• Title/Summary/Keyword: intrinsic pathway

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Neurotropin protects rotator cuff tendon cells from lidocaine-induced cell death

  • Abe, Ryunosuke;Ohzono, Hiroki;Gotoh, Masafumi;Nakamura, Yosuke;Honda, Hirokazu;Nakamura, Hidehiro;Kume, Shinichiro;Okawa, Takahiro;Shiba, Naoto
    • Clinics in Shoulder and Elbow
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    • v.24 no.4
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    • pp.224-230
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    • 2021
  • Background: Local anesthetics often are used in rotator cuff tears as therapeutic tools, although some cases have reported that they have detrimental effects. Neurotropin (NTP) is used widely in Japan as a treatment for various chronic pain conditions and is shown to have protective effects on cartilage and nerve cells. In this study, we investigated the protective effect of NTP against lidocaine-induced cytotoxicity. Methods: Tenocytes from rotator cuff tendons were incubated with lidocaine, NTP, lidocaine with NTP, and a control medium. Cell viability was evaluated using the WST-8 assay. Cell apoptosis was detected via annexin V staining using flow cytometry. The expression of BCL-2 and cytochrome c, which are involved in the intrinsic mitochondrial pathway of apoptosis, was evaluated via Western blotting and immunohistochemical staining. Results: In the cell viability assay, lidocaine decreased cell viability in a dose-dependent manner, and NTP did not affect cell viability. Moreover, NTP significantly inhibited the cytotoxic effect of lidocaine. The flow cytometry analysis showed that lidocaine significantly induced apoptosis in tenocytes, and NTP considerably inhibited this lidocaine-induced apoptosis. Western blotting experiments showed that lidocaine decreased the protein expression of BCL-2, and that NTP conserved the expression of BCL-2, even when used with lidocaine. Immunohistochemical staining for cytochrome c showed that 0.1% lidocaine increased cytochrome c-positive cells, and NTP suppressed lidocaine-induced cytochrome c expression. Conclusions: NTP suppresses lidocaine-induced apoptosis of tenocytes by inhibiting the mitochondrial apoptotic pathway. Intra-articular/bursal injection of NTP with lidocaine could protect tenocytes in rotator cuff tendons against lidocaine-induced apoptosis.

Targeted Therapies and Radiation for the Treatment of Head and Neck Cancer (두경부 암의 표적 지향적 방사선 치료)

  • Kim, Gwi-Eon
    • Radiation Oncology Journal
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    • v.22 no.2
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    • pp.77-90
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    • 2004
  • Purpose: The purpose of this review Is to provide an update on novel radiation treatments for head and neck cancer Recent Findings: Despite the remarkable advances In chemotherapy and radiotherapy techniques, the management of advanced head and neck cancer remains challenging. Epidermal growth factor receptor (EGFR) Is an appealing target for novel therapies In head and neck cancer because not only EGFR activation stimulates many important signaling pathways associated with cancer development and progression, and importantly, resistance to radiation. Furthermore, EGFR overexpression Is known to be portended for a worse outcome in patients with advanced head and neck cancer. Two categories of compounds designed to abrogate EGFR signaling, such as monoclonal antibodies (Cetuxlmab) and tyrosine kinase inhibitors (ZD1839 and 051-774) have been assessed and have been most extensively studied In preclinical models and clinical trials. Additional TKIs In clinical trials include a reversible agent, Cl-1033, which blocks activation of all erbB receptors. Encouraging preclinical data for head and neck cancers resulted In rapid translation Into the clinic. Results from Initial clinical trials show rather surprisingly that only minority of patients benefited from EGFR inhibition as monotherapy or In combination with chemotherapy. In this review, we begin with a brief summary of erbB- mediated signal transduction. Subsequently, we present data on prognostic-predictive value of erbB receptor expression in HNC followed by preclinlcal and clinical data on the role of EGFR antagonists alone or in combination with radiation In the treatment of HNC. Finally, we discuss the emerging thoughts on resistance to EGFR biockade and efforts In the development of multiple-targeted therapy for combination with chemotherapy or radiation. Current challenges for investigators are to determine (1 ) who will benefit from targeted agents and which agents are most appropriate to combine with radiation and/or chemotherapy, (2) how to sequence these agents with radiation and/or cytotoxlc compounds, (3) reliable markers for patient selection and verification of effective blockade of signaling in vivo, and (4) mechanisms behind intrinsic or acquired resistance to targeted agents to facilitate rational development of multi-targeted therapy, Other molecuiar-targeted approaches In head and neck cancer were briefly described, Including angloenesis Inhibitors, farnesyl transferase inhibitors, cell cycle regulators, and gene therapy Summary: Novel targeted theraples are highly appealing in advanced head and neck cancer, and the most premising strategy to use them Is a matter of intense Investigation.

