Linear IgA Bullous Dermatosis in Korea Using the Nationwide Health Insurance Database.

(1) Background: Linear immunoglobulin A bullous dermatosis (LABD) is a rare autoimmune, subepidermal blistering disease, characterized by linear IgA deposits along the epidermal basement membrane. LABD is idiopathic and is associated with medication and systemic autoimmune diseases. (2) Methods: We investigated the demographic characteristics, disease course, causative agents, and associated diseases in Korean patients with LABD. The Korean Health Insurance Review and Assessment Service database was used to obtain data. We identified 670 LABD cases between 2010 and 2022. (3) Results: The annual incidence of LABD was 1.3 per 100,000 persons, with a higher prevalence in individuals ≥60 years old. The patients were treated with dapsone for 30.7 ± 56.7 days, had 1.3 ± 0.7 hospital visits, and were hospitalized for 19.8 ± 19.7 days. Risk factors, including malignancy, commonly preceded LABD. Antibiotic use, specifically vancomycin and third-generation cephalosporins, was a risk factor. The mean age of LABD diagnosis was 55.9 ± 21.7 years. (4) Conclusion: This is the first published study to assess a nationwide cohort for LABD. The incidence of LABD was higher than that in other studies. Most case reports have linked LABD with the administration of specific antibiotics; however, this study shows there were more associations with other conditions.

Enhancement of Growth and Secondary Metabolites by the Combined Treatment of Trace Elements and Hydrogen Water in Wheat Sprouts.

This study aimed to evaluate the response of Triticum aestivum to hydrogen water (HW) and trace elements treated with HW. A pot experiment was conducted to assess the growth indices, secondary metabolites, and antioxidant levels. The response surface methodology (RSM) approach was used to ascertain the concentrations and significant interaction between treatments. The outcomes demonstrated that the combined treatment of Se acid and Mo oxide exhibited a notable positive effect on the growth and secondary metabolites, when treated with HW as compared to distilled water (DW). Notably, the interaction between these two treatments is significant, and the higher response was observed at the optimal concentration of 0.000005% for Se acid and 0.06% for Mo oxide. Additionally, an in vitro experiment revealed that the mixture treatment inhibits the accumulation of lipids in HepG2 hepatocytes cells. Moreover, metabolic analysis revealed that upregulated metabolites are linked to the inhibition of lipid accumulation. In addition, the analysis emphasizes that the continued benefits of higher plants as a renewable supply for chemicals compounds, especially therapeutic agents, are being expanded and amplified by these state-of-the-art technologies.

Brown Seaweed Consumption as a Promising Strategy for Blood Glucose Management: A Comprehensive Meta-Analysis.

Diabetes is a chronic condition that can lead to various complications; therefore, there is a need to emphasize prevention and management. Dietary interventions, such as the Mediterranean diet or calorie-restricted regimens, coupled with exercise-induced weight reduction, have been recommended for enhancing diabetes management. Seaweeds contain various functional components, such as polyphenols and fucoidan, which have been reported to exert multiple benefits, including blood glucose regulation, improved intestinal health, and enhanced of lipid profiles. The association between blood glucose and seaweed consumption has been established in previous research. We searched the PubMed, RISS, Google Scholar, ScienceDirect, and Cochrane Library databases to identify relevant studies after applying the selection/exclusion criteria, and 23 studies were ultimately included in this analysis. Comprehensive Meta-Analysis (CMA) software version 4.0 was used to assess statistical significance and heterogeneity. In this meta-analysis, postprandial blood glucose, glycated hemoglobin (HbA1c), and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) levels demonstrated significant improvements in the seaweed group compared to the control group. Conversely, fasting blood glucose and insulin levels did not show significant associations with seaweed consumption. Subgroup analysis revealed that a high dose (1000 mg or more) was more beneficial than a low dose, and seaweeds such as Laminaria digitata, Undaria pinnatifida, Acophyllum nodosum, and Fucus vesiculosus were found to be more effective at improving blood glucose levels than control treatments. Therefore, based on our research, seaweed supplementation appears to be a promising strategy for reducing postprandial blood glucose, HbA1c, and HOMA-IR levels, thereby enabling better blood glucose management and leading to a decreased risk of type 2 diabetes.

