) after cardiac surgery. METHODS: A retrospective study was conducted, and patients who received pulse indicator continuous cardiac output (PiCCO) monitoring were enrolled at the department of critical care medicine of Peking Union Medical College Hospital from January 1, 2016, to September 1, 2021. Patients were divided into two groups: the LCOS group [cardiac index (CI) < 33.34 mL×s-1×m-2, 25 cases] and the non-LCOS group (CI ≥ 33.34 mL×s-1×m-2, 125 cases) according to the CI at 6 hours after surgery. The general clinical data and hemodynamic parameters were collected. Correlations between PP/CVP ratio and PiCCO monitoring indicators were performed with Pearson or Spearman correlation test. Receiver operator characteristic curve (ROC curve) analysis was carried out to evaluate the predictive value of the parameters in patients with LCOS after cardiac surgery. RESULTS: A total of 150 patients with PiCCO monitoring after cardiac surgery were included. There were no differences in baseline characteristics between the two groups, while PP in the LCOS group was lower than that in the non-LCOS group [mmHg (1 mmHg ≈ 0.133 kPa): 40 (37, 44) vs. 55 (46, 64)], CVP was higher than that in the non-LCOS group [mmHg: 12 (11, 14) vs. 10 (8, 12)], and PP/CVP ratio in the LCOS group was lower than that in the non-LCOS group [3.3 (2.9, 3.7) vs. 5.5 (4.6, 6.8)], with significant differences (all P < 0.05). Correlation analysis results showed that PP/CVP ratio was positively correlated with CI, CO, and stroke volume index (SVI), respectively (rs = 0.660, 0.592, 0.600, all P < 0.001). CI was negatively correlated with PP (rs = 0.509, P < 0.001) and positively correlated with CVP (rs = -0.297, P < 0.001). ROC curve analysis revealed that compared with PP, CVP, SVI and cardiac function index (CFI), PP/CVP ratio was the best predictor of LCOS after cardiac surgery [area under the ROC curve (AUC) was 0.94±0.02, P < 0.001], when the optimum cut-off value was 4.41, the sensitivity was 80.00%, and the specificity was 96.00%. CONCLUSIONS: PP/CVP ratio was moderately positively correlated with CO after cardiac surgery, and PP/CVP ratio could be used as a prognostic predictor for LCOS after cardiac surgery.

9.
BMC Bioinformatics ; 23(Suppl 3): 399, 2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36171552

RESUMO

BACKGROUND: Protein histidine phosphorylation (pHis) plays critical roles in prokaryotic signal transduction pathways and various eukaryotic cellular processes. It is estimated to account for 6-10% of the phosphoproteome, however only hundreds of pHis sites have been discovered to date. Due to the inherent disadvantages of experimental methods, it is an urgent task for developing efficient computational approaches to identify pHis sites. RESULTS: Here, we present a novel tool, pHisPred, for accurately identifying pHis sites from protein sequences. We manually collected the largest number of experimental validated pHis sites to build benchmark datasets. Using randomized tenfold CV, the weighted SVM-RBF model shows the best performance than other four commonly used classification models (LR, KNN, RF, and MLP). From ten thousands of features, 140 and 150 most informative features were individually selected out for eukaryotic and prokaryotic models. The average AUC and F1-score values of pHisPred were (0.81, 0.40) and (0.78, 0.46) for tenfold CV on the eukaryotic and prokaryotic training datasets, respectively. In addition, pHisPred significantly outperforms other tools on testing datasets, in particular on the eukaryotic one. CONCLUSION: We implemented a python program of pHisPred, which is freely available for non-commercial use at https://github.com/xiaofengsong/pHisPred . Moreover, users can use it to train new models with their own data.


Assuntos
Histidina , Células Procarióticas , Sequência de Aminoácidos , Eucariotos/metabolismo , Células Eucarióticas/metabolismo , Fosforilação , Células Procarióticas/metabolismo
10.
J Mech Behav Biomed Mater ; 135: 105484, 2022 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-36179616

