Three indole derivatives (1–3) and a diketopiperazine (4) were isolated from the ethyl acetate extract of Chromobacterium violaceum. Their structures were elucidated based on the analysis of NMR and HR-MS data and by comparing those in the previous literature. The antibacterial activities of the isolated compounds were evaluated against Gram-positive bacteria, including human pathogenic methicillin-resistant Staphylococcus aureus (MRSA), Lacticaseibacillus paracasei subsp. paracasei, and Brevibacterium epidermidis. Compound 1 exhibited moderate antibacterial activity against all the three strains with MIC values ranging from 8.58 to 34.3 μg/mL.

Background: There are inconsistent reports regarding the association between general anesthesia and adverse neurodevelopmental and behavioral disorders in children. Methods: This nationwide administrative cohort study included children born in Korea between 2008 and 2009, and followed until December 31, 2017. The cohort included 93,717 participants who received general anesthesia with endotracheal intubation (ETI) who were matched to unexposed subjects in a 1:1 ratio. General anesthesia was defined by National Health Insurance Service treatment codes with intratracheal anesthesia, and the index date was the first event of general anesthesia. The primary outcome was attention deficit hyperactive disorder (ADHD), which was defined as at least a principal diagnosis of 10th revision of the International Classification of Diseases code F90.X after the age of 72 months.Neurodevelopment, which was assessed using a developmental screening test (Korean-Ages and Stages Questionnaire [K-ASQ]), was a secondary outcome. The K-ASQ is performed annually from 1 to 6 years of age and consists of 5 domains. The association between general anesthesia and ADHD was estimated using a Cox hazard model, and its association with neurodevelopment was estimated using a generalized estimation equation, with control for multiple risk factors beyond 1 year after the index date. Results: The median age at the index date was 3.8 (95% confidence interval [CI], 1.7–5.8) years, and there were 57,625 (61.5%) men. During a mean follow-up period of 5 years, the incidence rate of ADHD was 42.6 and 27.7 per 10,000 person-years (PY) in the exposed and unexposed groups, respectively (absolute rate difference 14.9 [95% CI, 12.5–17.3] per 10,000 PY). Compared to the unexposed group, the exposed group had an increased risk of ADHD (adjusted hazard ratio, 1.41 [95% CI, 1.30–1.52]). In addition, a longer duration of anesthesia with ETI and more general anesthesia procedures with ETI were associated with greater risk of ADHD. General anesthesia with ETI was also associated with poorer results in the K-ASQ. Conclusion Administration of general anesthesia with ETI to children is associated with an increased risk of ADHD and poor results in a neurodevelopmental screening test.

CCCTC-binding factor (CTCF) is a transcriptional regulator that binds to a complex DNA motif in various orientations and plays a crucial role in regulating gene expression, chromatin restructuring, and developmental processes. Mutations in the CTCF are associated with neurodevelopmental disorders. Here we report the first Korean case with a de novo heterozygous variant in the CTCF (c.1025G>A; p.Arg342His). She showed global developmental delay, failure to thrive, and dysmorphic face, which are phenotypes consistent with previous reports in the autosomal dominant intellectual developmental disorder 21 (MIM 615502). She also showed clinical features not previously reported, such as antral web and tracheobronchomalacia.Our case follows suit and expands understanding of this rare disorder by reporting common features and, on the other hand, unreported concomitant congenital anomalies.

Objective: Bone morphogenetic protein receptor type 2 (BMPR2) has been associated with radiographic changes in ankylosing spondylitis (AS), but further characterization of the cellular signaling pathway in osteoprogenitor (OP) is not clearly understood.The aim of this study was to investigate the expression of BMPR2 and bone morphogenetic protein 2 (BMP2)-mediated responsibility in AS. Methods: We collected 10 healthy control (HC) and 14 AS-OPs derived from facet joints. Subsequently, we then conducted RNA sequencing with two samples per group and selected BMP-related genes. Facet joint tissues and derived primary OPs were evaluated by validation of selected RNA sequencing data, immunohistochemistry, and comparison of osteogenic differentiation potential. Results: Based on RNA-sequencing analysis, we found that BMPR2 expression is higher in AS-OPs compared to in HC-OPs. We also validated the increased BMPR2 expression in facet joint tissues with AS and its derived OPs in messenger RNA and protein levels. Additionally, primary AS-OPs showed much greater response to osteogenic differentiation induced by BMP2 and a higher capacity for smad1/5/8-induced RUNX2 expression compared to HCs. Conclusion The expression of BMPR2 was found to be significantly increased in facet joint tissues of patients with AS. These findings suggest that BMPR2 may play a role in the BMP2-mediated progression of AS.

