13856 research outputs found
Sort by
Pyrazole compounds
No full text[[abstract]]Disclosed are pyrazole compounds, encompassed by formula (I) shown in the Specification, useful for treating peripheral cannabinoid 1 receptor mediated disorders. Also disclosed are pharmaceutical compositions and methods related to use of these compounds
雜環化合物及其用途
No full text[[abstract]]本发明是关于式(I)的杂环化合物，另揭露包含该杂环化合物的药物组合物以及使用该杂环化合物驱使造血干细胞(HSC)及内皮前驱细胞(EPC)进入周边血液循环的方法。本发明更提供一种使用该杂环化合物治疗组织损伤、癌症、发炎性疾病、或自体免疫性疾病的方法
Heterocyclic compounds and use thereof
No full text[[abstract]]Heterocyclic compounds of Formula (I) shown herein. Also disclosed are pharmaceutical compositions containing the heterocyclic compounds and methods of using the heterocyclic compounds to mobilize hematopoietic stem cells and endothelial progenitor cells into the peripheral circulation. Further provided are methods for treating tissue injury cancer inflammatory disease and autoimmune disease with the heterocyclic compounds
Developing a serum-free and cytokine-optimizing induction medium to increase the production of CD14+CD16+ and CD14+CD16− monocytes from human CD133+ hematopoietic stem and progenitor cells
No full text[[abstract]]Immunotherapy utilizes immune cells to target cancer and improves treatment outcomes with few side effects. Despite the effectiveness of immunotherapy, the limited availability of monocytes, which are essential for the differentiation of antigen-presenting cells, remains a major challenge. In this study, we developed a technique for inducing monocytes from hematopoietic stem and progenitor cells by using a serum-free (SF) medium supplemented with optimal concentrations of serum substitutes and cytokines. Three key serum substitutes, namely lipids, ascorbic acid, and beta-glycerophosphate, were identified through factorial design screening, with their concentrations optimized through steepest ascent path analysis. Iscove's modified Dulbecco's medium was identified as the optimal basal medium. Long-term culturing confirmed the successful induction of CD14+CD16+ and CD14+CD16- monocytes. Functional assays validated the efficacy of this technique with comparable gene expression, cytokine secretion, phagocytosis ability, and T-cell stimulating ability between SF and serum-containing cultures. Under SF conditions, high expression levels of CD16 were detected, indicating the broad range of potential applications of CD16+ monocytes. Overall, this technique represents a feasible SF alternative for monocyte generation, with potential benefits for immunotherapy
Building indigenous health: Insights from indigenous adults on knowledge integration and adaptive strategies
No full text[[abstract]]Over half of the older population faces inadequate dietary intake, posing higher risks of geriatric syndromes like frailty and sarcopenia. This community-based participatory research (CBPR) co-created a nutrition and cooking workshop in a Taiwanese Indigenous community. Employing the photovoice method alongside focus groups and individual interviews with 16 participants, we sought to understand the older Indigenous adults’ dietary patterns. Nutbeam’s health literacy model (2000) and Giddens’ structuration theory (1984) guided data analysis and conceptualization of food literacy construction in the Indigenous land. Four main themes emerged. First, ‘knowledge integration’ represents the conversation between traditional and scientific food/nutrition knowledge, strengthening functional food literacy to address health concerns. Second, ‘Indigenous adaptive strategies’ demonstrate their ability to apply food knowledge meaningfully in daily life, representing interactive food literacy. Third, ‘awareness of advanced nutrition literacy’ demonstrates the older adults’ ability to evaluate personal diets and critically reflect on the need for better health, representing critical food literacy. These food literacy constructs are iterative and interactive. Lastly, work is central to Indigenous life, shaping their identity and a sense of achievement, motivating older adults’ adaptive strategies and pursuing advanced nutrition literacy. However, the middle-aged population is less likely to attend health promotion activities due to work. Indigenous adaptive strategies reflect human agency’s potential to reproduce individual food ecosystems and healthcare practice systems within the community, overcoming structural barriers. CBPR can foster a sense of ownership among participants, enabling them to engage healthy behaviors as their personal priorities and take active initiatives toward better health
