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Background: Phototherapies based on sunlight, infrared, ultraviolet, visible, and laser-based treatments present advantages like high curative effects, small invasion, and negligible adverse reactions in cancer treatment. We aimed to explore the potential therapeutic effects of blue light emitting diode (LED) in human hepatoma cells and decipher the underlying cellular and molecular mechanisms. Methods: Wound healing and transwell assays were employed to probe the inhibition of the invasion and migration of hepatocellular carcinoma cells in the presence of blue LED. The sphere-forming test was used to evaluate the effect of LED blue light irradiation on cancer stem cell properties. Immunofluorescence and western blotting were used to detect the changes in γ-H2AX. The Cell Counting Kit-8 assay, 5-ethynyl-2'-deoxyuridine staining, and colony formation assay were used to detect the combined effect of blue LED and sorafenib on cell proliferation inhibition. Results: We demonstrated that the irradiation of blue LED light in hepatoma cells could lead to cell proliferation reduction along with the increase of cell apoptosis. Simultaneously, blue LED irradiation also markedly suppressed the migration and invasion ability of human hepatoma cells. Sphere formation analysis further revealed the decreased cancer stemness of hepatoma cells upon blue LED irradiation. Mechanistically, blue LED irradiation significantly promoted the expression of the phosphorylation of the core histone protein H2AX (γ-H2AX), a sensitive molecular marker of DNA damage. In addition, we found that the combined treatment of blue LED irradiation and sorafenib increased cancer cell sensitivity to sorafenib. Conclusion: Collectively, we demonstrated that blue LED irradiation exhibited anti-tumor effects on liver cancer cells by inducing DNA damage and could enhance chemosensitivity of cancer cells, which represents a potential approach for human hepatoma treatment. [ABSTRACT FROM AUTHOR]

Introduction: While acute Coronavirus disease 2019 (COVID-19) affects the cardiovascular (CV) system according to recent data, an increased CV risk has been reported also during long-term follow-up (FU). In addition to other CV pathologies in COVID-19 survivors, an enhanced risk for arrhythmic events and sudden cardiac death (SCD) has been observed. While recommendations on postdischarge thromboprophylaxis are conflicting in this population, prophylactic short-term rivaroxaban therapy after hospital discharge showed promising results. However, the impact of this regimen on the incidence of cardiac arrhythmias has not been evaluated to date. Methods: To investigate the efficacy of this therapy, we conducted a single center, retrospective analysis of 1804 consecutive, hospitalized COVID-19 survivors between April and December 2020. Patients received either a 30-day postdischarge thromboprophylaxis treatment regimen using rivaroxaban 10 mg every day (QD) (Rivaroxaban group (Riva); n = 996) or no thromboprophylaxis (Control group (Ctrl); n = 808). Hospitalization for new atrial fibrillation (AF), newhigher-degree Atrioventricular-block (AVB) as well as incidence of SCD were investigated in 12-month FU [FU: 347 (310/449) days]. Results: No differences in baseline characteristics (Ctrl vs Riva: age: 59.0 (48.9/66.8) vs 57 (46.5/64.9) years, p = n.s.; male: 41.5% vs 43.7%, p = n.s.) and in the history of relevant CV-disease were observed between the two groups. While hospitalizations for AVB were not reported in either group, relevant rates of hospitalizations for new AF (0.99%, n = 8/808) as well as a high rate of SCD events (2.35%, n = 19/808) were seen in the Ctrl. These cardiac events were attenuated by early post-discharge prophylactic rivaroxaban therapy (AF: n = 2/996, 0.20%, p = 0.026 and SCD: n = 3/996, 0.30%, p < 0.001) which was also observed after applying a logistic regression model for propensity score matching (AF: χ2-statistics = 6.45, p = 0.013 and SCD: χ²-statistics = 9.33, p = 0.002). Of note, no major bleeding complications were observed in either group. Conclusion: Atrial arrhythmic and SCD events are present during the first 12 months after hospitalization for COVID-19. Extended prophylactic Rivaroxaban therapy after hospital discharge could reduce new onset of AF and SCD in hospitalized COVID-19 survivors. [ABSTRACT FROM AUTHOR]

