Wnt signaling in cell adhesion, development, and colon cancer

Wnt signaling is essential for embryonic development, influencing processes such as axis formation, cell proliferation and differentiation, cell fate decisions, and axon guidance. It also plays a role in maintaining tissue homeostasis in adult organisms. The loss of normal cell polarity and adhesion caused by Wnt signaling activation is a fundamental step for tumor progression and metastasis. Activating the canonical Wnt pathway is a driving force in many human cancers, especially colorectal, hepatocellular, and mammary carcinomas. Wnt causes the stabilization and nuclear transport of newly synthesized transcriptional regulator β-catenin. The generally accepted view is that the canonical effects of Wnt growth factors are caused by the transcription of β-catenin target genes. Here, we review recent findings that indicate Wnt is a regulator of many other cellular physiological activities, such as macropinocytosis, endosome trafficking, protein stability, focal adhesions, and lysosomal activity. Some of these regulatory responses occur within minutes and do not require new protein synthesis, indicating that there is much more to Wnt beyond the well-established transcriptional role of β-catenin. The main conclusion that emerges from these studies is that in basal cell conditions, the activity of the key protein kinase GSK3, which is inhibited by Wnt pathway activation, normally represses the actin machinery that orchestrates macropinocytosis with implications in cancer. These contributions expand our understanding of the multifaceted roles of Wnt signaling in cellular processes, development, and cancer, providing insights into potential therapeutic targets and strategies

Ixora parviflora Protects against UVB-Induced Photoaging by Inhibiting the Expression of MMPs, MAP Kinases, and COX-2 and by Promoting Type I Procollagen Synthesis

Ixora parviflora with high polyphenol content exhibited antioxidant activity and reducing UVB-induced intracellular reactive oxygen species production. In this study, results of the photoaging screening experiments revealed that IPE at 1000 μg/mL reduced the activity of bacterial collagenase by 92.7 ± 4.2% and reduced the activity of elastase by 32.6 ± 1.4%. Therefore, we investigated the mechanisms by which IPE exerts its anti-photoaging activity. IPE at 1 μg/mL led to an increase in type I procollagen expression and increased total collagen synthesis in fibroblasts at 5 μg/mL. We found that IPE inhibited MMP-1, MMP-3, and MMP-9 expression at doses of 1, 5, and 10 μg/mL, respectively, in fibroblasts exposed to UV irradiation (40 mJ/cm2). Gelatin zymography assay showed that IPE at 50 μg/mL inhibited MMP-9 secretion/activity in cultured fibroblasts after UVB exposure. In addition, IPE inhibited the phosphorylation of p38, ERK, and JNK induced by UVB. Furthermore, IPE inhibited the UVB-induced expression of Smad7. In addition, IPE at 1 μg/mL inhibited NO production and COX-2 expression in UV-exposed fibroblasts. These findings show that IPE exhibits anti-inflammatory and anti-photoaging activities, indicating that IPE could be a potential anti-aging agent

Ontology-based HBIM for historic buildings with traditional woodwork in Taiwan

In recent years, the use of Historic Building Information Modeling (HBIM) has grown prevalent and thus provided a research opportunity. Differing from newly constructed buildings, structural components of historic buildings come with unique physical configurations and have amassed impressive amount of restoration data, all of which must be taken into consideration when incorporating Building Information Modeling. In terms of modelling, it is critical to determine the appropriate level of detail (LoD), level of information (LoI), especially the comprehensiveness and expandability of the database. International Committee for Documentation/Conceptual Reference Model (CIDOC CRM) is a widely accepted standard for ontology model. This study aims to integrate the HBIM and CIDOC CRM to construct a framework and comprehensive operational procedure for the modeling of traditional Minan architecture and a database with complete semantics archiving the background and restoration data. Autodesk A360 is ideal for collaborative. However, there are limitations when it comes to developing advanced models for data management or query; interactive experience; meeting model applications derived from future scenarios. Therefore, the study also offers a 3D modeling platform constructed using Unity, as well as a comparison of the platforms built with Unity, three.js and Autodesk A360 as a reference for users

