Alleviation of renal ischemia/reperfusion injury by exosomes from induced pluripotent stem cell-derived mesenchymal stem cells

Background/Aims@#Renal ischemia followed by reperfusion (I/R) is a leading cause of acute kidney injury (AKI), which is closely associated with high morbidity and mortality. Studies have shown that induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) exert powerful therapeutic effects in renal ischemia. However, the efficacy of iMSC-derived exosomes (iExo) on I/R injuries remains largely unknown. @*Methods@#Human iPSCs were differentiated into iMSCs using a modified one-step method. Ultrafiltration, combined with purification, was used to isolate iExo from iMSCs. iExo was administered following I/R injury in a mouse model. The effect of iExo on I/R injury was assessed through changes in renal function, histology, and expression of oxidative stress, inflammation, and apoptosis markers. Further, we evaluated its association with the extracellular signal-regulated kinase (ERK) 1/2 signaling pathway. @*Results@#Mice subjected to I/R injury exhibited typical AKI patterns; serum creatinine level, tubular necrosis, apoptosis, inflammatory cytokine production, and oxidative stress were markedly increased compared to sham mice. However, treatment with iExo attenuated these changes, significantly improving renal function and tissue damage, similar to the renoprotective effects of iMSCs on I/R injury. Significant induction of activated ERK 1/2 signaling molecules was observed in mice treated with iExo compared to those in the I/R injury group. @*Conclusions@#The present study demonstrates that iExo administration ameliorated renal damage following I/R, suggesting that iMSC-derived exosomes may provide a novel therapeutic approach for AKI treatment.

Modeling of endothelial cell dysfunction using human induced pluripotent stem cells derived from patients with end-stage renal disease

Background@#Endothelial cell (EC) dysfunction is a frequent feature in patients with end-stage renal disease (ESRD). The aim of this study was to generate human induced pluripotent stem cells, differentiate ECs (hiPSC-ECs) from patients with ESRD, and appraise the usefulness of hiPSC-ECs as a model to investigate EC dysfunction. @*Methods@#We generated hiPSCs using peripheral blood mononuclear cells (PBMCs) isolated from three patients with ESRD and three healthy controls (HCs). Next, we differentiated hiPSC-ECs using the generated hiPSCs and assessed the expression of endothelial markers by immunofluorescence. The differentiation efficacy, EC dysfunction, and molecular signatures of EC-related genes based on microarray analysis were compared between the ESRD and HC groups. @*Results@#In both groups, hiPSCs and hiPSC-ECs were successfully obtained based on induced pluripotent stem cell or EC marker expression in immunofluorescence and flow cytometry. However, the efficiency of differentiation of ECs from hiPSCs was lower in the ESRD-hiPSCs than in the HC-hiPSCs. In addition, unlike HC-hiPSC-ECs, ESRD-hiPSC-ECs failed to form interconnecting branching point networks in an in vitro tube formation assay. During microarray analysis, transcripts associated with oxidative stress and inflammation were upregulated and transcripts associated with vascular development and basement membrane extracellular matrix components were downregulated in ESRD-hiPSC-ECs relative to in HC-hiPSC-ECs. @*Conclusion@#ESRD-hiPSC-ECs showed a greater level of EC dysfunction than HC-hiPSC-ECs did based on functional assay results and molecular profiles. hiPSC-ECs may be used as a disease model to investigate the pathophysiology of EC dysfunction in ESRD.

