Search Results (14)

Myocardial infarction (MI) remains one of the most common cardiovascular diseases and a leading cause of morbidity and mortality worldwide. In recent years, natural polymeric patches have attracted increasing attention as a promising therapeutic platform for myocardial tissue repair. This study explored the fabrication and evaluation of screen-printed electrodes (SPEs) on chitosan film as a novel platform for cardiac patch applications. Chitosan is a biodegradable and biocompatible natural polymer that provides an ideal substrate for SPEs, providing mechanical stability and promoting cell adhesion. Silver ink was employed to enhance electrochemical performance, and the electrodes exhibited strong adhesion and structural integrity under wet conditions. Mechanical testing and swelling ratio analysis were conducted to assess the patch’s physical robustness and aqueous stability. Silver ink was employed to enhance electrochemical performance, which was evaluated using cyclic voltammetry. In vitro, electrical stimulation through the chitosan–SPE patch significantly increased the expression of cardiac-specific genes (GATA-4, β-MHC, troponin I) in bone marrow mesenchymal stem cells (BMSCs), indicating early cardiogenic differentiation potential. In vivo, the implantation of the chitosan–SPE patch in a rat MI model demonstrated good tissue integration, preserved myocardial structure, and enhanced ventricular wall thickness, indicating that the patch has the potential to serve as a functional cardiac scaffold. These findings support the feasibility of screen-printed electrodes fabricated on chitosan film substrates as a cost-effective and scalable platform for cardiac repair, offering a foundation for future applications in cardiac tissue engineering. Full article

This study presents a hybrid crow search algorithm–long short-term memory (CSLSTM) system for forecasting stock prices. This system allows investors to effectively avoid risks and enhance profits by predicting the closing price the following day. This method utilizes a stacking ensemble of long short-term memory (LSTM) networks, with the crow search algorithm (CSA) optimizing the weights assigned to the predictions from multiple LSTM models. To improve the overall accuracy, this system leverages three distinct datasets: technical analysis indicators; price fluctuation limits; and variation mode decomposition (VMD) subsignal sequences. The predictions for the three reference-data types are more comprehensive than single-model or single-data-type approaches. The prediction accuracies of the recurrent neural network, gate recurrent unit, and the LSTM network for five stocks were compared. The proposed CSLSTM system outperforms the other standalone models. Furthermore, we conducted backtesting to demonstrate that the prediction information from our model could generate profit in the stock market, enabling users to benefit from complex stock-market dynamics. The stock prices in this study are expressed in New Taiwan Dollars (TWD), the official currency of Taiwan. Full article

The rapid global spread of the coronavirus disease (COVID-19) has severely impacted daily life worldwide. As potential solutions, various digital contact tracing (DCT) strategies have emerged to mitigate the virus’s spread while maintaining economic and social activities. The computational epidemiology problems of DCT often involve parameter optimization through learning processes, making it crucial to understand how to apply machine learning techniques for effective DCT optimization. While numerous research studies on DCT have emerged recently, most existing reviews primarily focus on DCT application design and implementation. This paper offers a comprehensive overview of privacy-preserving machine learning-based DCT in preparation for future pandemics. We propose a new taxonomy to classify existing DCT strategies into forward, backward, and proactive contact tracing. We then categorize several DCT apps developed during the COVID-19 pandemic based on their tracing strategies. Furthermore, we derive three research questions related to computational epidemiology for DCT and provide a detailed description of machine learning techniques to address these problems. We discuss the challenges of learning-based DCT and suggest potential solutions. Additionally, we include a case study demonstrating the review’s insights into the pandemic response. Finally, we summarize the study’s limitations and highlight promising future research directions in DCT. Full article

