Dense and stiff extracellular matrix (ECM) in heterogeneous tumor tissues can inhibit deep penetration of nanoparticle drug carriers and decreases their therapeutic efficacy. Herein, we suggest the ...ECM remodeling strategy by the pulsed high intensity focused ultrasound (Pulsed-HIFU) technology for enhanced tumor-targeting of nanoparticles. First, we clearly observed that the tumor-targeting efficacy and tissue penetration of intravenously injected Cy5.5-labled glycol chitosan nanoparticles (Cy5.5-CNPs) were greatly inhibited in tumor tissue containing high collagen and hyaluronan contents in ECM-rich A549 tumor-bearing mice, compared to in ECM-less SCC7. When collagenase or hyaluronidase was treated by intra-tumoral injection, the amount of collagen and hyaluronan decreased in ECM-rich A549 tumor tissues and more Cy5.5-CNPs penetrated inside the tumor tissue, confirmed using non-invasive optical imaging. Finally, in order to break down the stiff ECM structure, ECM-rich A549 tumor tissues were treated with the relatively low power of Pulse-HIFU (20W/cm2), wherein acute tissue damage was not observed. As we expected, the A549 tumor tissues showed the remodeling of ECM structure after non-invasive Pulsed-HIFU exposure, which resulted in the increased blood flow, decreased collagen contents, and enhanced penetration of CNPS. Importantly, the tumor targeting efficiency in Pulsed-HIFU-treated A549 tumor tissues was 2.5 times higher than that of untreated tumor tissues. These overall results demonstrate that ECM remodeling and disruption of collagen structure by Pulse-HIFU is promising strategy to enhance the deep penetration and enhanced tumor targeting of nanoparticles in ECM-rich tumor tissues.
Display omitted
Objectives
This study aimed to develop a diagnostic support tool using pretrained models for classifying panoramic images of the temporomandibular joint (TMJ) into normal and osteoarthritis (OA) ...cases.
Subjects and Methods
A total of 858 panoramic images of the TMJ (395 normal and 463 TMJ‐OA) were obtained from 518 individuals from January 2015 to December 2018. The data were randomly divided into training, validation, and testing sets (6:2:2). We used pretrained Resnet152 and EfficientNet‐B7 as transfer learning models. The accuracy, specificity, sensitivity, area under the curve, and gradient‐weighted class activation mapping (grad‐CAM) of both trained models were evaluated. The performances of the trained models were compared to that of dentists (both TMD specialists and general dentists).
Results
The classification accuracies of ResNet‐152 and EfficientNet‐B7 were 0.87 and 0.88, respectively. The trained models exhibited the highest accuracy in OA classification. In the grad‐CAM analysis, the trained models focused on specific areas in osteoarthritis images where erosion or osteophyte were observed.
Conclusions
The artificial intelligence model improved the diagnostic power of TMJ‐OA when trained with two‐dimensional panoramic condyle images and can be effectively applied by dentists as a screening diagnostic tool for TMJ‐OA.
RNA-binding proteins (RBPs) and microRNAs (miRNAs) are potent post-transcriptional regulators of gene expression. Here, we show that the RBP HuR reduced c-Myc expression by associating with the c-Myc ...3' untranslated region (UTR) next to a miRNA let-7-binding site. Lowering HuR or let-7 levels relieved the translational repression of c-Myc. Unexpectedly, HuR and let-7 repressed c-Myc through an interdependent mechanism, as let-7 required HuR to reduce c-Myc expression and HuR required let-7 to inhibit c-Myc expression. Our findings suggest a regulatory paradigm wherein HuR inhibits c-Myc expression by recruiting let-7-loaded RISC (RNA miRNA-induced silencing complex) to the c-Myc 3'UTR.
PPtreeViz, an R package, was developed to explore projection pursuit methods for classification. It provides functions to calculate various projection pursuit indices for classification and to ...explore the results in the space of projection. It also provides functions for the projection pursuit classification tree. The visualization methods of the tree structure and the features of each node in PPtreeViz can be used to easily explore the projection pursuit classification tree structure and determine the characteristics of each class. To calculate the projection pursuit indices and optimize these indices, we use the Rcpp and RcppArmadillo packages in R to improve the speed.
