• Title/Summary/Keyword: extrinsic pathway

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Orthognathic surgery in a patient with Factor VII deficiency: A Case Report (응고인자 VII 부족 환자에서의 악교정 수술: 증례보고)

  • Baek, Rong Min;Oh, Myung June;Lee, Sang Woo
    • Archives of Plastic Surgery
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    • v.36 no.1
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    • pp.93-95
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    • 2009
  • Purpose: Congenital factor VII (FVII) deficiency is a rare bleeding disorder and surgery can cause excessive bleeding due to an extrinsic pathway problem. It can be diagnosed by increased PT and decreased FVII level in coagulation test. Symptom varies according to the level of FVII, but it is essential to prevent intraoperative excessive bleeding. Methods: In this report, we described the orthognatic surgery experience in a mandibular prognathism patient with congenital FVII deficiency, in which recombinant activated factor VII (rFVIIa) was used to manage the bleeding. Rsults: We could get a successful result without any complication and there was minimal intraoperative bleeding. Conclusion: The orthognathic surgery could therefore be safely performed in patients with congenital factor VII deficiency using rFVIIa.

The Roles of Estrogens in the Efferent Ductules of the Male Reproductive System : A Review

  • Min, Tae-Sun;Lee, Ki-Ho
    • Asian-Australasian Journal of Animal Sciences
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    • v.23 no.8
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    • pp.1118-1126
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    • 2010
  • Male reproduction is influenced by a number of intrinsic and extrinsic factors, including environmental endocrine disruptors. Testosterone is a well recognized intrinsic regulator for development and function of the male reproductive tract, and thus male fertility. The testis and semen of many mammalians contain an unusually high concentration of estrogen. Testosterone is converted into estrogen by the enzymatic action of cytochrome P450 aromatase complex (Cyp19a1). Of the male reproductive tract, the efferent ductules (EDs) possess exceptionally elevated levels of estrogen receptors (ERs), ER${\alpha}$ and ER${\beta}$, indicating that estrogen, in addition to testosterone, would have a functional role in regulation of male reproduction. First, this review has focused on description and summary of what is currently known for functions of estrogen in the EDs. The biosynthetic pathway of estrogen occurring in the testis is briefly covered, following by detailed explanation of the morphology and physiology of EDs. In the next section, the sources and targets of estrogen in the male reproductive tract are highlighted, and possible functional roles of estrogen in the EDs are justified from the aspect of physiology, molecular biology, and morphology in adult animal models. Also, this section covers the importance of estrogen and ERs in maintaining normal function and morphology of the EDs during postnatal development. In the last part of this review, the effects of extrinsic factors, especially environmental endocrine-disruptors, on the EDs is summarized. The intent of this review is to emphasize the importance of estrogen for regulation of physiological function of the EDs, and thus male fertility.

Snake Venom-enhanced Cytotoxic Effect of Natural Killer Cells on A549 Human Lung Cancer Cell Growth (사독의 인체 폐암세포(A549)에 대한 Natural Killer 세포 세포독성 촉진 효과)

