Background: Hepatic steatosis, which involves the excessive accumulation of lipid droplets in hepatocytes, presents a significant global health concern due to its association with obesity and metabolic disorders. Inflammation plays a crucial role in the progression of hepatic steatosis; however, the precise molecular mechanisms responsible for this process remain unknown. Methods: This study investigated the involvement of the nucleotide-binding oligomerization domain-like receptor pyrin domain-containing-3 (NLRP3) inflammasome and the forkhead box O6 (FoxO6) transcription factor in the pathogenesis of hepatic steatosis. We monitored the NLRP3 inflammasome and lipogenesis in mice overexpressing the constitutively active (CA)-FoxO6 allele and FoxO6-null mice. In an in vitro study, we administered palmitate to liver cells overexpressing CA-FoxO6 and measured changes in lipid metabolism. Results: We administered palmitate treatment to clarify the mechanisms through which FoxO6 activates cytokine interleukin (IL)-1β through the NLRP3 inflammasome. The initial experiments revealed that dephosphorylation led to palmitate-induced FoxO6 transcriptional activity. Further palmitate experiments showed increased expression of IL-1β and the hepatic NLRP3 inflammasome complex, including adaptor protein apoptotic speck protein containing a caspase recruitment domain (ASC) and pro-caspase-1. Furthermore, thioredoxin-interacting protein (TXNIP), a key regulator of cellular redox conditions upstream of the NLRP3 inflammasome, was induced by FoxO6 in the liver and HepG2 cells. Conclusion The findings of this study shed light on the molecular mechanisms underpinning the FoxO6-NLRP3 inflammasome axis in promoting inflammation and lipid accumulation in the liver.

The aim of this study was to investigate the relaxant effect of ethanol extract, fractions from Epimedium koreanum (E. koreanum) on penile corpus cavernosum smooth muscle (PCCSM) in a rabbit. The contractility on PCCSM was also evaluated with icariin, active major compound, from E. koreanum quantified using HPLC analysis. The pre-contracted PCCSM with 10 μM phenylephrine (Phe) was accumulatively treated with extract and fractions (n-hexane, ethyl acetate and n-butanol) from E. koreanum at concentrations of 1, 2, 3 and 4 mg/mL. Icariin was performed with final concentrations of 0.1, 1, 10 and 100 μM. The interaction of icariin with phosphodiesterase-5 (PDE-5) inhibitor, udenafil, was also examined on PCCSM contractility. Extract and three fractions had the relaxant effect on PCCSM in a dose-dependent manner and the maximum relaxation was obtained in ethyl acetate fraction. Icariin dose-dependently relaxed the PCCSM and efficiently enhanced the udenafil-induced relaxation at least two-fold. These results indicate the possibility that icariin fromE. koreanum may be a candidate for a new or alternative medicine in erectile dysfunction patients who do not completely respond to PDE-5 inhibitors.

Background: Unlike conventional T cells, innate and virtual-memory CD8 T cells in naïve mice acquire their memory phenotypes and functions in the absence of antigenic encounters in a cytokine-dependent manner. The relevant cytokines include interleukin-4 (IL-4), type I interferon, and interleukin-15 (IL-15). Moreover, exogenous IL-4 can also induce de novo generation and/or expansion of the virtual-memory CD8 T cell population. In this study, we investigated whether exogenous IL-4 could enhance the immune response to a viral infection. Results: In vivo administration of IL-4 and an anti-IL-4 antibody complex (IL-4C) increased CXCR3 expression in both memory and naïve phenotype CD8 T cells in the absence of antigenic stimulation, and protected mice from lethal influenza infection. Flow cytometric analysis of lung-infiltrating immune cells on day 5 after virus infection revealed higher numbers of antigen-specific and bystander CD8 T cells in IL-4C-treated mice than in control mice. In particular, the bystander CD8 T cells were a naïve or evident memory phenotypes. Crucially, an anti-CXCR3 blocking antibody abrogated this IL-4C effect, reflecting that the increased accumulation of CD8 T cells in the lungs after IL-4C treatment is dependent on CXCR3. Conclusions These data demonstrate that exogenous IL-4C plays a protective role by enhancing CXCR3-dependent migration of CD8 T cells into influenza-infected lungs.

