WW Domain-Containing Proteins YAP and TAZ in the Hippo Pathway as Key Regulators in Stemness Maintenance, Tissue Homeostasis, and Tumorigenesis

The Hippo pathway is a conserved signaling pathway originally defined in Drosophila melanogaster two decades ago. Deregulation of the Hippo pathway leads to significant overgrowth in phenotypes and ultimately initiation of tumorigenesis in various tissues. The major WW domain proteins in the Hippo pathway are YAP and TAZ, which regulate embryonic development, organ growth, tissue regeneration, stem cell pluripotency, and tumorigenesis. Recent reports reveal the novel roles of YAP/TAZ in establishing the precise balance of stem cell niches, promoting the production of induced pluripotent stem cells (iPSCs), and provoking signals for regeneration and cancer initiation. Activation of YAP/TAZ, for example, results in the expansion of progenitor cells, which promotes regeneration after tissue damage. YAP is highly expressed in self-renewing pluripotent stem cells. Overexpression of YAP halts stem cell differentiation and yet maintains the inherent stem cell properties. A success in reprograming iPSCs by the transfection of cells with Oct3/4, Sox2, and Yap expression constructs has recently been shown. In this review, we update the current knowledge and the latest progress in the WW domain proteins of the Hippo pathway in relevance to stem cell biology, and provide a thorough understanding in the tissue homeostasis and identification of potential targets to block tumor development. We also provide the regulatory role of tumor suppressor WWOX in the upstream of TGF-β, Hyal-2, and Wnt signaling that cross talks with the Hippo pathway

Phosphorylation of LCRMP-1 by GSK3β Promotes Filopoda Formation, Migration and Invasion Abilities in Lung Cancer Cells

LCRMP-1, a novel isoform of CRMP-1, can promote cancer cell migration, invasion and associate with poor clinical outcome in patients with non-small-cell lung cancer (NSCLC). However, the underlying regulatory mechanisms of LCRMP-1 in cancer cell invasiveness still remain obscure. Here, we report that GSK3β can phosphorylate LCRMP-1 at Thr-628 in consensus sequences and this phosphorylation is crucial for function of LCRMP-1 to promote filopodia formation, migration and invasion in cancer cells. Impediment of Thr-628 phosphorylation attenuates the stimulatory effects of LCRMP-1 on filopodia forming, migration and invasion abilities in cancer cells; simultaneously, kinase-dead GSK3β diminishes regulation of LCRMP-1 on cancer cell invasion. Furthermore, we also found that patients with low-level Ser-9-phosphorylated GSK3β expression and high-level LCRMP-1 expression have worse overall survival than those with high-level inactive GSK3β expressions and low-level LCRMP-1 expressions (P<0.0001). Collectively, these results demonstrate that GSK3β-dependent phosphorylation of LCRMP-1 provides an important mechanism for regulation of LCRMP-1 on cancer cell invasiveness and clinical outcome

Structure of human collapsin response mediator protein 1: A possible role of its C-terminal tail

[[abstract]]Collapsin response mediator protein 1 (CRMP-1) is the first identified member of the CRMP family and is crucial for both the mediation of neuronal differentiation and in suppressing the invasion of lung cancer. The crystal structure of full-length human CRMP-1 was determined at a resolution of 3 Å. Human CRMP-1 comprises a tetrameric assembly; its overall structure is similar to that of mouse CRMP-1, but the measured electron density of the C-terminal residues 488-496 show a randomly coiled link that connects the protomers to each other, within which residues 497-572 are proteolytically susceptible in vivo. Deletion of residues 472-572 by thrombin in vitro not only releases a randomly coiled tail but also transduces observable structural changes of CRMP-1, as revealed by analytical size-exclusive chromatography and circular dichroism spectra. These results indicate a possible alternative role in CRMP dynamics and function

Healthy Taiwanese Eating Approach (TEA) toward Total Wellbeing and Healthy Longevity

A healthy dietary pattern review for Asian countries is scarce, which is crucial for guiding healthy eating. We reviewed Taiwanese dietary pattern discovery studies. Included were 19 studies, the majority of which employed dimension reduction methods to find dietary patterns associated with various health conditions. To show what is a high or low intake of foods in Taiwan, we also report the average dietary content and the 25th and 75th percentile values of the adult population for six food groups gathered by the Nutrition and Health Survey in Taiwan, 2017–2020. The healthy Taiwanese dietary approach is cohesive across multiple health outcomes occurring at different ages. It is featured with higher intakes of plant-based foods, aquatic foods, and some beneficial ethnic foods (soy products), drinks (tea), and cooking methods (boiling and steaming); lower intakes of fast foods, fatty and processed meats, sugar, salt rich foods/drinks, and fried foods; but with mixed findings for dairy and egg. Yet, the average Taiwanese person consumed many refined staple foods and livestock, but not sufficient vegetables, fruits, whole grains and roots, beans, and nuts. Dairy consumption remains low. In conclusion, Taiwanese discovery studies point to a mortality-lowering total wellbeing dietary pattern consistent with the current knowledge, which discloses potential benefits of soy product, tea, and boiling and steaming

Influence of medications and psychotic symptoms on fall risk in acute psychiatric inpatients