RESUMO

OBJECTIVE: The human periodontal ligament (PDL) dominated by collagen fibers showed hyperelastic mechanical behavior under orthodontic force. Despite previous researches on the hyperelastic model of PDL, there were certain limitations because of the types of samples and the ignorance of distribution of collagen fibers. Therefore, the aim of this study was to quantify the effect of collagen fibers distribution of human PDL on its hyperelastic behavior. METHODS: A total of 6 human PDL samples of root neck, root middle and root apex were cut from human maxillary central incisor and lateral incisor. The spatial angles of collagen fibers were observed by optical microscope, the hyperelastic model was constructed combined with the observation results. The quasi-static uniaxial tensile tests with displacement load 0.05 mm/min were carried out, and the test data were used to identify the parameters of model. RESULTS: The mechanical behavior of human PDL conformed to the trend of hyperelastic materials, and greatly depended on the spatial angles of internal collagen fibers. The R2 value statistical fit of the constitutive model to the data is excellent (R2 > 0.98). This model could excellently describe the hyperelastic properties of human PDL. SIGNIFICANCE: In this study, we quantitatively described the effect of spatial distribution of collagen fibers on the mechanical properties of human PDL. The accuracy of this model was verified by the uniaxial test data, and the relevant model parameters were acquired, which have certain reference value in subsequent researches on hyperelasticity of human PDL and clinical treatment.

11.
Photodiagnosis Photodyn Ther ; 40: 103105, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36075520

RESUMO

BACKGROUND: Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy that can be easily confused with other diseases due to its diverse clinical manifestations, delaying the timing of treatment. Therefore, early diagnosis is extremely important. It has been reported that dermoscopy can be used to evaluate superficial skin tumors. OBJECTIVE: To investigate the dermoscopic characteristics of EMPD diagnosed by histopathology and to develop a decision tree model that can provide clinicians with a reference to facilitate early diagnosis. METHODS: All patients were evaluated by dermoscopic and histopathologic examinations. Dermoscopic images were assessed, and a decision tree model was constructed using SPSS (version 25.0). RESULTS: A total of 49 patients were included in this study. We found that EMPD was most likely to be misdiagnosed when the disease duration was less than 2.5 years. Porcelain-white patches were the only key clinical feature other varying dermoscopic features could not be differentiated from those of EMPD-mimicking diseases. Polymorphic vessels were considered to be significant when the duration of the disease ranged from 0.1 year to 2.5 years. However, when the duration was >2.5 years, present (or absent) glomerular vessels were all considered EMPD. CONCLUSIONS: Dermoscopy can be used as an auxiliary diagnostic tool for the diagnosis and management of EMPD. The decision tree can guide clinical diagnosis further validation studies are necessary due to the limited number of cases.

12.
Methods ; 207: 38-43, 2022 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-36100141

RESUMO

In recent years, anticancer peptides have emerged as a new viable option in cancer therapy, with the ability to overcome the considerable side effects and poor outcomes of standard cancer therapies. Accurate anticancer peptide identification can facilitate its finding and speed up its application in treating cancer. However, many recent approaches are based on machine learning, which not only restricts the representation ability of the models but also requires a complex hand-crafted feature extraction process. Here, we propose AntiMF, a deep learning model that utilizes multi-view mechanism based on different feature extraction models. Comparative results show that our model has a better performance than the state-of-the-art methods in the prediction of anticancer peptides. By using an ensemble learning framework to extract representation, AntiMF can capture the different dimensional information, which can make model representation more complete. Moreover, we visualize what AntiMF learns on one of its ensemble models to intuitively show the effectivity of our model, indicating that AntiMF has the great potential ability to be an effective and useful model to identify anticancer peptides accurately.

13.
Thorac Cancer ; 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36127731

RESUMO

Gene fusions can drive tumor development for multiple types of cancer. Currently, many drugs targeting gene fusions are being approved for clinical application. At present, tyrosine receptor kinase (TRK) inhibitors targeting neurotrophic tyrosine receptor kinase (NTRK) gene fusions are among the first "tumor agnostic" drugs approved for pan-cancer use. Representative TRK inhibitors, including larotrectinib and entrectinib, have shown high efficacy for many types of cancer. At the same time, several second-generation drugs designed to overcome first-generation drug resistance are undergoing clinical development. Due to the rarity of NTRK gene fusions in common cancer types and technical issues regarding the complexity of fusion patterns, effectively screening patients for TRK inhibitor treatment in routine clinical practice is challenging. Different detection methods including immunohistochemistry, fluorescence in situ hybridization, reverse transcription-polymerase chain reaction, and (DNA and/or RNA-based) next-generation sequencing have pros and cons. As such, recommending suitable tests for individual patients and ensuring the quality of tests is essential. Moreover, at present, there is a lack of systematic review for the clinical efficacy and development status of first- and second-generation TRK inhibitors. To resolve the above issues, our expert group has reached a consensus regarding the diagnosis and treatment of NTRK gene fusion solid tumors, aiming to standardize clinical practice with the goal of benefiting patients with NTRK gene fusions treated with TRK inhibitors.