Cinnamon (Cinnamomum cassia) hot water extract improves inflammation and tight junctions in the intestine in vitro and in vivo.

The natural byproduct Cinnamomum cassia was widely used in ancient Asia to cure disease because of its various pharmacological effects. Despite its ethnomedicinal benefits, few studies on the intestinal anti-inflammatory effect of C. cassia have been reported. Therefore, this study aimed to evaluate the potential beneficial effects of C. cassia on the intestine in vitro and in vivo. Herein, the effects of cinnamon hot water extract (CWE) on tight junction (TJ) barrier function, transepithelial electrical resistance, and mRNA expression were confirmed in Caco-2 cells. The CWE treatment groups showed significantly enhanced cell permeability, proinflammatory cytokine mRNA expression, and TJ expression. CWE-treated mice showed an improved histological index and decreased cytokine concentrations compared with those of colitis model mice. These results suggest that CWE alleviated inflammatory damage and improved the TJ barrier, indicating that CWE may be used as a functional food to improve intestinal health. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01292-3.

Operational Definitions of Colorectal Cancer in the Korean National Health Insurance Database.

OBJECTIVES: We reviewed the operational definitions of colorectal cancer (CRC) from studies using the Korean National Health Insurance Service (NHIS) and compared CRC incidence derived from the commonly used operational definitions in the literature with the statistics reported by the Korea Central Cancer Registry (KCCR). METHODS: We searched the MEDLINE and KoreaMed databases to identify studies containing operational definitions of CRC, published until January 15, 2021. All pertinent data concerning the study period, the utilized database, and the outcome variable were extracted. Within the NHIS-National Sample Cohort, age-standardized incidence rates (ASRs) of CRC were calculated for each operational definition found in the literature between 2005 and 2019. These rates were then compared with ASRs from the KCCR. RESULTS: From the 62 eligible studies, 9 operational definitions for CRC were identified. The most commonly used operational definition was "C18-C20" (n=20), followed by "C18-C20 with claim code for treatment" (n=3) and "C18-C20 with V193 (code for registered cancer patients' payment deduction)" (n=3). The ASRs reported using these operational definitions were lower than the ASRs from KCCR, except for "C18-C20 used as the main diagnosis." The smallest difference in ASRs was observed for "C18-C20," followed by "C18- C20 with V193," and "C18-C20 with claim code for hospitalization or code for treatment." CONCLUSIONS: In defining CRC patients utilizing the NHIS database, the ASR derived through the operational definition of "C18-C20 as the main diagnosis" was comparable to the ASR from the KCCR. Depending on the study hypothesis, operational definitions using treatment codes may be utilized.

Operational Definition of Liver Cancer in Studies Using Data from the National Health Insurance Service: A Systematic Review.

Data from the Korean National Health Insurance Service (NHIS) have been widely used to provide real-world evidence. Due to the nature of claims data, researchers use operational definitions to define patients with specific diseases. This study aimed to conduct a systematic review of the operational definitions of liver cancer used in studies based on the NHIS database and to suggest the most appropriate operational definition. Literature search was completed on January 6, 2021, using PubMed and KoreaMed. We applied the most frequently used operational definitions of liver cancer to the NHIS-National Sample Cohort and calculated age-standardized incidence rates (ASRs) of liver cancer by year. The ASRs using each operational definition were compared with the ASR from the Korea Central Cancer (KCCR) data. Among 236 articles, 90 were selected for review, covering histologically various kinds of liver cancer and varied by study subjects. Most studies (n = 79) did not mention whether the codes for the operational definition were from only the main diagnosis or from both the main and sub-diagnosis. The most frequently used operational definition was C22 (n = 39); however, the most similar operational definition was the ASR using "C22.0 or C22.9" for men and "C22.0" for women as the main diagnosis to the ASR from the KCCR. Based on the comparison with KCCR data, we suggest using "C22.0 or C22.9" for men and "C22.0" for women as the main diagnosis for the operational definition of liver cancer when using the NHIS data.

Highly Sensitive Two-Photon Lipid Droplet Tracker for In Vivo Screening of Drug Induced Liver Injury.

