{"title":"Heterotopic intestine and abdominal wall transplantation in a miniature swine: A model for graft immunology.","authors":"Yur-Ren Kuo, Yu-Han Chen, Yung-Sung Yeh, Chao-Wei Chang, Ching-Chun Li, Ting-Yu Cai, Han-Ching Chang, Yu-Tang Chang","doi":"10.1002/kjm2.12742","DOIUrl":"10.1002/kjm2.12742","url":null,"abstract":"<p><p>In order to accurately monitor graft immunology, we have developed a method for performing intestine and abdominal wall transplantation heterotopically in miniature swine. The procedure consisted of simultaneous segmental terminal ileum and full-thickness abdominal wall transplantation in Lanyu miniature swine, with the intestinal and the abdominal wall grafts being placed on the recipient's bilateral rear flank. Five transplantations were technically successful. One animal died on the first post-transplant day due to anesthesia-related issues, three abdominal wall and four intestinal grafts survived, while one abdominal wall graft failed due to vascular thrombosis. Acute cellular rejection (ACR) of the intestinal graft could occur preceding, simultaneously with or following ACR of the abdominal wall graft. Our experimental model demonstrates the technical feasibility of heterotopic intestine and abdominal wall transplantation in miniature swine without grafting in gastrointestinal continuity. This model could be suitable for further studies of graft immunology.</p>","PeriodicalId":49946,"journal":{"name":"Kaohsiung Journal of Medical Sciences","volume":" ","pages":"1129-1134"},"PeriodicalIF":3.3,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10353787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Silenced LASP1 interacts with DNMT1 to promote TJP2 expression and attenuate articular cartilage injury in mice by suppressing TJP2 methylation.","authors":"Lian Ren, Shi-Gao Cheng, Peng-Cheng Kang, Teng-Fei Li, Xun Li, Jiong-Zhe Xiao, Dong Jiang","doi":"10.1002/kjm2.12738","DOIUrl":"10.1002/kjm2.12738","url":null,"abstract":"<p><p>To investigate the regulatory mechanisms and effects of LIM and SH3 protein 1 (LASP1) on osteoarthritis (OA). IL-1β was used to induce OA in cell models. Viability and apoptosis of chondrocytes were assessed. The expressions of tumor necrsis factor-α (TNF-α) and IL-6 were measured by ELISA kit, and Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot were performed to test the expression of related proteins. The STRING database was used to predict the relationship between LASP1 and DNA methyltransferase 1 (DNMT1). The tight junction protein 2 (TJP2) and Gene Expression Omnibus data were analyzed for differential OA genes. Methylation-specific PCR detected methylation of the TJP2 promoter region, and chromatin immunoprecipitation detected the enrichment of DNMT1 in the TJP2 promoter region. Safranin O-Fast Green staining and hematoxylin and eosin staining were used to determine the OARSI score and evaluate the pathological conditions of the joint tissues. LASP1 was highly expressed in IL-1β-induced cell models. Silencing of LASP1 promoted chondrocyte proliferation and expression of Collagen II and Aggrecan and inhibited chondrocyte apoptosis, inflammatory factors, and matrix metalloprotein expression. TJP2 is weakly expressed in OA models, and LASP1 promotes methylation of the TJP2 promoter region by interacting with DNMT1. Silencing of LASP1 attenuated IL-1β-induced chondrocyte degeneration by promoting TJP2 expression. Similarly, silencing LASP1 promotes TJP2 expression to alleviate articular cartilage injury in mice with OA. Silencing of LASP1 inhibited the methylation of the TJP2 promoter region by interacting with DNMT1, thereby alleviating articular cartilage damage in OA mice.</p>","PeriodicalId":49946,"journal":{"name":"Kaohsiung Journal of Medical Sciences","volume":" ","pages":"1096-1105"},"PeriodicalIF":3.3,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9993773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Compare the effectiveness of extracorporeal shockwave and hyperbaric oxygen therapy on enhancing wound healing in a streptozotocin-induced diabetic rodent model.","authors":"Rong-Fu Chen, Yun-Nan Lin, Keng-Fan Liu, Chia-Chun Lee, Chieh-Ju Hu, Chun-Ting Wang, Ching-Jen Wang, Yur-Ren Kuo","doi":"10.1002/kjm2.12746","DOIUrl":"10.1002/kjm2.12746","url":null,"abstract":"<p><p>Studies have revealed that both extracorporeal shock-wave therapy (ESWT) and hyperbaric oxygen therapy (HBOT) can accelerate wound healing. This study aimed to compare the effectiveness of ESWT and HBOT in enhancing diabetic wound healing. A dorsal skin defect in a streptozotocin-induced diabetes rodent model was used. Postoperative