Tocotrienol regulates osteoclastogenesis in rheumatoid arthritis

Background/Aims@#The present study aimed to investigate whether tocotrienol regulates interleukin 17 (IL-17)-induced osteoclastogenesis in rheumatoid arthritis (RA). @*Methods@#We evaluated the effect of tocotrienol on IL-17-induced receptor activator of nuclear factor kappa B ligand (RANKL) production using RA fibroblast-like synoviocyte (FLS), together with real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Osteoclast differentiation was confirmed after culturing IL-17-treated RA FLS and Th17 cells with tocotrienol and monocytes. We analyzed the suppressive effect of tocotrienol on Th17 cells percentage or Th17-cytokine levels among peripheral blood mononuclear cells using flow cytometry. @*Results@#We found that IL-17 stimulated FLS to produce RANKL and tocotrienol decreased this IL-17-induced RANKL production. Tocotrienol decreased the IL-17-induced activation of mammalian target of rapamycin, extracellular signal-regulated kinase, and inhibitor of kappa B-alpha. When monocytes were incubated with IL-17, RANKL, IL-17-treated FLS or Th17 cells, osteoclasts were differentiated and tocotrienol decreased this osteoclast differentiation. Tocotrienol reduced Th17 cell differentiation and the production of IL-17 and sRANKL; however, tocotrienol did not affect Treg cell differentiation. @*Conclusions@#Tocotrienol inhibited IL-17- activated RANKL production in RA FLS and IL-17-activated osteoclast formation. In addition, tocotrienol reduced Th17 differentiation. Therefore, tocotrienol could be a new therapeutic choice to treat bone destructive processes in RA.

Cap-assisted Endoscopic Mucosal Resection of Rectal Perineurioma Mimicking a Neuroendocrine Tumor / 대한소화기학회지

Colorectal perineuriomas are benign mucosal-based mesenchymal tumors composed of perineurial cells and show serrated or hyperplastic crypts in epithelium on histopathological evaluation. Most perineuriomas are usually presented as sessile polyps and often as subepithelial tumors. In this case, colonoscopy revealed a rectal subepithelial tumor (measuring approximately 7 mm) with yellowish-colored normal mucosa. A rectal neuroendocrine tumor was suspected, and cap-assisted endoscopic mucosal resection was performed. Histopathological examination of the resected specimen revealed bland spindle cells showing immunopositivity for CD34.The patient was finally diagnosed with rectal perineurioma

Association between Relative Handgrip Strength and Dyslipidemia in Korean Adults: Findings of the 2014–2015 Korea National Health and Nutrition Examination Survey / 가정의학회지

Background@#Grip strength is a convenient method to measure muscle strength. Recently, relative handgrip strength (HGS) was recommended as a clinical predictor of metabolic health and disease, such as dyslipidemia, which is considered a risk factor for cardiovascular disease. The purpose of this study was to characterize the association between relative HGS and dyslipidemia. @*Methods@#We included 6,027 adults (2,934 men, 3,093 women) aged 30–69 years who participated in the Korea National Health and Nutrition Examination Survey in 2014 and 2015. Relative HGS was obtained by dividing the HGS by body mass index. Complex sampling analysis was conducted to compare the general characteristics of participants according to the quartiles of relative HGS. Logistic regression analysis was used to examine the association between quartiles of relative HGS and dyslipidemia. @*Results@#After adjustment for age, prevalence of diabetes mellitus, prevalence of hypertension, alcohol consumption, smoking status, exercise, income, and education level, relative HGS was inversely associated with dyslipidemia in both men and women. In multivariable logistic regression analysis, the odds ratios (95% confidence intervals) for dyslipidemia in quartiles 1, 2, and 3 relative to quartile 4 were 1.36 (1.00–1.83), 1.29 (0.98–1.70), 1.23 (0.95– 1.60) in men and 1.81 (1.30–2.50), 1.81 (1.32–2.47), 1.39 (1.07–1.81) in women, respectively. @*Conclusion@#Relative HGS was inversely associated with dyslipidemia risk in Korean adults. Muscle-strengthening exercise is recommended to enhance health outcomes.

N-acetyl-l-cysteine controls osteoclastogenesis through regulating Th17 differentiation and RANKL in rheumatoid arthritis