Background: Influenza A viruses (IAVs) have long posed a threat to humans, occasionally causing significant morbidity and mortality. The initial immune response is triggered by infected epithelial cells, alveolar macrophages and dendritic cells. However, an exaggerated innate immune response can result in severe lung injury and even host mortality. One notable pathology observed in hosts succumbing to severe influenza is the excessive influx of neutrophils and monocytes into the lung. In this study, we investigated a strategy for controlling lung immunopathology following severe influenza infection. Results: To evaluate the impact of innate immunity on influenza-associated lung injury, we employed CB17.SCID and NOD.SCID mice. NOD.SCID mice exhibited slower weight loss and longer survival than CB17.SCID mice following influenza infection. Lung inflammation was reduced in NOD.SCID mice compared to CB17.SCID mice. Bulk RNA sequencing analysis of lung tissue showed significant downregulation of 827 genes, and differentially expressed gene analysis indicated that the cytokine-cytokine receptor interaction pathway was predominantly downregulated in NOD.SCID mice. Interestingly, the expression of the Cxcl14 gene was higher in the lungs of influenza-infected NOD.SCID mice than in CB17.SCID mice. Therefore, we induced overexpression of the Cxcl14 gene in the lung using the adeno-associated virus 9 (AAV9)-vector system for target gene delivery. However, when we administered the AAV9 vector carrying the Cxcl14 gene or a control AAV9 vector to BALB/c mice from both groups, the morbidity and mortality rates remained similar. Both groups exhibited lower morbidity and mortality than the naive group that did not receive the AAV9 vector prior to IAV infection, suggesting that the pre-administration of the AAV9 vector conferred protection against lethal influenza infection, irrespective of Cxcl14 overexpression. Furthermore, we found that pre-inoculation of BALB/c mice with AAV9 attenuated the infiltration of trans-macrophages, neutrophils and monocytes in the lungs following IAV infection. Although there was no difference in lung viral titers between the naive group and the AAV9 pre-inoculated group, pre-inoculation with AAV9 conferred lung injury protection against lethal influenza infection in mice. Conclusions Our study demonstrated that pre-inoculation with AAV9 prior to IAV infection protected mouse lungs from immunopathology by reducing the recruitment of inflammatory cells.

BACKGROUND/OBJECTIVES: Male hypogonadism is a condition where the body does not produce enough testosterone and significantly impacts health. Age, obesity, genetics, and oxidative stress are some physiological factors that may contribute to testosterone deficiency.Previous studies have shown many pharmacological benefits of Schisandra chinensis (S. chinensis) Baillon as an anti-inflammatory and antioxidant. However, the molecular mechanism of attenuating hypogonadism is yet to be well established. This research was undertaken to study the effects of S. chinensis extract (SCE) on testosterone deficiency.MATERIALS/METHODS: S. chinensis fruit was pulverized and extracted using 60% aqueous ethanol. HPLC analysis was performed to analyze and quantify the lignans of the SCE. RESULTS: The 2,2-diphenyl-2-picrylhydrazyl and 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) scavenging assays confirmed that the SCE and its major lignans (schisandrol A and gomisin N) inhibit oxidative stress. Effects of SCE analysis on the testosterone level under oxidative stress conditions revealed that both schisandrol A and gomisin N were able to recover the lowered testosterone levels. Through mRNA expression of TM3 Leydig cell, we observed that the SCE lignans were able to induce the enzymes involved in testosterone biosynthesis-related genes such as 3β-HSD4 (P < 0.01 for SCE, and P < 0.001 for schisandrol A and gomisin N), 17β-HSD3 (P < 0.001 for SCE, schisandrol A and gomisin N), and 17, 20-desmolase (P < 0.01 for schisandrol A, and P < 0.001 for SCE and gomisin N). CONCLUSIONS These results support that SCE and its active components could be potential therapeutic agents for regulating and increasing testosterone production.

