研究成果

The failure of peripheral nerve regeneration is often associated with the inability to generate a permissive molecular and cellular microenvironment for nerve repair. Autologous therapies, such as platelet-rich plasma (PRP) or its derivative platelet-rich growth factors (PRGF), may improve peripheral nerve regeneration via unknown mechanistic roles and actions in macrophage polarization. In the current study, we hypothesize that excessive and prolonged inflammation might result in the failure of pro-inflammatory M1 macrophage transit to anti-inflammatory M2 macrophages in large nerve defects. PRGF was used in vitro at the time the unpolarized macrophages (M0) macrophages were induced to M1 macrophages to observe if PRGF altered the secretion of cytokines and resulted in a phenotypic...

Using the Taiwan Biobank, we aimed to identify traits and genetic variations that could predispose Han Chinese women to primary dysmenorrhea. Cases of primary dysmenorrhea included those who self-reported "frequent dysmenorrhea" in a dysmenorrhea-related Taiwan Biobank questionnaire, and those who have been diagnosed with severe dysmenorrhea by a physician. Controls were those without self-reported dysmenorrhea. Customized Axiom-Taiwan Biobank Array Plates were used to perform whole-genome genotyping, PLINK was used to perform association tests, and HaploReg was used to conduct functional annotations of SNPs and bioinformatic analyses. The GWAS analysis included 1186 cases and 24,020 controls. We identified 53 SNPs that achieved genome-wide significance (P < 5 × 10-8, which...

Hair follicle stem cells are regulated by dermal papilla fibroblasts, their principal signaling niche. Overactivation of Hedgehog signaling in the niche dramatically accelerates hair growth and induces follicle multiplication in mice. On single-cell RNA sequencing, dermal papilla fibroblasts increase heterogeneity to include new Wnt5ahigh states. Transcriptionally, mutant fibroblasts activate regulatory networks for Gli1, Alx3, Ebf1, Hoxc8, Sox18, and Zfp239. These networks jointly upregulate secreted factors for multiple hair morphogenesis and hair-growth-related pathways. Among these is non-conventional TGF-β ligand Scube3. We show that in normal mouse skin, Scube3 is expressed only in dermal papillae of growing, but not in resting follicles. SCUBE3 protein microinjection is sufficient...

The purpose of this study was to investigate the genetic and clinical characteristics of eyes shut homolog (EYS)-associated retinitis pigmentosa (RP). This was a retrospective cross-sectional observational study of 36 patients with EYS-associated autosomal recessive RP (arRP). The gene sequencing results revealed that c.6416G>A (p.Cys2139Tyr) and c.7228+1G>A were the two most predominant variants in our cohort and that variants near the C-terminus, which contains alternating laminin and epidermal growth factor (EGF) domains, accounted for the majority of the allele counts (58 of a total of 72) and relative allele frequencies (81%). Over half of the patients presented with pericentral-type RP (n = 19, 60%), which frequently occurred in combination with macular lesions (n = 10, 52%)...

Recessive variants in the MYO15A gene constitute an important cause of sensorineural hearing impairment (SNHI). However, the clinical features of MYO15A-related SNHI have not been systemically investigated. This study aimed to delineate the hearing features and outcomes in patients with pathogenic MYO15A variants. This study recruited 40 patients with biallelic MYO15A variants from 31 unrelated families. The patients were grouped based on the presence of N-terminal domain variants (N variants). The longitudinal audiological data and for those undergoing cochlear implantation, the auditory and speech performance with cochlear implants, were ascertained and compared between patients with different genotypes. At the first audiometric examination, 32 patients (80.0%) presented with severe to...

Obesity is associated with increased cancer risk and weak responses to vaccination and sepsis treatment. Although dendritic cells (DCs) are fundamental for the initiation and maintenance of competent immune responses against pathogens and tumors, how obesity alters the normal physiology of these myeloid cells remains largely unexplored. In this study, we report that obesity caused by prolonged high-fat diet feeding disrupts the metabolic and functional status of mouse splenic DCs (SpDCs). High-fat diet-induced obesity drastically altered the global transcriptional profile of SpDCs, causing severe changes in the expression of gene programs implicated in lipid metabolism and mitochondrial function. SpDCs isolated from obese mice demonstrated enhanced mitochondrial respiration provoked by...

Sudden cardiac death (SCD) remains a worldwide public health problem in need of better noninvasive predictive tools. Current guidelines for primary preventive SCD therapies, such as implantable cardioverter defibrillators (ICDs), are based on left ventricular ejection fraction (LVEF), but these guidelines are imprecise: fewer than 5% of ICDs deliver lifesaving therapy per year. Impaired cardiac metabolism and ATP depletion cause arrhythmias in experimental models, but to our knowledge a link between arrhythmias and cardiac energetic abnormalities in people has not been explored, nor has the potential for metabolically predicting clinical SCD risk. We prospectively measured myocardial energy metabolism noninvasively with phosphorus magnetic resonance spectroscopy in patients with no...

Brain-derived Neurotrophic Factor (BDNF) is markedly decreased in heart failure patients. Both BDNF and its receptor, Tropomyosin Related Kinase Receptor (TrkB), are expressed in cardiomyocytes, however the role of myocardial BDNF signaling in cardiac pathophysiology is poorly understood. Here we investigated the role of BDNF/TrkB signaling in cardiac stress response to exercise and pathological stress. We found that myocardial BDNF expression was increased in mice with swimming exercise, but decreased in a mouse heart failure model and human failing hearts. Cardiac-specific TrkB knockout (cTrkB KO) mice displayed a blunted adaptive cardiac response to exercise, with attenuated upregulation of transcription factor networks controlling mitochondrial biogenesis/metabolism, including...

Transient gene expression systems are powerful tools for studying gene interactions in plant species without available or stable genetic transformation protocols. We optimized a petal protoplast transformation protocol for Sinningia speciosa, a model plant, to study the development of floral symmetry. A high yield of petal protoplasts was obtained using a 6-h enzyme digestion in a solution of 1.5% cellulase and 0.4% macerozyme. Modest transfection efficiency (average 41.4%) was achieved. The viability of the transfected protoplasts remained at more than 90%. A fusion of green fluorescent protein and CYCLOIDEA (SsCYC), the Teosinte branched 1/Cincinnata/Proliferating cell factor transcription factor responsible for floral symmetry, was subcellularly localized inside the nuclei of the...

Thoracic aortic aneurysm and dissection (TAAD) is a devastating but treatable disease if detected early. The clinical manifestations and genetic characteristics underlying TAAD patients in Taiwan, however, remain unclear. We consecutively recruited patients referred for TAAD screening and/or management at a tertiary medical center in Taiwan. All patients received a comprehensive survey of the clinical manifestations and a genetic testing with a 29-gene next-generation sequencing (NGS) panel. Patients (n = 107) were referred for different reasons, and could be grouped into 4 categories: known aortic aneurysm or dissection (AoAD) (n = 57), Marfanoid features (n = 36), having family members of suspected AoAD (n = 11), and ectopic lens (n = 3). AoAD were confirmed in 73 (68.2%) of the entire...