• Title/Summary/Keyword: Radiation-induced

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Combination Treatment with Arsenic Trioxide and Sulindac Induces Apoptosis of NCI-H157 Human Lung Carcinoma Cells via ROS Generation with Mitochondrial Dysfunction (NCI-H157 폐암 세포주에서 활성산소종의 생성과 미토콘드리아 기능변화를 한 Arsenic Trioxide와 Sulindac 병합요법의 세포고사효과)

  • Kim, Hak-Ryul;Yang, Sei-Hoon;Jeong, Eun-Taik
    • Tuberculosis and Respiratory Diseases
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    • v.59 no.1
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    • pp.30-38
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    • 2005
  • Background : Arsenic trioxide ($As_2O_3$) has been used to treat acute promyelocytic leukemia, and it induces apoptosis in a variety of solid tumor cell lines including non-small cell lung cancer cells. However, nonsteroidal antiinflammatory drugs (NSAID) can enhance tumor response to chemotherapeutic drugs or radiation. It was previously demonstrated that a combination treatment with $As_2O_3$ and sulindac induces the apoptosis of NCI-H157 human lung carcinoma cells by activating the caspase cascade. This study aimed to determine if a combination treatment augmented its apoptotic potential through other pathways except for the activation of the caspase cascade. Material and Methods : The NCI-H157 cells were treated with $As_2O_3$, sulindac and antioxidants such as glutathione (GSH) and N-acetylcysteine (NAC). The cell viability was measured by a MTT assay, and the level of intracellular hydrogen peroxide ($H_2O_2$) generation was monitored fluorimetrically using a scopoletin-horse radish peroxidase (HRP) assay. Western blotting and mitochondrial membrane potential transition analysis were performed in order to define the mechanical basis of apoptosis. Results : The viability of the cells was decreased by a combination treatment of $As_2O_3$ and sulindac, and the cells were protected using antioxidants in a dose-dependent manner. The increased $H_2O_2$ generation by the combination treatment was inhibited by antioxidants. The combination treatment induced changes in the mitochondrial transmembrane potential as well as the expression of the Bcl-2 family proteins, and increased cytochrome c release into the cytosol. However, the antioxidants inhibited the effects of the combination treatment. Conclusion : Combination treatment with $As_2O_3$ and sulindac induces apoptosis in NCI-H157 human lung carcinoma cells via ROS generation with a mitochondrial dysfunction.

Activation Mechanism of Protein Kinase B by DNA-dependent Protein Kinase Involved in the DNA Repair System

  • Li, Yuwen;Piao, Longzhen;Yang, Keum-Jin;Shin, Sang-Hee;Shin, Eul-Soon;Park, Kyung-Ah;Byun, Hee-Sun;Won, Min-Ho;Choi, Byung-Lyul;Lee, Hyun-Ji;Kim, Young-Rae;Hong, Jang-Hee;Hur, Gang-Min;Kim, Jeong-Lan;Cho, Jae-Youl;Seok, Jeong-Ho;Park, Jong-Sun
    • Toxicological Research
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    • v.24 no.3
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    • pp.175-182
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    • 2008
  • DNA-dependent protein kinase(DNA-PK) is involved in joining DNA double-strand breaks induced by ionizing radiation or V(D)J recombination and is activated by DNA ends and composed of a DNA binding subunit, Ku, and a catalytic subunit, DNA-PKcs. It has been suggested that DNA-PK might be $2^{nd}$ upstream kinase for protein kinase B(PKB). In this report, we showed that Ser473 phosphorylation in the hydrophobic-motif of PKB is blocked in DNA-PK knockout mouse embryonic fibroblast cells(MEFs) following insulin stimulation, while there is no effect on Ser473 phosphorylation in DNA-PK wild type MEF cells. The observation is further confirmed in human glioblastoma cells expressing a mutant form of DNA-PK(M059J) and a wild-type of DNA-PK(M059K), indicating that DNA-PK is indeed important for PKB activation. Furthermore, the treatment of cells with doxorubicin, DNA-damage inducing agent, leads to PKB phosphorylation on Ser473 in control MEF cells while there is no response in DNA-PK knockout MEF cells. Together, these results proposed that DNA-PK has a potential role in insulin signaling as well as DNA-repair signaling pathway.