wound healing was assessed once every 3 days. Histologic examination was performed with hematoxylin and eosin staining. Proliferation marker protein Ki-67 (Ki-67), endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), and 8-hydroxy-2-deoxyguanosine (8-OHdG) were evaluated with immunohistochemical (IHC) staining. The wound area was significantly reduced in the ESWT and HBOT groups compared to that in the diabetic controls. However, the wound healing time was significantly increased in the HBOT group compared to the ESWT group. Histological findings showed a statistical increase in neovascularization and suppression of the inflammatory response by both HBOT and ESWT compared to the controls. IHC staining revealed a significant increase in Ki-67, VEGF, and eNOS but suppressed 8-OHdG expression in the ESWT group compared to the HBOT group. ESWT facilitated diabetic wound healing more effectively than HBOT by suppressing the inflammatory response and enhancing cellular proliferation and neovascularization and tissue regeneration.</p>","PeriodicalId":49946,"journal":{"name":"Kaohsiung Journal of Medical Sciences","volume":" ","pages":"1135-1144"},"PeriodicalIF":3.3,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10194667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Klf6 aggravates myocardial ischemia/reperfusion injury by activating Acsl4-mediated ferroptosis.","authors":"Ma-Li Qiu, Wei Yan, Mo-Mu Liu","doi":"10.1002/kjm2.12733","DOIUrl":"10.1002/kjm2.12733","url":null,"abstract":"<p><p>Ferroptosis is closely related to myocardial ischemia/reperfusion (I/R) damage. Kruppel-like factor 6 (Klf6) can aggravate renal I/R injury. We aimed to elucidate the role of Klf6 in myocardial I/R damage as well as its potential mechanism. Myocardial I/R mice model and hypoxia/reoxygenation (H/R)-treated HL-1 cells were established. The levels of Fe<sup>2+</sup> , MDA, lipid ROS, and ferroptosis-related proteins were measured for assessing ferroptosis. Infarct area, H&E staining, cardiac function, and cell viability were detected for evaluating myocardial injury. Immunohistochemistry, immunofluorescence, western blot, and RT-qPCR were applied for detecting the levels of related genes. The m6A modification of Klf6, as well as the relationships between Klf6 and Mettl3, Igf2bp2, or Acsl4 promoter, was evaluated using MeRIP, RNA immunoprecipitation, RNA pull-down, chromatin immunoprecipitation, and luciferase reporter assay accordingly.Klf6 protein and mRNA levels, as well as Klf6 m6A modification, were elevated in HL-1 cells subjected to H/R and in the heart tissues from I/R mice. In H/R-challenged HL-1 cells, the binding relationships between Klf6 mRNA and Igf2bp2 or Mettl3 were confirmed; moreover, Igf2bp2 or Mettl3 knockdown decreased the Klf6 level and inhibited Klf6 mRNA stability. Klf6 knockdown restrained H/R-triggered cell viability loss, improved I/R-induced myocardial injury, and inhibited ferroptosis in myocardial I/R damage models. Klf6 directly bound to the Acsl4 promoter and positively regulated its expression. Acsl4 overexpression compromised the Klf6 knockdown-generated protective effect in HL-1 cells.m6A modification-regulated Klf6 aggravated myocardial I/R damage through activating Acsl4-mediated ferroptosis, thereby providing one potential target for the treatment of myocardial I/R.</p>","PeriodicalId":49946,"journal":{"name":"Kaohsiung Journal of Medical Sciences","volume":" ","pages":"989-1001"},"PeriodicalIF":3.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10278210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sen Yang, Li-Juan Guo, Yong Liang, Zhi-Ming He, Jia Luo, Yan-Dong Mu
{"title":"ADCY6 is a potential prognostic biomarker and suppresses OTSCC progression via Hippo signaling pathway.","authors":"Sen Yang, Li-Juan Guo, Yong Liang, Zhi-Ming He, Jia Luo, Yan-Dong Mu","doi":"10.1002/kjm2.12725","DOIUrl":"10.1002/kjm2.12725","url":null,"abstract":"<p><p>Oral tongue squamous cell carcinoma (OTSCC) is a malignant tumor. Recently, studies have found that adenylate cyclase 6 (ADCY6) plays a pivotal role in many lethal tumors formation processes. The role of ADCY6 in OTSCC remains unknown. The expression of ADCY6 in OTSCC tissue samples was detected. The clinical significance of ADCY6 in OTSCC was analyzed by statistical methods. OTSCC cell lines were selected to analyze the biological function of ADCY6. Meanwhile, the effect of ADCY6 on the growth of OTSCC in vivo was explored using subcutaneous tumorigenesis assay. WB assay was used to detect the underlying signaling pathway. Cell function recovery test used to investigate the mechanism of ADCY6-promoting