BACKGROUND/AIMS: This study aimed to determine the regulatory role of N-acetyl-l-cysteine (NAC), an antioxidant, in interleukin 17 (IL-17)-induced osteoclast differentiation in rheumatoid arthritis (RA). METHODS: After RA synovial fibroblasts were stimulated by IL-17, the expression and production of receptor activator of nuclear factor κ-B ligand (RANKL) was determined by real-time polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). Osteoclastogenesis was also determined after co-cultures of IL-17-stimulated RA synovial fibroblasts, Th17 cells and various concentrations of NAC with monocytes. After human peripheral CD4⁺ T cells were cultured with NAC under Th17 condition, IL-17, interferon γ, IL-4, Foxp3, RANKL, and IL-2 expression and production was determined by flow cytometry or ELISA. RESULTS: When RA synovial fibroblasts were stimulated by IL-17, IL-17 stimulated the production of RANKL, and NAC reduced the IL-17-induced RANKL production in a dose-dependent manner. NAC decreased IL-17-activated phosphorylation of mammalian target of rapamycin, c-Jun N-terminal kinase, and inhibitor of κB. When human peripheral blood CD14⁺ monocytes were cultured with macrophage colony-stimulating factor and IL-17 or RANKL, osteoclasts were differentiated, and NAC reduced the osteoclastogenesis. After human peripheral CD4⁺ T cells were co-cultured with IL-17-pretreated RA synovial fibroblasts or Th17 cells, NAC reduced their osteoclastogenesis. Under Th17 polarizing condition, NAC decreased Th17 cell differentiation and IL-17 and RANKL production. CONCLUSIONS: NAC inhibits the IL-17-induced RANKL production in RA synovial fibroblasts and IL-17-induced osteoclast differentiation. NAC also reduced Th17 polarization. NAC could be a supplementary therapeutic option for inflammatory and bony destructive processes in RA.

Intravenous Immunoglobulin Controls Th17 Cell-Mediated Osteoclastogenesis

The purpose of this study was to determine the regulatory role of intravenous Ig (IVIg) in Th17 cytokine–induced RANK ligand (RANKL) expression and osteoclast (OC) differentiation from OC precursors (pre-OC). Human CD14⁺ monocytes were isolated and stimulated by Th17 cytokines (IL-17, IL-21, and IL-22) and RANKL expression was investigated using a real-time PCR. CD14⁺ monocytes were incubated with RANKL, Th17 cytokines, and M-CSF, with/without IVIg, and OC differentiation was determined by counting tartrate-resistant acid phosphatase-positive multinucleated cells. OC differentiation was investigated after monocytes were cocultured with Th17 cells in the presence of IVIg. Th17 cell differentiation was determined using enzyme-linked immunosorbent assay and flow cytometry after CD4⁺ T cells were cultured with IVIg under Th17 condition. Th17 cytokines stimulated monocytes to express RANKL and IVIg suppressed the Th17 cytokine-induced RANKL expression. OCs were differentiated when pre-OC were cocultured with RANKL or Th17 cytokines and IVIg reduced the osteoclastogenesis. IVIg also decreased osteoclastogenesis when pre-OC were cocultured with Th17 cells. IVIg decreased both Th17 and Th1 cell differentiation while it did not affect Treg cell differentiation. In summary, IVIg inhibited Th17 cytokine-induced RANKL expression and OC differentiation. IVIg reduced osteoclastogenesis when monocytes were cocultured with Th17 cells. IVIg also reduced Th17 polarization. IVIg could be a new therapeutic option for Th17 cell–mediated osteoclastogenesis.

Blood transcriptome resources of chinstrap (Pygoscelis antarcticus) and gentoo (Pygoscelis papua) penguins from the South Shetland Islands, Antarctica

The chinstrap (Pygoscelis antarcticus) and gentoo (P. papua) penguins are distributed throughout Antarctica and the sub-Antarctic islands. In this study, high-quality de novo assemblies of blood transcriptomes from these penguins were generated using the Illumina MiSeq platform. A total of 22.2 and 21.8 raw reads were obtained from chinstrap and gentoo penguins, respectively. These reads were assembled using the Oases assembly platform and resulted in 26,036 and 21,854 contigs with N50 values of 929 and 933 base pairs, respectively. Functional gene annotations through pathway analyses of the Gene Ontology, EuKaryotic Orthologous Groups, and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were performed for each blood transcriptome, resulting in a similar compositional order between the two transcriptomes. Ortholog comparisons with previously published transcriptomes from the Adélie (P. adeliae) and emperor (Aptenodytes forsteri) penguins revealed that a high proportion of the four penguins’ transcriptomes had significant sequence homology. Because blood and tissues of penguins have been used to monitor pollution in Antarctica, immune parameters in blood could be important indicators for understanding the health status of penguins and other Antarctic animals. In the blood transcriptomes, KEGG analyses detected many essential genes involved in the major innate immunity pathways, which are key metabolic pathways for maintaining homeostasis against exogenous infections or toxins. Blood transcriptome studies such as this may be useful for checking the immune and health status of penguins without sacrifice.

