Purpose: Junctional adhesion molecule (JAM)-A is an immunoglobulin-like molecule that colocalizes with tight junctions (TJs) in the endothelium and epithelium. It is also found in blood leukocytes and platelets. The biological significance of JAM-A in asthma, as well as its clinical potential as a therapeutic target, are not well understood. The aim of this study was to elucidate the role of JAM-A in a mouse model of asthma, and to determine blood levels of JAM-A in asthmatic patients. Materials and Methods: Mice sensitized and challenged with ovalbumin (OVA) or saline were used to investigate the role of JAM-A in the pathogenesis of bronchial asthma. In addition, JAM-A levels were measured in the plasma of asthmatic patients and healthy controls. The relationships between JAM-A and clinical variables in patients with asthma were also examined. Results: Plasma JAM-A levels were higher in asthma patients (n=19) than in healthy controls (n=12). In asthma patients, the JAM-A levels correlated with forced expiratory volume in 1 second (FEV1%), FEV1/forced vital capacity (FVC), and the blood lymphocyte proportion. JAM-A, phospho-JNK, and phospho-ERK protein expressions in lung tissue were significantly higher in OVA/OVA mice than in control mice. In human bronchial epithelial cells treated with house dust mite extracts for 4 h, 8 h, and 24 h, the JAMA, phospho-JNK, and phospho-ERK expressions were increased, as shown by Western blotting, while the transepithelial electrical resistance was reduced. Conclusion These results suggest that JAM-A is involved in the pathogenesis of asthma, and may be a marker for asthma.

Background: Proteomics and genomics studies have contributed to understanding the pathogenesis of chronic obstructive pulmonary disease (COPD), but previous studies have limitations. Here, using a machine learning (ML) algorithm, we attempted to identify pathways in cultured bronchial epithelial cells of COPD patients that were significantly affected when the cells were exposed to a cigarette smoke extract (CSE). Methods: Small airway epithelial cells were collected from patients with COPD and those without COPD who underwent bronchoscopy. After expansion through primary cell culture, the cells were treated with or without CSEs, and the proteomics of the cells were analyzed by mass spectrometry. ML-based feature selection was used to determine the most distinctive patterns in the proteomes of COPD and non-COPD cells after exposure to smoke extract.Publicly available single-cell RNA sequencing data from patients with COPD (GSE136831) were used to analyze and validate our findings. Results: Five patients with COPD and five without COPD were enrolled, and 7,953 proteins were detected. Ferroptosis was enriched in both COPD and non-COPD epithelial cells after their exposure to smoke extract. However, the ML-based analysis identified ferroptosis as the most dramatically different response between COPD and non-COPD epithelial cells, adjusted P value = 4.172 × 10−6 , showing that epithelial cells from COPD patients are particularly vulnerable to the effects of smoke. Single-cell RNA sequencing data showed that in cells from COPD patients, ferroptosis is enriched in basal, goblet, and club cells in COPD but not in other cell types. Conclusion Our ML-based feature selection from proteomic data reveals ferroptosis to be the most distinctive feature of cultured COPD epithelial cells compared to non-COPD epithelial cells upon exposure to smoke extract.

