The Role and Therapeutic Potential of miRNAs in Colorectal Liver Metastasis

poster abstractColorectal cancer (CRC) is the third most common malignancy worldwide. Liver metastasis occurs in 60% of CRC patients and responds poorly to the available treatments making it the major cause of their mortality. MicroRNAs (miRNAs) are highly conserved, endogenously encoded small, non-coding RNA molecules that regulate global gene expression. The role of microRNAs in cancer pathogenesis, including CRC, has been well documented. However, in-depth miRNA expression analysis on a large cohort of CRC tumors is needed to identify the clinically relevant miRNAs and explore their potential to target liver metastases. To this purpose, we analyzed miRNA expression data of 406 CRC tumors from the publicly available colorectal cancer genome sequencing project and identified 58 miRNAs that were significantly downregulated. 10 miRNAs were selected for further analyses that were either known to target genes in cellular pathways or located within the commonly lost chromosomal loci associated with CRC liver metastases. Of these 10 miRNAs, miR-132, miR-378f, miR-605 and miR-1976 showed significant downregulation with >2 fold change (p>0.05) in primary and CRC liver metastasis tissues and in CRC cell lines. To investigate their anti-tumorigenic and metastatic properties, we transfected 3 different CRC cell lines (SW620, HCT-116 and CT-26) with miR-mimics and subjected them to cell proliferation, apoptosis and cell transformation assays. Ectopic expression of miR-378f, -605 and -1976 suppressed CRC cell proliferation, anchorage independent growth, migration and invasion and induced apoptosis. Interestingly, CRC patients with high miR-378f and miR-1976 had better survival compared to low expressing patients (p<0.044). Our in vitro data suggest the anti-tumorigenic/metastatic properties of miR-378f, -605 and -1976 in CRC. Further understanding of their functions and in vivo therapeutic evaluations may help in developing novel therapeutic strategies for this malignancy

Specification of Drosophila Corpora Cardiaca Neuroendocrine Cells from Mesoderm Is Regulated by Notch Signaling

Drosophila neuroendocrine cells comprising the corpora cardiaca (CC) are essential for systemic glucose regulation and represent functional orthologues of vertebrate pancreatic α-cells. Although Drosophila CC cells have been regarded as developmental orthologues of pituitary gland, the genetic regulation of CC development is poorly understood. From a genetic screen, we identified multiple novel regulators of CC development, including Notch signaling factors. Our studies demonstrate that the disruption of Notch signaling can lead to the expansion of CC cells. Live imaging demonstrates localized emergence of extra precursor cells as the basis of CC expansion in Notch mutants. Contrary to a recent report, we unexpectedly found that CC cells originate from head mesoderm. We show that Tinman expression in head mesoderm is regulated by Notch signaling and that the combination of Daughterless and Tinman is sufficient for ectopic CC specification in mesoderm. Understanding the cellular, genetic, signaling, and transcriptional basis of CC cell specification and expansion should accelerate discovery of molecular mechanisms regulating ontogeny of organs that control metabolism

Effects of the Proprioceptive Neuromuscular Facilitation Technique on Scapula Function in Office Workers with Scapula Dyskinesis

Background and Objectives; Proprioceptive neuromuscular facilitation (PNF) are effective in improving and maintaining Range of motion(ROM), increasing muscular strength and power, and increasing athletic performance, especially after exercise. The scapula patterns defined in PNF are activated within the upper extremity patterns and scapula motions together. Proper function of the upper extremities requires both motion and stability of the scapula. The purpose of this study was to compare the effects of scapula stabilization exercise training involving muscle strengthening, muscle balance, and movement control exercises on office workers with scapula dysfunction. Materials and Methods: A total of 42 office workers with scapula dyskinesis were recruited and randomly divided into three groups: muscle strengthening exercise group (n = 14), muscle balance exercise group (n = 14), and movement control exercise group (n = 14). The participants underwent 18 sessions (25 min/session, 3 days a week for 6 weeks) of training involving the three types of exercises. Results: The measurement outcomes included the scapula index, measured using a digital Vernier caliper; scapula function, evaluated using the Disability of the Arm, Shoulder, and Hand (DASH) outcome questionnaire (pain and performing, work ability, and sports and art activities); and scapulohumeral movements (scapula upward rotation at humeral abduction angles of 0°, 45°, 90°, 135°, and 180°), evaluated using inclinometers. After the exercise intervention, the scapula index (p = 0.002), DASH pain and performing score (p = 0.000), DASH work ability score (p = 0.000), DASH sports and art activity score (p = 0.027), and scapulohumeral movements (scapula upward rotation at 0° (p = 0.013) and 45° (p = 0.043) humeral abduction) showed significantly greater improvements in the movement control group than in the muscle strengthening and muscle balance groups. Conclusions: Thus, proprioceptive neuromuscular facilitation can be used as a rehabilitation intervention for scapula position and movement, pain reduction, and functional improvement in office workers with scapula dyskinesis

A Systematic Review and Meta-Analysis of the Effectiveness of Virtual Reality-Based Rehabilitation Therapy on Reducing the Degree of Pain Experienced by Individuals with Low Back Pain