  • Lee, Ji In;Song, Ho Sueb
    • Journal of Acupuncture Research
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    • v.32 no.1
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    • pp.79-88
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    • 2015
  • Objectives : The purpose of this research was to investigate the cytotoxic effect of Natural Killer(NK)-92 cell and Snake Venom, and to elucidate its mechanism on human lung carcinoma cell A549. Methods : In order to figure out whether Snake Venom enhances the cytotoxic effect of NK-92 cell in A549 cell, Cell Viability Assay was conducted. Also, in order to observe the changes of Caspase-3 and Caspase-8, both of which are proteinases that advance apoptosis, and the changes of TNRF and DR3, which are Death Receptors of the extrinsic pathway of apoptosis, Western Blot Analysis was conducted. By conducting RT-PCR analysis, we have tried to confirm Perforin, Granzyme B, and GADPH, all of which are cytotoxic-related proteins. Lastly, in order to observe the effect of Snake Venom on NO formation within human lung carcinoma cells, NO determination was conducted. Results : 1. After conducting Cell Viability Assay, Snake Venom enhanced the cytotoxic effect of NK-92 cell and inhibited the growth of A549. 2. Western Blot Analysis caused proteinases Caspase-3 and Caspase-8, which advance apoptosis, to increase in the combined treatment group, but not in treatment groups that focused only on either Snake Venom or NK-92 cell in A549 lung carcinoma cells. 3. Western Blot Analysis caused an expression of TNFR2 and DR3, both of which are Death Receptors of the apoptosis extrinsic pathway, in the combined treatment group, but not intreatment groups that focused only on either Snake Venom or NK-92 cell in A549 human lung carcinoma cells. 4. After conducting NO determination, NO formation within A549 cell showed no significant changes in both treatment groups that focused NK-92 cell and combined treatment group. 5. After conducting RT-PCR, the expression of Granzyme B and Perforin, which are cytotoxic-related proteins within A549 human lung carcinoma cells, showed growth in the combined treatment group, but not the treatment group that focused only on NK-92 cell. Conclusion : It has been indicated that, when it comes to the A549 cell, Snake Venom enhances the increase of Death Receptor expression and continuous apoptosis reaction, leading to the enhancement of the cancer cell cytotoxic effect of the NK-92 cell. It is expected that Snake Venom can be used with the NK-92 cell for further lung cancer treatment.

Induction of apoptosis by water extract Glycyrrhizae radix in human bladder T24 cancer cells (인체 방광암 T24 세포에서 Glycyrrhizae radix 열수추출물에 의한 apoptosis 유도)

  • Eom, Jung Hye;Hwang, Buyng Su;Jeong, Yong Tae;Kim, Min-Jin;Shin, Su Young;Kim, Chul Hwan;Lee, Seung Young;Choi, Kyung Min;Cho, Pyo Yun;Jeong, Jin-Woo;Oh, Young Taek
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2019.04a
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    • pp.111-111
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    • 2019
  • Glycyrrhizae radix is one of the most frequently prescribed ingredients in Oriental medicine, and G. radix extract has been shown to exert anti-cancer effects. However, the cellular and molecular mechanisms of apoptosis by G. radix are poorly defined. In the present study, it was examined the biochemical mechanisms of apoptosis by water extract of G. radix (WEGR) in human bladder T24 cancer cells. It was found that WEGR could inhibit the cell growth of T24 cells in a dose-dependent manner, which was associated with the induction of apoptotic cell death, as evidenced by the formation of apoptotic bodies, DNA fragmentation and increased populations of annexin-V positive cells. The induction of apoptotic cell death by WEGR was connected with an up-regulation of pro-apoptotic Bax protein expression and down-regulation of anti-apoptotic Bcl-2 and Bcl-xL proteins, and inhibition of apoptosis family proteins (XIAP, cIAP-1 and cIAP-2). In addition, apoptosis-inducing concentrations of WEGR induced the activation of caspase-9, an initiator caspase of the mitochondrial-mediated intrinsic pathway, and caspase-3, accompanied by proteolytic degradation of poly (ADP-ribose)-polymerase. WEGR also induced apoptosis via a death receptor-mediated extrinsic pathway by caspase-8 activation, resulting in the down-regulation of total Bid and suggesting the existence of cross-talk between the extrinsic and intrinsic pathways. Taken together, the present results suggest that WEGR may be a potential chemotherapeutic agent for the control of human bladder cancer cells.

