• International Journal of Stem Cells
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• v.17 no.2
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• pp.130-140
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• 2024

Cardiac organoids have emerged as invaluable tools for assessing the impact of diverse substances on heart function. This report introduces guidelines for general requirements for manufacturing cardiac organoids and conducting cardiac organoid-based assays, encompassing protocols, analytical methodologies, and ethical considerations. In the quest to employ recently developed three-dimensional cardiac organoid models as substitutes for animal testing, it becomes imperative to establish robust criteria for evaluating organoid quality and conducting toxicity assessments. This guideline addresses this need, catering to regulatory requirements, and describes common standards for organoid quality and toxicity assessment methodologies, commensurate with current technological capabilities. While acknowledging the dynamic nature of technological progress and the potential for future comparative studies, this guideline serves as a foundational framework. It offers a comprehensive approach to standardized cardiac organoid testing, ensuring scientific rigor, reproducibility, and ethical integrity in investigations of cardiotoxicity, particularly through the utilization of human pluripotent stem cell-derived cardiac organoids.

• The Korean Journal of Pain
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• v.37 no.3
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• pp.247-255
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• 2024

Background: Little is known about the frequency and impact of the persistent headache and about the incidence of chronic daily headache (CDH) after coronavirus disease 2019 (COVID-19). The aim of this prospective cohort study was to assess the incidence, risk factors, characteristics, and impact of CDH in patients with COVID-19. Methods: In the first stage, 288 patients were interviewed by telephone after the acute phase of COVID-19. Subsequently, 199 patients who presented headache were reinterviewed at least one year after COVID-19. Headaches that persisted beyond the acute phase of COVID-19 for three or more months and presented frequency ≥ 45 days over the first three months were considered to be CDH. Results: One hundred and twenty-three patients were included, 56% were females; median age: 50 years (25th and 75th percentile: 41;58). The headache persisted beyond the acute phase of COVID-19 in 52%, and 20.3% had CDH (95% confidence interval: 13.6-28.2). Individuals who previously had headaches and who had headaches of greater intensity during the acute phase were at higher risk of developing CDH. The group with CDH included more females, greater impact of headache, more persistence of headache beyond the 120th day of COVID-19 and less throbbing headache than did the other individuals whose headache persisted. Conclusions: Patients who had COVID-19 had a high incidence of CDH. Previous headache and greater intensity of headache were associated with higher risk of CDH.

• The Journal of Korean Medicine
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• v.45 no.3
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• pp.154-167
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• 2024

Objectives: This study was performed to investigate the effects of Rhus verniciflua Stokes (RVS) on apoptosis and autophagy in the human leukemic cell line, MOLT-4. Methods: Cell viability was measured by MTS/PMS assay, and cell cycle distribution was analyzed by flow cytometry. The expression levels of mRNA implicated in apoptosis and ER-stress were investigated with RT-qPCR. Lastly, apoptosis- and autophagy-related protein expressions were measured by Western blot analysis. Results: RVS inhibited proliferation of MOLT-4 in a dose-dependent manner over 24, 48 and 72 hours. RVS treatment also induced an increase in subG1 phase. Exposure to RVS increased the expression of the mRNAs encoding Bax and caspase-3, while decreasing the expression of Bcl-2 mRNA, suggesting that RVS induced apoptosis in MOLT-4 cells. Additionally, RVS extract up-regulated ER-stress related mRNAs such as IRE1α, CHOP, PERK and ATF6. Changes in RVS extract-induced apoptosis and autophagy proteins on MOLT-4 cells were also investigated. The level of Bcl-2 was decreased, whereas the levels of Bax, caspase-3, AMPK, Beclin-1, Atg5, p62, and LC3II were increased. Conclusion: These results suggest that RVS would be beneficial in the treatment of Acute Lymphoblastic Leukemia.

• Parasites, Hosts and Diseases
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• v.62 no.3
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• pp.270-280
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• 2024

Trichomoniasis is caused by a sexually transmitted flagellate protozoan parasite Trichomonas vaginalis. T. vaginalis-derived secretory products (TvSP) contain lipid mediators such as leukotriene B₄ (LTB₄) and various cysteinyl leukotrienes (CysLTs) which included LTC₄, LTD₄, and LTE₄. However, the signaling mechanisms by which T. vaginalis-induced CysLTs stimulate interleukin (IL)-8 production in human mast cells remain unclear. In this study, we investigated these mechanisms in human mast cells (HMC-1). Stimulation with TvSP resulted in increased intracellular reactive oxygen species (ROS) generation and NADPH oxidase 2 (NOX2) activation compared to unstimulated cells. Pre-treatment with NOX2 inhibitors such as diphenyleneiodonium chloride (DPI) or apocynin significantly reduced ROS production in TvSP-stimulated HMC-1 cells. Additionally, TvSP stimulation increased NOX2 protein expression and the translocation of p47^phox from the cytosol to the membrane. Pretreatment of HMC-1 cells with PI3K or PKC inhibitors reduced TvSP-induced p47^phox translocation and ROS generation. Furthermore, NOX2 inhibitors or NOX2 siRNA prevented CREB phosphorylation and IL-8 gene expression or protein secretion induced by TvSP. Pretreatment with a CysLTR antagonist significantly inhibited TvSP-induced ROS production, CREB phosphorylation, and IL-8 production. These results indicate that CysLT-mediated activation of NOX2 plays a crucial role in ROS-dependent IL-8 production in human mast cells stimulated by T. vaginalis-secreted CysLTs. These findings enhance our understanding of the inflammatory response in trichomoniasis and may inform the development of targeted therapies to mitigate this response.