다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

[신간의 별자리x] 우리/미술, 그리고 ‘슬픔의 박물관’

On allergic rhinitis

Atopic dermatitis (AD) is a common pruritic and chronically relapsing inflammatory skin disease. The pathophysiology of AD includes disturbed skin barrier functions, frequent allergic responses against allergens, defects in the antimicrobial immune defense, and a genetic predisposition. In this review we summarize advances in our understanding of the complex interdependent network of members of the rapidly growing protein superfamilies of cytokines and chemokines that lead to the development of AD.

Cytokines and Chemokines Orchestrate Atopic Skin Inflammation

Tumor tissue is composed of cancer cells and surrounding stromal cells with diverse genetic/epigenetic backgrounds, a situation known as intra-tumoral heterogeneity. Cancer cells are surrounded by a totally different microenvironment than that of normal cells; consequently, tumor cells must exhibit rapidly adaptive responses to hypoxia and hypo-nutrient conditions. This phenomenon of changes of tumor cellular bioenergetics, called “metabolic reprogramming”, has been recognized as one of 10 hallmarks of cancer. Metabolic reprogramming is required for both malignant transformation and tumor development, including invasion and metastasis. Although the Warburg effect has been widely accepted as a common feature of metabolic reprogramming, accumulating evidence has revealed that tumor cells depend on mitochondrial metabolism as well as aerobic glycolysis. Remarkably, cancer-associated fibroblasts in tumor stroma tend to activate both glycolysis and autophagy in contrast to neighboring cancer cells, which leads to a reverse Warburg effect. Heterogeneity of monocarboxylate transporter expression reflects cellular metabolic heterogeneity with respect to the production and uptake of lactate. In tumor tissue, metabolic heterogeneity induces metabolic symbiosis, which is responsible for adaptation to drastic changes in the nutrient microenvironment resulting from chemotherapy. In addition, metabolic heterogeneity is responsible for the failure to induce the same therapeutic effect against cancer cells as a whole. In particular, cancer stem cells exhibit several biological features responsible for resistance to conventional anti-tumor therapies. Consequently, cancer stem cells tend to form minimal residual disease after chemotherapy and exhibit metastatic potential with additional metabolic reprogramming. This type of altered metabolic reprogramming leads to adaptive/acquired resistance to anti-tumor therapy. Collectively, complex and dynamic metabolic reprogramming should be regarded as a reflection of the “robustness” of tumor cells against unfavorable conditions. This review focuses on the concept of metabolic reprogramming in heterogeneous tumor tissue, and further emphasizes the importance of developing novel therapeutic strategies based on drug repositioning.

/pdf/metabolic-reprogramming-the-emerging-concept-and-associated-j4mnvsr6v4.pdf

Metabolic reprogramming: the emerging concept and associated therapeutic strategies

https://www.jidonline.org/article/S0022-202X(15)36492-7/pdf

TSLP Induces Mast Cell Development and Aggravates Allergic Reactions through the Activation of MDM2 and STAT6

Mast cells play an important role in tumorigenesis. Histamine released from mast cells stimulates new vessel formation by acting through the histamine1 (H1) receptor. Despite the evidence of the role of mast cells in tumor growth and angiogenesis, the potential mechanism remains to be elucidated. Therefore, we investigated the role of mast cell-derived HIF-1α in melanoma growth. Here, we identify that the most positive cells for HIF-1α staining are seen in mast cells of human and animal melanoma tissue. The number of the stromal cell types (fibroblasts, macrophages and endothelial cells) was also increased in melanoma tissues. In activated bone marrow-derived mast cells (BMMCs), expressions of HIF-1α and VEGF were increased. Histamine also induced the expressions of HIF-1α and VEGF in BMMCs. H1 receptor antagonists significantly improved overall survival rates and substantially suppressed tumor growth as well as the infiltration of mast cells and levels of VEGF through the inhibition of HIF-1α expression in B16F10 melanoma-bearing mice. Furthermore, the injection of HIF-1α depleted BMMCs markedly inhibited the growth of tumors and migration of mast cells and increased the survival rate of the mice. These findings emphasize that the growth of melanoma can actually be exacerbated by mast cell-derived HIF-1α. In aggregate, our results reveal a novel role for mast cell-derived HIF-1α in the melanoma microenvironment and have important implications for the design of therapeutic strategies.

The critical role of mast cell-derived hypoxia-inducible factor-1α in human and mice melanoma growth.

Atractylenolide III (1) is the major bioactive component of Atractylodes lancea. The aim of this study was to analyze the effect on the regulation of interleukin (IL)-6 secretion pathway caused by 1. This sesquiterpenoid inhibited the secretion and expression of IL-6 in phorbol 12-myristate 13-acetate- and calcium ionophore A23187-stimulated human mast cells (HMC)-1. In addition, 1 inhibited histamine release in stimulated HMC-1 cells. In stimulated HMC-1 cells, 1 suppressed activation of p38 mitogen-activated protein kinase, C-Jun-N-terminal protein kinase, and nuclear factor-κB. In addition, 1 suppressed the activation of caspase-1 and the expression of receptor interacting protein-2. These results provide new insights that atractylenolide III (1) may control immunological reactions by regulating the cellular functions of IL-6 in mast cells.

Blockade of IL-6 secretion pathway by the sesquiterpenoid atractylenolide III.

Tryptanthrin ameliorates atopic dermatitis through down-regulation of TSLP.

The compound β-sitosterol (BS) is one of the most common forms of phytosterols and has anti-cancer, anti-oxidant, anti-bacterial, and anti-inflammatory effects. However, the effect of BS on atopic dermatitis (AD) has not been elucidated. Therefore, we investigated whether BS would be an effective treatment against AD. We treated BS on 2,4-dinitrofluorobenzene (DNFB)-induced AD-like skin lesions in NC/Nga mice, anti-CD3/anti-CD28-stimulated splenocytes, and phorbol myristate acetate/calcium ionophore A23187-stimulated human mast cell line (HMC-1) cells. Histological analysis, ELISA, PCR, caspase-1 assay, and Western blot analysis were performed. BS reduced the total clinical severity in DNFB-treated NC/Nga mice. Infiltration of inflammatory cells and number of scratching were clearly reduced in the BS-treated group compared with the DNFB-treated group. BS significantly reduced the levels of inflammation-related mRNA and protein in the AD skin lesions. BS significantly reduced the levels of histamine, IgE, and interleukin-4 in the serum of DNFB-treated NC/Nga mice. The activation of mast cell-derived caspase-1 was decreased by treatment with BS in the AD skin lesions. BS also significantly decreased the production of tumor necrosis factor-α from the stimulated splenocytes. In the stimulated human mast cell line, HMC-1 cells, increased intracellular calcium levels were decreased by treatment with BS. Further, BS inhibited the production and mRNA expression of TSLP through blocking of caspase-1 and nuclear factor-κB signal pathways in the stimulated HMC-1 cells. These results provide additional evidence that BS may be considered an effective therapeutic drug for the treatment of AD.

Na-Ra Han

Papers

TSLP Induces Mast Cell Development and Aggravates Allergic Reactions through the Activation of MDM2 and STAT6

The critical role of mast cell-derived hypoxia-inducible factor-1α in human and mice melanoma growth.

Blockade of IL-6 secretion pathway by the sesquiterpenoid atractylenolide III.

Tryptanthrin ameliorates atopic dermatitis through down-regulation of TSLP.

The β-sitosterol attenuates atopic dermatitis-like skin lesions through down-regulation of TSLP