N-acetyl-l-cysteine controls osteoclastogenesis through regulating Th17 differentiation and RANKL production in rheumatoid arthritis

In the article cited above, there was an error in the title.

Validation Study of an Operational Tolerance Signature in Korean Kidney Transplant Recipients

Operational tolerance (OT), defined as maintaining stable graft function without immunosuppression after transplant surgery, is an ideal goal for kidney transplant recipients (KTRs). Recent investigations have demonstrated the distinctive features of B cells, T cells, and dendritic cell-related gene signatures and the distributions of circulating lymphocytes in these patients; nonetheless, substantial heterogeneities exist across studies. This study was conducted to determine whether previously reported candidate gene biomarkers and the profiles of lymphocyte subsets of OT could be applied in Korean KTRs. Peripheral blood samples were collected from 153 patients, including 7 operationally tolerant patients. Quantitative real-time PCR and flow cytometry were performed to evaluate gene expression and lymphocyte subsets, respectively. Patients with OT showed significantly higher levels of B cell-related gene signatures (IGKV1D-13 and IGKV4-1), while T cell-related genes (TOAG-1) and dendritic cell-related genes (BNC2, KLF6, and CYP1B1) were not differentially expressed across groups. Lymphocyte subset analyses also revealed a higher proportion of immature B cells in this group. In contrast, the distributions of CD4⁺ T cells, CD8⁺ T cells, mature B cells, and memory B cells showed no differences across diagnostic groups. An OT signature, generated by the integration of IGKV1D-13, IGKV4-1, and immature B cells, effectively discriminated patients with OT from those in other diagnostic groups. Finally, the OT signature was observed among 5.6% of patients who had stable graft function for more than 10 years while on immunosuppression. In conclusion, we validated an association of B cells and their related signature with OT in Korean KTRs.

Spontaneous uterine rupture due to placenta percreta in the second trimester of pregnancy: a case report / 고신대학교의과대학학술지

A 32-year-old multiparous woman (gravida 2, para 2) with a history of previous cesarean section had acute abdominal pain and collapsed at 21 weeks of gestation. Exploratory laparotomy was performed because of the patient's worsening condition; ultrasound examination results were suggestive of massive hemoperitoneum, and fetus in vertex presentation with bradycardia. Uterine rupture between the left lower segment and borderline of the cervix in the anterior wall with active bleeding was confirmed. An uncomplicated classical cesarean section was performed, but the fetus was stillborn due to preterm birth. Hysterectomy was performed after the cesarean section. The patient was admitted to intensive care units for 3 days and was discharged in 12 days following delivery. Placenta percreta at the anterior lower segment of the uterus was confirmed in the pathology report.

Safety and immunologic benefits of conversion to sirolimus in kidney transplant recipients with long-term exposure to calcineurin inhibitors

BACKGROUND/AIMS: Sirolimus (SRL) is a promising immunosuppressant replacingcalcineurin inhibitors (CNIs). This study was performed to evaluate the safetyand immunologic benefits of conversion to SRL in stable kidney transplant (KT)recipients exposed to CNIs for long periods. METHODS: Fourteen CNI-treated KT recipients with stable renal function for morethan 10 years were included. Either 2 or 3 mg per day of SRL was administeredwhile CNIs were reduced by half starting on day 1, and then stopped 2 weeks afterSRL introduction. The safety of SRL conversion was assessed considering thegraft function, acute rejection, and graft loss. Immunologic alterations were measuredvia serial changes of T cell and B cell subsets after SRL conversion. Adverseeffects of SRL conversion were also evaluated. RESULTS: Conversion to SRL was successful in nine patients (64.2%). Conversionto SRL preserved graft function as compared to the baseline value (p = 0.115). Noacute rejection or allograft loss was observed during the follow-up period. Immunemonitoring of T and B cells revealed a regulatory T cells increase after SRL conversion (p = 0.028). Most adverse events developed within 6 weeks after SRLconversion, and oral mucositis was the main cause of SRL withdrawal. CONCLUSIONS: Conversion to SRL can be safe and has immunologic benefits in KTrecipients with long-term CNI exposure. Close monitoring of mucocutaneous adverseevents is, however, required in the early period after SRL conversion.