14.
Front Microbiol ; 13: 956516, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046023

RESUMO

Heart failure (HF), a global health issue characterized by structural or functional cardiac dysfunction, which was found to be associated with the gut microbiome recently. Although multiple studies suggested that the gut microbiome may have an impact on the development of cardiovascular diseases, the underlying mechanism of the gut microbiome in HF remains unclear. The study of metabolites from gut microbiota influenced by dietary nutrition uptake suggested that gut microbiota may affect the process of HF. However, on the basis of the microbiota's complicated roles and their interactions with metabolites, studies of microbial metabolites in HF had rarely been described so far. In this review, we focused on dietary nutrition-related factors that were involved in the development and progression of HF, such as trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), and bile acids (BAs), to summarize their advances and several potential targets in HF. From a therapeutic standpoint, we discussed microbial metabolites as a potential strategy and their applications in HF as well.

15.
Materials (Basel) ; 15(17)2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36079293

RESUMO

In the process of orthodontic treatment, the remodeling of cancellous bone in alveolar bone (in this paper, cancellous bone in alveolar bone is abbreviated as CBAB) is key to promoting tooth movement. Studying the mechanical behavior of CBAB is helpful to predict the displacement of teeth and achieve the best effect of orthodontic treatment. Three CBAB samples were cut from alveolar bone around the root apex of human teeth. A uniaxial compression test was used to study the transient elastic properties of CBAB. A creep test was used to study the time-dependent viscoelastic properties of CBAB. Both tests were carried out at the loading rates of 0.02 mm/min, 0.1 mm/min and 0.5 mm/min. The results revealed that CBAB is a nonlinear viscoelastic and hyperelastic material. The stress-strain curve obtained from the uniaxial compression test could be divided into three stages: the collapse stage of the front section, the exponential stage of the middle section and the almost linear stage of the rear end. According to the strain-time curve obtained from the compression creep test, a trend of increasing strain over time was relatively obvious within the first 30 s. After 200 s, the curve gradually tended to plateau. Four hyperelastic models and three viscoelastic models were used to fit the test data. Finally, the fifth-order polynomial hyperelastic model (coefficient of determination "R2 > 0.999") was used to describe the hyperelastic properties of CBAB, and the seven-parameter model of the generalized Kelvin modified model ("R2 > 0.98") was used to describe the viscoelastic properties of CBAB.

16.
Artigo em Inglês | MEDLINE | ID: mdl-36100698

RESUMO

BACKGROUND: Prostate cancer (PCa) typically spreads to the bone, and this distribution is attributed to the central role of the microenvironment in progression. However, metastasis to the adrenal glands, while not as common, does occur. The biology that accounts for adrenal metastases may be attributed to the unique local steroid metabolome and co-clinical characterization may elucidate the role steroid biosynthesis plays in PCa progression. METHODS: Three patients with metastatic PCa who had archived tumor tissue from an adrenalectomy were retrospectively identified, and one adrenal metastasis was developed into a xenograft (MDA-PCa-250). The adrenal metastases were characterized by performing somatic DNA whole exome sequencing (WES), RNA-Seq, immunohistochemistry (IHC), and steroid metabolite quantitation. The influence of steroid metabolites on adrenal metastasis cells and tumor growth was tested in vitro and in vivo. RESULTS: Clinically, adrenalectomy was performed during castration-resistant oligometastatic disease, and two men experienced resensitization to leuprolide. Somatic DNA WES revealed heterogeneous alterations in tumor suppressor and DNA damage repair pathway genes. Adrenal metastases had active androgen receptor (AR) signaling by IHC, and RNA-Seq supported a potential role for adrenal androgen precursor metabolism in activating the AR. Steroid quantitation suggested the adrenal androgen precursors were converted into testosterone in these metastases, and stable isotope tracing of an organoid from MDA-PCa-250 confirmed the capability of adrenal metastases to biosynthesize testosterone from adrenal precursors. In vitro testing of a cell line derived from MDA-PCa-250 showed that testosterone and cortisol stimulated tumor cell growth. In vivo experiments demonstrated that MDA-PCa-250 grew in intact mice with circulating testosterone, but not in castrated mice. CONCLUSIONS: PCa adrenal metastases depend upon AR signaling driven by androgen precursors, androstenedione and dehydroepiandrosterone, available in the microenvironment, despite the presence of heterogeneous somatic DNA alterations. Moreover, MDA-PCa-250 provides a preclinical model that can recapitulate the unique androgen-dependence of adrenal metastases. CLINICAL TRIAL REGISTRATION: This study does not report the clinical results of a clinical trial, but it does use samples from a completed clinical trial that is registered with clinicaltrials.gov (NCT01254864).