Lipid droplets (LDs) are lipid-abundant organelles found in most cell lines and primarily consist of neutral lipids. They serve as a repository of various lipids and are associated with many cellular metabolic processes, including energy storage, membrane synthesis, and protein homeostasis. LDs are prominent in a variety of diseases related to lipid regulation, including obesity, fatty liver disease, diabetes, and atherosclerosis. To monitor LD dynamics in live samples, we developed a highly selective two-photon fluorescent tracker for LDs (LD1). It exhibited outstanding sensitivity with a remarkable two-photon-action cross section (Φδmax > 600 GM), photostability, and low cytotoxicity. In human hepatocytes and in vivo mouse liver tissue imaging, LD1 showed very bright fluorescence with high LD selectivity and minimized background signal to evaluate the stages of nonalcoholic fatty liver disease. Interestingly, we demonstrated that the liver sinusoid morphology became narrower with increasing LD size and visualized the dynamics including fusion of the LDs in vivo. Moreover, real-time and dual-color TPM imaging with LD1 and a two-photon lysosome tracker could be a useful predictive screening tool in the drug development process to monitor impending drug-induced liver injury inducing drug candidates.

Complete mitochondrial genome of a Korean endemic freshwater mussel Nodularia breviconcha (Bivalvia: Unionidae).

Mitochondrial genome sequences were first determined and analyzed for a Korean endemic freshwater mussel Nodularia breviconcha (synonym Nodularia douglasiae sinuolatus; Unionidae, Unionida, Bivalvia). The complete mitochondrial genome was 15,741 bp in length, including 13 protein-coding genes (PCGs), 22 tRNA genes, and 2 rRNA genes. The overall GC content of mitochondrial genome for N. breviconcha was 34.3%. Phylogenetic analysis of 18 species within the family Unionidae suggested that Nodularia douglasiae is the most closely related to N. breviconcha. Our study will provide baseline, but important information for future research on ecological and genetic/genomic characteristics of this species.

Reparative System Arising from CCR2(+) Monocyte Conversion Attenuates Neuroinflammation Following Ischemic Stroke.

Monocytes recruitment from the blood to inflamed tissues following ischemic stroke is an important immune response to wound healing and tissue repair. Mouse monocytes can be endogenously divided into two distinct populations: pro-inflammatory or classical monocytes that express CCR2highCX3CR1low and circulate in blood, and anti-inflammatory or non-classical monocytes that express CCR2lowCX3CR1high and patrol locally. In this study of transgenic mice with functional CX3CR1GFP/+ or CX3CR1GFP/+-CCR2RFP/+, we found that CCR2highCX3CR1low monocytes recruited to the injured brain were cytokine-dependently converted into CCR2lowCX3CR1high macrophages, especially under the influence of IL-4 and IL-13, thereby attenuating the neuroinflammation following sterile ischemic stroke. The overall data suggest that (1) the regulation of monocyte-switching is one of the ultimate reparative strategies in ischemic stroke, and (2) the adaptation of monocytes in a locally inflamed milieu is vital to alleviating the effects of ischemic stroke through innate immunity.

Neutrophils Return to Bloodstream Through the Brain Blood Vessel After Crosstalk With Microglia During LPS-Induced Neuroinflammation.

The circulatory neutrophil and brain tissue-resident microglia are two important immune cells involved in neuroinflammation. Since neutrophils that infiltrate through the brain vascular vessel may affect the immune function of microglia in the brain, close investigation of the interaction between these cells is important in understanding neuroinflammatory phenomena and immunological aftermaths that follow. This study aimed to observe how morphology and function of both neutrophils and microglia are converted in the inflamed brain. To directly investigate cellular responses of neutrophils and microglia, LysMGFP/+ and CX3CR1GFP/+ mice were used for the observation of neutrophils and microglia, respectively. In addition, low-dose lipopolysaccharide (LPS) was utilized to induce acute inflammation in the central nervous system (CNS) of mice. Real-time observation on mice brain undergoing neuroinflammation via two-photon intravital microscopy revealed various changes in neutrophils and microglia; namely, neutrophil infiltration and movement within the brain tissue increased, while microglia displayed morphological changes suggesting an activated state. Furthermore, neutrophils seemed to not only actively interact with microglial processes but also exhibit reverse transendothelial migration (rTEM) back to the bloodstream. Thus, it may be postulated that, through crosstalk with neutrophils, macrophages are primed to initiate a neuroinflammatory immune response; also, during pathogenic events in the brain, neutrophils that engage in rTEM may deliver proinflammatory signals to peripheral organs outside the brain. Taken together, these results both show that neuroinflammation results in significant alterations in neutrophils and microglia and lay the pavement for further studies on the molecular mechanisms behind such changes.