Targeting Membrane Trafficking as a Strategy for Cancer Treatment

Membrane trafficking is emerging as an attractive therapeutic strategy for cancer. Recent reports have found a connection between Wnt signaling, receptor-mediated endocytosis, V-ATPase, lysosomal activity, and macropinocytosis through the canonical Wnt pathway. In macropinocytic cells, a massive internalization of the plasma membrane can lead to the loss of cell-surface cadherins, integrins, and other antigens that mediate cell–cell adhesion, favoring an invasive phenotype. V-ATPase is a key regulator in maintaining proper membrane trafficking, homeostasis, and the earliest developmental decisions in the Xenopus vertebrate development model system. Here, we review how the interference of membrane trafficking with membrane trafficking inhibitors might be clinically relevant in humans

Real-time monitoring of magnetic drug targeting using fibered confocal fluorescence microscopy

Magnetic drug targeting has been proposed as means of concentrating therapeutic agents at a target site and the success of this approach has been demonstrated in a number of studies. However, the behavior of magnetic carriers in blood vessels and tumor microcirculation still remains unclear. In this work, we utilized polymeric magnetic nanocapsules (m-NCs) for magnetic targeting in tumors and dynamically visualized them within blood vessels and tumor tissues before, during and after magnetic field exposure using fibered confocal fluorescence microscopy (FCFM). Our results suggested that the distribution of m-NCs within tumor vasculature changed dramatically, but in a reversible way, upon application and removal of a magnetic field. The m-NCs were concentrated and stayed as clusters near a blood vessel wall when tumors were exposed to a magnetic field but without rupturing the blood vessel. The obtained FCFM images provided in vivo in situ microvascular observations of m-NCs upon magnetic targeting with high spatial resolution but minimally invasive surgical procedures. This proof-of-concept descriptive study in mice is envisaged to track and quantify nanoparticles in vivo in a non-invasive manner at microscopic resolution

THE EFFECT OF INSULIN AND CARBOHYDRATE SUPPLEMENTATION ON GLYCOGEN REPLENISHMENT AMONG DIFFERENT HINDLIMB MUSCLES IN RATS FOLLOWING PROLONGED SWIMMING

In the present study we investigated the interactive effects of insulin and carbohydrate on glycogen replenishment in different rat hindlimb muscles. Forty male Sprague Dawley rats were assigned to 5 groups, including 1) sedentary control with carbohydrate supplement (2 g glucose · kg body wt-1), 2) sedentary rats with 16 hours recovery, carbohydrate and insulin (0.5 U · kg body wt-1), 3) swimming without recovery, 4) swimming with 16 hours recovery and carbohydrate supplement, and 5) swimming with 16 hours recovery, carbohydrate and insulin. The swimming protocol consisted of two 3 h swimming sections, which were separated by a 45 min rest. The insulin and carbohydrate were administered to the rats immediately after exercise. At the end of the experiment, the soleus (S), plantaris (P), quadriceps (Q) and gastrocnemius (G) were surgically excised to evaluate glycogen utilization and replenishment. We observed that glycogen utilization was significantly lower in G and Q than S and P during swimming (p <0.05), and S showed the greatest capacity of glycogen resynthesis after post-exercise recovery (p <0.05). In the sedentary state, the glycogen synthesis did not differ among hindlimb muscles during insulin and carbohydrate treatments. Interestingly, with insulin and carbohydrate, the glycogen resynthesis in S and P were significantly greater than in Q and G following post-exercise recovery (p <0.05). We therefore concluded that the soleus and plantaris are the primary working muscles during swimming, and the greatest glycogen replenishment capacity of the soleus during post-exercise recovery is likely due to its highest insulin sensitivity

Inhibitory Effects of Terminalia catappa on UVB-Induced Photodamage in Fibroblast Cell Line

