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チアゾリジノン化合物及びその使用
No full text[[abstract]]A pharmaceutical composition containing a compound of Formula (I) for treating an opioid receptor-associated condition. Also disclosed is a method for treating an opioid receptor-associated condition using such a compound. Further disclosed are two sets of thiazolidinone compounds of formula (I): (i) compounds each having an enantiomeric excess greater than 90% and (ii) compounds each being substituted with deuterium
Pyrazole compounds and thiazole compounds as protein kinases inhibitors
No full text[[abstract]]A compound of formula (I):wherein A, B, D, X, Y, R1, R2, R3, m, p, and q are defined herein. Also disclosed is a method for inhibiting FMS-like tyrosine kinase 3, aurora kinase, or vascular endothelial growth factor receptor
[[alternative]]Pyrrolidine derivatives
No full text[[abstract]]본 발명은 피롤리딘 화합물, 디펩티딜 펩티다제 IV를 저해하기 위한 이의 이용 방법 및 II형 당뇨병을 치료하기 위한 이용 방법에 관한 것이다
Pyrrolidine derivatives
No full text[[abstract]]Pyrrolidine compounds described herein and methods for using them to inhibit dipeptidyl peptidase IV and treat Type II diabetes
CAPE combined with Cisplatin or Docetaxel inhibits the survival and proliferation of non-small cell lung cancer cells
No full text[[abstract]]The incidence and mortality rate of lung cancer is the highest cancer in the globally, whether in Europe, America or Asia. Lung cancer is mainly divided into two categories about small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), NSCLC is the most common, accounting for about 80% to 85%. Cisplatin and Docetaxel are currently the most commonly used chemotherapy drugs. Even though they are effective, they have serious side effects. Caffeic acid phenylethyl ester (CAPE) is the main component in poplar type propolis. We therefore explored if combined treatment of CAPE with Cisplatin or Docetaxel exhibits greater suprressive effects on survival of NSCLC cells. We observed that the combination of CAPE with Cisplatin or Docetaxel more effectively inhibited the cell proliferation and survival of H1299 and A549 cells than Cisplatin or Docetaxel alone and also more significantly suppressed expression of proteins involved in apoptosis, survival and cell cycle procession protein expression. Our observation suggested that combining CAPE with Cisplatin or Docetaxel can be a more effective treatment for NSCLC and may reduce undesired side effects
Plasma IgA as a biomarker and IL-21 as a potential therapeutic target in Inflammatory Bowel Disease
No full text[[abstract]]Background: B cells and their secreted immunoglobulin A (IgA) play an increasingly recognised role in Inflammatory Bowel Disease (IBD) therapy. While plasma IgA levels have been shown to be elevated in IBD patients compared to healthy controls and decrease with biologic therapy1, its relationship with clinical parameters and therapeutic outcomes remains unclear. Cytokines such as interleukin-21 (IL-21), interleukin-6 (IL-6), and B-cell activating factor (BAFF) are known to regulate B-cell activity in IBD2, but their role in IgA secretion requires further investigation. This study aimed to explore these relationships and identify key cytokines regulating IgA secretion. Methods: We enrolled 43 patients with IBD (31 ulcerative colitis (UC) and 12 with Crohn’s disease (CD)) between 2022 to 2024. Plasma levels of IgA, haemoglobin (Hb), haematocrit (HCT), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), albumin, calcium, and ferritin were measured at baseline for all patients and at week 14 for patients receiving biological therapy (adalimumab or vedolizumab, n=16). Clinical response was defined as a Crohn’s Disease Activity Index (CDAI) <150 for CD patients or a ≥2-point reduction in the partial Mayo score for UC patients. Statistical analysis was performed using the Student’s t-test and linear regression. Additionally, the DAKIKI cell line was used to assess which cytokines influence IgA secretion. Results: Plasma IgA levels significantly decreased at week 14 in most patients receiving biologic therapy (P = 0.0022) (Figure 1A), irrespective of clinical response. However, patients who did not achieve clinical response had significantly higher baseline IgA levels compared to those who did achieve (3057±217.2 vs 1880±214.1 μg/mL, P = 0.0032) (Figure 1B). In all patients, plasma IgA levels showed positive correlations with HCT and ESR, and a negative correlation with ferritin level. Notably, these correlations were stronger in CD patients, where IgA levels showed more significant associations with Hb (R² = 0.2754, P = 0.0369), ESR (R² = 0.3938, P = 0.0123), CRP (R² = 0.3003, P = 0.028), and CDAI (R² = 0.5739, P = 0.0017). In vitro, IL-21 and IL-6 both stimulated IgA secretion in DAKIKI cells, with IL-21 demonstrating greater potency (Figure 2). Conclusion: Plasma IgA levels are correlated with disease activity and clinical parameters, particularly in patients with CD, and may serve as a useful biomarker for monitoring therapeutic response. Baseline IgA levels may predictive clinical response at week 14. Additionally, IL-21 appears to be a key cytokine driving IgA secretion, suggesting its potential as a therapeutic target in IBD management
Neurofilament light chain as a potential indicator of delirium tremens among patients with alcohol dependence
