JNM : Original Article ; Relevance of Ultrastructural Alterations of Intercellular Junction Morphology in Inflamed Human Esophagus

( Chia Chin Liu ),( Jeng Woei Lee ),( Tso Tsai Liu ),( Chih Hsun Yi ),( Chien Lin Chen ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2013 Journal of Neurogastroenterology and Motility (JNM Vol.19 No.3

Background/Aims Detailed characterization of the ultrastructural morphology of intercellular space in gastroesophageal reflux disease has not been fully studied. We aimed to investigate whether subtle alteration in intercellular space structure and tight junction proteins might differ among patients with gastroesophageal reflux disease. Methods Esophageal biopsies at 5 cm above the gastroesophageal junction were obtained from 6 asymptomatic controls, 10 patients with reflux symptoms but without erosions, and 18 patients with erosions. The biopsies were morphologically evaluated by transmission electron microscopy, and by using immunohistochemistry for tight junction proteins (claudin-1 and claudin-2 proteins). Results The expressions of tight junction proteins did not differ between asymptomatic controls and gastroesophageal reflux disease patients. In patients with gastroesophageal reflux disease, altered desmosomal junction morphology was only found in upper stratified squamous epithelium. Dilated intercellular space occurred only in upper stratified squamous epithelium and in patients with erosive esophagitis.Conclusions This study suggests that dilated intercellular space may not be uniformly present inside the esophageal mucosa and predom - inantly it is located in upper squamous epithelium. Presence of desmosomal junction alterations is associated with increased severity of gastroesophageal reflux disease. Besides dilated intercellular space, subtle changes in ultrastructural morphology of intercellular space allow better identification of inflamed esophageal mucosa relevant to acid reflux. (J Neurogastroenterol Motil 2013; 19:324-331)

Significant down-regulation of growth hormone receptor expression revealed as a new unfavorable prognostic factor in hepatitis C virus-related hepatocellular carcinoma

( Ching-chih Lin ),( Ta-wei Liu ),( Ming-lun Yeh ),( Yi-shan Tsai ),( Pei-chien Tsai ),( Chung-feng Huang ),( Jee-fu Huang ),( Wan-long Chuang ),( Chia-yen Dai ),( Ming-lung Yu ) 대한간학회 2021 Clinical and Molecular Hepatology(대한간학회지) Vol.27 No.2

Background/Aims: Growth hormone (GH) is the main regulator of somatic growth, metabolism, and gender dimorphism in the liver. GH receptor (GHR) signaling in cancer is derived from a large body of evidence, although the GHR signaling pathway involved in the prognosis of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related HCC, remains unclear. We aimed to explore the expression of GHR and analyze its association with clinicopathologic features and prognosis of patients with chronic hepatitis C and HCC. Methods: The expression of GHR mRNA was investigated by quantitative real-time polymerase chain reaction in paired tumors and adjacent non-tumorous (ANT) liver tissues of 200 patients with chronic hepatitis C and HCC. Western blotting and immunofluorescence assays using the HCV-infected Huh7.5.1 cell model was performed. Results: GHR mRNA was significantly lower in HCV-HCC tissues than in corresponding ANT liver tissues. GHR mRNA and protein levels also decreased in the HCV-infected Huh7.5.1 cell model. Notably, lower GHR expression was associated with age of >60 years (P=0.0111) and worse clinicopathologic characteristics, including alpha-fetoprotein >100 ng/mL (P=0.0403), cirrhosis (P=0.0075), vascular invasion (P=0.0052), pathological stage II-IV (P=0.0002), and albumin ≤4.0 g/dL (P=0.0055), which were linked with poor prognosis of HCC. Most importantly, the high incidence of recurrence and poor survival rates in patients with a low ratio of tumor/ANT GHR (≤0.1) were observed, indicating that low expression levels of GHR had great risk for development of HCC in patients with chronic hepatitis C. Conclusions: Our study demonstrates a significant down-regulation of GHR expression as a new unfavorable independent prognostic factor in patients with chronic hepatitis C and HCC. (Clin Mol Hepatol 2021;27:313-328)