(1) Background: PTC124 (Ataluren) is an investigational drug for the treatment of nonsense mutation-mediated genetic diseases. With the exception of the TP53 tumor suppressor gene, there has been little research on cancers with nonsense mutation. By conducting a database search, we found that another two tumor suppressor genes, NOTCH1 and FAT1, have a high nonsense mutation rate in head and neck squamous cell carcinoma (HNSCC). PTC124 may re-express the functional NOTCH1 or FAT1 in nonsense mutation NOTCH1 or FAT1 in HSNCC (2) Methods: DOK (with NOTCH1 Y550X) or HO-1-u-1 (with FAT1 E378X) HNSCC cells were treated with PTC124, and the NOTCH1 or FAT1 expression, cell viability, and NOTCH1- or FAT1-related downstream gene profiles were assayed. (3) Results: PTC124 was able to induce NOTCH1 or FAT1 expression in DOK and HO-1-u-1 cells. PTC124 was able to upregulate NOTCH downstream genes HES5, AJUBA, and ADAM10 in DOK cells. PTC124 enhanced DDIT4, which is under the control of the FAT1–YAP1 pathway, in HO-1-u-1 cells. FLI-06 (a NOTCH signaling inhibitor) reversed PTC124-mediated cell growth inhibition in DOK cells. PTC124 could reverse TT-10 (a YAP signaling activator)-mediated HO-1-u-1 cell proliferation. (4) Conclusions: PTC124 can rescue nonsense mutation of NOTCH1 and FAT1 to repress HNSCC cell proliferation. Full article

The members of the p53 family comprise p53, p63, and p73, and full-length isoforms of the p53 family have a tumor suppressor function. However, p53, but not p63 or p73, has a high mutation rate in cancers causing it to lose its tumor suppressor function. The top and second-most prevalent p53 mutations are missense and nonsense mutations, respectively. In this review, we discuss possible drug therapies for nonsense mutation and a missense mutation in p53. p63 and p73 activators may be able to replace mutant p53 and act as anti-cancer drugs. Herein, these p63 and p73 activators are summarized and how to improve these activator responses, particularly focusing on p53 gain-of-function mutants, is discussed. Full article

Premature endothelial senescence decreases the atheroprotective capacity of the arterial endothelium. Apolipoprotein C3 (ApoC3) delays the catabolism of triglyceride-rich particles and plays a critical role in atherosclerosis progression. FBXO31 is required for the intracellular response to DNA damage, which is a significant cause of cellular senescence. Sesamol is a natural antioxidant with cardiovascular-protective properties. In this study, we aimed to examine the effects of ApoC3-rich low-density lipoprotein (AC3RL) mediated via FBXO31 on endothelial cell (EC) senescence and its inhibition by sesamol. AC3RL and ApoC3-free low-density lipoproteins (LDL) (AC3(-)L) were isolated from the plasma LDL of patients with ischemic stroke. Human aortic endothelial cells (HAECs) treated with AC3RL induced EC senescence in a dose-dependent manner. AC3RL induced HAEC senescence via DNA damage. However, silencing FBXO31 attenuated AC3RL-induced DNA damage and reduced cellular senescence. Thus, FBXO31 may be a novel therapeutic target for endothelial senescence-related cardiovascular diseases. Moreover, the aortic arch of hamsters fed a high-fat diet with sesamol showed a substantial reduction in their atherosclerotic lesion size. In addition to confirming the role of AC3RL in aging and atherosclerosis, we also identified AC3RL as a potential therapeutic target that can be used to combat atherosclerosis and the onset of cardiovascular disease in humans. Full article

Backgrounds: Leber’s hereditary optic neuropathy (LHON) is known as an inherited retinal disorder characterized by the bilateral central vision loss and degeneration of retinal ganglion cells (RGCs). Unaffected LHON carriers are generally asymptomatic, suggesting that certain factors may contribute to the disease manifestations between carriers and patients who carry the same mutated genotypes. Methods: We first aimed to establish the iPSC-differentiated RGCs from the normal healthy subject, the carrier, and the LHON patient and then compared the differential expression profile of circular RNAs (CircRNAs) among RGCs from these donors in vitro. We further overexpressed or knocked down the most upregulated circRNA to examine whether this circRNA contributes to the distinct phenotypic manifestations between the carrier- and patient-derived RGCs. Results: iPSCs were generated from the peripheral blood cells from the healthy subject, the carrier, and the LHON patient and successfully differentiated into RGCs. These RGCs carried equivalent intracellular reactive oxygen species, but only LHON-patient iPSC-derived RGCs exhibited remarkable apoptosis. Next-generation sequencing and quantitative real-time PCR revealed the circRNA hsa_circ_0087207 as the most upregulated circRNA in LHON-patient iPSC-derived RGCs. Overexpression of hsa_circ_0087207 increased the apoptosis in carrier iPSC-derived RGCs, while knockdown of hsa_circ_0087207 attenuated the apoptosis in LHON-patient iPSC-derived RGCs. Predicted by bioinformatics approaches, hsa_circ_0087207 acts as the sponge of miR-665 to induce the expression of a variety of apoptosis-related genes in LHON patient iPSC-derived RGCs. Conclusions: Our data indicated that hsa_circ_0087207 upregulation distinguishes the disease phenotype manifestations between iPSC-derived RGCs generated from the LHON patient and carrier. Targeting the hsa_circ_0087207/miR-665 axis might hold therapeutic promises for the treatment of LHON. Full article