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Inhibition of cell growth and induction of apoptosis by bilobalide in FaDu human pharyngeal squamous cell carcinoma

  • Jeong, Kyung In;Kim, Su-Gwan;Go, Dae-San;Kim, Do Kyungm
    • International Journal of Oral Biology
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    • v.45 no.1
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    • pp.8-14
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    • 2020
  • Bilobalide isolated from the leaves of Ginkgo biloba has several pharmacological activities such as neuroprotective, anti-inflammatory, and anticonvulsant. However, the effect of bilobalide on cancer has not been clearly established. The main purpose of this study was to investigate the effect of bilobalide on cell growth and apoptosis induction in FaDu human pharyngeal squamous cell carcinoma. This was examined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, nuclear 4′,6-diamidino-2-phenylindole dihydrochloride staining, DNA fragmentation analysis, and immunoblotting. Bilobalide inhibited the growth of FaDu cells in dose- and time-dependent manners. Treatment with bilobalide resulted in nuclear condensation and DNA fragmentation in FaDu cells. Furthermore, it promoted the proteolytic cleavage of procaspase-3/-7/-8/-9 with increase in the amount of cleaved caspase-3/-7/-8/-9. Bilobalide-induced apoptosis in FaDu cells was mediated by the expression of Fas and the activation of caspase-8, caspase-3, and poly (ADP-ribose) polymerase. Immunoblotting revealed that the antiapoptotic mitochondrial protein Bcl-2 was downregulated, but the proapoptotic protein Bax was upregulated by bilobalide in FaDu cells. Bilobalide significantly increased Bax/Bcl-2 ratio. These results suggest that bilobalide inhibits cell proliferation and induces apoptosis in FaDu human pharyngeal squamous cell carcinoma via both the death receptor-mediated extrinsic apoptotic pathway and the mitochondrial-mediated intrinsic apoptotic pathway.

Apoptotic activity of demethoxycurcumin in MG-63 human osteosarcoma cells

  • Kang, Kyeong-Rok;Kim, Jae-Sung;Kim, Tae-Hyeon;Seo, Jeong-Yeon;Park, Jong-Hyun;Chun, Hong Sung;Yu, Sun-Kyoung;Kim, Heung-Joong;Kim, Chun Sung;Kim, Do Kyung
    • International Journal of Oral Biology
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    • v.46 no.1
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    • pp.23-29
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    • 2021
  • Demethoxycurcumin (DMC), which is a curcuminoid found in turmeric, has anti-proliferative effects on cancer cells. However, the effect of DMC on osteosarcoma has not been established. The aim of this study was to examine the effects of DMC on cell growth and apoptosis induction in MG-63 human osteosarcoma cells. This study was investigated using 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyl tetrazolium bromid assay, Live/Dead cell assay, 4', 6-diamidino-2-phenylindole staining, and immunoblotting in MG-63 cells. DMC induced MG-63 cell death in a dose-dependent manner, with an estimated IC50 value of 54.4 µM. DMC treatment resulted in nuclear condensation in MG-63 cells. DMC-induced apoptosis in MG-63 cells was mediated by the expression of Fas and activation of caspase-8, caspase-3, and poly (ADP-ribose) polymerase. Immunoblotting results showed that Bcl-2 and Bcl-xL were downregulated, while Bax and Bad were upregulated by DMC in MG-63 cells. These results indicated that DMC inhibits cell proliferation and induces apoptotic cell death in MG-63 human osteosarcoma cells via the death receptor-mediated extrinsic apoptotic pathway and mitochondria-mediated intrinsic apoptotic pathway.

Stem cell maintenance by manipulating signaling pathways: past, current and future

  • Chen, Xi;Ye, Shoudong;Ying, Qi-Long
    • BMB Reports
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    • v.48 no.12
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    • pp.668-676
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    • 2015
  • Pluripotent stem cells only exist in a narrow window during early embryonic development, whereas multipotent stem cells are abundant throughout embryonic development and are retainedin various adult tissues and organs. While pluripotent stem cell lines have been established from several species, including mouse, rat, and human, it is still challenging to establish stable multipotent stem cell lines from embryonic or adult tissues. Based on current knowledge, we anticipate that by manipulating extrinsic and intrinsic signaling pathways, most if not all types of stem cells can be maintained in a long-term culture. In this article, we summarize current culture conditions established for the long-term maintenance of authentic pluripotent and multipotent stem cells and the signaling pathways involved. We also discuss the general principles of stem cell maintenance and propose several strategies on the establishment of novel stem cell lines through manipulation of signaling pathways.

