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Abstract Although esophageal stenting is one treatment option as a palliative treatment for tracheoesophageal fistulas, serious complications are associated with stent migration. Some reports have described stent fixation using various devices to prevent stent migration. However, these have yet to be sufficiently examined. We performed esophageal stent fixation using the MANTIS Clip (Boston Scientific), a novel re‐openable endoclip. An 89‐year‐old man developed a tracheoesophageal fistula after radiotherapy for esophageal squamous cell carcinoma. Esophageal stenting was considered because the patient had difficulty with oral intake. However, the patient had a mild stenosis, which suggested stent migration. Therefore, we performed esophageal stent fixation by grasping the mouth side of the stent and the normal mucosa of the esophagus with the MANTIS Clip after placement of the stent. The esophageal stent closed the fistula, and the patient was able to take food orally. Upper gastrointestinal endoscopy performed 3 weeks after stenting showed residual MANTIS Clip and no evidence of stent migration. Esophageal stent fixation with MANTIS clips for tracheoesophageal fistulas may be an option to prevent stent migration.

Ellagitannins (esters composed of glucose and ellagic acid) are hydrolyzed to generate ellagic acid in gut followed by conversion of ellagic acid to urolithins such as urolithin A by intestinal bacteria. Since urolithins are absorbed by gut easier than ellagitannins and ellagic acid, and show various physiological activities (e.g. anti-cancer, anti-cardiovascular disease, anti-diabetes mellitus, anti-obesity and anti-Alzheimer disease activities), they are expected as excellent health-promoting phytochemicals. Here, using human monoblast U937 cells, we investigated the effect of ellagic acid and urolithin A on the superoxide anion (O2−)-generating system of phagocytes, which is consisted of five specific protein factors (membrane proteins: p22-phox and gp91-phox, cytosolic proteins: p40-phox, p47-phox and p67-phox). Twenty micromolar of urolithin A enhanced the all-trans retinoic acid (ATRA)-induced O2−-generating activity (to ~175%) while 20 μM ellagic acid inhibited the ATRA-induced O2−-generating activity (to ~70%). Semiquantitative RT-PCR showed that transcription level of gp91-phox was certainly decreased (to ~70%) in ATRA plus ellagic acid-treated cells, while that of gp91-phox was significantly increased (to ~160%) in ATRA plus urolithin A-treated cells. Chromatin immunoprecipitation assay suggested that urolithin A enhanced acetylations of Lys-9 residues of histone H3 within chromatin surrounding the promoter region of gp91-phox gene, but ellagic acid suppressed the acetylations. Immunoblotting also revealed that ATRA plus urolithin A-treatment up-regulated protein levels of p22-phox (to ~160%) and gp91-phox (to ~170%) although ATRA plus ellagic acid-treatment down-regulated protein levels of p22-phox (to ~70%) and gp91-phox (to ~60%). These results suggested that conversion of ellagic acid to urolithin A in gut may bring about reverse effects on the gp91-phox gene expression, resulting in opposite alterations in O2−-generating activity of intestinal macrophages.

A major health outbreak in March 2024 with renal impairments occurred by ingested food supplements made from beni-koji (red yeast rice) in Japan, which has been considered as major health issue. A troponoid compound puberulic acid (PA) that was produced by contaminated Penicillium spp. is attracting attention as a causative agent of this health disaster occurred by beni-koji (red yeast rice). Regarding toxicity, it was reported that PA showed weak cytotoxicity against fetal human lung fibroblastlike MRC-5 cells with an IC50 value of about 289 µM (Iwatsuki et al., 2011). However, understandings about the physiological effects of PA against human tissues and cells still remain poor and insufficiently studied. Therefore, in this study, we investigated the effect of PA on the viability and the all-trans retinoic acid (ATRA)-induced superoxide anion (O2 -)-generating ability of human leukemia U937 cells. PA remarkably showed a strong cytotoxicity accompanied by apoptosis, which was enhanced by ATRA. Furthermore, PA dramatically down-regulated the ATRA-induced O2 --generating activity in a dose-dependent manner. Quantitative RT-PCR and immunoblot analyses showed that PA significantly reduces the ATRAinduced O2 --generating activity via down-regulating gene expression levels of gp91-phox, which is an essential factor for the O2 --generating activity of leukocytes. These findings revealed that PA has not only the strong ATRA-enhancible cytotoxic effect but also the drastic reducing effect on the ATRA-induced O2 --generating activity through down-regulating transcription of gp91-phox gene. We expect that our findings will contribute to resolve the large-scale health disaster caused by beni-koji (red yeast rice). [ABSTRACT FROM AUTHOR]