Acrylamide (ACR) is present in high-temperature-processed high-carbohydrate foods, cigarette smoke, and industrial pollution. Chronic exposure to ACR may induce neurotoxicity from reactive oxygen species (ROS); however, the mechanisms underlying ACR-induced neurotoxicity remain unclear. We studied 28-day subacute ACR toxicity by repeatedly feeding ACR (0, 15, or 30 mg/kg) to rats. We conducted RNA sequencing and Western blot analyses to identify differences in mRNA expression in the blood and in protein expression in the brain tissues, respectively, of the rats. AQP4 transient transfection was performed to identify potential associations with protein regulation. The rats treated with 30 mg/kg ACR exhibited hind-limb muscle weakness. Matrix metalloproteinase (MMP9) expression was higher in the ACR-treated group than in the control group. ACR induced MMP-9 and AQP4 protein expression in the brain tissues of the rats, which subsequently presented with neurotoxicity. In the in vitro study, Neuro-2a cells were transiently transfected with AQP4, which inhibited MMP-9 and TNF receptor-associated factor 6 (TRAF6) expression, and inhibited ACR induced expression of TRAF6, IκBα, and nuclear factor κB (NFκB). Using a combination of in vivo and in vitro experiments, this study revealed that depressive symptoms associated with ACR-induced neurotoxicity are associated with downregulation of AQP4 and induction of the TRAF6 pathway. Full article

Focal adhesion kinase (FAK), a non-receptor tyrosine kinase, is overexpressed and activated in many cancer types. FAK regulates diverse cellular processes, including growth factor signaling, cell cycle progression, cell survival, cell motility, angiogenesis, and the establishment of immunosuppressive tumor microenvironments through kinase-dependent and kinase-independent scaffolding functions in the cytoplasm and nucleus. Mounting evidence has indicated that targeting FAK, either alone or in combination with other agents, may represent a promising therapeutic strategy for various cancers. In this review, we summarize the mechanisms underlying FAK-mediated signaling networks during tumor development. We also summarize the recent progress of FAK-targeted small-molecule compounds for anticancer activity from preclinical and clinical evidence. Full article

Impairment of adiponectin production and function is closely associated with insulin resistance and type 2 diabetes, which are linked to obesity. Studies in animal models have documented the anti-diabetic effects of tetrahydrocurcumin (THC). Although several possible mechanisms have been proposed, the contribution of adiponectin signaling on THC-mediated antihyperglycemic effects remains unknown. Here, we report that adiposity, steatosis, and hyperglycemia were potently attenuated in high-fat diet/streptozotocin-induced diabetic obese mice after they received 20 and 100 mg/kg THC for 14 weeks. THC upregulated UCP-1 in adipose tissue and elevated adiponectin levels in the circulation. THC upregulated the AdipoR1/R2-APPL1-mediated pathway in the liver and skeletal muscle, which contributes to improved insulin signaling, glucose utilization, and lipid metabolism. Furthermore, THC treatment significantly (p < 0.05) preserved islet mass, reduced apoptosis, and restored defective insulin expression in the pancreatic β-cells of diabetic obese mice, which was accompanied by an elevation of AdipoR1 and APPL1. These results demonstrated a potential mechanism underlying the beneficial effects of THC against hyperglycemia via the adiponectin-AdipoR pathway, and thus, may lead to a novel therapeutic use for type 2 diabetes. Full article

