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Foam cells are one of the major cellular components of atherosclerotic plaques, within which the trace of periodontal pathogens has also been identified in recent studies. In line with these findings, the correlation between periodontitis and atherosclerotic cardiovascular incidences has been repetitively supported by evidence from a number of experimental studies. However, the direct role of periodontal pathogens in altered cellular signaling underlying such cardiovascular events has not been clearly defined. To determine the role of periodontal pathogens in the pathogenesis of atherosclerosis, especially in the evolution of macrophages into foam cells, we monitored the pattern of lipid accumulation within macrophages in the presence of periodontal pathogens, followed by characterization of these lipids and investigation of major molecules involved in lipid homeostasis. The cells were stained with the lipophilic fluorescent dye BODIPY 493/503 and Oil Red O to characterize the lipid profile. The amounts of Oil Red O-positive droplets, representing neutral lipids, as well as fluorescent lipid aggregates were prominently increased in periodontal pathogen-infected macrophages. Subsequent analysis allowed us to locate the accumulated lipids in the endoplasmic reticulum. In addition, the levels of cholesteryl ester in periodontal pathogen-infected macrophages were increased, implying disrupted lipid homeostasis. Further investigations to delineate the key messengers and regulatory factors involved in the altered lipid homeostasis have revealed alterations in cholesterol efflux-related enzymes, such as ABCG1 and CYP46A1, as contributors to foam cell formation, and increased Ca 2+ signaling and reactive oxygen species (ROS) production as key events underlying disrupted lipid homeostasis. Consistently, a treatment of periodontal pathogen-infected macrophages with ROS inhibitors and nifedipine attenuated the accumulation of lipid droplets, further confirming periodontal pathogen-induced alterations in Ca 2+ and ROS signaling and the subsequent dysregulation of lipid homeostasis as key regulatory events underlying the evolution of macrophages into foam cells.

A strong correlation between chronic periodontitis and systemic diseases (e.g., cardiovascular disease, metabolic disorders) has been suggested for several decades. However, the evidence supporting this correlation is restricted primarily to epidemiologic studies, with only a few experimental outcomes confirming such a correlation and providing information about the underlying molecular mechanisms. To reveal a correlation between periodontitis and systemic diseases as well as a relevant molecular pathway, we investigated the effects of Porphyromonas gingivalis and Fusobacterium nucleatum , which play roles in chronic periodontitis progression, on Raw264.7 and THP-1 macrophages. Infection with P. gingivalis or F. nucleatum significantly induced the expression of fatty acid binding protein 4 (FABP4), one of the most important adipokines that play a role in the progression of systemic diseases such as atherosclerosis and type 2 diabetes. Periodontal pathogen-induced FABP4 expression in macrophages promoted lipid uptake by these cells, as demonstrated by the diminished lipid accumulation in cells treated with an FABP4 inhibitor, BMS309403, or with knockdown of FABP4 expression. This periodontal pathogen-induced FABP4 expression was dependent on the JNK pathway, and JNK inhibition reduced lipid uptake by reducing FABP4 expression. Serum levels of antibodies against P. gingivalis correlated with serum FABP4 levels in humans, whereas no association occurred between F. nucleatum antibody titers and FABP4 levels. To our knowledge, this report is the first to experimentally demonstrate that periodontal pathogens stimulate lipid uptake in macrophages by modulating FABP4 expression. These findings strongly support the hypothesis that periodontitis may affect the progression of various systemic diseases.

