Prevention of neointimal hyperplasia after coronary artery bypass graft via local delivery of sirolimus and rosuvastatin: network pharmacology and in vivo validation.

BACKGROUND: Coronary artery bypass graft (CABG) is generally used to treat complex coronary artery disease. Treatment success is affected by neointimal hyperplasia (NIH) of graft and anastomotic sites. Although sirolimus and rosuvastatin individually inhibit NIH progression, the efficacy of combination treatment remains unknown. METHODS: We identified cross-targets associated with CABG, sirolimus, and rosuvastatin by using databases including DisGeNET and GeneCards. GO and KEGG pathway enrichment analyses were conducted using R studio, and target proteins were mapped in PPI networks using Metascape and Cytoscape. For in vivo validation, we established a balloon-injured rabbit model by inducing NIH and applied a localized perivascular drug delivery device containing sirolimus and rosuvastatin. The outcomes were evaluated at 1, 2, and 4 weeks post-surgery. RESULTS: We identified 115 shared targets between sirolimus and CABG among databases, 23 between rosuvastatin and CABG, and 96 among all three. TNF, AKT1, and MMP9 were identified as shared targets. Network pharmacology predicted the stages of NIH progression and the corresponding signaling pathways linked to sirolimus (acute stage, IL6/STAT3 signaling) and rosuvastatin (chronic stage, Akt/MMP9 signaling). In vivo experiments demonstrated that the combination of sirolimus and rosuvastatin significantly suppressed NIH progression. This combination treatment also markedly decreased the expression of inflammation and Akt signaling pathway-related proteins, which was consistent with the predictions from network pharmacology analysis. CONCLUSIONS: Sirolimus and rosuvastatin inhibited pro-inflammatory cytokine production during the acute stage and regulated Akt/mTOR/NF-κB/STAT3 signaling in the chronic stage of NIH progression. These potential synergistic mechanisms may optimize treatment strategies to improve long-term patency after CABG.

Association between watching eating broadcasts like mukbang and cookbang and generalized anxiety disorder among Korean adolescents.

BACKGROUND: Anxiety disorders are common during adolescence; therefore, detecting anxiety disorders among adolescents and providing appropriate treatment are crucial. Studies have suggested that watching online audiovisual broadcasts like mukbang and cookbang (hereafter mukbang), where hosts eat or cook food, may influence anxiety disorders. However, there is insufficient research on the association between watching mukbang and generalized anxiety disorder (GAD). Therefore, we investigated the association between watching mukbang and GAD among Korean adolescents. METHODS: We analyzed 51,764 adolescents who participated in the 2020 Korea Youth Risk Behavior Web-Based Survey (KYRBS). The participants were asked how frequently they watched mukbang per week over the past 12 months. Anxiety disorders were assessed using the generalized anxiety disorder-7 (GAD-7) questionnaire. A multiple logistic regression analysis was performed after adjusting for confounding variables. RESULTS: The prevalence of GAD was higher among adolescents who watched mukbang compared to those who did not (aOR: 1.100, 95% CI: 1.026-1.180, P = 0.008 in male participants; aOR: 1.090, 95% CI: 1.003-1.185, P = 0.042 in female participants). The frequency of watching mukbang showed a dose-dependent relationship with a greater likelihood of GAD in female adolescents. CONCLUSION: This study's results showed that watching mukbang is associated with GAD in Korean adolescents. Proper interventions for mental health are needed for adolescents who watch mukbang.

Measurement of Poly A Tail Length from Drosophila Larva Brain and Cell Line.

Polyadenylation is a crucial posttranscriptional modification that adds poly(A) tails to the 3' end of mRNA molecules. The length of the poly(A) tail is tightly regulated by cellular processes. Dysregulation of mRNA polyadenylation has been associated with abnormal gene expression and various diseases, including cancer, neurological disorders, and developmental abnormalities. Therefore, comprehending the dynamics of polyadenylation is vital for unraveling the complexities of mRNA processing and posttranscriptional gene regulation. This paper presents a method for measuring poly(A) tail lengths in RNA samples isolated from Drosophila larval brains and Drosophila Schneider S2 cells. We employed the guanosine/inosine (G/I) tailing approach, which involves the enzymatic addition of G/I residues at the 3' end of mRNA using yeast poly(A) polymerase. This modification protects the RNA's 3' end from enzymatic degradation. The protected full-length poly(A) tails are then reverse-transcribed using a universal antisense primer. Subsequently, PCR amplification is performed using a gene-specific oligo that targets the gene of interest, along with a universal sequence oligo used for reverse transcription. This generates PCR products encompassing the poly(A) tails of the gene of interest. Since polyadenylation is not a uniform modification and results in tails of varying lengths, the PCR products display a range of sizes, leading to a smear pattern on agarose gel. Finally, the PCR products are subjected to high-resolution capillary gel electrophoresis, followed by quantification using the sizes of the poly(A) PCR products and the gene-specific PCR product. This technique offers a straightforward and reliable tool for analyzing poly(A) tail lengths, enabling us to gain deeper insights into the intricate mechanisms governing mRNA regulation.

Assessing blood sugar measures for predicting new-onset diabetes and cardiovascular disease in community-dwelling adults.