ERCC1 as a Predictive Marker for FOLFOX Chemotherapy in an Adjuvant Setting

PURPOSE: The purpose of this study was to identify the excision repair cross-complementation group 1 (ERCC1) as a predictive marker for FOLFOX adjuvant chemotherapy in stages II and III colon cancer patients. METHODS: A total of 166 high risk stages II and III colon cancer patients were retrospectively enrolled in this study, and data were collected prospectively. They underwent a curative resection followed by FOLFOX4 adjuvant chemotherapy. We analyzed ERCC1 expression in the primary colon tumor by using immunohistochemical staining. The oncological outcomes included the 5-year disease-free survival (DFS) rate. The DFS was analyzed by using the Kaplan-Meier method with the log-rank test. A Cox proportional hazard model was used for the prognostic analysis. RESULTS: ERCC1-positive expression was statistically significant in the older patients (P = 0.032). In the multivariate analysis, the prognostic factors for DFS were female sex (P = 0.016), N stage (P = 0.009), and postoperative carcinoembryonic antigen level (P = 0.001), but ERCC1 expression was not a statistically significant prognostic factor for DFS in the univariate analysis (P = 0.397). The 5-year DFS rate was not significantly associated with the ERCC1 expression in all patients (P = 0.396) or with stage III disease (P = 0.582). CONCLUSION: We found that ERCC1 expression was not significantly correlated with the 5-year DFS as reflected by the oncologic outcomes in patients with high-risk stages II and III colon cancer treated with FOLFOX adjuvant chemotherapy.

Retraction Notice to "Endoscopic Resection for Rectal Carcinoid Tumors: Comparision of Polypectomy and Endoscopic Submucosal Resection with Band Ligation"

This retracts the below mentioned article upon the authors' request.

Relationships among Parent-child Communication, Self-esteem and Sexual Assertiveness for Male and Female University Students: Gender Difference

PURPOSE: The purpose of this study was to compare the relationships among parent-child communication, self-esteem and sexual assertiveness for male and female university students. METHODS: This descriptive study used a comparative survey design that utilized self-report questionnaires. A total of 470 participants were male and female university students in B metropolitan city. RESULTS: The degree of open communication use was higher for female students in comparison to male students, There were no differences in dysfunctional communication for both the father-child communication. There were no differences between males and females for the mother-child communication either. The degree of self-esteem was higher for male students in comparison to the female students. The degree of sexual assertiveness was higher for female students in comparison to the male students. The grade, religion, major, allowance source, marital status of parents, and relationship experience with opposite sex were influencing factors for the male students' sexual assertiveness whereas the individual's major and physical contact were influencing factors for the female students. CONCLUSION: Self-esteem and mother-child open communication were influencing factors of sexual assertiveness. Thus, the nursing intervention based on the influencing factors is needed in order for male and female students to express sexual assertiveness.

Effect of chicken egg yolk antibody on canine parvoviral enteritis in pups / 대한수의학회지

Preventive and therapeutic effects of egg yolk antibody, immunoglobulin Y (IgY), against canine parvovirus (CPV) was evaluated in 25 pups orally challenged with CPV-2a. Oral administration of IgY using powder, paste and coated paste delivery systems was compared. Each type of IgY was administered orally for 17 days from 3 days before challenge. The group of pups administered coated IgY showed mild symptoms such as a moderate decrease in total white blood cell count, no depression, vomiting and diarrhea when compared with other groups. The overall clinical score of the group of pups administered coated IgY was significantly lower than that of the challenge control group. However, mortality did not differ among groups because not all pups received symptomatic treatment. These results implied that oral treatment of coated IgY could improve therapeutic effects against CPV challenge if pups received symptomatic treatment.