Objective: Although leptin appears to be an important local and systemic factor influencing cartilage homeostasis, the role of leptin in chondrocyte death is largely unknown. Tumor necrosis factor α (TNF-α) is a pro-inflammatory cytokine that plays a central role in the pathogenesis of articular diseases. This study examines whether leptin modulates TNF-α-induced articular chondrocyte death., Methods: Primary rat articular chondrocytes were isolated from knee joint cartilage slices. To induce cell death, the chondrocytes were treated with TNF-α. To examine whether leptin modulates the extent of TNF-α-mediated chondrocyte death, the cells were pretreated with leptin for 3 h before TNF-α treatment followed by viability analysis. To examine the mechanism by which leptin modulates the extent of TNF-α-mediated chondrocyte death, we utilized mitochondrial membrane potential (MMP) measurements, flow cytometry, nuclear morphology observation, co-immunoprecipitation, western blot analysis and confocal microscopy., Results: We demonstrated that leptin suppresses TNF-α induced chondrocyte death. We further found that apoptosis partially contributes to TNF-α induced chondrocyte death while necroptosis primarily contributes to TNF-α induced chondrocyte death. In addition, we observed that leptin exerts anti-TNF-α toxicity via c-jun N-terminal kinase (JNK) in rat articular chondrocytes., Conclusion: Based on our findings, we suggest that the leptin present in the articular joint fluid protects articular chondrocytes against cumulative mechanical load and detrimental stresses throughout a lifetime, delaying the onset of degenerative changes in chondrocytes. We can further hypothesize that leptin protects articular chondrocytes against destructive stimuli even in the joints of osteoarthritis (OA) patients., (Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objectives: Protein kinase casein kinase II (PKCK2) has multiple, overlapping roles in induction of apoptosis. Apoptosis can be a common pathway of renal injury caused by a nephrotoxic drug or an injury. We evaluated the role of PKCK2 in cyclosporine (CsA)-induced nephropathy in rats by inhibiting PKCK2 with emodin., Methods: Male Sprague-Dawley rats fed a low-sodium diet were divided into four treatment groups: control (0.9% saline injection), CsA (15 mg/kg/d subcutaneously), CsA + emodin (CsA plus emodin 20 mg/kg/d subcutaneously), and emodin only. The expression levels of apoptosis-associated factors and of PKCK2 were examined by Western blot analysis., Results: Overexpression of PKCK2 noted with CsA treatment was prevented by emodin, a low-molecular-weight PKCK2 inhibitor, which dampend drug-induced up-regulation phosphorylated p53 and activation of caspases 3, 7, and 8. In addition, emodin prevented increased Bax/Bcl-2 ratio induced by CsA. Emodin prevented up-regulation of PKCK2 by CsA treatment, suggesting that its apoptotic-preventing activity was mediated via PKCK2., Conclusions: Our findings indicated that PKCK2 may play a role in apoptotic injury associated with CsA-induced nephropathy in rats., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: To study whether the synthetic ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) derivatives, which we have synthesized and have reported their apoptosis-inducing effect, have the effect on the proliferation of retinal pigment epithelial cells., Methods: UDCA, CDCA, and their synthetic derivatives were administered in culture to the human retinal pigment cell line, ARPE-19. The effect on cell viability and growth was assessed by trypan blue dye exclusion. In order to evaluate the type of cell death, mitochondrial membrane potential assay, DNA electrophoresis, TUNEL assay, nuclear staining and Western blotting for caspase-3 and poly(ADP-ribose) polymerase (PARP) activities were conducted., Results: Unlike UDCA and CDCA, which did not exhibit a significant effect on viability, their synthetic derivatives decreased the viability of ARPE-19 cells in a concentration-dependent manner. The cells treated with the synthetic derivatives did not demonstrate the characteristic findings of apoptosis, such as DNA ladder, DNA fragmentation, nuclear condensation or fragmentation, and caspase-3 and PARP activation. The reduction of mitochondrial membrane potential was shown. In electron microscopical study nuclear condensation was not shown., Conclusions: The synthetic UDCA and CDCA derivatives induced nonapoptotic death of ARPE-19 cells.