Structural insights of homotypic interaction domains in the ligand-receptor signal transduction of tumor necrosis factor (TNF)

  • Park, Young-Hoon;Jeong, Mi Suk;Jang, Se Bok
    • BMB Reports
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    • v.49 no.3
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    • pp.159-166
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    • 2016
  • Several members of tumor necrosis factor receptor (TNFR) superfamily that these members activate caspase-8 from death-inducing signaling complex (DISC) in TNF ligand-receptor signal transduction have been identified. In the extrinsic pathway, apoptotic signal transduction is induced in death domain (DD) superfamily; it consists of a hexahelical bundle that contains 80 amino acids. The DD superfamily includes about 100 members that belong to four subfamilies: death domain (DD), caspase recruitment domain (CARD), pyrin domain (PYD), and death effector domain (DED). This superfamily contains key building blocks: with these blocks, multimeric complexes are formed through homotypic interactions. Furthermore, each DD-binding event occurs exclusively. The DD superfamily regulates the balance between death and survival of cells. In this study, the structures, functions, and unique features of DD superfamily members are compared with their complexes. By elucidating structural insights of DD superfamily members, we investigate the interaction mechanisms of DD domains; these domains are involved in TNF ligand-receptor signaling. These DD superfamily members play a pivotal role in the development of more specific treatments of cancer.

Effect of Neurotrophic Factors on Neuronal Stem Cell Death

  • KimKwon, Yun-Hee
    • BMB Reports
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    • v.35 no.1
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    • pp.87-93
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    • 2002
  • Neural cell survival is an essential concern in the aging brain and many diseases of the central nervous system. Neural transplantation of the stem cells are already applied to clinical trials for many degenerative neurological diseases, including Huntington's disease, Parkinson's disease, and strokes. A critical problem of the neural transplantation is how to reduce their apoptosis and improve cell survival. Neurotrophic factors generally contribute as extrinsic cues to promote cell survival of specific neurons in the developing mammalian brains, but the survival factor for neural stem cell is poorly defined. To understand the mechanism controlling stem cell death and improve cell survival of the transplanted stem cells, we investigated the effect of plausible neurotrophic factors on stem cell survival. The neural stem cell, HiB5, when treated with PDGF prior to transplantation, survived better than cells without PDGF. The resulting survival rate was two fold for four weeks and up to three fold for twelve weeks. When transplanted into dorsal hippocampus, they migrated along hippocampal alveus and integrated into pyramidal cell layers and dentate granule cell layers in an inside out sequence, which is perhaps the endogenous pathway that is similar to that in embryonic neurogenesis. Promotion of the long term-survival and differentiation of the transplanted neural precursors by PDGF may facilitate regeneration in the aging adult brain and probably in the injury sites of the brain.

Anti-Thrombotic Effects of Egg Yolk Lipids In Vivo

  • Cho, Hyun-Jeong;Ju, Young-Cheol;Park, Hwa-Jin
    • Biomedical Science Letters
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    • v.16 no.4
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    • pp.377-380
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    • 2010
  • In this study, we investigated the effect of egg yolk lipids (EYL) on collagen ($10\;{\mu}g/ml$)-stimulated platelet aggregation in vivo. Dietary EYL significantly inhibited collagen-induced platelet aggregation, in addition, increased the formation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), intracellular $Ca^{2+}$-antagonist as aggregation-inhibiting molecules, in collagen-stimulated platelets. These results suggest that EYL inhibits the collagen-induced platelet aggregation by up-regulating the cAMP and cGMP production. On the other hands, prothrombin time (PT) on extrinsic pathway of blood coagulation was potently prolonged by dietary EYL in vivo. These findings suggest that EYL prolongs the internal time between the conversion of fibrinogen to fibrin. Accordingly, our data demonstrate that EYL may be a crucial tool for a negative regulator during platelet activation and blood coagulation on thrombotic diseases.