Background/Aims: Little is known about the association between infantile colic and the later onset of irritable bowel syndrome (IBS). Methods: This study examined all 917 707 children who were born in Korea between 2007 and 2008. Infantile colic was defined with 1 or more diagnoses of ICD-10 code R10.4 or R68.1 at the age of 5 weeks to 4 months, and infants with a diagnosis of infantile colic and without were allocated into the infantile colic group and the control group. IBS was defined as 2 or more diagnoses of ICD-10 code K58.X after 4 years of age. Each child was traced until 2017. The risk of IBS with infantile colic was evaluated using a Cox proportional hazards model with propensity score inverse probability of treatment weighting (IPTW). Results: After IPTW, 363 528 and 359 842 children were allocated to the control group and the infantile colic group, respectively. The infantile colic group had a higher risk of developing IBS in childhood (hazard ratio [95% CI], 1.12 [1.10 to 1.13]) than the control group.Moreover, the subgroup analyses according to the feeding status, birth weight, sex, or economic status, showed that the risk of IBS with former infantile colic remained statistically significant. Conclusions Children with a diagnosis of infantile colic during the infant period had a significant risk of developing IBS after 4 years of age.Understanding the pathogenesis of infantile colic in the neonatal period may reduce the prevalence and severity of functional gastrointestinal disorders from childhood to adolescence to adulthood.

Background: This study examined the relationship of infant feeding with anthropometric indices of children during their first six years of life relative to the Korean National Growth Charts (KNGC) and the World Health Organization Child Growth Standards (WHO-CGS). Methods: The study population consisted of 547,669 Korean infants and children who were 6 months-old to 6 years-old (born in 2008–2009) and participated in the National Health Screening Program for Infants and Children. Data on height, weight, and type of feeding during the first 6 months (exclusively breastfed [BF] vs. mixed- or formula-fed [FF]) were analyzed. Results: BF boys and girls were significantly shorter and lighter than FF counterparts from the age of 6 months to 4 years, but these differences were not significant after the age of 4 years. BF boys and girls only had significantly lower body mass index at the age of 2 years. Under the age of 2 years 6 months, and especially under the age of 1 year, BF boys and girls were significantly taller and heavier than the 50th percentile values of the 50th percentile value of the WHO-CGS. Conclusion In this study using large-scaled national data, Korean breastfed children are shorter and lighter by 3 years 6 months–4 years 6 months, but afterward, there is no significant difference from those who had mixed- or formula-feeding. Substantial disparities in the anthropometric indices of Korean infants under the age of 1 compared to KNCG and WHO-CGS were found, regardless of their infantile feeding types. Our results emphasize the importance of constructing a nationwide reference chart based on actual measurements of BF Korean infants.

METHODS: The efficiency of electroporation-based delivery of AsCpf1/mRNA and AsCpf1/RNP to target exon 3 of leukemia inhibitory factor (Lif) into mouse zygotes was evaluated. Embryos that developed to the two-cell stage after zygote electroporation were transferred into the oviducts of surrogate mothers to produce AsCpf1-mediated LIF KO mice. The genome editing efficiency of blastocysts and pups was tested using the T7E1 assay and/or DNA sequencing. Congenital abnormalities and reproductive phenotypes in LIF KO mice produced by electroporation with AsCpf1/RNP were examined. RESULTS: Survival and two-cell development of electroporated zygotes were comparable between the AsCpf1/mRNA and AsCpf1/RNP groups, whereas genome editing efficiency was relatively higher in the AsCpf1/RNP group (13.3% vs 18.1% at blastocyst and 33.3% vs 45.5% at offspring), respectively. Two mouse lines with a frameshift mutation in exon 3 of the Lif gene were established from the AsCpf1/RNP group. All congenital abnormalities of LIF KO mice produced by AsCpf1/RNP electroporation were observed. AsCpf1-mediated LIF KO mice showed postnatal growth retardation and implantation failure, both of which are major phenotypes of LIF KO mice generated by conventional gene targeting. CONCLUSION Electroporation of AsCpf1/RNP at the zygote stage is an efficient genome editing method to produce KO mice.