Primary Synovial Sarcoma of the Parietal Pleura: A Case Report

Synovial sarcoma is a malignant soft tissue tumor that most commonly occurs in the extremities of young and middle-aged adults, in the vicinity of large joints. Although synovial sarcoma is frequently associated with joints, it may arise in unexpected sites, such as the mediastinum, heart, lung, pleura, or chest wall. Primary synovial sarcoma of the pleura is rare. To date, nearly 36 cases of primary synovial sarcoma of the pleura have been reported since Gaertner et al. published the first case in 1996. The oncologic characteristics, treatment, and prognosis for pleural synovial sarcomas are not well defined because of a paucity of data. However, a multimodal approach, including surgical resection, chemotherapy, and radiotherapy, has generally been suggested. We report the outcome of one patient with primary pleural synovial sarcoma treated with radical resection and adjuvant treatment.

Endoscopic Resection for Rectal Carcinoid Tumors: Comparision of Polypectomy and Endoscopic Submucosal Resection with Band Ligation

BACKGROUND/AIMS: Rectal carcinoid tumors, at diagnosis, are as small as 10 mm or less in about 80% of patients. These tumors are generally removed by endoscopic resection. The aim of this study was to compare treatment efficacy and safety between endoscopic submucosal resection with band ligation (ESMR-L) and conventional polypectomy. METHODS: Between January 2005 and September 2010, a total of 88 patients, who visited at Busan Paik Hospital and Kosin University Gospel Hospital for endoscopic resection of rectal carcinoid, were reviewed, retrospectively. RESULTS: Thirty-three cases were treated by ESMR-L, and 55 cases by conventional polypectomy. There were no significant difference in the size of tumor between ESMR-L group and polypectomy group (6.02+/-2.36 vs. 6.49+/-3.24 mm, p=0.474). The rate of positive resection margin was significantly lower in ESMR-L group (2/33, 6.1%) than in polypectomy group (19/55, 34.5%; p=0.002). The rate of positive vertical resection margin, among others, was markedly lower in ESMR-L group (1/33, 3.0%) compared to polypectomy group (19/55, 34.5%; p<0.001). CONCLUSIONS: ESMR-L, rather than conventional polypectomy, is a useful treatment option for removal of rectal carcinoid tumors less than 10 mm in diameter.

A Case of Gastric Neuroendocrine Carcinoma Presenting as Early Gastric Cancer Diagnosed by Endoscopic Submucosal Dissection

Gastric neuroendocrine carcinomas are very rare, when compared with gastric adenocarinomas. In addition, it is difficult to distinguish between gastric adenocarcinoma and gastric neuroendocrine carcinoma histol-ogically without immunohistochemical staining. In most of the reported cases, neuroendocrine carcinomas were diagnosed at an advanced stage, confirmed postoperatively by histological examinations using immunohistochemical staining and associated with a poor prognosis. A 55-year-old woman was diagnosed as cellular atypia by screening endoscopy for her health check-up at a local clinic. Histological examination from the endoscopic specimen revealed suspicious early gastric cancer. Endoscopic submucosal dissection was performed for therapeutic and diagnostic purposes and the pathologic findings revealed neuroendocrine carcinoma. Herein, we report a case of gastric neuroendocrine carcinoma presenting as early gastric cancer that was diagnosed by endoscopic submucosal dissection.

A Case of Gastric Neuroendocrine Carcinoma Presenting as Early Gastric Cancer Diagnosed by Endoscopic Submucosal Dissection

Gastric neuroendocrine carcinomas are very rare, when compared with gastric adenocarinomas. In addition, it is difficult to distinguish between gastric adenocarcinoma and gastric neuroendocrine carcinoma histol-ogically without immunohistochemical staining. In most of the reported cases, neuroendocrine carcinomas were diagnosed at an advanced stage, confirmed postoperatively by histological examinations using immunohistochemical staining and associated with a poor prognosis. A 55-year-old woman was diagnosed as cellular atypia by screening endoscopy for her health check-up at a local clinic. Histological examination from the endoscopic specimen revealed suspicious early gastric cancer. Endoscopic submucosal dissection was performed for therapeutic and diagnostic purposes and the pathologic findings revealed neuroendocrine carcinoma. Herein, we report a case of gastric neuroendocrine carcinoma presenting as early gastric cancer that was diagnosed by endoscopic submucosal dissection.