1,522 research outputs found

    Cystamine induces AIF-mediated apoptosis through glutathione depletion

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    AbstractCystamine and its reduced form cysteamine showed protective effects in various models of neurodegenerative disease, including Huntington's disease and Parkinson's disease. Other lines of evidence demonstrated the cytotoxic effect of cysteamine on duodenal mucosa leading to ulcer development. However, the mechanism for cystamine cytotoxicity remains poorly understood. Here, we report a new pathway in which cystamine induces apoptosis by targeting apoptosis-inducing factor (AIF). By screening of various cell lines, we observed that cystamine and cysteamine induce cell death in a cell type-specific manner. Comparison between cystamine-sensitive and cystamine-resistant cell lines revealed that cystamine cytotoxicity is not associated with unfolded protein response, reactive oxygen species generation and transglutaminase or caspase activity; rather, it is associated with the ability of cystamine to trigger AIF nuclear translocation. In cystamine-sensitive cells, cystamine suppresses the levels of intracellular glutathione by inhibiting γ-glutamylcysteine synthetase expression that triggers AIF translocation. Conversely, glutathione supplementation completely prevents cystamine-induced AIF translocation and apoptosis. In rats, cysteamine administration induces glutathione depletion and AIF translocation leading to apoptosis of duodenal epithelium. These results indicate that AIF translocation through glutathione depletion is the molecular mechanism of cystamine toxicity, and provide important implications for cystamine in the neurodegenerative disease therapeutics as well as in the regulation of AIF-mediated cell death

    Chlorin e6 Prevents ADP-Induced Platelet Aggregation by Decreasing PI3K-Akt Phosphorylation and Promoting cAMP Production

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    A number of reagents that prevent thrombosis have been developed but were found to have serious side effects. Therefore, we sought to identify complementary and alternative medicinal materials that are safe and have long-term efficacy. In the present studies, we have assessed the ability of chlorine e6 (CE6) to inhibit ADP-induced aggregation of rat platelets and elucidated the underlying mechanism. CE6 inhibited platelet aggregation induced by 10 µM ADP in a concentration-dependent manner and decreased intracellular calcium mobilization and granule secretion (i.e., ATP and serotonin release). Western blotting revealed that CE6 strongly inhibited the phosphorylations of PI3K, Akt, c-Jun N-terminal kinase (JNK), and different mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase 1/2 (ERK1/2) as well as p38-MAPK. Our study also demonstrated that CE6 significantly elevated intracellular cAMP levels and decreased thromboxane A2 formation in a concentration-dependent manner. Furthermore, we determined that CE6 initiated the activation of PKA, an effector of cAMP. Taken together, our findings indicate that CE6 may inhibit ADP-induced platelet activation by elevating cAMP levels and suppressing PI3K/Akt activity. Finally, these results suggest that CE6 could be developed as therapeutic agent that helps prevent thrombosis and ischemia

    CanonicalFusion: Generating Drivable 3D Human Avatars from Multiple Images

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    We present a novel framework for reconstructing animatable human avatars from multiple images, termed CanonicalFusion. Our central concept involves integrating individual reconstruction results into the canonical space. To be specific, we first predict Linear Blend Skinning (LBS) weight maps and depth maps using a shared-encoder-dual-decoder network, enabling direct canonicalization of the 3D mesh from the predicted depth maps. Here, instead of predicting high-dimensional skinning weights, we infer compressed skinning weights, i.e., 3-dimensional vector, with the aid of pre-trained MLP networks. We also introduce a forward skinning-based differentiable rendering scheme to merge the reconstructed results from multiple images. This scheme refines the initial mesh by reposing the canonical mesh via the forward skinning and by minimizing photometric and geometric errors between the rendered and the predicted results. Our optimization scheme considers the position and color of vertices as well as the joint angles for each image, thereby mitigating the negative effects of pose errors. We conduct extensive experiments to demonstrate the effectiveness of our method and compare our CanonicalFusion with state-of-the-art methods. Our source codes are available at https://github.com/jsshin98/CanonicalFusion.Comment: ECCV 2024 Accepted (18 pages, 9 figures

    High-fidelity 3D Human Digitization from Single 2K Resolution Images

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    High-quality 3D human body reconstruction requires high-fidelity and large-scale training data and appropriate network design that effectively exploits the high-resolution input images. To tackle these problems, we propose a simple yet effective 3D human digitization method called 2K2K, which constructs a large-scale 2K human dataset and infers 3D human models from 2K resolution images. The proposed method separately recovers the global shape of a human and its details. The low-resolution depth network predicts the global structure from a low-resolution image, and the part-wise image-to-normal network predicts the details of the 3D human body structure. The high-resolution depth network merges the global 3D shape and the detailed structures to infer the high-resolution front and back side depth maps. Finally, an off-the-shelf mesh generator reconstructs the full 3D human model, which are available at https://github.com/SangHunHan92/2K2K. In addition, we also provide 2,050 3D human models, including texture maps, 3D joints, and SMPL parameters for research purposes. In experiments, we demonstrate competitive performance over the recent works on various datasets.Comment: code page : https://github.com/SangHunHan92/2K2K, Accepted to CVPR 2023 (Highlight