METHODS: The efficiency of electroporation-based delivery of AsCpf1/mRNA and AsCpf1/RNP to target exon 3 of leukemia inhibitory factor (Lif) into mouse zygotes was evaluated. Embryos that developed to the two-cell stage after zygote electroporation were transferred into the oviducts of surrogate mothers to produce AsCpf1-mediated LIF KO mice. The genome editing efficiency of blastocysts and pups was tested using the T7E1 assay and/or DNA sequencing. Congenital abnormalities and reproductive phenotypes in LIF KO mice produced by electroporation with AsCpf1/RNP were examined. RESULTS: Survival and two-cell development of electroporated zygotes were comparable between the AsCpf1/mRNA and AsCpf1/RNP groups, whereas genome editing efficiency was relatively higher in the AsCpf1/RNP group (13.3% vs 18.1% at blastocyst and 33.3% vs 45.5% at offspring), respectively. Two mouse lines with a frameshift mutation in exon 3 of the Lif gene were established from the AsCpf1/RNP group. All congenital abnormalities of LIF KO mice produced by AsCpf1/RNP electroporation were observed. AsCpf1-mediated LIF KO mice showed postnatal growth retardation and implantation failure, both of which are major phenotypes of LIF KO mice generated by conventional gene targeting. CONCLUSION Electroporation of AsCpf1/RNP at the zygote stage is an efficient genome editing method to produce KO mice.

Silent information regulator 2 (Sirtuin2 / SIRT2) is a NAD⁺-dependent deacetylase that regulates the cellular oxidative stress response. It modulates transcriptional silencing and protein stability through deacetylation of target proteins including histones. Previous studies have shown that SIRT2 plays a role in mood disorders and hippocampus-dependent cognitive function, but the underlying neurobiological mechanism is poorly understood. Here, we report that chronic stress suppresses SIRT2 expression in the hippocampus. Molecular and biochemical analyses indicate that the stress-induced decrease in the SIRT2 expression downregulates synaptic plasticity-related genes in the hippocampus through the increase of euchromatic histone-lysine N-methyltransferase 2 (Ehmt2) (also known as G9a). shRNA-mediated knockdown of SIRT2 in the dentate gyrus alters the expression of synaptic plasticity-related genes in a way similar to those induced by chronic stress, and produces depression-like behaviors. Our results indicate that SIRT2 plays an important role in the response to stress, thereby modulating depression-like behaviors.
Cognition ; Dentate Gyrus ; Depression ; Down-Regulation ; Hippocampus ; Histone-Lysine N-Methyltransferase ; Histones ; Mood Disorders ; Neuronal Plasticity ; Oxidative Stress ; Protein Stability ; Up-Regulation

Bioactivity-guided fractionation of MeOH extract of the dried fruits of Amomum tsao-ko led to isolation of nine compounds (1 – 9). Their structures were elucidated by spectroscopic methods including extensive 1D and 2D-NMR, as alpinetin (1), naringenin-5-O-methyl ether (2), naringenin (3), hesperetin (4), 2′,4′,6′-trihydroxy-4-methoxy chalcone (5), tsaokoin (6), boesenbergin B (7), 4-hydroxyboesenbergin B (8), and tsaokoarylone (9). Of these, compound 8 was isolated from a natural source for the first time, which was previously reported as a synthetic product. The isolated compounds (1 – 9) were tested for their inhibitory effects on LPS-induced nitric oxide production in RAW 264.7 macrophages. Among them, three chalcone derivatives (compounds 5, 7, and 8) and a diarylheptanoid (compound 9) exhibited significant inhibitory activity on the NO production with IC₅₀ values ranging from 10.9 to 22.5 µM.
Amomum ; Chalcone ; Ether ; Fruit ; Macrophages ; Nitric Oxide ; Zingiberaceae