Comparison of rCBF between Patients with Medial Temporal Lobe Epilepsy and Normal Controls using ${H_2}^{15}O\;PET$ (내측 측두엽 간질환자와 정상인의 ${H_2}^{15}O\;PET$을 이용한 뇌 혈류량 비교)

  • Kang, Eun-Joo;Lee, Jae-Sung;Nam, Hyun-Woo;Lee, Sang-Kun;Lee, Dong-Soo;Chung, June-Key;Lee, Myung-Chul
    • The Korean Journal of Nuclear Medicine
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    • v.36 no.3
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    • pp.155-165
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    • 2002
  • Purpose: The aim of this study was to identify the brain areas whose regional cerebral blood flow (rCBF) was changed in medial temporal lobe epilepsy (mTLE) using ${H_2}^{15}O-PET$. Materials and Methods: 12 patients with mTLE (6 left, 6 right mTLE) and 6 normal controls were scanned during a fixation baseline period and a sensory-motor condition where subjects pressed a button to an upward arrow. A voxel-based analysis using SPM99 software was peformed to compare the patient groups with the normal controls for the rCBF during fixation baseline period and for relative changes of rCBF during the sensory-motor task relative to fixation. Results: During the fixation baseline, a significant reduction of rCBF was found posterior insula bilaterally and right frontopolar regions in right mTLE patients compared to the normal controls. In left mTLE patients, the reduction was found in left frontopolar and temporal legions. During the sensory-motor task, rCBF increase over the fixation period, was reduced in left frontal and superior temporal legions in the right mTLE patients whereas in various areas of right hemisphere in left mTLE patients, relative to normal controls. However, the increased rCBF was also found in the left inferior parietal and anterior thalamic/fornix regions in both right and left mTLE patients compared to normal controls. Conclusion: Epilepsy induced changes were found not only in relative increase/decrease of rCBF during a simple sensory-motor control condition relative to a fixation rest condition but also in the relative rCBF distribution during the rest period.

Study on the Photoneutrons Produced in 15 MV Medical Linear Accelerators : Comparison of Three-Dimensional Conformal Radiotherapy and Intensity-Modulated Radiotherapy (15 MV 의료용 선형가속기에서 발생되는 광중성자의 선량 평가 - 3차원입체조형방사선치료와 세기조절방사선치료의 비교 -)

  • Yang, Oh-Nam;Lim, Cheong-Hwan
    • Journal of radiological science and technology
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    • v.35 no.4
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    • pp.335-343
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    • 2012
  • Intensity-modulated radiotherapy(IMRT) have the ability to provide better dose conformity and sparing of critical normal tissues than three-dimensional radiotherapy(3DCRT). Especially, with the benefit of health insurance in 2011, its use now increasingly in many modern radiotherapy departments. Also the use of linear accelerator with high-energy photon beams over 10 MV is increasing. As is well known, these linacs have the capacity to produce photonueutrons due to photonuclear reactions in materials with a large atomic number such as the target, flattening filters, collimators, and multi-leaf collimators(MLC). MLC-based IMRT treatments increase the monitor units and the probability of production of photoneutrons from photon-induced nuclear reactions. The purpose of this study is to quantitatively evaluate the dose of photoneutrons produced from 3DCRT and IMRT technique for Rando phantom in cervical cancer. We performed the treatment plans with 3DCRT and IMRT technique using Rando phantom for treatment of cervical cancer. An Rando phantom placed on the couch in the supine position was irradiated using 15 MV photon beams. Optically stimulated luminescence dosimeters(OSLD) were attached to 4 different locations (abdomen, chest, head and neck, eyes) and from center of field size and measured 5 times each of locations. Measured neutron dose from IMRT technique increased by 9.0, 8.6, 8.8, and 14 times than 3DCRT technique for abdomen, chest, head and neck, and eyes, respectively. When using IMRT with 15 MV photonbeams, the photoneutrons contributed a significant portion on out-of-field. It is difficult to prevent high energy photon beams to produce the phtoneutrons due to physical properties, if necessary, It is difficult to prevent high energy photon beams to produce the phtoneutrons due to physical properties, if necessary, it is need to provide the additional safe shielding on a linear accelerator and should therefore reduce the out-of-field dose.