Purpose: Single-port laparoscopic techniques can be optimized with confined incisions. This approach has an intraoperative advantage of excellent visualization of the correct intestinal segment for exteriorization, along with direct visual control of the extraction to avoid twisting. However, only a few studies have verified the efficacy of the technique. Thus, this study assessed the results of single-port laparoscopic stoma creation for fecal diversion, specifically focusing on feasibility, safety, and efficacy. Methods: Patients who underwent single-incision enterostomy performed by a single surgeon were included. Data on demographics, indications for and chosen procedure, and operation results were retrospectively collected and analyzed. Results: Between April 2015 and January 2018, a total of 13 patients (8 males, 5 females) with a mean age of 57.7 years (range, 41–83 years) underwent single-port ileostomy creation. The most common reason for diversion was palliative ileostomy for colon obstruction or fistula from peritoneal malignancy (n = 12), followed by colonic fistula with necrotizing pancreatitis (n = 1). There were no cases of conversion to open or multiport laparoscopic surgery. The mean operative time was 54 minutes (range, 37–118 minutes), and the median length of hospital stay was 8 days (range, 2–211 days). A postoperative complication, aspiration pneumonia, was documented in 1 patient and treated conservatively. The mean duration of bowel movement was 0.7 days (range, 0–4 days). All stomas had good function, and there was no 30-day mortality. Conclusion Single-port laparoscopic ileostomy in patients with a palliative setting could be a safe and feasible option for fecal diversion.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Although advances have been made in the treatment of MS, such as the use of IFN-β, glucocorticoids and stem cells, the therapeutic effects of these treatments are not sufficient. In the present study, we evaluated whether the combination of methylprednisolone (MP) and human bone marrow-derived mesenchymal stem cells (BM-MSCs) could enhance the therapeutic effectiveness in experimental autoimmune encephalomyelitis (EAE), a model for MS. EAE was induced by immunizing C57BL/6 mice with myelin oligodendrocyte glycoprotein 35-55 (MOG 35-55). The immunized mice received an intraperitoneal injection of MP (20 mg/kg), an intravenous injection of BM-MSCs (1 × 10⁶ cells) or both on day 14 after immunization. Combination treatment significantly ameliorated the clinical symptoms, along with attenuating inflammatory infiltration and demyelination, compared to either treatment alone. Secretion of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-17) was significantly reduced, and anti-inflammatory cytokines (IL-4, IL-10) was significantly increased by the combination treatment as compared to either treatment alone. Flow cytometry analysis of MOG-reactivated T cells in spleen showed that combination treatment reduced the number of CD4⁺CD45⁺ and CD8⁺ T cells, and increased the number of CD4⁺CD25⁺Foxp3⁺ regulatory T cells. Furthermore, combination treatment enhanced apoptosis in MOG-reactivated CD4⁺ T cells, a key cellular subset in MS pathogenesis. Combination treatment with MP and BM-MSCs provides a novel treatment protocol for enhancing therapeutic effects in MS.
Animals ; Apoptosis ; Central Nervous System ; Clinical Protocols ; Cytokines ; Demyelinating Diseases ; Encephalomyelitis, Autoimmune, Experimental* ; Flow Cytometry ; Glucocorticoids ; Humans* ; Immunization ; Injections, Intraperitoneal ; Injections, Intravenous ; Mesenchymal Stromal Cells* ; Methylprednisolone* ; Mice ; Multiple Sclerosis ; Myelin-Oligodendrocyte Glycoprotein ; Spleen ; Stem Cells ; T-Lymphocytes ; T-Lymphocytes, Regulatory ; Therapeutic Uses

Eleven compounds (1–11) were isolated from the rhizomes of Osmunda japonica, and their structures were elucidated based on 1H, 13C-NMR and LC-IT-TOF MS data. Of these compounds, all compounds (1 – 11) have been previously reported, although five (6 – 9, 11) have not previously been isolated from this plant. The antioxidant activities of isolated compounds (1 – 11) were measured by DPPH and ABTS assays, and compound 10 showed the high antioxidant activity.
Plants ; Rhizome*

Helicobacter pylori infection is associated with chronic gastritis, peptic ulcer, and gastric cancer. There is evidence that IL-1beta is associated with the development of gastric cancer. Therefore, downregulation of H. pylori-mediated IL-1beta production may be a way to prevent gastric cancer. Withaferin A (WA), a withanolide purified from Withania somnifera, is known to exert anti-inflammatory and anti-tumor effects. In the present study, we explored the inhibitory activity of WA on H. pylori-induced production of IL-1beta in murine bone marrow-derived dendritic cells (BMDCs) and the underlying cellular mechanism. Co-treatment with WA decreased IL-1beta production by H. pylori in BMDCs in a dose-dependent manner. H. pylori-induced gene expression of IL-1beta and NLRP3 (NOD-like receptor family, pyrin domain containing 3) were also suppressed by WA treatment. Moreover, IkappaB-alpha phosphorylation by H. pylori infection was suppressed by WA in BMDCs. Western blot analysis revealed that H. pylori induced cleavage of caspase-1 and IL-1beta, as well as increased procaspase-1 and pro IL-1beta protein levels, and that both were suppressed by co-treatment with WA. Finally, we determined whether WA can directly inhibit ac tivation of the NLRP3 inflammasome. NLRP3 activators induced IL-1beta secretion in LPS-primed macrophages, which was inhibited by WA in a dose-dependent manner, whereas IL-6 production was not affected by WA. Moreover, cleavage of IL-1beta and caspase-1 by NLRP3 activators was also dose-dependently inhibited by WA. These findings suggest that WA can inhibit IL-1beta production by H. pylori in dendritic cells and can be used as a new preventive and therapeutic agent for gastric cancer.
Blotting, Western ; Caspase 1 ; Dendritic Cells* ; Down-Regulation ; Gastritis ; Gene Expression ; Helicobacter pylori ; Helicobacter* ; Humans ; Interleukin-1beta ; Interleukin-6 ; Macrophages ; NF-kappa B* ; Peptic Ulcer ; Phosphorylation ; Stomach Neoplasms ; Withania