No full text[[abstract]]Background: Delirium tremens (DTs) is the most serious complication of alcohol withdrawal syndrome in patients with alcohol dependence (AD) as it is associated with high risk of mortality rate if not recognized promptly and treated adequately. Neurofilament light chain (NFL), as a measure of neuroaxonal injury, has recently gained attention in AD(Huang et al., 2023). However, whether NFL level differs between patients with and without DTs has not been explored yet. Aims & Objectives: We compared the blood NFL levels between patients with AD who had experience of DTs and those did not to test the hypothesis that NFL can identify the patients with AD to develop DTs. Methods: 224 inpatients fulfilled the DSM-IV-TR criteria for AD and 116 healthy controls were enrolled. Patients with AD were divided by the appearance of DTs into the DT group (n = 25) and non-DT group (n = 199). Blood levels of NFL were measured by Ella microfluid platform analysis. We performed the receiver operating characteristic (ROC) analysis to determine the possibility of NFL level to discriminate individuals with DTs. Results: Serum NFL levels differed significantly among the three groups, with highest in the DT group (63.1 ± 47.2 pg/mL), followed by non-DT group (24.0 ± 22.4 pg/mL) and then control group (11.8 ± 6.1 pg/mL) (p <0.0001). In addition, the ROC curve revealed that an NFL level of 31.2 pg/mL could significantly differentiate DTs group from non-DT group (sensitivity: 80.0%; specificity: 76.9%; area under the curve: 0.84; p <0.001; 95% Confidence Intervals for the AUC: 0.77-0.91). Discussion & Conclusion: Our study revealed the patients with AD experiencing DTs had a significantly higher NFL level, compared to those without such experiences. This result indicate the NFL can be an indicator of delirium tremens in patients with alcohol dependence.Furthermore, the pronounced increase of NFL levels in the patients with AD warrants further investigation of a potential neuroaxonal vulnerability of patients with AD to the development of DTs
Junceellolide Q, a new polyacetoxybriarane from the delicate sea whip octocoral Junceella fragilis
No full text[[abstract]]In this study, chemical screening of a zooxanthella-associated octocoral Junceella fragilis led to the identification of four briarane-type diterpenoids: one new compound, junceellolide Q (1), and three known analogs: fragilolide J (2), junceellin (3), and frajunolide N (4). The structures of compounds 2-4 were confirmed through single- crystal X-ray diffraction (SC-XRD) analysis, while the structure of compound 1 was elucidated using 2D-NMR techniques. Briaranes 1 and 2 were active in enhancing alkaline phosphatase (ALP) activity
Genetic architectures of childhood maltreatment and causal influence of childhood maltreatment on health outcomes in adulthood
No full text[[abstract]]Childhood maltreatment is increasingly recognized as a pivotal risk factor for adverse health outcomes. However, comprehensive analyses of its long-term impact are scarce. This study aims to fill this gap by examining the genetic architectures of childhood maltreatment and its influence on adult health and socioeconomic outcomes. Utilizing data from the UK Biobank (N = 129,017), we conducted sex-combined and sex-stratified genome-wide association studies to identify genomic loci associated with five childhood maltreatment subtypes. We then performed genetic correlation and Mendelian randomization (MR) analyses to assess the effects of childhood maltreatment on high-burden diseases, healthcare costs, lifespan, and educational attainment. We identified several novel loci for childhood maltreatment, including one locus for sexual abuse in sex-combined analysis, one novel locus for sexual abuse in males, one locus for emotional neglect in females, and one locus for sexual abuse in females. The pairwise genetic correlations between subtypes of childhood maltreatment were moderate to high, and similar patterns of genetic correlations between childhood maltreatment subtypes were observed in males and females. Childhood maltreatment was genetically correlated with ten out of 16 high-burden diseases significantly after multiple testing correction. Moreover, MR analyses suggest childhood maltreatment may increase the risk of age-related and other hearing loss, low back pain, major depressive disorder, and migraine in adulthood, and reduce the lifespan. Our study elucidates the genetic architecture of specific childhood maltreatment subtypes and the influence of childhood maltreatment on health outcomes in adulthood, highlighting the enduring influence of childhood maltreatment on lifelong health consequences. It is important to develop prevention strategies to lower the incidence of childhood maltreatment and provide support and care for victims of childhood maltreatment for better long-term health outcomes in the population
Upregulation of cathepsin S expression contributes to neuronal damage following kainic acid-induced status epilepticus
No full text[[abstract]]Status epilepticus (SE) is a life-threatening neurological emergency characterized by persistent seizures, leading to brain damage that increases the risk of recurrent seizures due to abnormal electrical impulses produced by damaged neurons. However, the molecular mechanism by which convulsive SE leads to neuronal damage is not completely understood. Cathepsin S (Ctss), a lysosomal cysteine protease, has been implicated in secondary injury after traumatic brain injury. This study sought to explore whether Ctss is also involved in SE-induced neuronal damage in the hippocampus. Immunohistochemistry and Western blotting were utilized to detect the expression of Ctss in the hippocampal subregions of male C57BL/6J mice at various times following kainic acid (KA)-induced SE. The reactivity of microglia was assessed using immunohistochemistry, and Fluoro-Jade C (FJC) staining was employed to identify damaged neurons. We found that the mature form of Ctss is barely observed in naïve adult (12-week-old) mouse hippocampus, but its expression is significantly evident at 50 weeks of age. In adult mice, the expression of both pro-and mature forms of Ctss in the hippocampal CA3 region was increased as early as 16 h following KA-induced SE. The increased Ctss immunoreactivity was mainly found in microglia following KA-induced SE. The damaged neurons visualized by FJC staining were prominent in the CA3 region at 16 h following KA-induced SE. Ctss knockdown did not affect KA-induced behavioral seizures but significantly reduced SE-induced microglia activation and neuronal damage. An increase in chemokine CX3C motif ligand 1 (CX3CL1) immunoreactivity on microglia was observed following KA-induced SE, and CX3C motif chemokine receptor 1 (CX3CR1) antagonist AZD8797 treatment significantly attenuated SE-induced microglia activation and neuronal damage. Altogether, these results indicate a crucial role of Ctss in SE-induced neuronal damage, possibly through CXC3L1-mediated microglial activation, and provide a new perspective for preventing SE-induced neuronal damage