A Study on the Relationship between Motivation and Community Satisfaction of Audience for Non-profit Performing Arts (지역사회 비영리 공연 관람객의 관람동기와 지역사회만족도 간의 관계)

  • Jongeun Jwa;Seolwoo Park
    • Journal of Service Research and Studies
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    • v.13 no.4
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    • pp.47-69
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    • 2023
  • The main purpose of this study is to examine the mediating effects of performance satisfaction and audience loyalty through the motivation and community satisfaction of non-profit performance attendees in the local community. Motivations were examined by distinguishing between intrinsic and extrinsic factors to understand the profound desires of the audience. A survey was conducted targeting attendees who had experienced non-profit performances in the Jeju area over the past year to gather data. Ultimately, the survey responses from 363 participants were used as the basis for analysis. The results of the analysis indicated that higher levels of intrinsic and extrinsic motivations generally led to greater satisfaction and loyalty towards performances (H1, H2, H3). However, extrinsic motivation did not directly influence loyalty (H4). Nevertheless, both types of motivations were found to positively influence loyalty through performance satisfaction (H5, H8). While satisfaction with performances did not have a direct impact on community satisfaction (H6), audience loyalty was found to have a positive influence on community satisfaction (H7). Regarding motivations, performance satisfaction did not mediate the relationship between motivations and community satisfaction (H9). In the case of audience loyalty, intrinsic motivation showed mediating effects, while extrinsic motivation did not (H10). The process of motivation-satisfaction-loyalty-community satisfaction demonstrated a sequential pathway (H11). In conclusion, if local residents show interest and participate in non-profit performances, they develop a positive perception of the respective community. Therefore, performances provided at the local level should be recognized as crucial elements for the development of the community.

Anticancer Effect of Thymol on AGS Human Gastric Carcinoma Cells

  • Kang, Seo-Hee;Kim, Yon-Suk;Kim, Eun-Kyung;Hwang, Jin-Woo;Jeong, Jae-Hyun;Dong, Xin;Lee, Jae-Woong;Moon, Sang-Ho;Jeon, Byong-Tae;Park, Pyo-Jam
    • Journal of Microbiology and Biotechnology
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    • v.26 no.1
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    • pp.28-37
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    • 2016
  • Numerous plants have been documented to contain phenolic compounds. Thymol is one among these phenolic compounds that possess a repertoire of pharmacological activities, including anti-inflammatory, anticancer, antioxidant, antibacterial, and antimicrobial effects. Despite of the plethora of affects elicited by thymol, its activity profile on gastric cancer cells is not explored. In this study, we discovered that thymol exerts anticancer effects by suppressing cell growth, inducing apoptosis, producing intracellular reactive oxygen species, depolarizing mitochondrial membrane potential, and activating the proapoptotic mitochondrial proteins Bax, cysteine aspartases (caspases), and poly ADP ribose polymerase in human gastric AGS cells. The outcomes of this study displayed that thymol, via an intrinsic mitochondrial pathway, was responsible for inducing apoptosis in gastric AGS cells. Hence, thymol might serve as a tentative agent in the future to treat cancer.

Biosynthesis of Rhamnosylated Anthraquinones in Escherichia coli

  • Nguyen, Trang Thi Huyen;Shin, Hee Jeong;Pandey, Ramesh Prasad;Jung, Hye Jin;Liou, Kwangkyoung;Sohng, Jae Kyung
    • Journal of Microbiology and Biotechnology
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    • v.30 no.3
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    • pp.398-403
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    • 2020
  • Rhamnose is a naturally occurring deoxysugar present as a glycogenic component of plant and microbial natural products. A recombinant mutant Escherichia coli strain was developed by overexpressing genes involved in the TDP-ʟ-rhamnose biosynthesis pathway of different bacterial strains and Saccharothrix espanaensis rhamnosyl transferase to conjugate intrinsic cytosolic TDP-ʟ-rhamnose with anthraquinones supplemented exogenously. Among the five anthraquinones (alizarin, emodin, chrysazin, anthrarufin, and quinizarin) tested, quinizarin was biotransformed into a rhamoside derivative with the highest conversion ratio by whole cells of engineered E. coli. The quinizarin glycoside was identified by various chromatographic and spectroscopic analyses. The anti-proliferative property of the newly synthesized rhamnoside, quinizarin-4-O-α-ʟ-rhamnoside, was assayed in various cancer cells.

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.

