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[[alternative]]High-growth enterovirus 71 strains and vaccines
No full text[[abstract]]本發明係關於一種用於提高哺乳動物疫苗產量的馴化腸病毒71型(EV71)疫苗株。該EV71疫苗株包含至少一個經修飾的腸病毒蛋白，可自哺乳動物宿主細胞(如Vero細胞)快速增殖EV71病毒。本發明亦關於一種從馴化之EV71病毒疫苗株產生的疫苗以及該疫苗的製造方法
幹細胞からエクソソームを生成する方法およびその使用
No full text[[abstract]]A method of producing induced exosomes, the method comprising: contacting an isolated population of stem cells with an amount of a prostaglandin E receptor 4 (EP4) antagonist effective for inducing release of exosomes, whereby induced exosomes are released from the stem cells, and isolating the induced exosomes
Methods to enhance nerve regeneration utilizing neural stem cells and IL12P40
No full text[[abstract]]The present application provides a composition and methods to enhance nerve regeneration utilizing at least one component of neural stem cells or IL12p40. The composition comprises neural stem cells and a neurotrophic factor, which is constructed by IL12p40 as at least one subunit. The methods to enhance nerve regeneration comprise providing a nerve regeneration composition comprising a neurotrophic factor containing IL12p40 as at least one subunit to a subject. The composition of the methods can further comprise neural stem cells
產生免疫調節細胞之方法、依該方法所製備之細胞及其應用
No full text[[abstract]]The present invention develops a straightforward and rapid method for generating immunomodulatory cells from peripheral mononuclear cells, comprising treating periphera
The role of dual specificity phosphatase 22 (DUSP22) in rheumatoid arthritis: Mechanism and genetic investigations
No full text[[abstract]]Background/Purpose: Rheumatoid arthritis (RA) is a debilitating autoimmune disorder characterized by chronic inflammation and joint damage. This study investigates the role of Dual Specificity Phosphatase 22 (DUSP22), also known as JKAP, in the pathogenesis of RA, with a specific focus on its interaction with UBR2 and the downstream effects on T cell activation. We also explore the hypothesis that single nucleotide polymorphisms (SNPs) within the UBR2 gene may lead to functional changes in the protein, affecting its role in the immune response and contributing to the variability in RA disease progression observed among patients. Methods: Peripheral blood samples were collected from 14 RA patients and 6 healthy controls. DUSP22 expression was analyzed using Western blotting. T cells were purified and activated, followed by proximity ligation assays (PLA) to assess Lck ubiquitination and UBR2-Lck interactions. JKAP knockout (KO) mice were generated to evaluate arthritis severity and cytokine profiles. Histological analyses and ELISAs were performed to assess joint damage and cytokine levels, respectively. Genotyping of the UBR2 gene in RA patients and healthy controls was conducted using next-generation sequencing to identify prevalent SNPs. Results: DUSP22 expression was significantly reduced in the peripheral blood leukocytes and T cells of RA patients compared to healthy controls. UBR2 is implicated in protein degradation pathways and interacts with key signaling molecules involved in immune cell activation, such as Lck. UBR2 modulates Lck activity through K63-linked ubiquitination, suggesting a critical role in T cell signaling and autoimmune disease pathogenesis. JKAP KO mice exhibited more severe arthritis with increased synovial proliferation and cartilage damage. Elevated levels of pro-inflammatory cytokines IL-6 and IL-17A were observed in the serum and joint tissues of JKAP KO mice. Genotyping revealed significant SNPs within the UBR2 gene, which may lead to functional changes in the protein and affect immune response variability, potentially contributing to RA disease progression. Conclusion: Our findings suggest that DUSP22 plays a critical role in modulating inflammatory processes in RA. The downregulation of DUSP22 in RA patients may influence UBR2-mediated pathways, contributing to the heightened T cell activation and inflammation observed in RA. Additionally, SNPs within the UBR2 gene may lead to functional changes affecting immune response variability and RA disease progression. These results highlight DUSP22 and UBR2 as potential therapeutic targets for RA and provide insights into the molecular mechanisms underlying RA pathogenesis
Polygenic dissection of the genetic architecture of treatment-resistant depression in the UK biobank