Objective: In this study, we investigated the incidence rate and risk factors related to falls among acute psychiatric inpatients in a regional hospital. Methods: We included 521 patients who were admitted to the acute psychiatric ward in Taoyuan Armed Forces General Hospital from January 2015 to January 2016 and analyzed their medical records within a 1-year period. We compared differences between the fall and nonfall groups in demographic characteristics, psychiatric diagnoses, medication use, psychotic symptoms, and Timed Up and Go scores. Chi-square tests were used for comparison of categorical variables and t-test was used for continuous variables. Results: A total of 521 patients with an average age of 38.9 years were included in our study; 167 (32.1%) patients were female. Among the inpatients in our study, 3.07% were fallers. Patients with female gender, older age, psychotic symptoms, and use of more types of medication, especially mood stabilizers, laxatives, and other classes of medications, were significantly more likely to experience falls (P < 0.05). Conclusion: Determining the risk factors for falls in an acute psychiatric ward is useful for clinical care. As we identified patients in a high-risk group, fall prevention can be performed to help them to avoid possible injury. However, further studies are needed to determine more quantitative measures to evaluate or predict the risk of falls in acute psychiatric units

Inhibitor of DNA-Binding Protein 4 Suppresses Cancer Metastasis through the Regulation of Epithelial Mesenchymal Transition in Lung Adenocarcinoma

Metastasis is a predominant cause of cancer death and the major challenge in treating lung adenocarcinoma (LADC). Therefore, exploring new metastasis-related genes and their action mechanisms may provide new insights for developing a new combative approach to treat lung cancer. Previously, our research team discovered that the expression of the inhibitor of DNA binding 4 (Id4) was inversely related to cell invasiveness in LADC cells by cDNA microarray screening. However, the functional role of Id4 and its mechanism of action in lung cancer metastasis remain unclear. In this study, we report that the expression of Id4 could attenuate cell migration and invasion in vitro and cancer metastasis in vivo. Detailed analyses indicated that Id4 could promote E-cadherin expression through the binding of Slug, cause the occurrence of mesenchymal-epithelial transition (MET), and inhibit cancer metastasis. Moreover, the examination of the gene expression database (GSE31210) also revealed that high-level expression of Id4/E-cadherin and low-level expression of Slug were associated with a better clinical outcome in LADC patients. In summary, Id4 may act as a metastatic suppressor, which could not only be used as an independent predictor but also serve as a potential therapeutic for LADC treatment

Comparison of In-Hospital Major Adverse Cardiovascular Events in Patients with Acute Myocardial Infarction Treated with Ticagrelor or Clopidogrel in the Emergency Department: A Propensity Score Matched Retrospective Cohort Study

Background: Dual antiplatelet therapy (DAPT) is a standard treatment option for acute myocardial infarction (AMI). The difference between the efficacy of ticagrelor and clopidogrel in the emergency department (ED) before percutaneous coronary intervention (PCI) remains unknown. The present study compared the in-hospital major adverse cardiovascular event (MACE) rates between patients with AMI treated with clopidogrel and those treated with ticagrelor in the ED before PCI. Methods: We retrospectively collected the data of patients diagnosed as having AMI in the ED. Patients were only included if they had successfully received complete DAPT with aspirin and ticagrelor/clopidogrel in the ED and had undergone PCI. The patients were divided into two groups according to their DAPT regimen. The primary outcome was the rate of in-hospital MACEs. The secondary outcomes included an unexpected return to the ED within 72 h, readmission within 14 d, and revascularization. Results: A total of 1836 patients were enrolled. Patients in the ticagrelor group had a lower in-hospital MACE rate (3.01% versus 7.51%, p p p = 0.013). After propensity score matching, the risk of in-hospital MACEs remained significantly lower in the ticagrelor group (OR 0.42, 95% CI: 0.21–0.85, p = 0.016). Conclusion: DAPT with ticagrelor and aspirin in the ED before PCI is associated with a lower in-hospital MACE rate among patients with AMI

Phosphorylation of LCRMP-1 at Thr-628 is required for filopodia formation.

<p>(A) Nonphosphorylated LCRMP-1 (T628A) mutant impairs filopodia formation. CL1-0 cells were transiently transfected with GFP-tagged LCRMP-1 (WT), LCRMP-1 (T628A), and LCRMP-1 (T628D). At 24 hours after transfection, these cells were fixed, permeabilized and then immunostained with rhodamine-conjugated phalloidin (red) for actin and DAPI (blue) for visualizing nuclei. Representative immunofluorescence images were visualized using fluorescence microscope. Scale bar, 10 µm. Insets show higher magnifications (400×). (B) Numbers of filopodia were counted with at least six cells per group. Data were presented as means ± SEM.</p

Dietary Characteristics of Elders with Frailty and with Mild Cognitive Impairment: Cross-Sectional Findings and Implications from the Nutrition and Health Survey in Taiwan 2014&ndash;2017

It is unclear whether low dietary intake accompanied with multiple nutrient deficiencies or specific nutrient inadequacy is associated with geriatric syndrome. This study aimed to examine the nutrition inadequacy profiles associated with frailty and cognitive impairment (CI). With information from the Nutrition and Health Survey in Taiwan, 2014&ndash;2017, sex-specific nutrient intakes and intake per kg of body weight (BW) were estimated from 24-hour recall data for two age groups (65&ndash;74 years; &ge;75 years) regarding the three frailty and three CI subgroups. Total energy intakes were significantly lower with the severity of both frailty and CI in analysis combining both gender and age groups, and in both the 65-to-74-year-old women or the over-75-year-old women. These trends were observed but not significant in either of the two age groups in men. Significantly lower levels of energy intake have been observed when age, sex, and sampling strata were adjusted. Intake levels of multiple nutrients also decreased with the severity of frailty and CI. A greater number of nutrient inadequacies for the frail and the CI was found in the 65-to-74-year-old group than the over-75-year-old age group. However, most of the associations between micronutrients and the two geriatric syndromes disappeared after energy adjustment. The remaining few did not show consistency across age&ndash;sex subgroups. In conclusion, frailty or CI was associated with low amounts of food consumption accompanied by multiple nutrient insufficiencies. Dietary intervention to ensure adequate total energy and multiple nutrient intakes should be trialed in the geriatric population to address both the causal and efficacy issues