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Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common genetic disorder among those responsible for hereditary strokes, and it is caused by a mutation in the NOTCH3 gene on chromosome 19. Blood biomarkers related to the Notch signaling pathway have not been investigated extensively in CADASIL. In this study, we measured the serum and plasma levels of NOTCH3 extracellular domain (N3ECD) and its ligand, Jagged-1, in 279 healthy subjects. The levels of N3ECD and Jagged-1 showed significant correlations in both serum (p < 0.0001, r = 0.2681) and plasma (p < 0.0001, r = 0.4065). The N3ECD levels were significantly higher in the serum than in plasma and tend to increase with age. In contrast, there was no significant difference between the serum and plasma levels of Jagged-1 levels. To summarize, we were able to measure N3ECD and Jagged-1 protein levels in healthy human serum and plasma. Taken together, our findings provide the basis for further studies investigating the clinical use of blood N3ECD and Jagged-1 levels for CADASIL and other Notch signaling-related diseases.

Zoysia japonica Steud. is a warm-season lawn grass popular in Korea and elsewhere. They are cultivated in many places such as river banks, roadside, and play grounds. However, there still is a disadvantage of frequent mowing, and the grass grows poorly under the chilly conditions. To develop a grass variety that circumvents these drawbacks, we cloned the chitin-inducible gibberellins-responsive1 gene (CIGR1) from zoysiagrass. The full length of the ZjCIGR1 (Zj; Zoysia japonica Steud.) gene was obtained by 5′/3′ RACE PCR and the phylogenetic tree showed that it belonged to the CIGR1-subgroup in the PAT1-group of GRAS protein family. Expression of the ZjCIGR1 in wild-type plants was confirmed in roots, meristems, leaves, and flowers, especially high in the flowers. The transgenic zoysiagrass was confirmed by PCR using gene-specific primers, phosphinothricin-acetyl-transferase (PAT) strip test, and Southern blot analysis. ZjCIGR1-overexpressing plants acquired tolerance to cold stress displaying morphological phenotypes characteristic of stress resistance. In addition, in the transformants, expression of the ZjCIGR1 as well as cold-regulated (COR) gene was increased compared to the wild-type plants under cold stress condition. These results suggest that ZjCIGR1 gene is an important candidate for regulating cold stress resistance.

ObjectiveThis study aimed to determine the frequency of pathogenic NOTCH3 variants among Koreans.MethodsIn this cross-sectional study, we queried for pathogenic NOTCH3 variants in 2 Korean public genome databases: the Korean Reference Genome Database (KRGDB) and the Korean Genome Project (Korea1K). In addition, we screened the 3 most common pathogenic NOTCH3 variants (p.Arg75Pro, p.Arg544Cys, and p.Arg578Cys) for 1,000 individuals on Jeju Island, where the largest number of patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) have been reported in Korea.ResultsThe pathogenic NOTCH3 variant (p.Arg544Cys) was found in 0.12% of sequences in the KRGDB, and 3 pathogenic variants (p.Arg75Pro, p.Arg182Cys, and p.Arg544Cys) were present in 0.44% of the Korea1K database. Of the 1,000 individuals on Jeju Island, we found 2 cysteine-altering NOTCH3 variants (p.Arg544Cys variant in 9 and p.Arg578Cys in 1 individual) in 1.00% of the participants (95% confidence interval: 0.48%–1.83%). The presence of cysteine-altering NOTCH3 variants was significantly associated with a history of stroke (p < 0.001).DiscussionPathogenic NOTCH3 variants are frequently found in the general Korean population. Such a high prevalence of pathogenic variants could threaten the brain health of tens of thousands to hundreds of thousands of older adults in Korea.

Gotjawal is forest that was formed by the lava flow along the slopes as a result of the volcanic activity of the parasite volcanoes which distributed over Jeju Island, the Republic of Korea. Since Gotjawal has very shallow soil layer and wetland in Gotjawal does not have water for a long time, infiltration characteristics are very important. Study wetland is 48m in diameter and 2.2m in depth and water level change with respect to time was measured in 2019. The results showed that annual rainfall in this area was measured to 2,748mm and 5 rainfall events with daily rainfall more than 100mm were recorded in 2019. When the wetland was full of water, the period of drainage was 12 days. Water level started to change when the rainfall was 43~70mm taking 10~15 hours and this seems to vary depending on the period of no rainfall. This result will be helpful for estimating groundwater sources in lava flows area and for developing conservation plan of Gotjawal.

This study was designed to determine optimal extraction conditions of Chrysanthemum zawadskii (CZ) with high yield of bioactive compounds (linarin, polyphenols, and flavonoids) and improved in vitro activities. Ethanol extracts were examined at different concentrations (0, 30, 50, 70, and 95%) and temperatures (50 and 70°C). The recommended extraction conditions were 50% ethanol at 70°C for 4 h, which gave the highest yield of linarin, polyphenols, and flavonoids. This extract appeared to have the greatest ABTS and DPPH radical scavenging activities (87.81% and 51.42% at 500 μg/mL, respectively) and α-glucosidase (74.59%) and pancreatic lipase inhibitory activities (90.44%). As contents of linarin increased, antioxidative activity, inhibitory effects of carbohydrates and lipid absorption of CZ extracts increased as well. From these results, CZ extracts can be used in functional food industries.