Delayed Human Neutrophil Apoptosis by Trichomonas vaginalis Lysate

  • Song, Hyun-Ouk;Lim, Young-Su;Moon, Sun-Joo;Ahn, Myoung-Hee;Ryu, Jae-Sook
    • Parasites, Hosts and Diseases
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    • v.48 no.1
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    • pp.1-7
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    • 2010
  • Neutrophils play an important role in the human immune system for protection against such microorganisms as a protozoan parasite, Trichomonas vaginalis; however, the precise role of neutrophils in the pathogenesis of trichomoniasis is still unknown. Moreover, it is thought that trichomonal lysates and excretory-secretory products (ESP), as well as live T. vaginalis, could possibly interact with neutrophils in local tissues, including areas of inflammation induced by T. vaginalis in humans. The aim of this study was to investigate the influence of T. vaginalis lysate on the fate of neutrophils. We found that T. vaginalis lysate inhibits apoptosis of human neutrophils as revealed by Giemsa stain. Less altered mitochondrial membrane potential (MMP) and surface CD16 receptor expression also supported the idea that neutrophil apoptosis is delayed after T. vaginalis lysate stimulation. In contrast, ESP stimulated-neutrophils were similar in apoptotic features of untreated neutrophils. Maintained caspase-3 and myeloid cell leukemia-1 (Mcl-1) in neutrophils co-cultured with trichomonad lysate suggest that an intrinsic mitochondrial pathway of apoptosis was involved in T. vaginalis lysate-induced delayed neutrophil apoptosis; this phenomenon may contribute to local inflammation in trichomoniasis.

Analysis of in vitro apoptosis induced by virulent Korean isolate of classical swine fever virus in peripheral blood B cell line

  • Kim, Seon-Mi;Lim, Seong-In;Song, Jae-Young;Hyun, Bang-Hun
    • Korean Journal of Veterinary Research
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    • v.52 no.4
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    • pp.259-262
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    • 2012
  • Classical swine fever (CSF) is a highly contagious disease among swine that has an important economic impact on worldwide. One clinical symptom of CSF is leukopenia, in particular lymphopenia, which is a characteristic event that occurs early in the course of CSF. Though lymphopenia associated with apoptosis, the pathogenic mechanism underlying the lymphopenia has not been well studied. To understand these mechanisms, we investigated the response of porcine B cell lines to infection with SW03, virulent strain isolated from swine tissue in Korea. This study demonstrated that SW03-infected L35 cell were induced apoptosis through the detection of activated caspase-3. In addition, SW03 infection leaded to alterations in pro-apoptotic, Bax, and anti-apoptotic, Bcl-xL proteins of Bcl-2 family. Our results would suggest that SW03-infected L35 cells induced apoptosis via intrinsic mitochondrial pathway.

Antioxidant and Anticoagulant Activities of Water and Ethanol Extracts of Phyllostachys pubescence Leaf Produced in Geoje (거제 맹종죽엽 물 추출물과 에탄올 추출물의 항산화 활성 및 항혈전 활성)

  • Cho, Eun-Ah;Kim, So-Young;Na, In-Ho;Kim, Dong-Chung;In, Man-Jin;Chae, Hee-Jeong
    • Journal of Applied Biological Chemistry
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    • v.53 no.3
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    • pp.170-173
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    • 2010
  • Antioxidant and anticoagulant activities of water extract and 70% ethanol extract of Phyllostachys pubescence leaf (PPL) produced in Geoje were investigated. Total polyphenol contents of PPL-water extract and PPL-70%, EtOH extract were measured as $80.6{\pm}3.2$ and $71.3{\pm}2.7$ mg/g, respectively. DPPH radical scavenging activity of PPL-water extract and PPL-70% EtOH extract were 50% and 90%, respectively. The anticoagulant activity, in intrinsic pathway of activated partial thromboplastin time (APTT) showed a concentration-dependency. This results showed that PPL-water extract and PPL-70% EtOH extract have high antioxidant and anticoagulant activities.

Protective Effects of Jihwangeumja on Oxidative Stress-induced Injury of Human Umbilical Vein Endothelial Cells (혈관내피세포의 산화적 손상에 대한 지황음자의 방어기전 연구)

  • 정용준;장재호;이대용;이민구;전인철;정대영;이인;신선호;문병순
    • The Journal of Korean Medicine
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    • v.25 no.2
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    • pp.173-183
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    • 2004
  • Objectives : Oxidative stress can induce negative responses such as growth inhibition or cell death by necrosis or apoptosis due to the intensity of the oxidative stress, as well as positive responses such as cellular proliferation or activation. We examined the effect of Jihwangeumja on this process. Methods and Results : We analyzed the influence of oxidative stress and agents that modify its effect in human umbilical vein endothelial cell (HUVEC). Oxidative stress was induced by $B_2O_2$. With induced oxidative stress the results obtained indicate that it has a harmful effect over cell function and viability, and that this effect is dose and time dependent. When oxidative stress increased, Jihwangeumja reduced cell damage and had protective functions. $B_2O_2$, induced the apoptosis of HUVEC through the activation of intrinsic caspases pathway as well as mitochondrial dysfunction. A significant increase in cell survival was observed in culture cells with oxidative stress when they were treated with Jihwangeumja. Conclusions : These results suggest that Jihwangeumja may be potentially useful to treat HUVEC against oxidative damages mediated by modulation of caspase protease and mitochondrial dysfunction.

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