[The Effect of COVID-19 on Pediatric Intussusception: A Retrospective Study of a Single Center in South Korea with 10-Year Experience]. / 코로나바이러스감염증­2019 ìœ í–‰ 후 소아 장중첩증의 변화: 단일기관 10ë „ 의무 기록을 이용한 연구.

Purpose: To evaluate the effect of the emergence of coronavirus disease-19 (COVID-19) on pediatric intussusception. Materials and Methods: Patients (< 18 years) who were diagnosed with intussusception and received enema reduction from 2011 to 2020 were included. We reviewed the demographics, yearly/monthly/seasonal incidence of intussusception, method and failure rate of enema reduction, recurrence rate of intussusception, surgical record, and pathologic report. Subsequently, we investigated the differences in mean age, failure rate of enema reduction, and recurrence rate of intussusception between the cases in 2020 and those in the period from 2011 to 2019. Results: A total of 859 enema reductions were performed during the past decade, more in males and in the age < 1 year (mean age, 22.2 months). The yearly incidence was highest in 2014 and lowest in 2020, and the monthly incidence was highest on December and September. The cases in 2020 (n = 27) had a lower mean age (18.1 months vs. 22.8 months), higher failure rate of enema reduction (7.4% vs. 2.4%), and higher recurrence rate of intussusception (14.8% vs 7.3%) compared with those that occurred between 2011 and 2019 (n = 832). However, these results did not show statistical significance (p = 0.07, p = 0.15, p = 0.14, respectively). Conclusion: With the emergence of COVID-19, the number of enema reductions was remarkably decreased with a lower mean age, higher failure rate, and higher recurrence rate.

Suppressive activity of RGX-365 on HMGB1-mediated septic responses

Abstract RGX-365 is the main fraction of black ginseng conmprising protopanaxatriol (PPT)-type rare ginsenosides (ginsenosides Rg4, Rg6, Rh4, Rh1, and Rg2). No studies on the antiseptic activity of RGX-365 have been reported. High mobility group box 1 (HMGB1) is recognized as a late mediator of sepsis, and the inhibition of HMGB1 release and recovery of vascular barrier integrity have emerged as attractive therapeutic strategies for the management of sepsis. In this study, we examined the effects of RGX-365 on HMGB1-mediated septic responses and survival rate in a mouse sepsis model. RGX-365 was administered to the mice after HMGB1 challenge. The antiseptic activity of RGX-365 was assessed based on the production of HMGB1, measurement of permeability, and septic mouse mortality using a cecal ligation and puncture (CLP)-induced sepsis mouse model and HMGB1-activated human umbilical vein endothelial cells (HUVECs). We found that RGX-365 significantly reduced HMGB1 release from LPS- activated HUVECs and CLP-induced release of HMGB1 in mice. RGX-365 also restored HMGB1-mediated vascular disruption and inhibited hyperpermeability in the mice. In addition, treatment with RGX-365 reduced sepsis-related mortality in vivo. Our results suggest that RGX- 365 reduces HMGB1 release and septic mortality in vivo, indicating that it is useful in the treatment of sepsis.

Suppressive Effects of Ginsenoside Rh1 on HMGB1-Mediated Septic Responses.

