研究成果

Mitochondria are dynamic organelles that integrate bioenergetics, biosynthesis, and signaling in cells and regulate redox homeostasis, apoptotic pathways, and cell proliferation and differentiation. Depending on the environmental conditions, the mitochondrial morphology dynamically changes to match the energy demands. The mitochondrial dynamics is related to the initiation, migration, and invasion of diverse human cancers and thus affects cancer metastasis, metabolism, drug resistance, and cancer stem cell survival. We reviewed the current image-based analytical tools and machine-learning techniques for phenotyping mitochondrial morphology in different cancer cell lines from confocal microscopy images. We listed and applied pipelines and packages available in ImageJ/Fiji, CellProfiler,...

Entry inhibitors against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently needed to control the outbreak of coronavirus disease 2019 (COVID-19). This study developed a robust and straightforward assay that detected the molecular interaction between the receptor-binding domain (RBD) of viral spike protein and the angiotensin-converting enzyme 2 (ACE2) receptor in just 10 min. A drug library of 1068 approved compounds was used to screen for SARS-CoV2 entry inhibition, and 9 active drugs were identified as specific pseudovirus entry inhibitors. A plaque reduction neutralization test using authentic SARS-CoV-2 virus in Vero E6 cells confirmed that 2 of these drugs (Etravirine and Dolutegravir) significantly inhibited the infection of SARS-CoV-2. With molecular docking...

To investigate the relationship between different CYP4V2 disease-causing variants and disease severity in Bietti crystalline dystrophy (BCD). Twenty-one subjects from 19 unrelated families with a clinical diagnosis of BCD were enrolled. A novel severity prediction score for BCD based on the predicted molecular impact of CYP4V2 variants was applied for grouping and subsequent analyses. The more severe variants led to less CYP4V2 protein function preservation and a higher severity prediction score. All subjects harbored two alleles of CYP4V2 disease-causing variants, of which c.802-8_810del17insGC was the most prevalent (14/21, 66.67%) and c.1507G>C was novel. According to the severity score, the subjects were categorized into severe, moderate, and mild groups with different preservation...

Mitochondria are crucial organelles that provide energy via oxidative phosphorylation in eukaryotic cells and also have critical roles in growth, division, and the cell cycle, as well as the rapid adaptation required to meet the metabolic needs of the cell. Mitochondrial processes are highly dynamic; fusion and fission can vary with cell type, cellular context, and stress levels. Accumulating evidence demonstrates that an imbalance in mitochondrial dynamics leads to death in numerous types of human cancer cells. Therefore, modulating mitochondrial dynamics could be a therapeutic target. In this review, we provide an overview of the protein interaction networks involved in mitochondrial dynamics as effective and feasible drug targets and discuss the related potential therapeutic strategies...

Hepatocellular carcinoma (HCC) is characterized by rapid growth, early vascular invasion, and high metastasis. Currently available US Food and Drug Administration (FDA)-approved drugs show low therapeutic efficacy, limiting HCC treatment to chemotherapy. We designed and synthesized a novel small molecule, SCT-1015, that allosterically activated adenosine monophosphate-activated protein kinase (AMPK) to suppress the aerobic glycolysis in HCC. SCT-1015 was shown to bind the AMPK α and β-subunit interface, thereby exposing the kinase α domain to the upstream kinases, resulting in the increased AMPK activity. SCT-1015 dramatically reduced HCC cell growth in vitro and tumor growth in vivo. We further found that AMPK formed protein complexes with hypoxia-inducible factor 1-alpha (HIF1α) and...

Depilatory laser targeting melanin has been widely applied for the treatment of hypertrichosis. Both selective photothermolysis and thermal diffusion have been proposed for its effect, but the exact mechanism of permanent hair reduction remains unclear. In this study, we explore the role of thermal diffusion in depilatory laser-induced permanent hair loss and determine whether nonpigmented cells are injured by thermal diffusion. C57BL/6 mice in anagen and telogen were treated with alexandrite laser (wavelength 755 nm, pulse duration 3 milliseconds, fluence 12 J/cm2 , spot size 12 mm), respectively. Histological analysis, terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, and transmission electron microscopic imaging were employed to evaluate the injury to hair follicle (...

LEOPARD syndrome (OMIM #151100), also referred to as Noonan syndrome with multiple lentigines, is characterised by various congenital defects, including Lentigines, Electrocardiographic conduction (or other cardiac) abnormalities, Ocular hypertelorism, Pulmonary stenosis, Abnormalities of genitalia, Retarded growth and Deafness. The disease is inherited in an autosomal dominant manner, with the pathogenic variant either inherited from an affected parent or occurring de novo in a patient without any family history. Sensorineural hearing impairment (SNHI), ranging from mild to profound in severity, has been documented in approximately 15%–20% of patients with LEOPARD syndrome.1 There still is inadequate literature regarding the surgical indications and postoperative outcomes of cochlear...

Dystonia is a clinically and genetically heterogeneous movement disorder. However, genetic causes of dystonia remain largely unknown in Asian subjects. To address this, we applied an integrated two-step approach that included gene dosage analysis and a next-generation sequencing panel containing 72 known genes causative for dystonia and related movement disorders to 318 Taiwanese patients with isolated or combined dystonia. Whole-genome sequencing was performed for one multiplex family with no known causative variant. The panel confirmed the genetic diagnosis in 40 probands (12.6%). A genetic diagnosis was more likely with juvenile onset compared with adult onset (24.2% vs 10.8%; P = 0.03) and those with combined features, especially with myoclonus, compared with isolated dystonia (35.3%...

Background: Epithelial ovarian cancer is the sixth most common cancer worldwide: 295,414 new cases were diagnosed in 2018, with 184,799 deaths. The lack of an effective screening strategy has led to the majority of women being diagnosed at an advanced stage. For these women, intravenous carboplatin combined with paclitaxel for six cycles is widely accepted as the standard first-line treatment for epithelial ovarian cancer, in combination with debulking surgery. However, there is conflicting evidence regarding the optimal dosing schedule of paclitaxel when combined with carboplatin in this setting. Objectives: To compare the efficacy and tolerability of intravenous weekly paclitaxel with that of tri-weekly paclitaxel, in combination with intravenous carboplatin, as first-line treatment...

Single-cell RNA sequencing (scRNA-seq) approach can broadly and specifically evaluate the individual cells with minimum detection bias. To explore the individual compositional and transcriptional alteration of intestinal leukocytes in the Dual Specificity Phosphatase six knockout (D6KO) mice, we performed a scRNA-seq followed by the cell type annotation based on ImmGen database. Composition assessments found that D6KO-derived intestinal leukocytes tend to stay inactivate or immature status. The enrichment analysis showed that D6KO-derived intestinal leukocytes are less sensitive to microbes. The mod PhEA phenotypic analysis showed that the D6KO leukocytes may link to not only immune-associated but also diverse previously non-immune-related diseases. Integrating our dataset with the...