The aim of this study is to identify potential biomarkers for early diagnosis of gynecologic cancer in order to improve survival. Cervical cancer (CC) and endometrial cancer (EC) are the most common malignant tumors of gynecologic cancer among women in the world. As the underlying molecular mechanisms in both cervical and endometrial cancer remain unclear, a comprehensive and systematic bioinformatics analysis is required. In our study, gene expression profiles of GSE9750, GES7803, GES63514, GES17025, GES115810, and GES36389 downloaded from Gene Expression Omnibus (GEO) were utilized to analyze differential gene expression between cancer and normal tissues. A total of 78 differentially expressed genes (DEGs) common to CC and EC were identified to perform the functional enrichment analyses, including gene ontology and pathway analysis. KEGG pathway analysis of 78 DEGs indicated that three main types of pathway participate in the mechanism of gynecologic cancer such as drug metabolism, signal transduction, and tumorigenesis and development. Furthermore, 20 diagnostic signatures were confirmed using the least absolute shrink and selection operator (LASSO) regression with 10-fold cross validation. Finally, we used the GEPIA2 online tool to verify the expression of 20 genes selected by the LASSO regression model. Among them, the expression of PAMR1 and SLC24A3 in tumor tissues was downregulated significantly compared to the normal tissue, and found to be statistically significant in survival rates between the CC and EC of patients (p < 0.05). The two genes have their function: (1.) PAMR1 is a tumor suppressor gene, and many studies have proven that overexpression of the gene markedly suppresses cell growth, especially in breast cancer and polycystic ovary syndrome; (2.) SLC24A3 is a sodium–calcium regulator of cells, and high SLC24A3 levels are associated with poor prognosis. In our study, the gene signatures can be used to predict CC and EC prognosis, which could provide novel clinical evidence to serve as a potential biomarker for future diagnosis and treatment. Full article

Thyroid cancer (TC) is the most common endocrine malignancy, and its global incidence has steadily increased over the past 15 years. TC is broadly divided into well-differentiated, poorly differentiated, and undifferentiated types, depending on the histological and clinical parameters. Thus far, there are no effective treatments for undifferentiated thyroid cancers or advanced and recurrent cancer. Therefore, the development of an effective therapeutic is urgently needed for such patients. Piperlongumine (PL) is a naturally occurring small molecule derived from long pepper; it is selectively toxic to cancer cells by generating reactive oxygen species (ROS). In this study, we demonstrate the potential anticancer activity of PL in four TC cell lines. For this purpose, we cultured TC cell lines and analyzed the following parameters: Cell viability, colony formation, cell cycle, apoptosis, and cellular ROS induction. PL modulated the cell cycle, induced apoptosis, and suppressed tumorigenesis in TC cell lines in a dose- and time-dependent manner through ROS induction. Meanwhile, an intrinsic caspase-dependent apoptosis pathway was observed in the TC cells under PL treatment. The activation of Erk and the suppression of the Akt/mTOR pathways through ROS induction were seen in cells treated with PL. PL-mediated apoptosis in TC cells was through the ROS-Akt pathway. Finally, the anticancer effect and safety of PL were also demonstrated in vivo. Our findings indicate that PL exhibits antitumor activity and has the potential for use as a chemotherapeutic agent against TC. This is the first study to show the sensitivity of TC cell lines to PL. Full article

Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) specifically binds and isomerizes the phosphorylated serine/threonine-proline (pSer/Thr-Pro) motif, which leads to changes in protein conformation and function. Pin1 is widely overexpressed in cancers and plays an important role in tumorigenesis. Mounting evidence has revealed that targeting Pin1 is a potential therapeutic approach for various cancers by inhibiting cell proliferation, reducing metastasis, and maintaining genome stability. In this review, we summarize the underlying mechanisms of Pin1-mediated upregulation of oncogenes and downregulation of tumor suppressors in cancer development. Furthermore, we also discuss the multiple roles of Pin1 in cancer hallmarks and examine Pin1 as a desirable pharmaceutical target for cancer therapy. We also summarize the recent progress of Pin1-targeted small-molecule compounds for anticancer activity. Full article

In the last decade, great advances have been made in epidermal stem cell studies at the cellular and molecular level. These studies reported various subpopulations and differentiations existing in the epidermal stem cell. Although controversies and unknown issues remain, epidermal stem cells possess an immune-privileged property in transplantation together with easy accessibility, which is favorable for future clinical application. In this review, we will summarize the biological characteristics of epidermal stem cells, and their potential in orthopedic regenerative medicine. Epidermal stem cells play a critical role via cell replacement, and demonstrate significant translational potential in the treatment of orthopedic injuries and diseases, including treatment for wound healing, peripheral nerve and spinal cord injury, and even muscle and bone remodeling. Full article