Aristolochic acids (AAs) with strong bio-toxicity are the natural compounds that consist in Aristolochiaceae plants. There are the governing health issues regarding toxicities of AAs although Aristolochiaceae plants have been used as herbal medicines. For example, AAs are known as significant risk factors for nephropathy, urological cancer, liver cancer and so on. However, the understandings about the molecular mechanisms of toxicity of each AA derivative have been still poor and insufficiently studied. In this study, we investigated the effects of four AA derivatives (AA-A, AA-B, AA-C and AA-D) on the viability and the all-trans retinoic acid (ATRA)-induced superoxide anion (O2-)-generating ability of human leukemia U937 cells. AA-A and AA-C remarkably reduced cell viability when co-treated with ATRA while AA-B and AA-D had little effect on viability of U937 cells. On the other hand, only AA-C among the four AAs dramatically up-regulated the ATRA-induced O2--generating ability. Quantitative RT- PCR and immunoblotting analyses showed that AA-C significantly enhances the ATRA-induced O2--gen- erating ability via up-regulating gene expression levels of gp91-phox, which is an essential factor for the O2--generating ability of phagocytes. These findings revealed that AA-C has not only the ATRA-enhanced cytotoxic effect but also the remarkable enhancing effect on the ATRA-induced O2--generating ability via up-regulating transcription of gp91-phox gene. [ABSTRACT FROM AUTHOR]

Using endoscopic ultrasonography (EUS), it is practicable to diagnose subepithelial lesions (SEL) with originating layer, echo level, and internal echo pattern etc. Lipoma, lymphangioma, and cyst have characteristic features; therefore, there is no need for endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Ectopic pancreas and glomus tumors, which originate from the third and fourth layers, are frequently seen in the antrum. However, ectopic pancreas located in the fundus or body is large and originates from the third and fourth layers (thickening of fourth layer). Each subepithelial lesion has characteristic findings. However, imaging differentiation of tumors originating from the fourth layer is very difficult, even if contrast echo is used. Therefore, EUS-FNA should be done in these tumors, but the diagnostic yield for small lesions is not sufficient for clinical demands. Generally, those tumors, including small ones, should be first followed up in 6 months, then yearly follow up in cases of no significant change in size and features. When those tumors become larger than 1-2 cm, EUS-FNA is recommended. Furthermore, unusual SEL and SEL with malignant findings such as nodular, heterogeneous, anechoic area, and ulceration indicate EUS-FNA. Cap-attached forward-viewing echoendoscope is very helpful for EUS-FNA of small SEL. [ABSTRACT FROM AUTHOR]

To understand the function of B cell antigen receptor (BCR)-related complex on pre-B cells (pre-BCR, Vpre_Bλ5/μ heavy chain/lg-α/lg-β), we examined pre-BCR- and BCR-mediated signaling events in human and mouse pre-B (Nalm-6, 697, NFS-5), Immature B (lgM+ Daudi, WEHI-231) and mature B (lgM+lgD+ BALL1) cell lines. Antl-u. cross-linking induced tyrosine phosphorylation of the cytoplasmlc proteins In each cell type, but did not induce a detectable Ca2+ mobilization response in pre-B cells. While the pre-B cells expressed Syk protein at levels similar to those found In B cell lines, pre-BCR cross-linkage did not induce phosphorylation of Syk tyrosine residues. Different protein kinase C Isozymes were expressed by pre-B (PKC-α), Immature B (PKC-α and -β) and mature B (PKC-β) cell lines. Anti-μ cross-linking Induced PKC translocatlon from the cytosollc to the membrane compartment In Immature and mature B cells, but did not have this effect In a pre-B cell line. Antl-μ cross-linking induced tyrosine phosphorylation of the p85 and p110 subunits of phophatldylinositol PI3-kinase (PI3-kinase) In both pre-B and B cell lines, but the pre-BCR induced PI3-kinase activation was Syk independent. Ligation of the pre-BCR complex thus triggers a characteristic signaling pattern In pre-B cells. [ABSTRACT FROM AUTHOR]