17.
Exp Cell Res ; 420(1): 113340, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36075446

RESUMO

Oxidative stress damage to the lens is a key factor in most cataracts. Forkhead box O 4 (FOXO4), a member of the forkhead box O family, plays a pivotal role in oxidative stress. FOXO4 is upregulated in lens of age-related cataract patients, but its role in cataract has not been elucidated. Herein, we investigated the role and mechanism of FOXO4 during oxidative stress damage in lens epithelial cells. H2O2 treatment enhanced FOXO4 expression in HLEpiC cells. Short hairpin RNAs mediated FOXO4 silence aggravated H2O2-induced cell apoptosis. In addition, upon H2O2 exposure, silencing of FOXO4 reduced SOD and CAT activities, as well as increased intracellular MDA and ROS levels. FOXO4 silencing also inhibited Nrf2 nuclear translocation, followed by reducing the expressions of Nrf2-governed antioxidant genes HO-1 and NOQ-1. Exogenous overexpression of FOXO4 was also involved in this study and exhibited opposite effects of FOXO4-silencing. Mechanistically, FOXO4 directly bound the promoter of TRIM25 and regulated its transcription, thereby activating the Nrf2 signaling. Taken together, in the condition of oxidative stress, the expression of FOXO4 showed a compensatory upregulation and it exhibited an anti-oxidative effect by modulating the transcription of TRIM25, thus activating the Nrf2 signaling. The FOXO4/TRIM25/Nrf2 axis may be associated with the pathological mechanisms of cataract.


Assuntos
Catarata , Fator 2 Relacionado a NF-E2 , Antioxidantes/farmacologia , Apoptose/genética , Catarata/genética , Catarata/patologia , Proteínas de Ciclo Celular/metabolismo , Células Epiteliais/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Fatores de Transcrição/metabolismo , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina-Proteína Ligases
18.
Genes (Basel) ; 13(9)2022 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-36140715

RESUMO

Root restriction is a physical and ecological cultivation mode which restricts plant roots into a limited container to regulate vegetative and reproduction growth by reshaping root architecture. However, little is known about related molecular mechanisms. To uncover the root-related regulatory network of endogenous RNAs under root restriction cultivation (referred to RR), transcriptome-wide analyses of mRNAs, long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) involved in root development were performed. During root development, RR treatment had a positive effect on root weight, typically, young roots were significantly higher than conventional cultivation (referred to NR) treatment, suggesting that root architecture reconstruction under RR was attributed to the vigorous induction into lateral roots. Furthermore, a total of 26,588 mRNAs, 1971 lncRNAs, and 2615 circRNAs were identified in root of annual "Muscat Hamburg" grapevine by the transcriptomic analyses. The expression profile of mRNAs, lncRNAs and circRNA were further confirmed by the quantitative real-time PCR (RT-qPCR). Gene ontology enrichment analysis showed that a majority of the differentially expressed mRNAs, lncRNAs and circRNAs were enriched into the categories of cellular process, metabolic process, cell part, binding, and catalytic activity. In addition, the regulatory network of endogenous RNAs was then constructed by the prediction of lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA network, implying that these RNAs play significant regulatory roles for root architecture shaping in response to root restriction. Our results, for the first time, the regulatory network of competitive endogenous RNAs (ceRNAs) functions of lncRNA and circRNA was integrated, and a basis for studying the potential functions of non-coding RNAs (ncRNAs) during root development of grapevine was provided.


Assuntos
MicroRNAs , RNA Longo não Codificante , Vitis , Redes Reguladoras de Genes , MicroRNAs/genética , RNA Circular/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transcriptoma/genética , Vitis/genética , Vitis/metabolismo
19.
Clin Lab ; 68(9)2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36125159

