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- 저자 : ( Manoj Nepal ) (검색결과 5 건)
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An activator of PHD2, KRH102140, decreases angiogenesis via inhibition of HIF‐1<i>α</i>
Nepal, Manoj,Gong, Young‐,Dae,Park, Young Ran,Soh, Yunjo John Wiley Sons, Ltd. 2011 CELL BIOCHEMISTRY AND FUNCTION Vol.29 No.2
<P><B>Abstract</B></P><P>Hypoxia‐inducible transcription factors (HIFs) play a pivotal role in the response of cells to hypoxia. HIFs are dimers of an oxygen‐sensitive <I>α</I>‐subunit (HIF‐1<I>α</I> or HIF‐2<I>α</I>), and a constitutively expressed <I>β</I>‐subunit. In normoxia, HIF‐1<I>α</I> is destabilized by post‐translational hydroxylation of Pro‐564 and Pro‐402 by a family of oxygen‐sensitive dioxygenases. Prolyl hydroxylation leads to von Hippel–Lindau protein‐dependent ubiquitination and rapid degradation of HIF‐1<I>α</I>. We previously reported that KRH102053, an activator of PHD2, rapidly decreased HIF‐1<I>α</I> and eventually inhibited angiogenesis. Here, we report a potent activator of PHD2, KRH102140, which has a structure similar to KRH102053. KRH102140 more efficiently suppressed HIF‐1<I>α</I> than KRH102053 in human osteosarcoma cells under hypoxia. Furthermore, KRH102140 decreased the mRNA levels of HIF‐regulated downstream target genes associated with angiogenesis and energy metabolism such as vascular endothelial growth factor, adrenomedullin, Glut1, aldolase A, enolase 1 and monocarboxylate transporter 4. KRH102140 also inhibited tube formation in human umbilical vein endothelium cells. The results suggest that KRH102140 has potential therapeutic effects in alleviating various diseases associated with HIFs. Copyright © 2011 John Wiley & Sons, Ltd.</P>
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Gender-Based Violence and Women Reproductive Health in War Affected Area
Shalak Manar,Markson Favor,Nepal Manoj 대한가정의학회 2024 Korean Journal of Family Medicine Vol.45 No.1
Manifestations of gender-based violence although many, and sometimes more pronounced in areas of armed con-flict, go unnoticed due to multiple factors. Gender-based violence targeted towards women, affect their overall health negatively, particularly the reproductive well-being. Major conflicts arising in the Middle East over the past 10–15 years, ranging from the Arab uprising to the Syrian civil war, have drawn attention world-wide. This study aims to shed light on the importance of recognizing violence against women, its effect on their reproductive health, and the policies that should be implemented to limit its adverse impact. Towards this end, we have highlighted the important role played by all healthcare professionals, epidemiologists, and surveyors working in peace and war ar-eas to recognize such atrocities towards women.
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Park, Young-Ran,Eun, Jae-Soon,Choi, Hwa-Jung,Nepal, Manoj,Kim, Dae-Keun,Seo, Seung-Yong,Li, Rihua,Moon, Woo-Sung,Cho, Nam-Pyo,Cho, Sung-Dae,Bae, Tae-Sung,Kim, Byung-Il,Soh, Yun-Jo The Korean Society of Pharmacology 2009 The Korean Journal of Physiology & Pharmacology Vol.13 No.6
Osteoclasts, derived from multipotent myeloid progenitor cells, play homeostatic roles in skeletal modeling and remodeling, but may also destroy bone in pathological conditions such as osteoporosis and rheumatoid arthritis. Osteoclast development depends critically on a differentiation factor, the receptor activator of NF-${\kappa}B$ ligand (RANKL). In this study, we found that the hexane soluble fraction of the common fig Ficus carica (HF6-FC) is a potent inhibitor of osteoclastogenesis in RANKL-stimulated RAW264.7 cells and in bone marrow-derived macrophages (BMMs). HF6-FC exerts its inhibitory effects by suppression of p38 and NF-${\kappa}B$ but activation of ERK. In addition, HF6-FC significantly decreased the expression of NFATc1 and c-Fos, the master regulator of osteoclast differentiation. The data indicate that components of HF6-FC may have therapeutic effects on bone-destructive processes such as osteoporosis, rheumatoid arthritis, and periodontal bone resorption.