In vivo monitoring of dynamic interaction between neutrophil and human umbilical cord blood-derived mesenchymal stem cell in mouse liver during sepsis.

BACKGROUND: Sepsis is a global inflammatory disease that causes death. It has been reported that mesenchymal stem cell (MSC) treatment can attenuate inflammatory and septic symptoms. In this study, we investigated how interactions between neutrophils and human umbilical cord blood (hUCB)-MSCs in the liver of septic mice are involved in mitigating sepsis that is mediated by MSCs. Accordingly, we aimed to determine whether hUCB-MSC application could be an appropriate treatment for sepsis. METHODS: To induce septic condition, lipopolysaccharide (LPS) was intraperitoneally (i.p.) injected into mice 24 h after the intravenous (i.v.) injection of saline or hUCB-MSCs. To determine the effect of hUCB-MSCs on the immune response during sepsis, histologic analysis, immunoassays, and two-photon intravital imaging were performed 6 h post-LPS injection. For the survival study, mice were monitored for 6 days after LPS injection. RESULTS: The injection (i.v.) of hUCB-MSCs alleviated the severity of LPS-induced sepsis by increasing IL-10 levels (p < 0.001) and decreasing mortality (p < 0.05) in septic mice. In addition, this significantly reduced the recruitment of neutrophils (p < 0.001) to the liver. In hUCB-MSC-treated condition, we also observed several distinct patterns of dynamic interactions between neutrophils and hUCB-MSCs in the inflamed mouse liver, as well as vigorous interactions between hepatic stellate cells (HSCs or ito cells) and hUCB-MSCs. Interestingly, hUCB-MSCs that originated from humans were not recognized as foreign in the mouse body and consequently did not cause graft rejection. CONCLUSIONS: These distinct interaction patterns between innate immune cells and hUCB-MSCs demonstrated that hUCB-MSCs have beneficial effects against LPS-induced sepsis through associations with neutrophils. In addition, the immunomodulatory properties of hUCB-MSCs might enable immune evasion in the host. Taken together, our results suggest the prospects of hUCB-MSCs as a therapeutic tool to inhibit inflammation and alleviate pathological immune responses such as sepsis.

A bright blue fluorescent dextran for two-photon in vivo imaging of blood vessels.

Fluorescence-based in vivo imaging is one of the most important tools for monitoring of biological processes in cells and tissues of live animal models. Fluorescence imaging agents have also been used to monitor the microcirculation. Tracking microcirculation of the blood is vital to gain further insight into various vascular disease-related anomalies within the human body. As monitoring of vascular circulation is performed with visualization of both immune cells and pathogens, which are mainly labelled with red and green, the favorable color option for blood vessels could be blue. However, currently available blueish color-labeled agents for vascular monitoring is generally confronted with quick bleaching, because of its short excitation and emission wavelengths. Hereby, what we propose in this report is a newly generated bright blue fluorescent dextran, named HCD-70K that monitors the blood vessels using blue and inter-compatible typical fluorescent materials. DBCO-functionalized dextran-70K was fabricated with hydroxy-coumarin dye via metal-free bioorthogonal click chemistry, and generated HCD-70K, which can flow within the blood vessel and decipher the whole structure of the blood vessel successfully. The synthesis, spectroscopic analysis, and quantum chemical calculations were conducted. Using two-photon microscopy, efficient deep in vivo blood vessel imaging of a mouse model revealed exceptional bio-imaging capabilities of the HCD-70K and consequently it provided a promising opportunity for efficient vascular visualization in various research areas.

Use of complementary and alternative medicine in pregnancy: a cross-sectional survey on Iraqi women.