In those days, commercial and cultural exchanges between South Korea and North Korea become more active than before. But in medicine, there has been no activities of exchange and we don't know much about medicine in North Korea. We have some information on medical systems in the North, but we know little about how the medical activities are, what achievements they have made and what kind of medical books have been published. The authors classified 575 books according to their specialties and publishing years and analysed the characteristics and tendencies of medical books publishing in North Korea.

Choe Han-Ki was a philosopher of the 19th century who resided in Seoul. He accumulated vast amount of knowledge of Western science and on the basis of them he built his own philosophical system different from those of the philosophers before him. Not only has he wrote books on philosophy, but many books on science as well. Among them Shin-Ki-Chon-Hum is a very unique medical book which reveals his original medical philosophy. He acquired medical knowledge through the medical books put into Chinese by missionary doctor Hobson and on the basis of them he criticized traditional medicine. He criticized traditional medicine because it explained vital phenomenon through the reductionist theory, such as Oh-Haeng (theory of five phases). And he also criticized it because it lacked in exact anatomical knowledge and that the exact origin of the disease was not known and it had limitations on treatment. He also criticized Western Medicine because it supposed God as a creator. He saw the possibility of communication between Western Medicine and traditional medicine. He didn't regard medicine as concerning disease and health only, but it included everything in it. His philosophy of medicine is just a part of his original system of science, Ki-Hak.

Lucifer yellow was injected intracellularly into mouse cerebellar neurons in 200 micron thick slices of tissue that had been lightly fixed by cardiac perfusion with paraformaldehyde. Direct observation of fluorescence at the time of injection established that dye diffusion was very rapid and was confined to an intracellular distribution, so that the detailed shapes of neuron cell bodies and dendrites, and some features of axons, were visualized. Different types of cerebellar neurons were identified. With sequential penetration of different neuron types near one another within a given tissue slice, synaptic relationships could be visualized. The validity of the method was tested with cells whose form and relationships are well known. The presence of axonal baskets, for example, around the somata of a row of Purkinje cells after penetration of a single basket cell axon identify cells that are related by a common inhibitory input. Once the baskets were visualized, it was possible to penetrate and fill these related postsynaptic neurons. By filling several Purkinje cells spaced along a given folium, variations in cell form can be 'correlated with' position along the changing curvature of the folium. Immature forms of cerebellar neurons could be penetrated and filled with dye in neonatal animals so that the morphology of cerebellar neurons can be compared at different stages of development.

Two populations of neurons in the paraventricular nucleus of the hypothalamus that have different efferent projections and physiological roles in the regulation of visceral responses were characterized morphologically with a combined intracellular filling, retrograde tracer, and immunohistochemical method. Neuroendocrine cells were retrogradely labeled by an intravenous injection of Fast blue, and distinguished from descending neurons that were retrogradely labeled by an injection of fluorogold into the spinal cord. Retrogradely labeled neurons were selectively penetrated and filled intracellularly with Lucifer yellow to visualize detailed features of their morphology. Corticotropin-releasing hormone (CRH)-containing neurons were distinguished from other neuroendocrine cells by immunostaining the tissue with an antiserum to rat CRH. Morphometric features of defined populations of neurons were then quantified and reconstructed graphically to generate multicellular montage drawings that demonstrate their spatial organization. Descending neurons were further separated into dorsal and ventral medial parvicellular components, while the neuroendocrine population was differentiated into parvicellular and magnocellular groups. The mean somal areas, total dendritic lengths, and spine densities were compared between groups of neurons, and these showed significant differences across cell types. These measures were also dramatically affected by colchicine, which appears to induce the formation of new dendritic appendages, swelling of the soma, and reduction of dendritic length. Whether colchicine is acting directly upon cytoskeletal structures or indirectly by altering the physiology of the cell is unclear. However, the precise effects of colchicine on mean somal area, total dendritic length, and spine density appear to be dependent upon individual cell type. Colchicine may therefore act in a nonspecific, but nonetheless highly selective, manner in disrupting an endogenous mechanism regulating the number, morphology, and location of spines.