High mobility group box 1 (HMGB1) is considered as a late mediator of sepsis and the inhibition of HMGB1-mediated severe inflammatory responses, and restoration of endothelial integrity have emerged as attractive therapeutic strategies for the management of sepsis. Ginsenoside Rh1, a protopanaxatriol type ginsenoside, is one of the major bioactive components of Korean red ginseng, which has been increasingly used for enhancing cognition and physical health worldwide. Ginsenoside Rh1 exhibits potent biological activities such as antistress, anti-oxidant, anti-inflammatory and immunomodulatory effects. We examined the effects of ginsenoside Rh1 on HMGB1-mediated septic responses and survival rate in a mouse model of sepsis. Ginsenoside-Rh1 was administered after the HMGB1 challenge. The antiseptic activity of ginsenoside Rh1 was determined by measuring the permeability, leukocyte adhesion and migration, activation of pro-inflammatory proteins in HMGB1-activated human umbilical vein endothelial cells (HUVECs) and mice, and the survival rate in a sepsis mouse model. Ginsenoside Rh1 significantly reduced HMGB1 release in lipopolysaccharide (LPS)-activated HUVECs. Furthermore, ginsenoside Rh1 suppressed the production of tumor necrosis factor (TNF)- α , interleukin (IL)-6, activation of nuclear factor (NF)- κ B and extracellular signal-regulated kinase (ERK) 1/2 by HMGB1. Ginsenoside Rh1 also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with ginsenoside Rh1 reduced the cecal ligation and puncture (CLP)-induced release of HMGB1, sepsis-related mortality and tissue injury in vivo. Our results indicated that ginsenoside Rh1 might be useful in the treatment of sepsis by targeting HMGB1.

JH-4 reduces HMGB1-mediated septic responses and improves survival rate in septic mice.

Inhibition of high mobility group box 1 (HMGB1) and restoration of endothelial integrity are emerging as attractive therapeutic strategies for the management of severe vascular inflammatory diseases. Recently, we found that JH-4, a synthesized decursin derivative, exhibited a strong anti-Hutchinson-Gilford progeria syndrome by efficiently blocking progerin-lamin A/C binding. In this study, we examined the effects of JH-4 on HMGB1-mediated septic responses and the survival rate in a mouse sepsis model. The anti-inflammatory activities of JH-4 were monitored based on its effects on lipopolysaccharide- or cecal ligation and puncture (CLP)-mediated release of HMGB1. The antiseptic activities of JH-4 were determined by measuring permeability, leukocyte adhesion, migration, and the activation of proinflammatory proteins in HMGB1-activated human umbilical vein endothelial cells and mice. JH-4 inhibited the release of HMGB1 and downregulated HMGB1-dependent inflammatory responses in human endothelial cells. JH-4 also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. In addition, treatment with JH-4 reduced CLP-induced release of HMGB1, sepsis-related mortality, and pulmonary injury in vivo. Our results indicate that JH-4 is a possible therapeutic agent to treat various severe vascular inflammatory diseases via the inhibition of the HMGB1 signaling pathway.

Interruption of progerin-lamin A/C binding ameliorates Hutchinson-Gilford progeria syndrome phenotype.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare autosomal dominant genetic disease that is caused by a silent mutation of the LMNA gene encoding lamins A and C (lamin A/C). The G608G mutation generates a more accessible splicing donor site than does WT and produces an alternatively spliced product of LMNA called progerin, which is also expressed in normal aged cells. In this study, we determined that progerin binds directly to lamin A/C and induces profound nuclear aberrations. Given this observation, we performed a random screening of a chemical library and identified 3 compounds (JH1, JH4, and JH13) that efficiently block progerin-lamin A/C binding. These 3 chemicals, particularly JH4, alleviated nuclear deformation and reversed senescence markers characteristic of HGPS cells, including growth arrest and senescence-associated ß-gal (SA-ß-gal) activity. We then used microarray-based analysis to demonstrate that JH4 is able to rescue defects of cell-cycle progression in both HGPS and aged cells. Furthermore, administration of JH4 to LmnaG609G/G609G-mutant mice, which phenocopy human HGPS, resulted in a marked improvement of several progeria phenotypes and an extended lifespan. Together, these findings indicate that specific inhibitors with the ability to block pathological progerin-lamin A/C binding may represent a promising strategy for improving lifespan and health in both HGPS and normal aging.

Evaluation of 3,4-dihydroquinazoline-2(1H)-thiones as inhibitors of alpha-MSH-induced melanin production in melanoma B16 cells.