BACKGROUND: Due to the lack of strong evidence on safety and efficacy of complementary and alternative medicine (CAM) approaches, the use of CAM in women during pregnancy could be hazardous for mother and fetus. Meanwhile, little is known regarding the patterns, the reasons and the factors affecting use of CAM among pregnant women in Iraq. METHODS: A cross sectional survey design was used to carry out face-to-face interviews with 335 consecutive pregnant women. The questionnaire comprised of three sections: socio-demographic characteristics, pregnancy-related aspects and the patterns and attitudes towards use of CAM. Determinants of CAM use were assessed through the logistic regression analysis. RESULTS: Three hundred thirty-five pregnant women completed the questionnaire. 56.7 % reported using at least one form of CAM modalities. In total, 24 different types of CAM were used; with herbal medicine (53.7 %) and multivitamins (36.3 %) the most commonly used modalities. From the logistic regression analysis, the variables positively associated with CAM use were: rural residence (odds ratio (OR) 2.0, p < 0.01), no occupation (OR 2.7, p < 0.05), high income (OR 2.0, p < 0.05), perceived healthy status (OR 2.6, p < 0.05) and ever use of contraception (OR 2.0, p < 0.01). Only 0.5 % of CAM users disclosed their CAM use to physicians. CONCLUSIONS: The proportion of CAM users among pregnant women is relatively high and it is important to learn what types of CAM they use. However, disclosure of CAM use was extraordinarily low. Given the low rate of disclosure, it should be ensured that physicians establish good level of communication with pregnant women and have adequate knowledge of CAM.

Altered ganglioside expression modulates the pathogenic mechanism of thyroid-associated ophthalmopathy by increase in hyaluronic acid.

PURPOSE: The aim of this study was to determine the role of gangliosides in pathogenic mechanisms of thyroid-associated ophthalmopathy (TAO). METHODS: The gangliosides profile and mRNA level of sialyltransferases of the orbital tissues from TAO patients (n = 5) and non-TAO subjects (n = 4) were investigated. In addition, the effect of exogenous gangliosides on the expression of hyaluronic acid was examined in orbital fibroblasts. For in vitro experiments, we used four different strains of cells obtained from non-TAO subjects with at least three replicates for each strain. RESULTS: Trisialoganglioside 1b (GT1b) was significantly overexpressed in the orbital tissue of TAO patients compared with control tissue, whereas no significant difference was observed for either monosialoganglioside 1 (GM1) or disialoganglioside 1a (GD1a) by digital analyses of immunohistochemical images. Moreover, mRNA levels of sialyltransferase (SAT)-I and SAT II were increased in TAO patients compared with control. Exogenous GT1b strongly induced the morphologic changes related to an accumulation of sparse flocculent precipitates in lysosomes and increased the extracellular hyaluronic acid level in orbital fibroblasts with the induction of hyaluronic acid synthase, which were less by GD1a but not by GM1. The GT1b-induced morphologic changes of cells were due, at least in part, to an increase of intracellular hyaluronic acid. Co-treatment of hyaluronidase nicely attenuated the morphologic changes in orbital fibroblasts. Thy-1(+) orbital fibroblasts were more capable of producing hyaluronic acid by exogenous GT1b. CONCLUSIONS: The results suggest that gangliosides, particularly GT1b, may play a role in the pathologic mechanisms of TAO by stimulating an increase in hyaluronic acid.

Clinical meaning of pepsinogen test and Helicobacter pylori serology in the health check-up population in Korea.