cope Yuja (Citrus junos Tanaka) possesses various health benefits, but its effects on bone health are unknown. In this study, the preventative effects of yuja peel ethanol extract (YPEE) on osteopenia were determined in ovariectomized (OVX) rats, and the mechanisms by which YPEE and its flavanones regulate osteoblastogenesis were examined in vitro. Methods and results The effects of YPEE on osteoblastogenesis were investigated in MC3T3-E1 cells. YPEE promoted alkaline phosphatase (ALP) activity, mineralization, and the expression of osteoblast differentiation marker genes, such as ALP, runt-related transcription factor 2 (Runx2), and osteocalcin. YPEE and its flavanones promoted osteoblast differentiation via BMP-2-mediated p38 and the Smad1/5/8 signaling pathway. YPEE supplementation significantly decreased body weight and increased uterine weight and bone mineral density in OVX rats. Based on a micro-CT analysis of femurs, YPEE significantly attenuated osteopenia and increased trabecular volume fraction, trabecular separation, and trabecular number (p < 0.05). Conclusion Dietary YPEE has a protective effect on OVX-induced osteopenia. YPEE and its flavanones promote osteoblastogenesis via the activation of the BMP/p38/Smad/Runx2 pathways. These results extend our knowledge of the beneficial effects of YPEE and provide a basis for the development of novel therapies for osteoporosis.

Chrysanthemum zawadskii (CZ) is a perennial herb belonging to the Asteraceae family. CZ is used medicinally to treat inflammatory and uterine diseases in Asia. CZ was extracted with 50% ethanol and CZ extract (CZE; at 125, 250, and 500 mg/kg body weight) was administered orally every day for 5 or 6 weeks to investigate the anti-diabetic effects in streptozotocin (STZ)-induced rats and STZ + high-fat diet (HFD)-fed mice. CZE significantly decreased fasting blood glucose levels in STZ- and STZ + HFD-induced diabetic models. In addition, glucose tolerance and insulin tolerance were improved in the STZ + HFD + CZE group by increasing insulin levels and decreasing hemoglobin A1c (HbA1c) levels in serum. Furthermore, CZE supplements decreased components of the serum lipid profile such as triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels. These results suggest that CZE may be a potential candidate for controlling hyperglycemia.

Tyrosol is considered a potential antioxidant; however, little is known regarding the pharmacokinetics of its metabolites. To study the pharmacokinetics of tyrosol-derived metabolites after oral administration of a single dose of tyrosol, we attempted to identify tyrosol metabolites in rat plasma by using ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Two tyrosol metabolites (M1 and M2) were detected in the plasma. M1 was identified as tyrosol-4-sulfate (T4S) with an [M - H](-) ion at m/z 217. While M2 showed an [M - H](-) ion at m/z 151.0, its metabolite was not identified. Pharmacokinetic analysis of T4S and M2 showed rapid uptake after oral administration of tyrosol within 1 h. The metabolites were rapidly distributed in most organs and tissues and eliminated within 4 h. The greatest T4S deposition by tissue weight was observed in the liver, followed by the kidney and spleen, while M2 was most concentrated in the kidney followed by the liver and spleen. These findings indicate that T4S and M2 were distributed mainly in tissues with an abundant blood supply and were rapidly excreted in urine.

Allergic contact dermatitis (ACD) remains a leading skin disease in many countries. In this study, we investigated the preventive effect of Piper nigrum fruit extract (PFE) on trimellitic anhydride (TMA)-induced dermatitis and its potential mechanism of action. Oral administration of PFE and prednisolone (PS) significantly suppressed TMA-induced increases in ear, epidermal thickness, and infiltration of CD4+ cells, while abnormal expression of IgE, mMCP-1, IL-1B and IL-1B mRNA was also significantly counteracted by oral administration of PFE. PFE also significantly suppresses TMA-induced IL-4 and IL-5 production and IL-4 mRNA expression in vivo, as well as OVA-induced IL-4, IL-5, and IL-13 production and GATA3 mRNA expression ex vivo, and IL-4 induced STAT6 phosphorylation in primary cultured splenocytes and HaCaT cells. Interestingly, the PFE component piperine significantly suppressed OVA-induced IL-4, IL-5, and IL-13 secretion ex vivo. Taken together, these results suggest that PFE could be useful in suppressing allergic contact dermatitis.

The seeding sources and concentration of ammonia on anaerobic digestion were investigated by batch culture bioreactors. The sources of seeding on anaerobic digestion were from swine wastewater collection pit of a hog raising farm and from anaerobic digestion sludge of a municipal sewage treatment plant. The inhibition of ammonia on anaerobic microorganisms was initiated at ammonia concentration of and it`s effect was increased by increased by increasing ammonia concentration up to regardless the sources of seeding as evidenced by decreases in COD removal efficiencies and biogas yields. The inhibition occurred to not only methanogens but also acidogens since the concentration of volatile fatty acids was maintained at 50 mg/L The COD removal efficiency and biogas yield were Maintained constantly while increasing ammonia concentration up to when swine wastewater collection pit was used as a seeding; however, those were decreased while increasing ammonia concentration when anaerobic digestion sludge was used as a seeding. The results indicate that the seeding acclimated to high concentrations of ammonia for long time was easy in adaptation to high ammonia concentration and less subjective to ammonia inhibitory effects.