The functional and morphologic cardiac developments are determined by the morphogenesis, growth and remodeling of the heart resulted from the cell proliferation and apoptosis. We studied the distribution of the proliferation and apoptotic activity of myocardial cells according to the developmental stages in embryos of C57bl/6 mice. Serial histologic sections were stained with PCNA and TUNEL method and were analyzed with image analyzer (BMI, Seoul). The ventricular myocardium of an embryonic heart could be divided into trabecular, inner compact and outer compact layers. Proliferation indices at layers of the left ventricular myocardium on embryonal days (ED) 13, 14, 16, 17 and 18 were 19.9%/47.4%/60.4%, 16.1%/45.8%/60.3%, 24.6%/45.6%/38.1%, 23.3%/17.7%/18.3% and 31.2%/28.0%/19.4% (trabecular/ inner compact/ outer compact) and the right ventricle, 11.0%/34.4%/60.5%, 23.0%/44.0%/69.0%, 29.2%/42.9%/35.1%, 30.4%/30.5%/22.3% and 32.4%/28.4%/16.3%. The apoptotic indices of the left ventricle/VIF were 0.23%/3.66% on ED 13-14, 0.42%/1.31% on ED 16 and 0.05%/0.60% on ED 17-18. The results show that the proliferation of the myocytes was maximal at the outer compact layer on ED 13 and 14 but lowest on ED 17 and 18. This decrease was more pronounced at the left ventricle. The innermost trabecular layer showed a constant proliferation activity of 11.0-32.4%. The presence of spatiotemporal differences in the cell proliferation reveals regional regulation in the developmental timing of cardiac development. Functional maturation is considered to be responsible for the change of proliferation activity. The apoptosis was most frequent and intense in the VIF and crux throughout the periods of each embryonal day where as rarely seen in the ventricular myocardium, especially in the trabecular layer of myocardium. These findings suggest that the apoptosis plays the role in the development of atrioventricular, ventriculoarterial septation and valve formation. Our results also reveal that the participation of apoptosis in formation of the trabeculation can be denied.
Animals ; Apoptosis* ; Cell Proliferation* ; Embryonic Structures ; Heart ; Heart Ventricles ; In Situ Nick-End Labeling ; Mice ; Morphogenesis ; Muscle Cells ; Myocardium ; Proliferating Cell Nuclear Antigen

BACKGROUND: Identification of atrial situs is the initial step in any segmental analysis and classification of congenital heart malformations. To elucidate the differences for both atria of the normal and congenitally malformed heart, we performed morphological studies on the human heart with or without abnormal laterality syndrome. METHODS: Five normally formed human hearts, five hearts with right isomerism and five hearts with left isomerism were used in this study. The postero-superior walls of the atrial chambers were examined. RESULTS: Although the division line of the ventral and dorsal compartments was not as conspicuous as was seen in the right atrium of rat embryo previously studied, this division line existed as a well-developed terminal crest and vestigial structure of the antero-lateral extension of the terminal crest. These structures were noted in the right atrial chambers of normal human hearts and in the bilateral atrial chambers of right isomerism. However, they were totally absent in the bilateral atrial chambers in hearts with left isomerism. CONCLUSIONS: Our study showed that the right atrial chamber in the normally developed human heart has vestigial components of division between the ventral and dorsal compartment, and hearts with right isomerism and left isomerism have differential development of the ventral and the dorsal compartment.
Animals ; Classification ; Embryonic Structures ; Heart Atria ; Heart Defects, Congenital ; Heart* ; Humans ; Isomerism ; Morphogenesis ; Rats

BACKGROUND: Protease-sensing molecular optical imaging can potentially identify vulnerable atherosclerotic plaques before cerebral infarcts occur. However, several translational issues need to be resolved before implementing human trials and clinical applications of the technique. We investigated whether molecular optical imaging reflects (1) atherosclerosis pathophysiology and (2) the atherosclerosis-modulating effect of a Western diet or atorvastatin treatment in ApoE-knockout mice. METHODS: We fed 21 8-week-old ApoE-knockout mice a normal chow diet (n=7), a Western diet (n=7), or a Western diet with atorvastatin (n=7) for 14 weeks. Blood was collected for measuring cholesterol levels at 24 hours after injecting the cathepsin-B (CatB) probe into the tail vein. Near-infrared fluorescence reflectance imaging of CatB activity was performed after excising the aorta. RESULTS: CatB molecular optical imaging precisely reflected the pathophysiologic alteration of atherosclerosis. The CatB activity signal was significantly stronger in the Western diet group (49.3+/-26.0 [mean+/-SD], arbitrary units) than in the atorvastatin group (25.3+/-8.7) and the normal chow diet group (20.6+/-21.1). The effect of the statin on CatB activity was independent of cholesterol lowering. CONCLUSIONS: CatB-sensing molecular optical imaging represents a valuable tool for evaluating atherosclerosis pathophysiology and for monitoring the effects of antiatherosclerotic therapeutic interventions.
Animals ; Aorta ; Atherosclerosis ; Cathepsins ; Cholesterol ; Diet ; Fluorescence ; Heptanoic Acids ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Mice ; Molecular Imaging ; Optical Imaging ; Plaque, Atherosclerotic ; Pyrroles ; Veins ; Atorvastatin Calcium