Background: As an anesthesia induced during cesarean section, spinal anesthesia is preferred over general and epidural anesthesia. This study aimed to review the trend of anesthetic methods for cesarean section based on data obtained from the Korean Health Insurance Review and Assessment Service from 2013 to 2018. Methods: The anesthetic methods were analyzed in 753,285 parturients who underwent a cesarean section in Korea from 2013 to 2018. We determined the association between each anesthetic method and hospital type and maternal and fetal factors. We also evaluated whether the anesthetic method was associated with the parturients’ length of hospital stay. Results: General anesthesia, spinal anesthesia, and epidural anesthesia were induced in 28.8%, 47.7%, and 23.6% of parturients from 2013 to 2018, respectively. Trend analyses showed that spinal anesthesia increased from 40.0% in 2013 to 53.7% in 2018. The opposite trend applied to general anesthesia, decreasing from 37.1% in 2013 to 22.2% in 2018. The factors that were significantly associated with the anesthetic method were parturient’s parity, emergency condition, gestational age, and fetal weight. The type of hospital, parturient’s age, and multiple birth were also associated with the anesthetic methods. There was a strong association between general anesthesia and hospital stay longer than 7 days. Conclusions Spinal anesthesia is currently the main anesthetic method used for cesarean delivery, and the rate of spinal anesthesia is gradually increasing in Korea.

Marine sponges of the genus are well known as rich sources of diverse and complex biologically relevant natural products, including alkaloids, terpenoids, peptides, lipids, and steroids. Some of these metabolites, with novel structures and promising biological activities, have attracted a lot of attention from chemists seeking to perform their total synthesis in parallel to intensive biological studies towards new drug leads. In this review, we summarized the distribution of the chemically investigated sponges, the isolation, synthesis and biological activities of their secondary metabolites, covering the literature from 1982 to early 2018.

Epidemic keratoconjunctivitis (EKC) and acute hemorrhagic conjunctivitis (AHC) are common diseases caused by human adenoviruses (HAdV) and enteroviruses, respectively, in South Korea. However, there are limited studies on the molecular epidemiology of viral conjunctivitis in South Korea. The main objective of this study was to characterize the genotypes of adenoviruses and enteroviruses causing viral conjunctivitis in the southwest region of South Korea. We collected conjunctival swabs from 492 patients with suspected cases of viral conjunctivitis from 6 ophthalmic hospitals in Gwangju Metropolitan City, in South Korea, between 2012 and 2016. Of the 492 samples tested, HAdVs and enteroviruses were detected in 249 samples (50.6%) and 19 samples (3.9%), respectively. The genotype analysis detected HAdV-8 in 183 samples (73.5%), HAdV-37 in 14 samples (5.6%), and HAdV-3, and HAdV-4 in 9 samples (3.6%) each. We detected coxsackievirus A24 (CVA24) and coxsackievirus B1 (CVB1) in 8 samples (42.0%) and 4 samples (21.0%), respectively. We also reported for the first time HAdV-56-infected cases of EKC in South Korea. Furthermore, we found three cases of coinfection with HAdV and enterovirus genotypes in our samples. HAdV-8 and CVA24, the main causes of EKC and AHC, respectively, worldwide, were also found to be the predominant genotypes in our study.
Adenoviridae ; Adenoviruses, Human ; Coinfection ; Conjunctivitis, Acute Hemorrhagic ; Conjunctivitis, Viral* ; Enterovirus ; Genotype ; Gwangju ; Humans ; Keratoconjunctivitis ; Korea* ; Molecular Epidemiology*