Protective Effect of Isoflavone, Genistein from Soybean on Singlet Oxygen Induced Photohemolysis of Human Erythrocytes ($^1O_2$으로 유도된 사람 적혈구의 광용혈에 있어서 대두의 아이소플라본인 제니스테인의 보호작용)

  • Park, Soo-Nam
    • Korean Journal of Food Science and Technology
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    • v.35 no.3
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    • pp.510-518
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    • 2003
  • Protective effects of natural components including genistein (4',5,7-trihydroxyisoflavone) from Glycine max MERRILL on the rose-bengal sensitized photohemolysis of human erythrocytes were investigated. Genistein $(10{\sim}100\;{\mu}m)$ suppressed photohemolysis in a concentration-dependent manner, and was more effective than the lipid peroxidation chain blocker, ${\alpha}$-tocopherol (Vit. E). Glycoside of genistein, genistin, the water-soluble antioxidant, L-ascorbate, and the iron chelator, myo-inositol hexaphosphoric acid dodecasodium salt (sodium phytate) did not exhibit protective effect against photohemolysis. L-Ascorbate and sodium phytate stimulated photohemolysis at high concentration $(500\;{\mu}m)$. ${\alpha}$-Carotene 3,3'-diol (lutein), a singlet oxygen $(^1O_2)$ quencher, exhibited pronounced protective effect, an indication that $^1O_2$ is important in photohemolysis sensitized by rose-bengal. Reactive oxygen scavenging activities $(OSC_{50})$ of natural antioxidants including genistein on reactive oxygen species (ROS) generated in $Fe^{3+}-EDTA/H_2O_2$ system using the luminol-dependent chemiluminescence assay were in the order of sodium phytate > L-ascorbate > ${\alpha}$-tocopherol > genistein > genistin. $OSC_{50}$ value of genistein, genistin, ${\alpha}$-tocopherol, L-ascorbate, and sodium phytate were 41.0, 109.0, 9.0, 5.2, and $0.56{\mu}m$ respectively. The order of free radical (1,1-diphenyl-2-picrylhydrazyl, DPPH) scavenging activity $(FSC_{50})$ was L-ascorbate > ${\alpha}$-tocopherol > genistein > genistin. These results indicate that genistein can function as an antioxidant in biological systems, particularly skin exposed to solar UV radiation by scavenging $^1O_2$ and other ROS, and to protect cellular membranes against ROS.

The Activity of c-Jun N -terminal Kinase (JNKb) in Patients with UIP (UIP 환자에서 c-Jun N-terminal Kinase (JNK) 활성화에 관한 연구)