Angelica dahurica attenuates melanogenesis in B16F0 cells by repressing Wnt/β-catenin signaling

Fang Chien-Liang,Goswami Debakshee,Kuo Chia-Hua,Day Cecilia Hsuan,Lin Mei-Yi,Ho Tsung-Jung,Yang Liang-Yo,Hsieh Dennis Jine-Yuan,Lin Tzu-Kai,Huang Chih-Yang 대한독성 유전단백체 학회 2023 Molecular & cellular toxicology Vol.19 No.1

Background Melanogenesis is a complex process which is tightly regulated by several enzymes. However, abnormal melanogenesis can cause severe dermatological problems. Roots of Angelica dahurica have been used for skin care as a part of traditional Chinese medicine for many generations. However, the role of A. dahurica in melanogenesis remains unclear. Objective Previous in vitro and in vivo studies have demonstrated that NK-1R exerts positive effects in melanogenesis via the Wnt/βcatenin signaling pathway. In this study, we investigated the effects of A. dahurica ethanol extract (ADE) on NK-1R and Wnt/β-catenin signaling, and evaluated the effect of NK-1R on melanogenesis in B16F0 cells. Results Angelica dahurica ethanol extract efficiently downregulated Neurokinin-1 receptor and Wnt/β-catenin signaling by decreasing the expression of β-catenin, MITF, LEF-1, TYR, TRP1, and TRP2 and increasing the expression of GSK3β, which resulted from the weakened expression of the Neurokinin-1 receptor inhibitor [Sar9,Met(O2 )11]-Substance P (SMSP). Furthermore, the intracellular melanin assay and cellular tyrosinase activity confirmed these findings. Conclusion This study suggests that ADE has potential to downregulate Neurokinin-1 receptor in SMSP-induced B16F0 cells, thereby repressing the Wnt/β-catenin signaling and reduces melanin production.

Galangin Prevents Acute Hepatorenal Toxicity in Novel Propacetamol-Induced Acetaminophen-Overdosed Mice

Ming-Shiun Tsai,Chia-Chih Chien,Ting-Hui Lin,Chia-Chi Liu,Rosa Huang Liu,Hong-Lin Su,Yung-Tsung Chiu,Sue-Hong Wang 한국식품영양과학회 2015 Journal of medicinal food Vol.18 No.11

Acetaminophen (APAP) overdose causes severe liver and kidney damage. APAP-induced liver injury (AILI) represents the most frequent cause of drug-induced liver failure. APAP is relatively insoluble and can only be taken orally; however, its prodrug, propacetamol, is water soluble and usually injected directly. In this study, we examined the timedependent effects of AILI after propacetamol injection in mice. After analyses of alanine aminotransferase and aspartate aminotransferase activities and liver histopathology, we demonstrated that a novel AILI mouse model can be established by single propacetamol injection. Furthermore, we compared the protective and therapeutic effects of galangin with a known liver protective extract, silymarin, and the only clinical agent for treating APAP toxicity, N-acetylcysteine (NAC), at the same dose in the model mice. We observed that galangin and silymarin were more effective than NAC for protecting against AILI. However, only NAC greatly improved both the survival time and rate consequent to a lethal dose of propacetamol. To decipher the hepatic protective mechanism(s) of galangin, galangin pretreatment significantly decreased the hepatic oxidative stress, increased hepatic glutathione level, and decreased hepatic microsomal CYP2E1 levels induced by propacetamol injection. In addition, propacetamol injection also reproduced the probability of APAP-induced kidney injury (AIKI), appearing similar to a clinical APAP overdose. Only galangin pretreatment showed the protective effect of AIKI. Thus, we have established a novel mouse model for AILI and AIKI using a single propacetamol injection. We also demonstrated that galangin provides significant protection against AILI and AIKI in this mouse model.