OTSCC malignant biological behavior via Hippo signaling pathway. We report that ADCY6 was obviously downregulated in OTSCC tissue samples and cell lines. Importantly, lower expression of ADCY6 indicates a poorer prognosis in patients with OTSCC, and its expression is significantly correlated with TNM stage and tumor size. Functionally, forced expression of ADCY6 can significantly inhibit the proliferation, migration, invasion, and promote apoptosis of OTSCC cells. Mechanistically, we demonstrated that ADCY6 upregulation impaired Hippo signaling pathway to reduce the malignant biological behavior of OTSCC. Generally, our findings suggest that ADCY6 suppressed Hippo signaling pathway to regulate malignant biological behavior in OTSCC, which provide new cues for further exploring the mechanism of occurrence and development of OTSCC.</p>","PeriodicalId":49946,"journal":{"name":"Kaohsiung Journal of Medical Sciences","volume":" ","pages":"978-988"},"PeriodicalIF":3.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9991174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yu-Han Alice Hsu, Ting-Ting Yang, Shu-Mei Huang, Cheng-Che Eric Lan
{"title":"The effect of dipeptidyl peptidase-4 inhibitor on incidence and clinical course in bullous pemphigoid patients in a tertiary medical center.","authors":"Yu-Han Alice Hsu, Ting-Ting Yang, Shu-Mei Huang, Cheng-Che Eric Lan","doi":"10.1002/kjm2.12731","DOIUrl":"10.1002/kjm2.12731","url":null,"abstract":"<p><p>Several studies have reported an association between dipeptidyl peptidase 4 inhibitor (DPP4i), a commonly prescribed second-line oral antihyperglycemic drug, and bullous pemphigoid (BP). However, the benefits of DPP4i withdrawal in patients with BP remain controversial. This study primarily aimed to evaluate the clinical severity of DPP4i-associated BP by comparing it to those without Type 2 diabetes mellitus (DM). The secondary objective was to determine whether cessation of DPP4i is necessary for all patients with BP. This retrospective case-control study included 83 patients. The participants were divided into three groups according to their diabetic status and the status of discontinuance or continuance of DPP4i. The 12-month follow-up of the monthly dosage of systemic steroids per body weight (kg) and the percentage of systemic steroid off-therapy in these participants were recorded since the diagnosis of BP. Compared to patients with BP without DM, the 1st, 3rd, and 12th systemic prednisolone doses were significantly lower in the DPP4i group (p = 0.01684, 0.02559, and 0.009336, respectively). The 12th systemic prednisolone dose was significantly lower in patients who discontinued DPP4i (p = 0.0338). Nevertheless, several spontaneous remissions with systemic steroid off-therapy were also noted in the DPP4i-continuance group within 12 months of follow-up. This article supports the favorable impact of DPP4i withdrawal in patients with BP and shows that DPP4i may incite or aggravate BP, resulting in a milder disease course.</p>","PeriodicalId":49946,"journal":{"name":"Kaohsiung Journal of Medical Sciences","volume":" ","pages":"1038-1044"},"PeriodicalIF":3.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9975266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhao Su, Beier Hu, Jing Li, Zhichun Zeng, Hu Chen, Yuhang Guo, Yun Mao, Wen Cao
{"title":"Paeoniflorin inhibits colorectal cancer cell stemness through the miR-3194-5p/catenin beta-interacting protein 1 axis.","authors":"Zhao Su, Beier Hu, Jing Li, Zhichun Zeng, Hu Chen, Yuhang Guo, Yun Mao, Wen Cao","doi":"10.1002/kjm2.12736","DOIUrl":"10.1002/kjm2.12736","url":null,"abstract":"<p><p>Paeoniflorin (PF) is a natural plant ingredient with remarkable antitumor effects. Herein, we investigated the biological effects and mechanism of PF in colorectal cancer (CRC) cell stemness. The messenger RNA (mRNA) and protein expressions were assessed using quantitative real-time polymerase chain reaction and western blot. The viability, proliferation, and migration and invasion of CRC cells were evaluated using cell counting kit-8, clone-formation, and transwell migration and invasion assays, respectively. The sphere-formation capacity was determined using the sphere-formation assay. A dual-luciferase reporter gene assay was employed to analyze the interaction between miR-3194-5p and catenin beta-interacting protein 1 (CTNNBIP1). The viability, migration, invasion, epithelial-mesenchymal transition, and stemness of CRC cells were repressed by PF. MiR-3194-5p was upregulated in CRC tissues and cells. MiR-3194-5p knockdown suppressed CRC cell stemness, while miR-3194-5p overexpression had the opposite effect. In addition, the inhibition of CRC cell stemness caused by PF was eliminated by miR-3194-5p overexpression. CTNNBIP1 functioned as the target of miR-3194-5p, whose knockdown abrogated the repression of CRC cell stemness and Wnt/β-catenin signaling activation by PF.PF regulated the miR-3194-5p/CTNNBIP1/Wnt/β-catenin axis to repress CRC cell stemness.