    Menthol Enhances an Antiproliferative Activity of 1α,25-Dihydroxyvitamin D3 in LNCaP Cells

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    1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], the most active form of vitamin D3, and its analogues have therapeutic benefits for prostate cancer treatment. However, the development of hypercalcemia is an obstacle to clinical applications of 1α,25(OH)2D3 for cancer therapy. In this study, we provide evidence that menthol, a key component of peppermint oil, increases an anti-proliferation activity of 1α,25(OH)2D3 in LNCaP prostate cancer cells. We found that menthol per se does not exhibit antiproliferative activity, but it is able to enhance 1α,25(OH)2D3-mediated growth inhibition in LNCaP cells. Fluorometric assays using Fura-2 showed that 1α,25(OH)2D3 does not induce acute Ca2+ response, whereas menthol evokes an increase in [Ca2+]i, which suggests that cross-talks of menthol-induced Ca2+ signaling with 1α,25(OH)2D3-mediated growth inhibition pathways. In addition, Western blot analysis revealed that 1α,25(OH)2D3 and menthol cooperatively modulate the expression of bcl-2 and p21 which provides the insight into the molecular mechanisms underlying the enhanced 1α,25(OH)2D3-mediated growth inhibition by menthol. Thus, our findings suggest that menthol may be a useful natural compound to enhance therapeutic effects of 1α,25(OH)2D3

    Atypical iliac vein compression in patients with symptomatic May–Thurner syndrome

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    PURPOSEWe aimed to investigate the incidence, etiology, treatment, and clinical course of atypical iliac vein compressions (AIVCs) among patients with May–Thurner syndrome (MTS).METHODSA total of 173 patients who presented with MTS were retrospectively analyzed at a single center. Computed tomographic venography (CTV) was used to diagnose MTS. An AIVC was defined as the compression of the left common iliac vein (LCIV) by structures other than the right common iliac artery (RCIA) or the compression of other venous structures in the pelvic cavity instead of the LCIV. The patients with AIVC were categorized into the LCIV compression group (category A) and non-LCIV compression group (category B).RESULTSTen patients with AIVC were identified (5.8%; male/female, 5/5), five in category A and five in category B. The median age of patients was 76 years (range, 51–94 years), and the median follow-up duration was 388 days (range, 12–4694 days). In category A, the LCIVs were compressed by the left common iliac artery (LCIA) (n=2), uterine leiomyoma (n=1), LCIA aneurysm (n=1), and RCIA aneurysm (n=1). In category B, the right common iliac veins were compressed by the RCIA (n=4) and L5 osteophyte (n=1). Endovascular treatment, including balloon angioplasty and stent placement, was performed in six patients, three from each group. Three patients underwent conservative treatment due to their advanced age and comorbidities. Endovascular aneurysm repair was performed in one patient with RCIA aneurysm. Follow-up images were available for six patients, and all of them had patent venous flow.CONCLUSIONThe AIVC had an incidence of 5.8% (10/173) among symptomatic MTS patients and wide spectrum of etiologies. Pathogenesis-tailored endovascular treatments are safe and effective

    Clinical characteristics of myelin oligodendrocyte glycoprotein antibody-associated disease according to their epitopes

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    BackgroundThe detection of myelin oligodendrocyte glycoprotein autoantibodies (MOG-Ab) is essential for the diagnosis of MOG-Ab-associated disease (MOGAD). The clinical implications of different epitopes recognized by MOG-Ab are largely unknown. In this study, we established an in-house cell-based immunoassay for detecting MOG-Ab epitopes and examined the clinical characteristics of patients with MOG-Ab according to their epitopes.MethodsWe conducted a retrospective review of patients with MOG-Ab-associated disease (MOGAD) in our single center registry, and collected serum samples from enrolled patients. Human MOG variants were generated to detect epitopes recognized by MOG-Ab. The differences in clinical characteristics according to the presence of reactivity to MOG Proline42 (P42) were evaluated.ResultsFifty five patients with MOGAD were enrolled. Optic neuritis was the most common presenting syndrome. The P42 position of MOG was a major epitope of MOG-Ab. The patients with a monophasic clinical course and childhood-onset patients were only observed in the group that showed reactivity to the P42 epitope.ConclusionWe developed an in-house cell-based immunoassay to analyze the epitopes of MOG-Ab. The P42 position of MOG is the primary target of MOG-Ab in Korean patients with MOGAD. Further studies are needed to determine the predictive value of MOG-Ab and its epitopes

    High Mobility in a Stable Transparent Perovskite Oxide

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    We discovered that La-doped BaSnO3 with the perovskite structure has an unprecedentedly high mobility at room temperature while retaining its optical transparency. In single crystals, the mobility reached 320 cm^2(Vs)^-1 at a doping level of 8x10^19 cm^-3, constituting the highest value among wide-band-gap semiconductors. In epitaxial films, the maximum mobility was 70 cm^2(Vs)^-1 at a doping level of 4.4x10^20 cm^-3. We also show that resistance of (Ba,La)SnO3 changes little even after a thermal cycle to 530 Deg. C in air, pointing to an unusual stability of oxygen atoms and great potential for realizing transparent high-frequency, high-power functional devices.Comment: 15 pages, 3 figure
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