BACKGROUND AND PURPOSE: Evaluating instrumental activities of daily living (IADL) is an important part of procedure to diagnose dementia. The Korean-Instrumental Activities of Daily Living (K-IADL) has been used extensively in Korea. However, its cut-off score has not been reformulated since 2002. The purpose of this study was to yield a new optimal cut-off score for the K-IADL and confirm the validity of this new cut-off score with various dementia groups. METHODS: We retrospectively collected a total of 2,347 patients' K-IADL data from 6 general hospitals in Korea. These patients had mild cognitive impairment (MCI) or dementia with various etiologies for cognitive impairment. We also recruited a normal control group (n=254) from the community. Korean-Mini Mental State Examination, Short version of the Geriatric Depression Scale, Clinical Dementia Rating, and Global Deterioration Scale were administered to all participants. Caregivers completed K-IADL and Barthel Index. RESULTS: K-IADL scores were significantly different among dementia subgroups, but not significantly different among MCI subgroups. Based on internal consistency, correlations with other scales, and factor analysis, K-IADL showed excellent reliability and validity. The new optimal cut-off score to diagnose dementia was 0.40, which gave a sensitivity of 0.901 and a specificity of 0.916. Positive predictive value for dementia using the new cut-off score was 94.2% for Alzheimer's disease, 100% for vascular dementia, and 84% for Parkinson's disease. CONCLUSIONS: Our results illustrate that the new K-IADL cut-off score of 0.40 is reliable and valid for screening impairments of daily functioning resulting from various etiologies.
Activities of Daily Living* ; Alzheimer Disease ; Caregivers ; Cognition Disorders ; Dementia ; Dementia, Vascular ; Depression ; Hospitals, General ; Humans ; Korea ; Mass Screening ; Mild Cognitive Impairment ; Parkinson Disease ; Reproducibility of Results ; Retrospective Studies ; Sensitivity and Specificity ; Weights and Measures

BACKGROUND: Recent studies have shown an association between thyroid hormone levels and metabolic syndrome (MetS) among euthyroid individuals; however, there have been some inconsistencies between studies. Here, we evaluated the relationship between thyroid hormone levels and MetS in euthyroid middle-aged subjects in a large cohort. METHODS: A retrospective analysis of 13,496 euthyroid middle-aged subjects who participated in comprehensive health examinations was performed. Subjects were grouped according to thyroid stimulating hormone, total triiodothyronine (T3), total thyroxine (T4), and T3-to-T4 ratio quartile categories. We estimated the odds ratios (ORs) for MetS according to thyroid hormone quartiles using logistic regression models, adjusted for potential confounders. RESULTS: Of the study patients, 12% (n=1,664) had MetS. A higher T3 level and T3-to-T4 ratio were associated with unfavourable metabolic profiles, such as higher body mass index, systolic and diastolic blood pressure, triglycerides, fasting glucose and glycated hemoglobin, and lower high density lipoprotein cholesterol levels. The proportion of participants with MetS increased across the T3 quartile categories (P for trend <0.001) and the T3-to-T4 ratio quartile categories (P for trend <0.001). The multi-variate-adjusted OR (95% confidence interval) for MetS in the highest T3 quartile group was 1.249 (1.020 to 1.529) compared to the lowest T3 quartile group, and that in the highest T3-to-T4 ratio quartile group was 1.458 (1.141 to 1.863) compared to the lowest T3-to-T4 ratio quartile group, even after adjustment for potential confounders. CONCLUSION: Serum T3 levels and T3-to-T4 ratio are independently associated with MetS in euthyroid middle-aged subjects. Longitudinal studies are needed to define this association and its potential health implications.
Blood Pressure ; Body Mass Index ; Cholesterol, HDL ; Cohort Studies ; Fasting ; Glucose ; Hemoglobin A, Glycosylated ; Humans ; Logistic Models ; Longitudinal Studies ; Metabolome ; Odds Ratio ; Retrospective Studies ; Thyroid Gland ; Thyroid Hormones ; Thyrotropin ; Thyroxine ; Triglycerides ; Triiodothyronine*