Lack of Association between Apolipoprotein E Polymorphism with Age at Onset of Subcortical Vascular Dementia

Background and Purpose: The relationship between apolipoprotein E (ApoE) and onset of vascular dementia remains controversial. The aim of this study was to evaluate the relationship between ApoE polymorphism and the onset of subcortical vascular dementia (SVaD) compared to Alzheimer’s disease (AD) and normal controls. Methods: The study was comprised of 61 patients with SVaD (42 Binswanger type, 19 lacunar type) and 112 patients with AD (16 early-onset AD, 96 late-onset AD) as well as 284 age-, gender- and education-matched normal controls. The diagnosis of SVaD was based on modified NINDS-AIREN criteria, and the diagnosis of AD was based on NINCDS-ADRDA criteria. ApoE polymorphism was genotyped in all participants. Results: None of the three ApoE alleles was more prevalent in SVaD patients compared to normal controls, which was the case when both Binswanger and lacunar types were analyzed separately. ApoE Ε4 did not accelerate the onset of SVaD (OR 1.66, 95% CI: 0.8–3.4), in contrast to a significant relation with late-onset AD (OR 3.78, 95% CI: 2.2–6.5). Conclusion: Our results suggest that ApoE polymorphism is not associated with the onset of SVaD and that the two subtypes of SVaD may share similar pathophysiologies

Relationship between Physical Disability and Depression by Gender:A Panel Regression Model

Background Depression in persons with physical disabilities may be more common than in the general population. The purpose of this study was to examine the relationship between physical disability and depression by gender among adults, using a large, nationally representative sample. Methods This study used data from the Korean Longitudinal Study of Aging, Wave one through four, and ran a series of random effect panel regression models to test the relationship between physical disability status and depression by gender. We tested the moderating effect of gender on the relationship between disability status and depression level by examining the significance of the cross-product term between disability status and gender. Results After controlling for self-rated health, marital status, employment status, education, and age, subjects who were female or diagnosed as having any disability presented higher levels of depression scores. Further, the difference in terms of their depression level measured by Center for Epidemiologic Studies Short Depression Scale (CES-D 10) scores between those who were diagnosed as having any disability and those who were not was greater for females than for their male counterparts. Conclusion This study reaffirmed that disability is the risk factor of depression, using longitudinal data. In addition, female gender is the effect modifier rather than the risk factor. The effect of gender in the non-disability group, mostly composed of older persons, is limited. On the contrary, the female disability group showed more depressive symptoms than the male disability group. The gender difference in the disability group and the role of culture on these differences need further research

Interleukin-2 induces the in vitro maturation of human pluripotent stem cell-derived intestinal organoids.

Human pluripotent stem cell (hPSC)-derived intestinal organoids (hIOs) form 3D structures organized into crypt and villus domains, making them an excellent in vitro model system for studying human intestinal development and disease. However, hPSC-derived hIOs still require in vivo maturation to fully recapitulate adult intestine, with the mechanism of maturation remaining elusive. Here, we show that the co-culture with human T lymphocytes induce the in vitro maturation of hIOs, and identify STAT3-activating interleukin-2 (IL-2) as the major factor inducing maturation. hIOs exposed to IL-2 closely mimic the adult intestinal epithelium and have comparable expression levels of mature intestinal markers, as well as increased intestine-specific functional activities. Even after in vivo engraftment, in vitro-matured hIOs retain their maturation status. The results of our study demonstrate that STAT3 signaling can induce the maturation of hIOs in vitro, thereby circumventing the need for animal models and in vivo maturation

Effects of creatine and β-guanidinopropionic acid and alterations in creatine transporter and creatine kinases expression in acute seizure and chronic epilepsy models

<p>Abstract</p> <p>Background</p> <p>In order to confirm the roles of creatine (Cr) in epilepsy, we investigated the anti-convulsive effects of Cr, creatine transporter (CRT) and creatine kinases (CKs) against chemical-induced acute seizure activity and chronic epileptic seizure activity.</p> <p>Results</p> <p>Two hr after pilocarpine (PILO)-seizure induction, ubiquitous mitochondrial CK (uMtCK) immunoreactivity was unaltered as compared to control level. However, brain-type cytoplasm CK (BCK) immunoreactivity was decreased to 70% of control level. CRT immunoreactivity was decreased to 60% of control level. Following Cr or Tat-CK treatment, uMtCK or CRT immunoreactivity was unaffected, while BCK immunoreactivity in Cr treated group was increased to 3.6-fold of control levels. β-Guanidinopropionic acid (GPA, a competitive CRT inhibitor) reduced BCK and CRT expression. In addition, Cr and tat-BCK treatment delayed the beginning of seizure activity after PILO injection. However, GPA treatment induced spontaneous seizure activity without PILO treatment. In chronic epilepsy rats, both uMtCK and CRT immunoreactivities were reduced in the hippocampus. In contrast, BCK immunoreactivity was similar to that observed in control animals. Cr-, GPA and tat-BCK treatment could not change EEG.</p> <p>Conclusion</p> <p>Cr/CK circuit may play an important role in sustaining or exacerbating acute seizure activity, but not chronic epileptic discharge.</p