Molecular Identification of Diphyllobothrium latum from a Pediatric Case in Taiwan

Yu-Chin An,Chia-Cheng Sung,Chih-Chien Wang,Hsin-Chung Lin,Kuang-Yao Chen,Fu-Man Ku,Ruei-Min Chen,Mei-Li Chen,Kuo-Yang Huang 대한기생충학열대의학회 2017 The Korean Journal of Parasitology Vol.55 No.4

Malignant transformation of ovarian mature cystic teratoma into squamous cell carcinoma: a Taiwanese Gynecologic Oncology Group (TGOG) study

An Jen Chiang,Min-Yu Chen,Chia-Sui Weng,Hao Lin,Chien-Hsing Lu,Peng-Hui Wang,Yu-Fang Huang,Ying-Cheng Chiang,Mu-Hsien Yu,Chih-Long Chang 대한부인종양학회 2017 Journal of Gynecologic Oncology Vol.28 No.5

Objective: The malignant transformation (MT) of ovarian mature cystic teratoma (MCT)to squamous cell carcinoma (SCC) is very rare. This study analyzed cases from multiplemedical centers in Taiwan to investigate the clinicopathologic characteristics, treatment, andprognostic factors of this disease and reviewed related literature. Methods: Pathological reports of 16,001 patients with primary ovarian cancer who weretreated at Taiwan medical centers from 1990 to 2011 were reviewed. In total, 52 patients withMT of MCT to SCC were identified. Results: Among all ovarian MCTs, the incidence of MT to SCC is 0.2%. The median age ofpatients was 52 years (range, 29–89 years), and the mean tumor size was 10.5 cm (range, 1–40cm). We analyzed the patients in our study and those in the literature and determined thatearly identification and complete surgical resection of the tumor are essential for long-termsurvival. In addition, adjuvant chemotherapy or concurrent chemoradiotherapy can be usedto treat this malignancy. Old age, large tumor size (≥15.0 cm), and solid components in MCTsare suitable indicators predicting the risk of MT of MCT to SCC. Conclusion: Similar to general epithelial ovarian cancers, the early detection of MT of MCTto SCC is critical to long-term survival. Therefore, older patients with a large tumor or those with a tumor containing a solid component in a clinically diagnosed MCT should beevaluated to exclude potential MT to SCC.

Indoxyl sulfate, homocysteine, and antioxidant capacities in patients at different stages of chronic kidney disease

Chen Cheng-Hsu,Huang Shih-Chien,Yeh En-Ling,Lin Pei-Chih,Tsai Shang-Feng,Huang Yi-Chia 한국영양학회 2022 Nutrition Research and Practice Vol.16 No.4

BACKGROUND/OBJECTIVES Increased levels of uremic toxins and decreased antioxidant capacity have a significant impact on the progression of chronic kidney disease (CKD). However, it remains unclear whether they interact with each other to mediate the damage of kidney function. The purpose of this study was to investigate whether uremic toxins (i.e., homocysteine and indoxyl sulfate [IS]), as well as glutathione-dependent antioxidant enzyme activities are dependently or independently associated with kidney function during different stages of CKD patients. SUBJECTS/METHODS One hundred thirty-two patients diagnosed with CKD at stages 1 to 5 participated in this cross-sectional study. RESULTS Patients who had reached an advanced CKD stage experienced an increase in plasma uremic toxin levels, along with decreased glutathione peroxidase (GSH-Px) activity. Plasma homocysteine, cysteine, and IS concentrations were all positively associated with each other, but negatively correlated to GSH-Px activity levels after adjusting for potential confounders in all CKD patients. Although plasma homocysteine, cysteine, IS, and GSH-Px levels were significantly associated with kidney function, only plasma IS levels still had a significant association with kidney function after these parameters were simultaneously adjusted. In addition, plasma IS could interact with GSH-Px activity to be associated with kidney function. CONCLUSIONS IS plays a more dominant role than homocysteine and GSH-Px activity in relation to kidney function.