</p>","PeriodicalId":49946,"journal":{"name":"Kaohsiung Journal of Medical Sciences","volume":" ","pages":"1011-1021"},"PeriodicalIF":3.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9975260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Same MYH7 gene mutation but different phenotypes of cardiomyopathy in one family.","authors":"Ting Liu, Yuan Yao, Yu Kang, Qing Zhang","doi":"10.1002/kjm2.12741","DOIUrl":"10.1002/kjm2.12741","url":null,"abstract":"A 51-year-female presented to our hospital for repeated syncope. Eighteen years before, she had been diagnosed with hypertrophic obstructive cardiomyopathy and discharged after alcohol septal ablation with symptoms relieved. Family history revealed the patient's mother and her older brother had died suddenly at the age of 40 years of unidentified reason. Blood test was negative except for N-terminal pro-brain natriuretic peptide (NT-proBNP) 636 pg/mL and troponin T 35.4 ng/L. Echocardiography revealed asymmetric left ventricular hypertrophy with the interventricular septum (IVS) of 19 mm (Figure 1A) and left ventricular posterior wall (LVPW) of 12 mm, along with left atrial enlargement, normal systolic function (left ventricular ejection fraction: 57%) and Grade II diastolic dysfunction (transmitral E/A ratio 0.5). Cardiac magnetic resonance (CMR) showed multiple patchy late gadolinium enhancement (LGE) in the IVS (Figure 1B). Implantable cardioverter defibrillator was implanted for sudden cardiac death prevention. Family screening reported her asymptomatic daughter to have similar asymmetric and extreme LV hypertrophy (IVS 20 mm) with no left ventricular outflow tract obstruction on echocardiography and patchy LGE in the same area on CMR. However, the patient's younger brother, who suffered recurrent cerebral infarction with atrial fibrillation and recently admitted due to exertional shortness of breath, developed different abnormalities on echocardiography. Both atria were remarkably enlarged, exceeding his ventricles (Figure 1C). LV systolic function was preserved (left ventricular ejection fraction: 54%) while E/A ratio (>2) and E/e0 ratio (>15) was prominently increased, suggesting a typical restrictive filling pattern. Unlike the proband's, his left ventricular wall was only mildly thickened (IVS 12 mm and LVPW 12 mm) on echocardiography while CMR revealed no obvious thickening but diffuse patchy LGE in the left ventricular walls (Figure 1D). Based on these findings, his final diagnosis was restrictive cardiomyopathy.","PeriodicalId":49946,"journal":{"name":"Kaohsiung Journal of Medical Sciences","volume":" ","pages":"1052-1053"},"PeriodicalIF":3.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10059658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yi-An Chen, Hsiang-Lin Tsai, Peir-In Liang, Jaw-Yuan Wang
{"title":"A rare case of Menetrier's disease-induced gastric outlet obstruction.","authors":"Yi-An Chen, Hsiang-Lin Tsai, Peir-In Liang, Jaw-Yuan Wang","doi":"10.1002/kjm2.12735","DOIUrl":"10.1002/kjm2.12735","url":null,"abstract":"A 66-year-old female patient was brought to the emergency department (ED) of our hospital. She had a 3-day history of epigastric discomfort, nausea, coffee-ground emesis, and tarry stool passage. She also had gastric gastrointestinal stromal tumor (GIST) with partial gastrectomy in March 2021. The laboratory data demonstrated severe anemia, hypochlorhydria and hypoalbuminemia, with edema of her four limbs also noted. Emergent esophagogastroduodenoscopy (EGD) revealed hyperemic mucosal change in the body and a large ulcerated polypoid lesion in the posterior wall of the middle body spreading to pylorus-induced gastric outlet obstruction and much bloody material (Figure 1A), with biopsy reporting chronic gastritis and no evidence of Helicobacter pylori (H.P.) infection. The abdominal computed tomography scans (CT scans) showed gastric mucosal thickening along the greater curvature and antrum portion (Figure 1B). Although there was no evidence of malignancy, symptoms including epigastric","PeriodicalId":49946,"journal":{"name":"Kaohsiung Journal of Medical Sciences","volume":" ","pages":"1054-1055"},"PeriodicalIF":3.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9975264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}