Skin ageing results from enhanced activation of intracellular enzymes such as collagenases, elastases and tyrosinase, stimulated by intrinsic ageing and photoageing factors. Recently, caffeine-based ...cosmetics are introduced that demonstrates to slow down skin photoageing process. However, no attempts have been done so for to understand caffeine functional inhibitory activity against photoageing related enzymes. Hence, this study established the caffeine molecular interaction and inhibition activity profiles against respective enzymes using in silico and in vitro methods, respectively. Results from in silico study indicates that caffeine has comparatively good affinity with collagenase (−4.6 kcal/mol), elastase (−3.36 kcal/mol) and tyrosinase (−2.86 kcal/mol) and formed the stable protein-ligand complex as validated by molecular dynamics simulation (protein-ligand contacts, RMSD, RMSF and secondary structure changes analysis). Moreover, in vitro data showed that caffeine (1000 µg/mL) has statistically significant maximum inhibition activity of 41.86, 36.44 and 13.72% for collagenase, elastase and tyrosinase, respectively.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
2′-Fucosyllactose (2FL) is the most abundant component of the oligosaccharide content in human milk. It has been reported that 2FL has the ability to protect against infectious disease caused by ...bacterial pathogens. In this study, we investigated the protective effects of 2FL on particulate matter (PM)10-induced pro-inflammatory cytokines in HaCaT keratinocytes. 2FL reduced PM10-induced excess expression of interleukin (IL)-6, IL-8, IL-1α and IL-1β in HaCaT keratinocytes. In addition, PM10 also increased hypoxia-inducible factor (HIF)-1α protein levels; however, 2FL inhibited the accumulation of HIF-1α protein and the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/Akt stimulated by PM10. Furthermore, 2FL improved PM10-induced the decrease in epidermal thickness and integrity of the cornified layer in the reconstructed human epidermal skin model (RHE). In our results, 2FL inhibited PM10-induced pro-inflammatory mediators by regulating the HIF-1α/PI3K/Akt pathway and protected the skin epidermis against PM10 irritation. Taken together, these results suggest that 2FL can be used as a primary ingredient in cosmeceutical products to alleviate skin irritation and inflammation caused by urban air pollution.
•Frailty and cognitive impairment independently predict mortality in older adults.•The association between frailty and mortality is moderated by cognitive impairment.•Those who are frail and ...cognitively impaired exhibit the highest risk of mortality.
Frailty and cognitive impairment in late life increase the risk of mortality. Physical frailty is closely associated with cognitive impairment. The aim of the study was to examine the independent and interaction effects of frailty and cognitive impairment in predicting mortality.
A nationally representative sample of community-dwelling Koreans aged 65 years and older (n=11,266) was followed for 3 years.
Frailty was categorized using Fried’s phenotype model. Cognitive impairment was defined as more than 1.5 standard deviations below the age-, gender-, and education-specific norm of the Mini-Mental State Examination. Cox proportional hazards regression was used to analyze the mortality risk by frailty status and the moderating effect of cognitive impairment.
Frailty was associated with cognitive impairment, with 922 (19.1%), 1609 (28.1%), and 392 (42.8%) of the nonfrail, prefrail, and frail group, respectively, being cognitively impaired. Compared with the nonfrail group, those who were prefrail (hazard ratio HR=1.38; 95% confidence interval CI: 1.10, 1.73) and frail (HR=1.78, 95% CI: 1.29, 2.46) had higher mortality rates, after adjusting for sociodemographic variables, health behaviors, and chronic conditions. Cognitive impairment was associated with a 30% increased mortality rate. A significant interaction between frailty and cognitive impairment was observed (p=0.003). Compared with those nonfrail and not cognitively impaired, frail persons with cognitive impairment had a lower survival rate (HR=1.92, 95% CI: 1.26, 2.93).
Frailty was a significant predictor of 3-year mortality in community-dwelling older adults, with the association being moderated by baseline cognitive status. Taking cognitive function into account may allow better prediction of adverse outcomes of frailty in later life.