Novel 3,4-dihydroquinazoline-2(1H)-thiones (QNTs) 1 were found to be potent inhibitors of alpha-MSH-induced melanin production. The effect of QNTs to inhibit melanin formation in B16 melanoma cells was screened in the presence of alpha-MSH. In defining the mechanism of activity, the effects on tyrosinase activity, on tyrosinase synthesis and on the depigmentation of melanin were evaluated. QNTs did not affect the catalytic activity of tyrosinase, but rather acted as an inhibitor of tyrosinase synthesis.

The expression of iron-repressible outer membrane proteins in Helicobacter pylori and its association with iron deficiency anemia.

BACKGROUND: Helicobacter pylori infection is known to be a cause of iron deficiency anemia (IDA) that is unresponsive to iron supplements. H. pylori bind iron to a specific receptor by iron-repressible outer membrane proteins (IROMPs) under conditions of restricted iron. MATERIALS AND METHODS: We compared the expression of IROMPs from strains of H. pylori under both iron-restricted and iron-supplemented conditions to determine the difference between strains with and without IDA. One standard strain, two clinical strains, and three IDA strains were cultured; and then the IROMPs were extracted under iron-restricted and iron-supplemented conditions. We used SDS-PAGE to compare the expression of the IROMPs from each strain. RESULTS: IROMPs were found in IDA strains under iron-restricted conditions and their molecular sizes were estimated to be 56, 48, 41, and 37 kDa. In the iron-repleted media, the IROMPs were no longer present. CONCLUSION: In the iron-depleted state, specific H. pylori strains associated with IDA demonstrated an advantage in iron acquisition due to a higher expression of IROMPs. Our results can explain in part why some patients with H. pylori infection are more prone to develop clinical IDA under restricted iron conditions in the host.

Allergic proctitis and abdominal distention mimicking Hirschsprung's disease in infants.

AIM: To determine the incidence and clinical aspects of allergic proctitis (AP) in infants with symptoms that mimic Hirschsprung's disease (HD). METHODS: One hundred and five patients less than 6 months of age, who underwent barium enema, anorectal manometry and rectal suction biopsy due to suspicion of HD, were enrolled. Comparison of the patient characteristics associated with each disease was based on the results of the triple testing. The sensitivity and specificity of the three tests, for the diagnosis of HD, were evaluated. RESULTS: The mean age of enrolled patients was 2.1+/-0.9 months. Based on the three tests, 39 patients (37.1%) were diagnosed with HD, seven patients (6.7%) with AP, and 53 (50.5%) had normal results. Of the 54 patients with transitional zone and a reversed rectosigmoid index on the barium enema, four (7.4%) were patients with AP. The mean age of the AP patients (3.1+/-1.5 months old) was older than the HD children (1.4+/-0.9 months old). The sensitivity of the three tests for HD was 97.4%, 87.2% and 92.3% and the specificity was: 74.2%, 78.8% and 100%, respectively. CONCLUSIONS: In the infants with severe abdominal distention, the incidence of AP mimicking HD was relatively high. Therefore, consideration of AP should be part of the differential diagnosis in infants with severe abdominal distention or findings that mimic HD. For differentiation of these disorders, a rectal suction biopsy is very useful.

Decursin suppresses human androgen-independent PC3 prostate cancer cell proliferation by promoting the degradation of beta-catenin.

Alterations in the Wnt/beta-catenin pathway are associated with the development and progression of human prostate cancer. Decursin, a pyranocoumarin isolated from the Korean Angelica gigas root, inhibits the growth of androgen-independent human prostate cancer cells, but little is known about its mechanism of action. Using a cell-based screen, we found that decursin attenuates the Wnt/beta-catenin pathway. Decursin antagonized beta-catenin response transcription (CRT), which was induced with Wnt3a-conditioned medium and LiCl, by promoting the degradation of beta-catenin. Furthermore, decursin suppressed the expression of cyclin D1 and c-myc, which are downstream target genes of beta-catenin and thus inhibited the growth of PC3 prostate cancer cells. In contrast, decursinol, in which the (CH3)2-C=CH-COO- side chain of decursin is replaced with -OH, had no effect on CRT, the level of intracellular beta-catenin, or PC3 cell proliferation. Our findings suggest that decursin exerts its anticancer activity in prostate cancer cells via inhibition of the Wnt/beta-catenin pathway.