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( Jae Ha Ryu ),( Jae Soon Eun ),( Yun Jo Soh ),( Bo Yun Choi ),( Liang Li ),( Hyoung Kwon Cho ),( Manoj Nepal ) 한국응용약물학회 2012 Biomolecules & Therapeutics(구 응용약물학회지) Vol.20 No.3
Endochondral bone formation is the process by which mesenchymal cells condense to become chondrocytes, which ultimately form new bone. The process of chondrogenic differentiation and hypertrophy is critical for bone formation and as such is regulated by many factors. In this study, we aimed to indentify novel factors that regulate chondrogenesis. We investigated the possible role of isopsoralen in induction of chondrogenic differentiation in clonal mouse chondrogenic ATDC5 cells. Isopsoralen treatment stimulated the accumulation of cartilage nodules in a dose-dependent manner. Further, ATDC5 cells treated with isopsoralen were stained more intensely with Alcian blue than control cells, suggesting that isopsoralen increases the synthesis of matrix proteoglycans. Similarly, isopsoralen markedly induced the activation of alkaline phosphatase activity compared with control cells. Isopsoralen enhanced the expressions of chondrogenic marker genes such as collagen II, collagen X, OCN, Smad4 and Sox9 in a time-dependent manner. Furthermore, isopsoralen induced the activation of extracellular signal-regulated kinase (ERK) and p38 MAP kinase, but not that of c-jun N-terminal kinase (JNK). Isopsoralen signifi cantly enhanced the protein expression of BMP-2 in a time-dependent manner. PD98059 and SB 203580, inhibitors of ERK and p38 MAPK, respectively, decreased the number of stained cells treated with isopsoralen. Taken together, these results suggest that isopsoralen mediates a chondromodulating effect by BMP-2 or MAPK signaling pathways, and is therefore a possible therapeutic agent for bone growth disorders.
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( Tae Sung Bae ),( Mi Kyung Lee ),( Byung Il Kim ),( Jae Soon Eun ),( Yun Jo Soh ),( Bo Yun Choi ),( Manoj Nepal ) 한국응용약물학회 2011 Biomolecules & Therapeutics(구 응용약물학회지) Vol.19 No.1
Bone remodeling is a dynamic process involving a constant balance between osteoclast-induced bone resorption and osteoblast induced bone formation. Osteoclasts play a crucial homeostatic role in skeletal modeling and remodeling, and destroy bone in many pathological conditions. Previously, we reported that the hexane soluble fraction of Ficus carica inhibited osteoclast differentiation. Poly unsaturated fatty acids, such as ethyl docosahexaenoate (E-DHA), docosahexaenoic acid (DHA), cis-11,14-eicosadienoic acid (EDA) and eicosapentaenoic acid (EPA), were identified from the hexane soluble fraction of Ficus carica. Among them, E-DHA most potently inhibited osteoclastogenesis in RAW264.7 cells. E-DHA reduced the activities of JNK and NF-KB. E-DHA suppressed the expression of c-Fos and nuclear factor of activated T cells c1 (NFATc1). Interestingly, DHA increased the activity of alkaline phosphatase and expression of bone morphogenetic protein 2 (BMP2) more than E-DHA in MC3T3-E1 cells, suggesting that DHA may induce osteoblast differentiation. The data suggests that a combination of E-DHA and DHA has potential use in the treatment of diseases involving abnormal bone lysis, such as osteoporosis, rheumatoid arthritis and periodontal bone erosion.
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