Silymarin from milk thistle (Silybum marianum) has been reported to show an anti-cancer activity. In previous study, we reported that silymarin induces cyclin D1 proteasomal degradation through NF-κB-mediated threonine-286 phosphorylation. However, mechanism for the inhibition of Wnt signaling by silymarin still remains unanswered. Thus, we investigated whether silymarin affects Wnt signaling in human colorectal cancer cells to elucidate the additional anti-cancer mechanism of silymarin. Transient transfection with a TOP and FOP FLASH luciferase construct indicated that silymarin suppressed the transcriptional activity of β-catenin/TCF. Silymarin treatment resulted in a decrease of intracellular β-catenin protein but not mRNA. The inhibition of proteasome by MG132 and GSK3β inhibition by SB216763 blocked silymarin-mediated downregulation of β-catenin. In addition, silymarin increased phosphorylation of β-catenin and a point mutation of S33Y attenuated silymarin-mediated β-catenin downregulation. In addition, silymarin decreased TCF4 and increased Axin expression in both protein and mRNA level. From these results, we suggest that silymarin-mediated downregulation of β-catenin and TCF4 may result in the inhibition of Wnt signaling in human colorectal cancer cells.
Colorectal Neoplasms* ; Cyclin D1 ; Down-Regulation ; Humans* ; Luciferases ; Milk Thistle ; Phosphorylation ; Point Mutation ; Proteasome Endopeptidase Complex ; RNA, Messenger ; Silymarin* ; Transfection

Morphologic features and pathogenesis of arterial changes occurring in Buerger's disease (thromboangiitis obliterans) are still controversial. This study describes histopathologic features of medium sized arteries from patients with Buerger's disease, particularly of the internal elastic lamina in relation to the immunologic mechanism of the injury. Seventeen segments of occluded arteries (femoral or popliteal arteries) from 17 patients with Buerger's disease were analyzed by histopathological and immunohistochemical methods. The most characteristic features were total luminal obliteration, together with a varying degree of recanalization and deposition of hemosiderin pigments. Detailed analysis, however, showed marked undulation and multiplication of the internal elastic lamina (100%) associated with basophilic degeneration and delicate linear calcification (47%). Lymphocytic infiltration along the internal elastic lamina was seen in 71% and was associated with localized edema. Lymphocytes along the lamina were consistently positive for T cell marker. Mild to moderate fibrosis was present at the media in 24%. Adventitial changes included mild, nonspecific and irregular fibrosis seen in 53%. Immunologic injury to the internal elastic lamina associated with T-lymphocytic infiltration might be the initial morphogenetic mechanism of the thrombotic occlusion and organization of medium-sized arteries in Buerger's disease.
Adult ; B-Lymphocytes/pathology ; Elastic Tissue/pathology ; Elastic Tissue/immunology ; Female ; Femoral Artery/pathology* ; Femoral Artery/immunology ; Femoral Artery/anatomy & histology ; Fibrosis ; Human ; Male ; Middle Age ; Popliteal Artery/pathology* ; Popliteal Artery/immunology ; Popliteal Artery/anatomy & histology ; T-Lymphocytes/pathology ; Thromboangiitis Obliterans/pathology* ; Thromboangiitis Obliterans/immunology

Naringenin (NAR) as one of the flavonoids observed in grapefruit has been reported to exhibit an anti-cancer activity. Activating transcription factor 3 (ATF3) is associated with apoptosis in human colon cancer cells. This study was performed to investigate the molecular mechanism by which NAR stimulates ATF3 expression and apoptosis in human colon cancer cells. NAR reduced the cell viability and induced an apoptosis in human colon cancer cells. ATF3 overexpression increased NAR-mediated cleaved PARP, while ATF3 knockdown attenuated the cleavage of PARP by NAR. NAR increased ATF3 expression in both protein and mRNA level, and increased the luciferase activity of ATF3 promoter in a dose-dependent manner. The responsible region for ATF3 transcriptional activation by NAR is located between -317 and -148 of ATF3 promoter. p38 inhibition blocked NAR-mediated ATF3 expression, its promoter activation and apoptosis. The results suggest that NAR induces apoptosis through p38-dependent ATF3 activation in human colon cancer cells.
Activating Transcription Factor 3 ; Apoptosis* ; Cell Survival ; Citrus paradisi ; Colon* ; Colonic Neoplasms* ; Flavonoids ; Humans* ; Luciferases ; RNA, Messenger ; Transcriptional Activation