  • Kim, Ki-Up;Lee, Young-Mok;Kim, Do-Jin;Moon, Seung-Hyuk;Uh, Soo-Taek;Kim, Yong-Hoon;Park, Choon-Sik;Kim, Hyun-Jo;Youm, Wook;Hwang, Jung-Hwa
    • Tuberculosis and Respiratory Diseases
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    • v.51 no.5
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    • pp.437-447
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    • 2001
  • Background: TNF-alpha is related to the generation of lung fibrosis in patients with UIP. The precise mechanism leading to lung fibrosis by TNF-alpha is unknown. However, the activation of a transcription factor like AP-1(down stream of c-jun N-terminal kinase, JNK) by TNF-alpha may be related to the induction of fibrogenic cytokines like PDGF or IGF-I. Furthermore, JNK was reported to be activated in the radiation-induced lung fibrosis model. This study examined JNK activity in patients with UIP. Methods : The expression of phosphorous JNK(p-JNK), macrophage/monocyte specific markers, CD68, and cytokeratin was evaluated by immunohistochemical(IHC) staining of lung tissues from patients with UIP and lung cancer. An in vitro kinase assay was performed with alveolar macrophages obtained by a bronchol-avleolar lavage from patients with UIP and healthy persons as the control. Results : The IHC stain showed that p-JNK is expressed in the almost all of the alveolar macrophages and smooth muscle cells in patients with UIP. In case of the normal areas of the lung from patients with lung cancer, the alveolar macrophages showed little p-JNK expression. Interestingly, increased JNK activity was not found in the in vitro kinase assay of the alveolar macrophages obtained from both patients with UIP and healthy persons as the control. Furthermore, 10 ng/mL of TNF-alpha failed to increase the JNK activity of the alveolar macrophages in both patients with UIP and healthy people. Conclusion : The JNK was activated constitutionally in patients with UIP. However, the role of JNK in the pathogenesis of lung fibrosis needs to be clarified.

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The Effect of Translationally Controlled Tumor Protein (TCTP) of the Arctic Copepod Calanus glacialis on Protecting Escherichia coli Cells against Oxidative Stress (북극 동물플랑크톤 Calanus glacialis TCTP (Translationally Controlled Tumor Protein)가 산화적 스트레스 상태에서 E. coli 세포의 저항성에 미치는 효과)

  • Park, Yu Kyung;Lee, Chang-Eun;Lee, Hyoungseok;Koh, Hye Yeon;Kim, Sojin;Lee, Sung Gu;Kim, Jung Eun;Yim, Joung Han;Hong, Ju-Mi;Kim, Ryeo-Ok;Han, Se Jong;Kim, Il-Chan
    • Journal of Life Science
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    • v.30 no.11
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    • pp.931-938
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    • 2020
  • Translationally controlled tumor protein (TCTP) is one of the most abundant proteins in various eukaryotic organisms. TCTPs play important roles in cell physiological processes in cancer, cell proliferation, gene regulation, and heat shock response. TCTP is also considered an important factor in the resistance to oxidative stress induced by dithiothreitol or hydrogen peroxide (H2O2). Arctic calanoid copepods have a variety of antioxidant defense systems to regulate the levels of potentially harmful reactive oxygen species generated by ultraviolet radiation in the Arctic marine ecosystem. However, information on the antioxidant activity of TCTP in the Arctic Calanus glacialis is still scarce. To understand the putative antioxidant function of the Arctic copepod C. glacialis TCTP (Cg-TCTP), its gene was cloned and sequenced. The Cg-TCTP comprised 522 bp and encoded a 174-amino acid putative protein with a calculated molecular weight of ~23 kDa. The recombinant Cg-TCTP (Cg-r TCTP) gene was overexpressed in Escherichia coli (BL21), and Cg-rTCTP-transformed cells were grown in the presence or absence of H2O2. Cg-rTCTP-transformed E. coli showed increased tolerance to high H2O2 concentrations. Therefore, TCTP may be an important antioxidant protein related to tolerance of the Arctic copepod C. glacialis to oxidative stress in the harsh environment of the Arctic Ocean.