Background: Cardiomyocytes derived from human embryonic stem cells (hESCs) are regulated by complex and stringent gene networks during differentiation. Long non-coding RNAs (lncRNAs) exert critical epigenetic regulatory functions in multiple differentiation processes. However, the involvement of lncRNAs in the differentiation of hESCs into cardiomyocytes has not yet been fully elucidated. Here, we identified the key roles of ZFAS1 (lncRNA zinc finger antisense 1) in the differentiation of cardiomyocytes from hESCs. Methods: A model of cardiomyocyte differentiation from stem cells was established using the monolayer differentiation method, and the number of beating hESCs-derived cardiomyocytes was calculated. Gene expression was analyzed by quantitative real-time PCR (qRTPCR). Immunofluorescence assays were performed to assess the expression of cardiac troponin T (cTnT) and αactinin protein in cardiomyocytes. Results: qRT-PCR showed that ZFAS1 expression in the mesoderm was significantly higher than that in embryonic stem cells, cardiac progenitor cells, and cardiomyocytes. Knockdown of ZFAS1 inhibited cardiomyocyte differentiation from hESCs, which was characterized by reduced expression of the cardiac-specific markers cTnT, α-actinin, myosin heavy chain 6 (MYH6), and myosin heavy chain 7 (MYH7). In contrast, ZFAS1 overexpression remarkably increased the percentage of spontaneously beating cardiomyocytes. In terms of the mechanism, we found that ZFAS1 is an antisense lncRNA at the 5′ end of the protein-coding gene ZNFX1. Knockdown of ZFAS1 could increase the mRNA expression level of ZNFX1. Furthermore, qRT-PCR demonstrated that the silencing of ZNFX1 led to an increase in cardiac-specific markers that predicted the promotion of cardiomyocyte differentiation. Conclusion: Altogether, these data suggest that lncRNA-ZFAS1 is required for cardiac differentiation by functionally inhibiting the expression of ZNFX1, which may provide a reference for the treatment of heart disease to a certain extent. [ABSTRACT FROM AUTHOR]

The stem cell-based therapy has emerged as the promising therapeutic strategies for cardiovascular diseases (CVDs). Recently, increasing evidence suggest stem cell-derived active exosomes are important communicators among cells in the heart via delivering specific substances to the adjacent/distant target cells. These exosomes and their contents such as certain proteins, miRNAs and lncRNAs exhibit huge beneficial effects on preventing heart damage and promoting cardiac repair. More importantly, stem cell-derived exosomes are more effective and safer than stem cell transplantation. Therefore, administration of stemcell-derived exosomes will expectantly be an alternative stem cell-based therapy for the treatment of CVDs. Furthermore, modification of stem cell-derived exosomes or artificial synthesis of exosomes will be the new therapeutic tools for CVDs in the future. In addition, stem cell-derived exosomes also have been implicated in the diagnosis and prognosis of CVDs. In this review, we summarize the current advances of stem cell-derived exosome-based treatment and prognosis for CVDs, including their potential benefits, underlying mechanisms and limitations, which will provide novel insights of exosomes as a new tool in clinical therapeutic translation in the future. [ABSTRACT FROM AUTHOR]

Background/Aims: Blue light emitting diodes (LEDs) have been proven to affect the growth of several types of cells. The effects of blue LEDs have not been tested on bone marrowderived mesenchymal stem cells (BMSCs), which are important for cell-based therapy in various medical fields. Therefore, the aim of this study was to determine the effects of blue LED on the proliferation, apoptosis and osteogenic differentiation of BMSCs. Methods: BMSCs were irradiated with a blue LED light at 470 nm for 1 min, 5 min, 10 min, 30 min and 60 min or not irradiated. Cell proliferation was measured by performing cell counting and EdU staining assays. Cell apoptosis was detected by TUNEL staining. Osteogenic differentiation was evaluated by ALP and ARS staining. DCFH-DA staining and γ-H2A.X immunostaining were used to measure intracellular levels of ROS production and DNA damage. Results: Both cell counting and EdU staining assays showed that cell proliferation of BMSCs was significantly reduced upon blue LED irradiation. Furthermore, treatment of BMSCs with LED irradiation was followed by a remarkable increase in apoptosis, indicating that blue LED light induced toxic effects on BMSCs. Likewise, BMSC osteogenic differentiation was inhibited after exposure to blue LED irradiation. Further, blue LED irradiation was followed by the accumulation of ROS production and DNA damage. Conclusions: Taken together, our study demonstrated that blue LED light inhibited cell proliferation, inhibited osteogenic differentiation, and induced apoptosis in BMSCs, which are associated with increased ROS production and DNA damage. These findings may provide important insights for the application of LEDs in future BMSCbased therapies. [ABSTRACT FROM AUTHOR]