Triterpenoid saponins from the roots of Pulsatilla koreana.

Six new saponins, five lupanes (1-5) and one oleanane (6), along with 11 known saponins, were isolated from the roots of Pulsatilla koreana. The structures of the new saponins were found to be 23-hydroxy-3beta-[(O-alpha-L-rhamnopyranosyl-(1-->2)-O-[O-beta-D-glucopyranosyl-(1-->4)]-alpha-L-arabinopyranosyl)oxy]lup-20(29)-en-28-oic acid (1), 23-hydroxy-3beta-[(O-beta-D-glucopyranosyl-(1-->3)-O-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl)oxy]lup-20(29)-en-28-oic acid (2), 3beta-[(O-alpha-L-rhamnopyranosyl-(1-->2)-O-[O-beta-D-glucopyranosyl-(1-->4)]-alpha-L-arabinopyranosyl)oxy]lup-20(29)-en-28-oic acid (3), 3beta-[(O-beta-D-glucopyranosyl-(1-->3)-O-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl)oxy]lup-20(29)-en-28-oic acid (4), 23-hydroxy-3beta-[(O-beta-D-glucopyranosyl-(1-->4)-alpha-L-arabinopyranosyl)oxy]lup-20(29)-en-28-oic acid (5), and hederagenin 3-O-beta-D-glucopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside (6). Their structures were determined on the basis of 1D and 2D NMR ((13)C NMR, (1)H NMR, (1)H-(1)H COSY, HMQC, and HMBC) methods, FABMS, and hydrolysis. All isolated compounds were evaluated for their cytotoxic activity against A-549 human lung carcinoma cells.

Peroxynitrite scavenging activity of indole derivatives: interaction of indoles with peroxynitrite.

One of the products of nitrogen-derived free radicals, peroxynitrite (ONOO(-)), is formed by the reaction of superoxide anion (O(2)(*-)) with nitric oxide (NO). ONOO(-) can cause damage to proteins and DNA through nitration. In particular, proteins and their constituent amino acids have been proven to be extremely sensitive to ONOO(-). However, the lack of specific endogenous defense enzymes to protect against ONOO(-) has prompted many researchers to search for endogenous scavengers. We previously found 5-hydroxytryptamine (HT), which is an indole derivative (ID), to be an efficient ONOO(-) scavenger. In the present study, the interaction of several other indoles was further investigated: tryptophan (TRP), 5-hydroxyL-tryptophan (HLT), HT, N-acetyl-5-hydroxytryptamine (AHT), 5-methoxyindole-3-acetate (MIA), 5-methoxytryptamine (MT), and melatonin. The ONOO(-) scavenging activity of ID was assayed by measuring the formation of oxidized dihydrorhodamine-123 (DHR-123). The scavenging efficacy was expressed as the IC(50), denoting the concentration of each indole required to cause 50% inhibition of DHR-123 formation. In a separate in vitro study, the protective effect of IDs against ONOO(-)-induced nitration of bovine serum albumin was investigated. Nitration was quantified using an immunoassay with a monoclonal anti-nitrotyrosine antibody, and a horseradish peroxidase-conjugated anti-mouse secondary antibody from sheep. The results revealed that the inhibitory activities of indoles were as follows: HLT, IC(50) = 0.73 microM; HT, IC(50) = 1.03 microM; and AHT, IC(50) = 0.98 microM), showing relatively strong activities against ONOO(-). Interestingly, TRP, MIA, MT, and melatonin were less effective. Regarding the protection of albumin by IDs, the data showed that the formation of ONOO(-) was inhibited in a dose-dependent manner. Further probing of the mode of the interaction of indoles revealed that the hydroxyl groups in IDs are required for the enhanced scavenging action. It was concluded that several indole derivatives with hydroxyl groups are effective scavengers against ONOO(-), and that the scavenging efficacy depends on the presence of hydroxyl groups located within the indole ring structure.