Naringenin (NAR) as one of the flavonoids observed in grapefruit has been reported to exhibit an anti-cancer activity. However, more detailed mechanism by which NAR exerts anti-cancer properties still remains unanswered. Thus, in this study, we have shown that NAR down-regulates the level of cyclin D1 in human colorectal cancer cell lines, HCT116 and SW480. NAR inhibited the cell proliferation in HCT116 and SW480 cells and decreased the level of cyclin D1 protein. Inhibition of proteasomal degradation by MG132 blocked NAR-mediated cyclin D1 downregulation and the half-life of cyclin D1 was decreased in the cells treated with NAR. In addition, NAR increased the phosphorylation of cyclin D1 at threonine-286 and a point mutation of threonine-286 to alanine blocked cyclin D1 downregulation by NAR. p38 inactivation attenuated cyclin D1 downregulation by NAR. From these results, we suggest that NAR-mediated cyclin D1 downregulation may result from proteasomal degradation through p38 activation. The current study provides new mechanistic link between NAR, cyclin D1 downregulation and cell growth in human colorectal cancer cells.
Alanine ; Cell Line ; Cell Proliferation ; Citrus paradisi ; Colorectal Neoplasms* ; Cyclin D1* ; Down-Regulation* ; Flavonoids ; Half-Life ; Humans ; Phosphorylation ; Point Mutation

Adult pancreatic hemangioma is an extremely rare disease, with only 22 cases reported since 1939. Pancreatic hemangioma has no specific symptoms, diagnostic imaging, or laboratory findings, making it difficult to be clinically suspected and diagnosed. The majority are confirmed after surgery. In this report, a 61-year-old woman presented with melena and showed multiple small hyper- vascular lesions in the pancreas. A pancreatic neuroendocrine tumor was suspected, and the patient underwent a distal pancreatectomy. The pathology examination and immunohistochemical study revealed a pancreatic hemangioma.

Hepatocellular carcinoma(HCC) of unknown origin presents unusually in the elderly as a huge abdominal mass. Though most commonly associated with viral infections, about 10% of HCC in Korea arise from an unknown cause. HCC of unknown origin has a varying clinical picture and prognosis. It is known to have relatively good reserve liver function and rarely complications with previous cirrhosis or active hepatitis. Its pathogenesis may be not associated with an inflammation-dysplasia-carcinoma sequence. We recently managed an unusual case of moderately differentiated hepatocellular carinoma of unknown origin presenting with a huge abdominal mass. The 82-year-old female patient had no history of viral hepatitis and no other metabolic diseases were diagnosed. She received palliative care.
Aged ; Aged, 80 and over ; Carcinoma, Hepatocellular ; Female ; Fibrosis ; Hepatitis ; Humans ; Korea ; Liver ; Metabolic Diseases ; Neoplasms, Unknown Primary ; Prognosis

Background: To identify work–family balance and level of happiness among married women dental hygienists in Seoul and Gyeonggi Province. The goal of this study is to use the outcome as basic data to determine the compatibility of dental hygienists with work and family, systems, and improvement of happiness levels. Methods: From July 3 to August 10, 2020, 250 dental hygienists in Seoul and Gyeonggi Province were targeted. The questionnaire comprised 65 questions, including general characteristics (perception of work–family balance, perception of work–family balance system, job satisfaction, parenting type, happiness level) whether or not they were implemented. The results were obtained through a self-control questionnaire. Results: The perception of work–family balance was significantly different in job rank and average income, while that of the work– family balance system had significant differences in workplace type, total work experience, current job work experience, childcare system status, and parental leave period. Happiness level and job satisfaction were significantly different in job rank, average income, and childcare system status. Additionally, the perception of work–family balance and that of the work–family balance system showed a positive correlation with job satisfaction and happiness level. Finally, the perception of married women dental hygienists toward work–family compatibility was determined, where the higher the satisfaction with the job, the higher the level of happiness. Conclusion To improve the work–family balance and job satisfaction of dental hygienists and their levels of happiness, changes in social perception and improvement of the working environment such as proper staffing, flexible work systems, and incentive systems should be considered.