Background/Aims: Blue light emitting diodes (LEDs) have been proven to affect the growth of several types of cells. The effects of blue LEDs have not been tested on bone marrow-derived mesenchymal stem cells (BMSCs), which are important for cell-based therapy in various medical fields. Therefore, the aim of this study was to determine the effects of blue LED on the proliferation, apoptosis and osteogenic differentiation of BMSCs. Methods: BMSCs were irradiated with a blue LED light at 470 nm for 1 min, 5 min, 10 min, 30 min and 60 min or not irradiated. Cell proliferation was measured by performing cell counting and EdU staining assays. Cell apoptosis was detected by TUNEL staining. Osteogenic differentiation was evaluated by ALP and ARS staining. DCFH-DA staining and γ-H2A.X immunostaining were used to measure intracellular levels of ROS production and DNA damage. Results: Both cell counting and EdU staining assays showed that cell proliferation of BMSCs was significantly reduced upon blue LED irradiation. Furthermore, treatment of BMSCs with LED irradiation was followed by a remarkable increase in apoptosis, indicating that blue LED light induced toxic effects on BMSCs. Likewise, BMSC osteogenic differentiation was inhibited after exposure to blue LED irradiation. Further, blue LED irradiation was followed by the accumulation of ROS production and DNA damage. Conclusions: Taken together, our study demonstrated that blue LED light inhibited cell proliferation, inhibited osteogenic differentiation and induced apoptosis in BMSCs, which are associated with increased ROS production and DNA damage. These findings may provide important insights for the application of LEDs in future BMSC-based therapies. [ABSTRACT FROM AUTHOR]

Atrial pacing to reduce paroxysmal atrial fibrillation recurrences is performed in right atrial appendage (RAA) traditionally. However, recent studies indicate that atrial septal (AS) pacing produces better outcomes than the RAA pacing. The underlying mechanisms for this difference remained unclear. One possible explanation for the superiority of AS pacing over RAA pacing is that the two different regions have distinct electrophysiological properties. The study was to explore whether there indeed exist regional differences of electrical activities between RAA and AS, using whole-cell patch clamp techniques. The results showed that RAA cells had longer action potential duration, more negative resting potential and greater amplitude of action potential, whereas AS cells had more rapid depolarizing velocity. The sodium current was significantly smaller in RAA cells, whereas the calcium current was markedly smaller in AS cells. The transient outward K+ current was similar in both regions. The ultrarapid delayed rectifier K+ current was greater in RAA than that in AS cells. The inward rectifier K+ current was similar at potentials more negative to -60 mV in both regions. The results indicate that RAA and AS of patients with rheumatic heart disease possess distinct electrophysiological properties. These differences provided a rational explanation for the different efficacies in treating atrial fibrillation by atrial pacing in RAA and AS regions. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

: Aims The present study was designed to decipher molecular mechanisms underlying nicotines promoting atrial fibrillation (AF) by inducing atrial structural remodelling. : Methods and results The canine model of AF was successfully established by nicotine administration and rapid pacing. The atrial fibroblasts isolated from healthy dogs were treated with nicotine. The role of microRNAs (miRNAs) on the expression and regulation of transforming growth factor-β1 (TGF-β1), TGF-β receptor type II (TGF-βRII), and collagen production was evaluated in vivo and in vitro. Administration of nicotine for 30 days increased AF vulnerability by ∼eight- to 15-fold in dogs. Nicotine stimulated remarkable collagen production and atrial fibrosis both in vitro in cultured canine atrial fibroblasts and in vivo in atrial tissues. Nicotine produced significant upregulation of expression of TGF-β1 and TGF-βRII at the protein level, and a 60–70% decrease in the levels of miRNAs miR-133 and miR-590. This downregulation of miR-133 and miR-590 partly accounts for the upregulation of TGF-β1 and TGF-βRII, because our data established TGF-β1 and TGF-βRII as targets for miR-133 and miR-590 repression. Transfection of miR-133 or miR-590 into cultured atrial fibroblasts decreased TGF-β1 and TGF-βRII levels and collagen content. These effects were abolished by the antisense oligonucleotides against miR-133 or miR-590. The effects of nicotine were prevented by an α7 nicotinic acetylcholine receptor antagonist. : Conclusion We conclude that the profibrotic response to nicotine in canine atrium is critically dependent upon downregulation of miR-133 and miR-590. [ABSTRACT FROM AUTHOR]