Background: The concept of virtual reality (VR)-based rehabilitation therapy for treating people with low back pain is of growing research interest. However, the effectiveness of such therapy for pain reduction in clinical settings remains controversial. Methods: The present study was conducted according to the reporting guidelines presented in the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. We searched the PubMed, Embase, CENTRAL, and ProQuest databases for both published and unpublished papers. The Cochrane risk of bias tool (version 2) was used to evaluate the quality of the selected studies. GRADEprofiler software (version 3.6.4) was used to evaluate the level of evidence. We analyzed the included research results using RevMan software (version 5.4.1). Results: We included a total of 11 articles in the systematic review and meta-analysis, with a total of 1761 subjects. Having assessed the quality of these studies, the risk of bias was generally low with high heterogeneity. The results revealed a small to medium effect (standardized mean difference = ±0.37, 95% confidence interval: 0.75 to 0) based on evidence of moderate overall quality. Conclusion: There is evidence that treatment using VR improves patients’ pain. The effect size was small to medium, with the studies presenting evidence of moderate overall quality. VR-based treatment can reduce pain; therefore, it may help in rehabilitation therapy

Effects of Curved-Path Gait Training on Gait Ability in Middle-Aged Patients with Stroke: Protocol for a Randomized Controlled Trial

(1) Introduction: This study aimed to investigate the effects of curved-path stride gait training on the gait ability of patients with stroke. (2) Materials and Methods: Thirty patients with stroke were randomly assigned to curved-path stride gait training (n = 15) and general gait training groups (n = 15). Both groups underwent training for 30 min five times a week for 8 weeks. The gait ability of each was assessed using the Dynamic Gait Index (DGI), Timed-Up-and-Go (TUG) test, 10-meter walk test, and Figure-of-8 walk test (F8WT). (3) Results: The curved-path gait training group showed significant differences in the DGI, TUG test, 10-m walk test, and F8WT pre- versus post- intervention (p p > 0.05). Additionally, there was a statistically significant intergroup difference in gait ability (p < 0.05). (4) Conclusions: Curved-path gait training resulted in greater improvement in gait ability than general gait training. Therefore, curved-path gait training can be a meaningful intervention for improving the gait ability of patients with stroke

KLF10 Inhibits TGF-β-Mediated Activation of Hepatic Stellate Cells via Suppression of ATF3 Expression

Liver fibrosis is a progressive and debilitating condition characterized by the excessive deposition of extracellular matrix proteins. Stellate cell activation, a major contributor to fibrogenesis, is influenced by Transforming growth factor (TGF-β)/SMAD signaling. Although Krüppel-like-factor (KLF) 10 is an early TGF-β-inducible gene, its specific role in hepatic stellate cell activation remains unclear. Our previous study demonstrated that KLF10 knockout mice develop severe liver fibrosis when fed a high-sucrose diet. Based on these findings, we aimed to identify potential target molecules involved in liver fibrosis and investigate the mechanisms underlying the KLF10 modulation of hepatic stellate cell activation. By RNA sequencing analysis of liver tissues from KLF10 knockout mice with severe liver fibrosis induced by a high-sucrose diet, we identified ATF3 as a potential target gene regulated by KLF10. In LX-2 cells, an immortalized human hepatic stellate cell line, KLF10 expression was induced early after TGF-β treatment, whereas ATF3 expression showed delayed induction. KLF10 knockdown in LX-2 cells enhanced TGF-β-mediated activation, as evidenced by elevated fibrogenic protein levels. Further mechanistic studies revealed that KLF10 knockdown promoted TGF-β signaling and upregulated ATF3 expression. Conversely, KLF10 overexpression suppressed TGF-β-mediated activation and downregulated ATF3 expression. Furthermore, treatment with the chemical chaperone 4-PBA attenuated siKLF10-mediated upregulation of ATF3 and fibrogenic responses in TGF-β-treated LX-2 cells. Collectively, our findings suggest that KLF10 acts as a negative regulator of the TGF-β signaling pathway, exerting suppressive effects on hepatic stellate cell activation and fibrogenesis through modulation of ATF3 expression. These results highlight the potential therapeutic implications of targeting the KLF10-ATF3 axis in liver fibrosis treatment

Enhancement of Marine Lantern&rsquo;s Visibility under High Haze Using AI Camera and Sensor-Based Control System

This thesis describes research to prevent maritime safety accidents by notifying navigational signs when sea fog and haze occur in the marine environment. Artificial intelligence, a camera sensor, an embedded board, and an LED marine lantern were used to conduct the research. A deep learning-based dehaze model was learned by collecting real marine environment and open haze image data sets. By applying this learned model to the original hazy images, we obtained clear dehaze images. Comparing those two images, the concentration level of sea fog was derived into the PSNR and SSIM values. The brightness of the marine lantern was controlled through serial communication with the derived PSNR and SSIM values in a realized sea fog environment. As a result, it was possible to autonomously control the brightness of the marine lantern according to the concentration of sea fog, unlike the current marine lanterns, which adjust their brightness manually. This novel-developed lantern can efficiently utilize power consumption while enhancing its visibility. This method can be used for other fog concentration estimation systems at the embedded board level, so that applicable for local weather expectations, UAM navigation, and autonomous driving for marine ships