This study investigated whether Terminalia catappa L. hydrophilic extract (TCLW) prevents photoaging in human dermal fibroblasts after exposure to UVB radiation. TCLW exhibited DPPH free radical scavenging activity and protected erythrocytes against AAPH-induced hemolysis. In the gelatin digestion assay, the rates of collagenase inhibition by TCL methanol extract, TCLW, and its hydrolysates were greater than 100% at the concentration of 1 mg/mL. We found that serial dilutions of TCLW (10–500 μg/mL) inhibited collagenase activity in a dose-dependent manner (82.3% to 101.0%). However, TCLW did not significantly inhibit elastase activity. In addition, TCLW inhibited MMP-1 and MMP-9 protein expression at a concentration of 25 μg/mL and inhibited MMP-3 protein expression at a concentration of 50 μg/mL. TCLW also promoted the protein expression of type I procollagen. We also found that TCLW attenuated the expression of MMP-1, -3, and -9 by inhibiting the phosphorylation of ERK, JNK, and p38. These findings suggest that TCLW increases the production of type I procollagen by inhibiting the activity of MMP-1, -3 and -9, and, therefore, has potential use in anti-aging cosmetics

Effectiveness of mechanical chest compression for out-of-hospital cardiac arrest patients in an emergency department

AbstractBackgroundTo increase the chance of restoring spontaneous circulation, cardiopulmonary resuscitation (CPR) with high-quality chest compressions is needed. We hypothesized that, in a municipal hospital emergency department, the outcome in nontraumatic out-of-hospital cardiac arrest patients treated with standard CPR followed by mechanical chest compression (MeCC) was not inferior to that followed by manual chest compression (MaCC). The purposes of the study were to test our hypothesis and investigate whether the use of MeCC decreased human power demands for CPR.MethodsA total of 455 consecutive out-of-hospital cardiac arrest patients of presumed cardiac etiology were divided into two groups according to the chest compressions they received (MaCC or MeCC) in this retrospective review study. Human power demand for CPR was described according to the Basic Life Support/Advanced Cardiovascular Life Support guidelines and the device handbook. The primary endpoint was recovery of spontaneous circulation during resuscitation, and the secondary endpoints were survival to hospital admission and medical human power demands.ResultsIn this study, recovery of spontaneous circulation was achieved in 33.3% of patients in the MeCC group and in 27.1% in the MaCC group (p = 0.154), and the percentages of patients who survived hospitalization were 22.2% and 17.6%, respectively (p = 0.229). A ratio of 2:4 for the human power demand for CPR between the groups was found. Independent predictors of survival to hospitalization were ventricular fibrillation/pulseless ventricular tachycardia as initial rhythm and recovery of spontaneous circulation.ConclusionNo difference was found in early survival between standard CPR performed with MeCC and that performed with MaCC. However, the use of the MeCC device appears to promote staff availability without waiving patient care in the human power-demanding emergency departments of Taiwan hospitals

In situ‐crosslinked Zippersomes enhance cardiac repair by increasing accumulation and retention

Mesenchymal stem cell (MSC)‐derived extracellular vesicles (EVs) are a promising treatment for myocardial infarction (MI), but their therapeutic efficacy is limited by inefficient accumulation at the target site. A minimally invasive MSC EV therapy that enhances EV accumulation at the disease site and extends EV retention could significantly improve post‐infarct cardiac regeneration. Here, we show that EVs decorated with the next‐generation of high‐affinity (HiA) heterodimerizing leucine zippers, termed HiA Zippersomes, amplify targetable surface areas through in situ crosslinking and exhibited ~7‐fold enhanced accumulation within the infarcted myocardium in mice after 3 days and continued to be retained up to Day 21, surpassing the performance of unmodified EVs. After MI in mice, HiA Zippersomes increase the ejection fraction by 53% and 100% compared with unmodified EVs and phosphate‐buffered saline (PBS), respectively. This notable improvement in cardiac function played a crucial role in restoring healthy heart performance. HiA Zippersomes also robustly decrease infarct size by 52% and 60% compared with unmodified EVs and PBS, respectively, thus representing a promising platform for minimally invasive vesicle delivery to the infarcted heart compared to intramyocardial injections