The trend of aging society is occurring globally, and with it, one of the health problems that is emerging is frailty. Efforts are being made to account for the increasing prevalence of frailty, and ...various modifiable factors are being considered in regards to frailty. Because social contact has shown beneficial effects in terms of health in previous studies, it is increasingly being considered in relation to frailty. The purpose of this study was to assess the association of different types of social contact with frailty status.
A total of 1,200 Korean elders aged 70-84 years old were included in the study. Using Fried's Cardiovascular Health Study index to categorize the frailty status, the relationship between frailty status and frequency of contact (i.e., with family members, friends, or neighbors) was analyzed using multinomial logistic regression accounting for confounders.
Adjusting for all covariates, frequency of contact with friends was the most statistically significant. Less frequent contact was associated with a significantly higher odds of pre-frailty: monthly (odds ratio OR, 2.02; 95% confidence interval CI, 1.27-3.20), and rarely (OR, 1.87; 95% CI, 1.17-2.99), with daily contact group as reference. Also, those contacting friends monthly (OR, 5.04; 95% CI, 2.29-11.08) or rarely (OR, 3.23; 95% CI, 1.58-6.61) were more likely to be frail compared to the daily group.
Frequency of social contact, especially with friends, is strongly associated with frailty.
This study aimed to quantitatively assess three-dimensional changes in the mandibular condyle with osteoarthritis using cone-beam computed tomography (CBCT). Pre- and post-treatment CBCT images of ...temporomandibular joints (TMJs) from 66 patients were used to assess longitudinal changes in condylar volume within individual patients using 3D slicer software. Total volume difference (dV), net increase (dV + , bone deposition), and net decrease (dV- , bone resorption) after treatment were analyzed based on clinical and radiological factors. Condyles with surface erosion at their first visit showed significantly decreased volume after treatment compared to condyles without erosion (p < 0.05). Amounts of bone resorption and deposition were higher in condyles with surface erosion (both p < 0.01). In patients with condylar erosion, the presence of joint pain was associated with a decrease in condylar volume and an increase in net resorption (both p < 0.01). When both joint pain and condylar erosion were present, patients with parafunctional habits showed reduced condylar volume after treatment (p < 0.05). Condylar volume change after treatment was negatively correlated with the duration of pain relief (R = - 0.501, p < 0.05). These results indicate that condylar erosion and TMJ pain could be significant variables affecting TMJ volume changes after treatment. Establishing appropriate treatment strategies is crucial for managing condylar erosion and TMJ pain.
In Korea, there has been recent interest in nursing simulation education. In nursing, simulation education has many advantages, such as improving nursing students' problem-solving and judgment ...skills. Simulation education satisfaction is an indicator for evaluating educational performance from the learners' perspective and an important criterion for the development and progress of nursing education. Therefore, based on NLN/Jeffries simulation theory, this study aims to identify the relationship between simulation design and educational satisfaction and to confirm the mediating effect of flow.
This cross-sectional study was conducted using 143 fourth-year nursing students who had participated in classes using simulations at three universities in Seoul, Daegu, and Jeonbuk. Data were collected from April 24 to May 3, 2023. Demographic data, simulation design scale (SDS), flow in simulation, and the educational satisfaction scale in simulation were collected via an online questionnaire. The collected data were analyzed through t-test, ANOVA, Scheffé test, and Pearson's correlation coefficient using SPSS 25.0. The mediating effect of flow was analyzed through the three-stage mediation effect procedure using hierarchical regression analysis and the Sobel test.
The simulation educational satisfaction had a statistically significant positive correlation with simulation design (r = .65, p < .001) and flow (r = .47, p < .001), and simulation design was positively correlated with the flow (r = .55, p < .001). The simulation design had a statistically significant effect on flow, which was the mediating variable (β = 0.55, p < .001). Additionally, simulation design had a statistically significant effect on simulation educational satisfaction (β = 0.56, p < .001). The significance of the mediating effect of flow on the relationship between simulation design and simulation educational satisfaction was investigated using the Sobel test, and the mediating effect of flow was found to be statistically significant (Z = 5.36, p < .001).
The significance of the current study lies in its confirmation of the link between simulation design and simulation educational satisfaction, as well as the mediating function of flow. Nursing students can achieve simulation educational satisfaction through simulation-based education if simulation educators follow best practices that improve flow through well-organized simulation design.
PDF