Sulforaphane Increases Cyclin-Dependent Kinase Inhibitor, p21 Protein in Human Oral Carcinoma Cells and Nude Mouse Animal Model to Induce G2/M Cell Cycle Arrest

Previously, our group reported that sulforaphane (SFN), a naturally occurring chemopreventive agent from cruciferous vegetables, effectively inhibits the proliferation of KB and YD-10B human oral squamous carcinoma cells by causing apoptosis. In this study, treatment of 20 and 40 µM of SFN for 12 h caused a cell cycle arrest in the G2/M phase. Cell cycle arrest induced by SFN was associated with a significant increase in the p21 protein level and a decrease in cyclin B expression, but there was no change in the cyclin A protein level. In addition, SFN increased the p21 promoter activity significantly. Furthermore, SFN induced p21 protein expression in a nude mouse xenograft model suggesting that SFN is a potent inducer of the p21 protein in human oral squamous carcinoma cells. These findings show that SFN is a promising candidate for molecular-targeting chemotherapy against human oral squamous cell carcinoma

Exosomes from Human Adipose Tissue-Derived Mesenchymal Stem Cells Promote Epidermal Barrier Repair by Inducing de Novo Synthesis of Ceramides in Atopic Dermatitis.

Atopic dermatitis (AD) is a multifactorial, heterogeneous disease associated with epidermal barrier disruption and intense systemic inflammation. Previously, we showed that exosomes derived from human adipose tissue-derived mesenchymal stem cells (ASC-exosomes) attenuate AD-like symptoms by reducing multiple inflammatory cytokine levels. Here, we investigated ASC-exosomes' effects on skin barrier restoration by analyzing protein and lipid contents. We found that subcutaneous injection of ASC-exosomes in an oxazolone-induced dermatitis model remarkably reduced trans-epidermal water loss, while enhancing stratum corneum (SC) hydration and markedly decreasing the levels of inflammatory cytokines such as IL-4, IL-5, IL-13, TNF-α, IFN-γ, IL-17, and TSLP, all in a dose-dependent manner. Interestingly, ASC-exosomes induced the production of ceramides and dihydroceramides. Electron microscopic analysis revealed enhanced epidermal lamellar bodies and formation of lamellar layer at the interface of the SC and stratum granulosum with ASC-exosomes treatment. Deep RNA sequencing analysis of skin lesions demonstrated that ASC-exosomes restores the expression of genes involved in skin barrier, lipid metabolism, cell cycle, and inflammatory response in the diseased area. Collectively, our results suggest that ASC-exosomes effectively restore epidermal barrier functions in AD by facilitating the de novo synthesis of ceramides, resulting in a promising cell-free therapeutic option for treating AD

Alkyl Glycosides from the Flowers of Magnolia obovata

Abstract The flowers of Magnolia obovata were extracted with aqueous MeOH and fractionated into EtOAc, n-BuOH, and H 2 O fractination. Three alkyl glycosides were isolated from the EtOAc fraction through repeated silica gel and ODS column chromatography. The structures were identified to be 2-methylbutan-1-ol-β-Dgalacto-pyranoside (1), 2-methylbutan-1-ol-β-D-glucopyranoside (2), and 2-methylpropan-1-ol-β-D-glucopyranoside (3) on the basis of spectroscopic analyses such as fast atom bombardment mass spectrometry, infrared spectroscopy, 1D nuclear magnetic resonance (NMR) ( 1 H and 13 C-NMR), and 2D NMR (gCOSY, gHSQC, and gHMBC). These compounds were isolated for the first time from the flower of M. obovata in this study

In Vitro and In Vivo Studies on Quercus acuta

Quercus acuta Thunb. (Fagaceae) (QA) is cultivated as a dietary and ornamental plant in China, Japan, South Korea, and Taiwan. It has been widely used as the main ingredient of acorn tofu, a traditional food in China and South Korea. The aim of this study was to determine in vitro and in vivo xanthine oxidase (XO) inhibitory and antihyperuricemic activities of an ethyl acetate extract of QA leaf (QALE) and identify its active phytochemicals using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography (LC) systems. The QALE was found to possess potent in vitro antioxidant and XO inhibitory activities. In vivo study using hyperuricemic mice induced with potassium oxonate demonstrated that the QALE could inhibit hepatic XO activity at a relatively low oral dose (50 mg/kg) and significantly alleviate hyperuricemia to a similar extent as allopurinol. Several active compounds including vitamin E known to possess XO inhibitory activity were identified from the QALE. To the best of our knowledge, this is the first study that reports the active constituents and antihyperuricemic effect of QA, suggesting that it is feasible to use QALE as a food therapy or alternative medicine for alleviating hyperuricemia and gout