RESUMO

BACKGROUND: At present, the most direct method to evaluate mucosal healing in patients with ulcerative colitis (UC) is endoscopy, but it is costly and invasive. Therefore, it is necessary to find a biomarker with low cost, easy access, high sensitivity and specificity as an indicator of UC activity. This study aimed to examine the level of platelet to lymphocyte ratio (PLR) and interleukin-8 (IL-8) in UC patients and evaluate their roles in differential diagnosis and disease activity assessment. METHODS: A retrospective study involving 130 UC patients and 141 irritable bowel syndrome (IBS) patients was performed. The UC patients were divided into remission group and active group according to the Modified Mayo score. The receiver operating characteristic curve (ROC) analysis was performed to determine the optimal cutoff value of PLR and IL-8 in differential diagnosis between UC patients and IBS patients. RESULTS: The levels of WBC, PLR, and IL-8 in UC patients were higher than those compared with IBS controls. The optimal cutoff to differentiate UC and IBS patients was 6.76 109/L, 114.70, and 19.42 pg/mL for WBC, PLR, and IL-8, respectively (sensitivity, 36.9% vs. 83.8% vs. 72.3%; specificity, 83.0% vs. 65.2% vs. 94.3%; AUC, 0.601 vs. 0.815 vs. 0.859). IL-8 had the highest AUC and specificity. Among 130 patients, 75 patients (57.6%) had mucosal inflammation. The cutoff value of IL-8 for predicting disease severity of UC patients was 22.21 pg/mL (AUC: 0.861). The sensitivity, specificity, and Youden index of IL-8 for predicting severe UC were 92.0%, 81.8%, and 0.702, respectively. CONCLUSIONS: PLR and IL-8 showed great performance in distinguishing UC from IBS patients. Moreover, elevated IL-8 level indicated mucosal inflammation, reflecting disease severity in UC patients.


Assuntos
Colite Ulcerativa , Interleucina-8/sangue , Síndrome do Intestino Irritável , Biomarcadores , Colite Ulcerativa/diagnóstico , Diagnóstico Diferencial , Humanos , Inflamação , Síndrome do Intestino Irritável/diagnóstico , Linfócitos , Estudos Retrospectivos
20.
Phytomedicine ; 106: 154399, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36057143

RESUMO

BACKGROUND: 6-acetylacteoside (6-AA) is a phenylethanoid glycoside isolated from Cistanche deserticola which had been previously proven to possess anti-osteoporotic activity previously. Currently, it is still unknown whether 6-AA plays a crucial role on the anti-osteoporotic effects of C. deserticola. PURPOSE: To elucidate the therapeutic effect and mechanism of 6-AA on osteoporosis by employing an ovariectomized mouse model in vivo and RAW264.7 cells in vitro. METHODS: Sixty female ICR mice were randomly assigned into six groups: sham-operated control group (SHAM, vehicle), ovariectomized model group (OVX, vehicle), positive group (EV, 1 mg/kg/day of estradiol valerate), low dosage (10 mg/kg/day of 6-AA), medium dosage (20 mg/kg/day of 6-AA) and high dosage (40 mg/kg/day of 6-AA) treatment groups. All substances were administered daily by intragastric gavage. After 12 weeks of intervention, trabecular bone microarchitecture was estimated and bone biomechanics were determined. Bone formation and resorption factors were determined by using the corresponding Elisa kits. The related proteins and metabolites were estimated by using western-blot and metabolomics techniques. RESULTS: OVX mice demonstrated significant atrophy of the uterine and vagina, declined biomechanical parameters such as flexural strength and maximum load, deteriorated trabecular bone microarchitecture such as decreased BMD, BMC, TMC, TMD, BVF, Tb. N, and Tb. Th and increased Tb. Sp, as well as increased bone resorption factors such as TRAP, cathepsin K, and DPD, all after 12 weeks of ovariectomy operation. Following administration of 6-AA to OVX mice, parameters related to the bone microarchitecture, bone resorption activities as well as biomechanical properties were all significantly improved. Meanwhile, the levels of NF-κB, NFATc1, RANK, RANKL and TRAF6 were significantly downregulated, while OPG, PI3K and AKT were upregulated after 6-AA intervention. This indicates that, 6-AA could prevent bone resorption by regulating the RANKL/RANK/OPG mediated NF-κB and PI3K/AKT pathways. Furthermore, 26 different metabolites corresponding to 25 metabolic pathways were identified, and 5 of which were related to the formation of osteoporosis. Interestingly, 23 abnormal metabolites were recovered after 6-AA treatment. CONCLUSION: Our results revealed the significant anti-osteoporotic effects of 6-AA on ovariectomized mice which were probably exerted via suppression of osteoclast formation and bone resorption.


Assuntos
Reabsorção Óssea , Osteoporose , Animais , Densidade Óssea , Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/metabolismo , Catepsina K/metabolismo , Estradiol/farmacologia , Feminino , Glicosídeos/farmacologia , Glicosídeos/uso terapêutico , Camundongos , Camundongos Endogâmicos ICR , NF-kappa B/metabolismo , Osteoporose/tratamento farmacológico , Osteoporose/etiologia , Osteoporose/metabolismo , Ovariectomia/efeitos adversos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ligante RANK/metabolismo , Salicilamidas , Fator 6 Associado a Receptor de TNF/metabolismo
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