TGF-beta induces IgA class switching by B cells. We previously reported that Smad3 and Smad4, pivotal TGF-beta signal-transducing transcription factors, mediate germline (GL) alpha transcription induced by TGF-beta1, resulting in IgA switching by mouse B cells. Post-translational sumoylation of Smad3 and Smad4 regulates TGF-beta-induced transcriptional activation in certain cell types. In the present study, we investigated the effect of sumoylation on TGF-beta1-induced, Smad3/4-mediated GLalpha transcription and IgA switching by mouse B cell line, CH12F3-2A. Overexpression of small ubiquitin-like modifier (SUMO)-1, SUMO-2 or SUMO-3 did not affect TGF-beta1-induced, Smad3/4-mediated GLalpha promoter activity, expression of endogenous GLalpha transcripts, surface IgA expression, and IgA production. Next, we tested the effect of the E3 ligase PIASy on TGF-beta1-induced, Smad3/4-mediated GLalpha promoter activity. We found that PIASy overexpression suppresses the GLalpha promoter activity in cooperation with histone deacetylase 1. Taken together, these results suggest that SUMO itself does not affect regulation of GLalpha transcription and IgA switching induced by TGF-beta1/Smad3/4, while PIASy acts as a repressor.
Animals ; B-Lymphocytes* ; Cell Line ; Histone Deacetylase 1 ; Immunoglobulin A ; Immunoglobulin Class Switching ; Mice ; Small Ubiquitin-Related Modifier Proteins* ; SUMO-1 Protein* ; Sumoylation ; Transcription Factors ; Transcriptional Activation ; Transforming Growth Factor beta ; Transforming Growth Factor beta1 ; Ubiquitin-Protein Ligases

BACKGROUND/OBJECTIVES: Rubus Coreanus Miquel (RCM), used as a traditional Korean medicine, reduces chronic inflammatory diseases such as cancer and rheumatoid arthritis. However, its mechanism has not been elucidated. In this study, we examine the anti-inflammatory effects of RCM and their possible mechanisms using RAW 264.7 cells. MATERIALS/METHODS: Unripe RCM ethanol extract (UE), unripe RCM water extract (UH), ripe RCM ethanol extract (RE), and ripe RCM water extract (RH) were prepared. Inflammatory response was induced with LPS treatment, and expression of pro-inflammatory mediators (iNOS, COX-2, TNF-alpha, IL-1beta, and IL-6) and NO and PGE2 productions were assessed. To determine the anti-inflammatory mechanism of RCM, we measured NF-kappaB and MAPK activities. RESULTS: UE and UH treatment significantly reduced NF-kappaB activation and JNK and p38 phosphorylation and reduced transcriptional activities decreased iNOS, COX-2, and pro-inflammatory cytokines expressions, and NO and PGE2 productions. RE and RH treatments reduced IL-1beta and IL-6 expressions through suppressions of JNK and p38 phosphorylation. CONCLUSIONS: In this study, we showed that RCM had anti-inflammatory effects by suppression of pro-inflammatory mediator expressions. Especially, unripe RCM showed strong anti-inflammatory effects through suppression of NF-kappaB and MAPK activation. These findings suggest that unripe RCM might be used as a potential functional material to reduce chronic inflammatory responses.
Arthritis, Rheumatoid ; Cytokines ; Dinoprostone ; Ethanol ; Inflammation ; Interleukin-6 ; NF-kappa B* ; Phosphorylation ; Phosphotransferases* ; Tumor Necrosis Factor-alpha ; Water

Gastric bezoars are concretion of undigested material in the gastrointestinal tract. In the past, gastric bezoars were generally treated with surgical management. Recently, the efficacy of oral intake or endoscopic injection therapy with Coca-Cola has been reported. We report a case of a 47-year-old-man with huge gastric bezoar (4x2.5 cm) that was successfully removed by endoscopic fragmentation with Coca-Cola injection. Compared with a single endoscopic fragmentation therapy, the combination therapy with Coca-Cola injection shortened the procedure time and reduced the complication associated with fragmented bezoar.
Bezoars ; Cola ; Endoscopy ; Gastrointestinal Tract

The purposes of this study were to determine phenolic compounds and to evaluate antioxidant activities of plums (Soldam, Oishiwase and Formosa). Soldam contains the highest amount of total phenolics among cultivars (Formosa: 4.0%, Oishiwase: 3.3%, Soldam: 6.4% for total phenolic) as well as the total flavonoids of which constituents were mainly myricetin and anthocyanidin. The antioxidant activities were measured by DPPH, ABTS radical scavenging, and SOD-like activities. The DPPH radical scavenging activity of Korean plum extracts (200 microg/mL) showed more than 43%, and the Soldam turned out to be the highest : ID50 value: 160-177 microg/mL for Formosa and Oishiwase; 58-64 microg/mL for Soldam. The ABTS radical scavenging activity of Korean plum extracts (200 microg/mL) was found to be more than 50%. The SOD-like activity of Korean plum extracts (200 microg/mL) showed more than 70%. Among three kinds of cultivars, Soldam had the highest antioxidant activity. The nitrite scavenging activity of Soldam was 61.5%, which is the highest, compared with that of the other cultivars, about 50%. From these results, Korean plums turned out to be phytochemical rich fruit as well as to show high antioxidant activities.
Anthocyanins ; Benzothiazoles ; Flavonoids ; Fruit ; Phenol ; Prunus domestica ; Sulfonic Acids ; Taiwan