Characteristics and hospitalization of people living with dementia after home healthcare: A nationwide cohort study
No full text[[abstract]]The need for home healthcare (HHC) is increasing among people living with dementia (PLWD) to achieve their desire to age. This study aimed to investigate the determinants of hospitalization among PLWD receiving HHC. This retrospective cohort study used data from the National Health Insurance Research Database of Taiwan from 2007 to 2017. The primary outcome was subsequent hospitalization after HHC for PLWD. Using multivariate Poisson regression, baseline and follow-up HHC-related characteristics were examined as covariates and influencing factors. A total of 95,831 PLWD received HHC (mean age: 80.2 years), and 81.7% had at least one subsequent hospitalization during the follow-up period. Regarding baseline characteristics, prior admission was the strongest determinant of subsequent hospitalization, especially being admitted three to six months before HHC use (aRR = 1.47, 95% confidence interval [CI] 1.39-1.56, P < .001), followed by dementia duration from diagnosis to index date more than 3.5 years (aRR = 1.22, 95% CI 1.19-1.24). Among HHC-related characteristics, a higher frequency of HHC visits (more than 2 counts/month) (aRR = 4.81, 95% CI 4.63-5.00) and visits by both physicians and nurses (aRR = 2.03, 95% CI 1.98-2.07) were associated with a higher risk of hospitalization. Our findings suggest that prior admission, longer dementia duration from diagnosis to the index date, and frequency of HHC were positively associated with increased hospitalization. Future interventions and strategies can focus on these factors to decrease hospitalization among PLWD receiving HHC
Regulation of interferon alpha production by the MAGUK-family protein CASK under H5N1 infection
No full text[[abstract]]CASK, a MAGUK family scaffold protein, regulates gene expression as a transcription co-activator in neurons. However, the mechanism of CASK nucleus translocation and the regulatory function of CASK in myeloid cells remains unclear. Here, we investigated its role in H5N1-infected macrophages. We found that H5N1 triggers CASK nuclear translocation via PKR and SRC signaling. HCK, a SRC family kinase, enhances CASK phosphorylation at S395 via CDK5, facilitating CASK's nuclear entry. Knocking out CASK in myeloid cells specifically reduces interferon-alpha (IFNA) production by hindering the nuclear export of Ifna mRNA, while leaving its mRNA levels unchanged. Myeloid-specific CASK knockout (KO) mice display exacerbated lung inflammation, which correlates with reduced IFNA levels during H5N1 infection. Interactome studies show that H5N1 triggers associations between CASK and CCT4, STIP1, and TNK1. These associations recruit IRF7, POLR2C, TAF15, HNRNPs, and CRM1, enabling the CASK complex to bind to the Ifna promoter, bind co-transcriptionally to Ifna mRNA, and facilitate CRM1-dependent Ifna mRNA export. This underscores CASK's critical role in the antiviral response
Fused bicyclic pyrimidine compounds as aurora kinase inhibitors
No full text[[abstract]]Fused bicyclic pyrimidine compounds of formula (I) defined herein. Also disclosed are a method for inhibiting Aurora kinase activity and a method for treating cancer with these compounds
Fused bicyclic pyrimidine compounds as aurora kinase inhibitors
No full text[[abstract]]Fused bicyclic pyrimidine compounds of formula (I): wherein R1, R3, R4, X1, X2, Y, Z, A, B, C, D, n, and the two bonds are defined herein. Also disclosed are a method for inhibiting Aurora kinase activity and a method for treating cancer with these compounds
作为蛋白激酶抑制剂的稠合多环化合物
No full text[[abstract]]本发明公开了如在此限定的式(I)的稠合多环化合物。本发明也公开了一种抑制蛋白激酶(如极光激酶)活性的方法，以及一种以这些化合物治疗蛋白激酶介导的疾病(如癌症)的方法。Fused multicyclic compounds of formula (I): wherein R′, R″, X, Y, Z, A, B, C, D, an