PURPOSE: Diabetes mellitus (DM) is a global health concern linked to various complications, including cardiovascular disease (CVD). However, long-term follow-up studies on the risk of DM and CVD using different blood glucose assessment methods in the general Korean population are lacking. This study aimed to assess the predictive abilities of fasting plasma glucose (FPG), 2-h oral glucose tolerance test (OGTT), and glycosylated hemoglobin (HbA1c) for new-onset DM and high CVD risk in a middle-aged and older Korean population. METHODS: This study used data from the Korean Genome and Epidemiology Study, a population-based prospective cohort. Blood sugar measures (FPG, OGTT, and HbA1c) were examined. The primary endpoint was the development of new-onset DM, and CVD risk was evaluated using the Framingham risk score. The predictive abilities for new-onset DM based on glycemic values were evaluated using Harrell's Concordance index and 95% confidence intervals. RESULTS: Among the 10,030 participants, data of 6813 participants without DM at baseline were analyzed. The study revealed that OGTT outperformed FPG and HbA1c in predicting new-onset DM. The combination of FPG and HbA1c did not significantly enhance predictions for DM compared with OGTT alone. OGTT also outperformed FPG and HbA1c in predicting high CVD risk, and this difference remained significant even after adjusting for additional confounders. CONCLUSION: OGTT has superior predictive capabilities in identifying new-onset DM and high CVD risk in the Korean population. This suggests that relying solely on individual blood sugar measures may be insufficient for assessing DM and CVD risks.

Effect of RNF113A deficiency on oxidative stress-induced NRF2 pathway.

The ring finger protein 113A (RNF113A) serves as an E3 ubiquitin ligase and a subunit of the spliceosome. Mutations in the RNF113A gene are associated with X-linked trichothiodystrophy (TTD). However, the cellular roles of RNF113A remain largely unknown. In this study, we performed transcriptome profiling of RNF113A knockout (KO) HeLa cells using RNA sequencing and revealed the upregulation of NRF2 pathway-associated genes. Further analysis confirmed that the KO of RNF113A promotes nuclear localization of the NRF2 protein and elevates the mRNA levels of NRF2 target genes. RNF113A KO cells showed high levels of intracellular reactive oxygen species (ROS) and decreased resistance to cell death following H2O2 treatment. Additionally, RNF113A KO cells more sensitively formed stress granules (SGs) under arsenite-induced oxidative stress. Moreover, RNF113A KO cells exhibited a decrease in glutathione levels, which could be attributed to a reduction in GLUT1 expression levels, leading to decreased glucose uptake reactions and lower intracellular glucose levels. These alterations potentially caused a reduction in ROS scavenging activity. Taken together, our findings suggest that the loss of RNF113A promotes oxidative stress-mediated activation of the NRF2 pathway, providing novel insights into RNF113A-associated human diseases.

DW71177: A novel [1,2,4]triazolo[4,3-a]quinoxaline-based potent and BD1-Selective BET inhibitor for the treatment of acute myeloid leukemia.

The bromodomain and extraterminal domain (BET) family proteins recognize acetyl-lysine (Kac) at the histone tail through two tandem bromodomains, i.e., BD1 and BD2, to regulate gene expression. BET proteins are attractive therapeutic targets in cancer due to their involvement in oncogenic transcriptional activation, and bromodomains have defined Kac-binding pockets. Here, we present DW-71177, a potent BET inhibitor that selectively interacts with BD1 and exhibits strong antileukemic activity. X-ray crystallography, isothermal titration calorimetry, and molecular dynamic studies have revealed the robust and specific binding of DW-71177 to the Kac-binding pocket of BD1. DW-71177 effectively inhibits oncogenes comparable to the pan-BET inhibitor OTX-015, but with a milder impact on housekeeping genes. It efficiently blocks cancer-associated transcriptional changes by targeting genes that are highly enriched with BRD4 and histone acetylation marks, suggesting that BD1-selective targeting could be an effective and safe therapeutic strategy against leukemia.

Effect of bodybuilding athletes' weight loss method on performance factors and immune function.

This study was conducted on elite bodybuilders for 6 weeks using two weight loss methods (traditional method=high-weight loss vs. new method=low-weight loss). The subjects of this study were 26 male active elite bodybuilders who voluntarily wanted to participate in this experiment, and were divided into experimental group and traditional group. The traditional and experimental groups underwent dietary restrictions and training for 6 weeks. The conclusion obtained from the results of this study is that in the case of anthropometric variables, there is a difference in weight class between the two groups. The experimental group's upper arm circumference was maintained compared to the pre-measured value after post-measurement, while the traditional group decreased, and a significant interaction effect was observed. In particular, a significant interaction effect was observed. In that the absolute value of maximum oxygen intake was significantly increased only in the post-experimental group compared to the pretest, and an interaction effect was observed, the use of low-weight loss method is more effective than the traditional method of high-weight loss method. An increase in some cytokines was observed despite traditional weight loss, but it did not cause an excessive decrease in immunity or a sharp decrease in performance factors. As a result of this experiment, it is judged that the use of a low-weight loss method is more preferable than the traditional high-weight loss method in relation to performance variables.

Development and Validation of an Artificial Intelligence-Based Motion Analysis System for Upper Extremity Rehabilitation Exercises in Patients with Spinal Cord Injury: A Randomized Controlled Trial.

In this study, we developed an AI-based real-time motion feedback system for patients with spinal cord injury (SCI) during rehabilitation, aiming to enhance their interest and motivation. The effectiveness of the system in improving upper-limb muscle strength during the Thera band exercises was evaluated. The motion analysis program, including exercise repetition counts and calorie consumption, was developed using MediaPipe, focusing on three key motions (chest press, shoulder press, and arm curl) for upper extremity exercises. The participants with SCI were randomly assigned to the experimental group (EG = 4) or control group (CG = 5), engaging in 1 h sessions three times a week for 8 weeks. Muscle strength tests (chest press, shoulder press, lat pull-down, and arm curl) were performed before and after exercises. Although both groups did not show significant differences, the EG group exhibited increased strength in all measured variables, whereas the CG group showed constant or reduced results. Consequently, the computer program-based system developed in this study could be effective in muscle strengthening. Furthermore, these findings may serve as a valuable foundation for future AI-driven rehabilitation exercise systems.