No full text[[abstract]]Background :Major depressive disorder (MDD) is a prevalent mental illness with a significant burden, affecting 5% of adults worldwide. About one-third of MDD patients suffer from treatment resistance despite adequate dosage and duration of multiple anti-depressants (ADs). Previous pharmacogenetic studies suggest that the discrepancy in medication response may partially arise from genetic variability. However, these studies are often limited by sample size and exhibit heterogeneity in study designs and definitions of treatment-resistant depression (TRD). To conduct a well-powered genetic investigation considering a range of TRD phenotypes within a single source, we leveraged the real-world primary care data from the UK Biobank. Methods: We identified 15,528 MDD patients of White British descent with no prior psychiatric comorbidities. By examining AD prescription patterns, we constructed various proxy TRD definitions (TRDp) to identify patients who had ever changed ≥2 ADs (Change_AD: = 1,879); received ≥3 types of ADs (Receive_AD: 4,671); used augmentation alongside AD (AUG_Antipsychotics: 3,110; Mood stabilizers: 2,717; Valproate: 305; Lithium: 287); or undergone electroconvulsive therapy (ECT: 85). To increase the confidence of phenotyping, we considered symptom severity and additionally identified hospitalized TRDp patients (HOSP-TRDp). We then performed genome-wide association studies (GWAS) for each TRDp definition vs. non-TRDp or control group and estimated SNP-heritability (h2) using LD Score Regression. Finally, we assessed the genetic burden of nine common psychiatric diseases in TRDp through polygenic risk score (PRS) analysis. Results :MDD patients classified with TRDp tended to be females and have a higher rate of unemployment, lower education and income levels, and a higher BMI. Hospitalization was twice as common in TRDp as in non-TRDp across definitions, highest for ECT (65% vs. 26%). Although no credible single variant discoveries emerged from GWAS, heritability analysis revealed a significant genetic influence on TRDp, even larger for hospitalized patients (liability h2 = 9%, 10-20%, 15-25% for non-TRDp, TRDp, and HOSP-TRDp vs. control; 18-23%, 28-32% for TRDp and HOSP-TRDp vs. non-TRDp). TRDp identified as Change_AD, Receive_AD, AUG_A, or AUG_M carried a stronger polygenic burden of MDD, ADHD, BD, SCZ, and alcohol dependence than non-TRDp (odds ratio [OR] per SD = 1.05-1.14), with PRS of BD and SCZ more enriched in AUG_A than in other definitions. More profoundly, MDD patients with a higher BD PRS were more likely to receive intensive treatments like ECT or lithium, valproate augmentation (ORs = 1.73, 1.52, and 1.35, p <0.001). Lastly, compared to the average PRS group, those in the highest 10% were at a 15-20% elevated risk of experiencing TRDp, and the effects were more pronounced in the HOSP-TRDp group (e.g., ORBD = 1.53 [95% CI: 1.3-1.8] for AUG_A; ORADHD = 1.43 [1.2-1.7] for AUG_M). Discussion : Our findings support a significant role of common genetic variations in the etiology of TRD, underscoring a polygenic basis. While challenging to accurately ascertain treatment response from medical records, our results highlight distinction between TRDp vs. non-TRDp both genetically and phenotypically. By employing broader to more extreme phenotyping (e.g., ECT), we also showed how various TRDp definitions may capture the underlying genetic liability to a spectrum of mental illnesses, together advancing our understanding of the genetic architecture of TRD
Polygenic risk scores indicates genetic overlap between methamphetamine use and other psychiatric disorders
No full text[[abstract]]Background: There has been evidence that methamphetamine (METH) use disorder is heritable and probably highly polygenic. Shared genetic factors may explain the high comorbidity between METH use and other psychiatric disorders. Previous studies also suggest possible shared etiological mechanisms between METH-associated psychosis and primary psychosis. We aimed to examine whether METH use disorders are genetically correlated with other psychiatric disorders using a polygenic risk score (PRS) approach. Methods: A total of 1,227 patients with MA use were recruited. Genome-wide single nucleotide polymorphism (SNP) genotyping, demographic, and clinical information were obtained. Healthy controls were 91,582 individuals, who self-reported no history of psychiatric and neurologic disorders, with genome-wide genotypic data available from Taiwan Biobank. We used PRS-CSx to calculate PRS for schizophrenia (SCZ), bipolar disorder (BPD), major depressive disorder (MDD), attention deficit hyperactivity disorder (ADHD), alcohol dependence (AD), and cigarette smoking (CS), and tested their associations with METH use and METH-associated psychosis. Results: METH use was significantly associated with PRS of MDD (P= 9.85E-08), ADHD (P= 1.44E-08), AD (P= 1.14E-17), and CS (P= 1.56E-17). METH-associated psychosis was significantly associated with PRS of SCZ (P=3.02E-12). Discussion: METH use was genetically correlated with MDD, ADHD, AD, and CS, while METH-associated psychosis was genetically correlated with SCZ