OBJECTIVE: This study was performed to assess the affects of age, sex, and Helicobacter pylori status on pepsinogen testing for atrophic gastritis and to establish the clinical implications of pepsinogen test results and H. pylori serology in a Korean population presenting for a health check-up. METHODS: Serum pepsinogen (PG) I and PG II, and H. pylori IgG were measured in 1485 adults. The PG values were analyzed based on age, sex, and H. pylori status, and the cutoff value for atrophic gastritis was determined. RESULTS: Serum PG I (sPGI) and sPGII were higher in H. pylori positive than in H. pylori negative individuals (sPGI, 56.3 vs. 42.2 microg/l, P<0.001; sPGII, 17.5 vs. 8.0 microg/l, P<0.001). The PG I/II ratio was lower in H. pylori positive than in H. pylori negative individuals (3.7 vs. 6.0, P<0.001). The sPGII and PG I/II ratio had a positive (r=0.132, P<0.001) and negative correlation with age (r=-0.229, P<0.001), respectively. Men had a higher sPGI (54.7 microg/l) than did women (48.4 microg/l) (P<0.001) but the PG I/II ratio was not statistically different and neither the atrophic gastritis. The PG I/II cutoff value for atrophic gastritis was 6.0 for H. pylori negative and 3.0 for H. pylori positive individuals. sPGI and sPGII were, however, not specific for atrophic gastritis. CONCLUSION: The H. pylori IgG status, age, and sex were associated with the serum PG levels. To increase the efficacy of the PG I/II ratio for the detection of atrophic gastritis, the cutoff value of the PG I/II ratio should be stratified according to the H. pylori IgG status in the Korean population presenting for a health check-up.

Effects of Genetic Polymorphisms of Glutathione S-transferase P1 on Helicobacter pylori-associated Gastric Cancer.

BACKGROUND/AIMS: Glutathione S-transferase P1 (GSTP1) scavenges radicals via its peroxidase activity. The purpose of this study was to determine the association of GSTP1 genetic polymorphisms with the expression of H. pylori-associated gastroduodenal disease. METHODS: This study involved 1,911 subjects, comprising patients with four diseases (gastric cancer, dysplasia, benign gastric ulcer, and duodenal ulcer disease) and controls. Biallelic polymorphisms were genotyped by restriction fragment length polymorphism techniques. RESULTS: The frequency of the genetic polymorphism at nucleotide 313 of GSTP1 did not differ among the five study groups. However, when the gastric cancer group was subdivided into advanced gastric cancer (AGC) and early gastric cancer, the frequency of the G/G genotype was significantly higher in the AGC group than in all the control subgroups (OR: 1.2, 95% CI: 1.1-4.9). The frequency of this genotype differed significantly in the H. pylori-positive AGC group (OR: 2.7, 95% CI: 1.1-6.3) but not in the H. pylori-negative group. Furthermore, the difference was greater in the intestinal type, and was not found in diffuse types of disease. CONCLUSIONS: This study found that genetic polymorphisms of GSTP1 were associated with H. pylori-associated gastric cancer only during the advanced stage of gastric cancer, with intestinal-type histology evident in H. pylori-positive subjects.

Second-line treatment for Helicobacter pylori infection: 10-day moxifloxacin-based triple therapy versus 2-week quadruple therapy.

BACKGROUND AND AIM: The aim of this study was to test the efficacy of 10-day moxifloxacin-based triple therapy versus 2-week quadruple therapy for the second-line treatment of Helicobacter pylori infection. METHODS: One hundred and ninety-two patients who had failed previous H. pylori eradication on standard triple therapy were randomized to one of two regimens: 1, moxifloxacin (400 mg q.d.), amoxicillin (1000 mg b.i.d.), and esomeprazole (20 mg b.i.d.) for 10 days (the 10MEA group), or 2, esomeprazole (20 mg b.i.d.), tripotassium dicitrate bismuthate (300 mg q.i.d.), metronidazole (500 mg t.i.d.), and tetracycline 500 mg (q.i.d.) for 14 days (the 14EBMT group). The eradication rates, drug compliances, and side-effect rates of these two regimens were compared. RESULTS: Eradication rates by intention-to-treat and per-protocol analyses in the 10MEA and 14EMBT groups were 71.9% and 82.6%, and 71.7% and 90.5% (p = .973 and .321), respectively. The 10MEA group was significantly superior to the 14EMBT group in terms of side-effect rates (12.2% vs. 39.6%, p = .001), and discontinuation rates due to side-effects were lower in the 10MEA group than in the 14EMBT group (0.7% vs. 13.2%, p < .001). Moreover, compliance was higher in the 10MEA group (94.2% (131/139)) than in the 14EBMT group (83.0% (44/53)) (p = .014). CONCLUSION: The 10-day moxifloxacin-based triple therapy was found to have a high eradication rate with few side-effects and good drug compliance. These findings suggest that this regimen is a safe and effective second-line treatment option for H. pylori infection in Korea.