Immunotherapy targeting plasma ASM is protective in a mouse model of Alzheimer's disease.

Acid sphingomyelinase (ASM) has been implicated in neurodegenerative disease pathology, including Alzheimer's disease (AD). However, the specific role of plasma ASM in promoting these pathologies is poorly understood. Herein, we explore plasma ASM as a circulating factor that accelerates neuropathological features in AD by exposing young APP/PS1 mice to the blood of mice overexpressing ASM, through parabiotic surgery. Elevated plasma ASM was found to enhance several neuropathological features in the young APP/PS1 mice by mediating the differentiation of blood-derived, pathogenic Th17 cells. Antibody-based immunotherapy targeting plasma ASM showed efficient inhibition of ASM activity in the blood of APP/PS1 mice and, interestingly, led to prophylactic effects on neuropathological features by suppressing pathogenic Th17 cells. Our data reveals insights into the potential pathogenic mechanisms underlying AD and highlights ASM-targeting immunotherapy as a potential strategy for further investigation.

Validation and application of new NGS-based HLA genotyping to clinical diagnostic practice.

Next-generation sequencing (NGS) has revolutionized clinical genotyping, providing high-resolution HLA genotyping with a low ambiguity rate. This study aimed to develop new NGS-based HLA genotyping (HLAaccuTest, NGeneBio, Seoul, KOREA) on the Illumina MiSeq platform and validate the clinical performance. The analytical performance of HLAaccuTest was validated for 11 loci comprising HLA-A, -B, -C, -DRB1/3/4/5, -DQA1, -DQB1, -DPA1, and -DPB1 using 157 reference samples. Among the 345 clinical samples, 180 were tested for performance evaluation and protocol optimization, and 165 were used in clinical trials in the validation phase for five loci, including HLA-A, -B, -C, -DRB1, and -DQB1. In addition, the improvement in the resolution of ambiguous alleles was also evaluated and compared with other NGS-based HLA genotyping for 18 reference samples, including five overlapping samples in analytical performance validation. All reference materials produced 100% concordant results for 11 HLA loci, 96.9% (2092 of 2160 HLA alleles) of the clinical samples were matched with the SBT results in the pre-validation phase. After the optimization phase, the clinical trials in the validation phase showed 99.7% (1645/1650 alleles) concordance with the complete resolution for 34 ambiguity results. The retesting of five discordant cases resolved all issues and yielded 100% concordant results with the SBT method. Additionally, for ambiguity using 18 reference materials with ambiguous alleles, about 30% of ambiguous alleles were more resolved than Trusight HLA v2. HLAaccuTest was successfully validated using a large volume of clinical samples and is fully applicable to the clinical laboratory.

Augmented ERAD (ER-associated degradation) activity in chondrocytes is necessary for cartilage development and maintenance.

Chondrocytes secrete massive extracellular matrix (ECM) molecules that are produced, folded, and modified in the endoplasmic reticulum (ER). Thus, the ER-associated degradation (ERAD) complex-which removes misfolded and unfolded proteins to maintain proteostasis in the ER- plays an indispensable role in building and maintaining cartilage. Here, we examined the necessity of the ERAD complex in chondrocytes for cartilage formation and maintenance. We show that ERAD gene expression is exponentially increased during chondrogenesis, and disruption of ERAD function causes severe chondrodysplasia in developing embryos and loss of adult articular cartilage. ERAD complex malfunction also causes abnormal accumulation of cartilage ECM molecules and subsequent chondrodysplasia. ERAD gene expression is decreased in damaged cartilage from patients with osteoarthritis (OA), and disruption of ERAD function in articular cartilage leads to cartilage destruction in a mouse OA model.

Comparison of antioxidant activity in wild plant (Adenophora triphylla) leaves and roots as a potential source of functional foods.

Adenophora triphylla is commonly used in food materials and oriental medicine as an analgesic, anti-inflammatory, and antitussive. In the present study, the leaves and roots of A. triphylla were extracted with water and ethanol, respectively, to examine the extracts' in vitro antioxidant activities and total phenolic contents, as well as A. triphylla's potential as a new functional food source and safe and inexpensive supply of antioxidants. Different antioxidant tests were employed and the results were compared with ascorbic acid as a standard antioxidant. The total extractable contents of phenolic compounds and flavonoids, which relate to antioxidant activity in medicinal plants, were also measured. The leaf extracts had notable levels of total phenolics and flavonoids and showed high radical and nitrite scavenging activities as well as inhibition activity against enzymes that induce oxidation. These results suggest that A. triphylla leaves are a potential ingredient for food supplements and a natural source of antioxidants.

Depressive symptoms in elementary school children in Jeju Island, Korea: prevalence and correlates.

We investigated the prevalence and correlates of depressive symptoms in elementary school children in Jeju Island, Korea. The study participants were 2305 children enrolled in elementary schools in Jeju-si, Seogwipo-si, Namjeju-gun, and Bukjeju-gun and their parents who completed questionnaires about sociodemographics, health habits, family relationship information, and the Korean form of the Kovac's children's depression inventory (CDI) in September to December 2005. Multiple logistic regression showed that higher age (OR = 1.259, 95% CI 1.098-1.445), short time spent developing a relationship with the mother (OR = 2.770, 95% CI 1.280-5.944), and a low level of body image satisfaction (OR = 3.397, 95% CI 1.823-6.330) were correlates of depressive symptoms in children. Our results suggest that the following are essential to prevent depressive symptoms in elementary school children in Jeju, Korea: advanced education and social activity programs at home, in school, and in the community to help children have a positive self-image, and much time spent building a relationship with the mother.