Investigating the relationship between the emulsification parameters and physical-chemical properties of poly(D,L-lactic acid) particles for dermal fillers
No full text[[abstract]]Poly(L-lactic acid) (PLLA) and poly(D,L-lactic acid) (PDLLA) particles have been applied as dermal fillers for soft-tissue augmentation because they can induce foreign-body reactions, resulting in fibroblast proliferation and collagen formation. Although PLLA and PDLLA fillers are safe and biocompatible, clinical complications such as nodules and granulomas have been reported, possibly due to incomplete reconstitution. PDLLA particles were prepared via emulsification in this study, and three stirring speeds were investigated when adding PDLLA into carboxymethyl cellulose solution. The particle size, molecular weight of PDLLA, optical rotation, pH value, osmotic pressure, and reconstitution time were analyzed. A rabbit dorsal ear model was established to evaluate the soft-tissue augmentation of a commercial PDLLA filler. The results demonstrated that the stirring speed affected the particle size, but not other physical-chemical properties of the PDLLA particles. All the PDLLA particles were reconstituted in less than 7 min, which is faster than the process for the other commercial PDLLA dermal filler products. In addition, the PDLLA particles could induce inflammation and fibroblast proliferation. Although the PDLLA particles generated in this study have not yet been investigated in vivo, the results demonstrated here suggest their potential for application as dermal fillers
Techno-strain and techno-insecurity are associated with poor mental well-being in specific age and occupation groups
No full text[[abstract]]OBJECTIVES: Innovative technology at work can lead to stress and has been linked with adverse work and health consequences. This study aims to examine the association of techno-insecurity and techno-strain with mental well-being in different age and occupational groups. METHODS: We utilized a nationally representative survey of the working population and restricted our analyses to 2,814 employees who reported being engaged with new technology. Techno-insecurity and techno-strain were evaluated by a single question each. Mental health status was assessed by a 5-item scale, and burnout status was assessed by the Copenhagen Burnout Inventory. We used logistic regression analysis to examine the association of techno-insecurity and techno-strain with mental well-being, adjusting for job control, psychological demands, job insecurity, and workplace violence. We further stratified study participants by age and occupational group and examined the association in each group. RESULTS: One-fifth of the study participants reported having techno-insecurity and techno-strain. Techno-insecurity was associated with a 1.8-fold risk of poor mental health and high burnout, whereas techno-strain was associated with a 2.2-fold risk of having poor mental health and high burnout. The associations between techno-insecurity or techno-strain and poor mental health were most profound among middle-aged workers. Among all occupational groups, the associations between techno-insecurity or techno-strain and burnout were most profound among manual workers. CONCLUSION: Techno-strain and techno-insecurity are emerging occupational mental health threats, particularly among middle-aged and manual workers. To promote mental health, resources provided by the organization is needed to help employees cope and work with technology
Exposure risk and characteristics of bisphenol A and its substitutes in the general Taiwanese
No full text[[abstract]]In 2023, EFSA released a new tolerable daily intake following the latest re-risk assessment of BPA, emphasized the need for cumulative risk assessments in population. This study aimed to identify the exposure risk and characteristics of BPA and its substitutes in the general Taiwanese (N = 1,964; adult: 1,345; minor: 619). We evaluated the potential health risks of BPA and its substitute’s exposure by estimating daily intake (DI), hazard quotients and hazard index values using measured urinary concentrations. We found that DI of BPA and its substitutes in Taiwanese varied by age and sex, and personal care products and plastic packaging usage could increase the exposure risk of BPA and its substitutes. Our findings revealed that exposure risks of BPA and its substitutes were high-risk substances in Taiwanese based on the new EFSA’s regulation, and further human bio-monitoring surveillance as well as restricted regulation are suggested