Antioxidative Activities of Aronia melanocarpa Fruit and Leaf Extracts (아로니아 베리 열매 및 잎 추출물의 항산화 활성)

  • Lee, Hye Mi;Kong, Bong Ju;Kwon, Soon Sik;Kim, Kyeong Jin;Kim, Hae Soo;Jeon, So Ha;Ha, Ji Hoon;Kim, Jin-Sook;Park, Soo Nam
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.39 no.4
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    • pp.337-345
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    • 2013
  • In this study, the antioxidative effects of Aronia melanocarpa fruit and leaf extracts were investigated. The free radical (1,1-diphenyl-2-picrylhydrazyl, DPPH) scavenging activities ($FSC_{50}$) of the ethylacetate and aglycone fractions of fruit extracts were 16.29 ${\mu}g/mL$, and 12.29 ${\mu}g/mL$, respectively. The free radical scavenging activity of fruit extract was higher than that of leaf extracts. Reactive oxygen species (ROS) scavenging activities ($OSC_{50}$) of the ethylacetate and aglycone fractions of fruit extracts on ROS generated in $Fe^{3+}-EDTA/H_2O_2$ system using the luminol-dependent chemiluminescence assay showed 2.86 ${\mu}g/mL$, and 1.80 ${\mu}g/mL$, respectively. ROS scavenging activity of the aglycone fraction of fruit extracts was similar to that of L-ascorbic acid (1.50 ${\mu}g/mL$). The ROS scavenging activity of fruit extracts was higher than that of leaf extracts. The cellular protective effects of aglycone fraction of fruit extracts (${\tau}_{50}$ = 72.3 min) on the $^1O_2$-induced cellular damage of human erythrocytes especially were increased in a concentration dependent manner (5 ~ 50 ${\mu}g/mL$). ${\tau}_{50}$ (72.3 min) of the aglycone fraction showed 1.9 times higher than (+)-${\alpha}$-tocopherol (38 min), known as lipophilic antioxidant at 10 ${\mu}g/mL$. These results incidicate that A. melanocarpa fruit extracts have higher antioxidant effects than leaf extracts and could be applicable to functional cosmetics materials for antioxidants by protecting skin exposed to solar UV radiation against ROS including $^1O_2$.

Regeneration of Low Heat - Treated Sciatic Nerve of Rabbit (저온 열처리한 가토 좌골 신경의 재생)

  • Kim, Jae-Do;Kim, Sang-Jin;Jung, Cheoul-Yun;Hong, Young-Gi;Kim, Ghi-Chan
    • The Journal of the Korean bone and joint tumor society
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    • v.3 no.2
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    • pp.80-88
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    • 1997
  • Malignant tumors of extremeties involving major neurovascular structures have been treated by amputation. However recent development of diagnostic tools(CT, MRI etc.), surgical techniques, anticancer chemotherapeutic agents, and radiation techniques allow surgeons to treat malignant tumors in the limb without amputation. It has been reported that a local application of low-heat to the tissue with tumor can kill tumor cells. It is, however, not known if the attendant neural and vascular injuries may be recovered. The present study was, therefore, undertakn to address this question in rabbit sciatic nerves. A low-heat injury to the sciatic nerve was induced by perfusing the nerve with $60^{\circ}C$ saline for 30 minutes and the courses of functional and morphological recovery of the nerve were evaluated for 16 weeks. The results are summerized as follows : 1. In the electromyographic nerve conduction test the average amplitude was markedly attenuated at 4 and 8 weeks after the low-heat treatment, but it progressively increased to the level 89.5% of the control at 16 week post-treatment. The average latency in the control group was 0.62 msec. The latency in the experimental group was much longer than this at 4 and 8 week post-treatment, but it progressively reverted to the control level, showing 0.622 msec at 16 weeks. 2. In the needle EMG, many fibrillation potentials and positive sharp waves were appeared until 8 weeks post-treatment. After 16 weeks, however, no fibrillation potential was observed. 3. In the early phase of post-treatment period, the myelinated nerve fibers contained many vacuoles and the number of myelinated nerve fibers appeared to be considerably reduced. However, as time goes myelinated nerve fibers were regenerated, such that after 16 weeks the histologic appearance of the nerve was similar to that of the control group.

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Microprogation And Environment Conditions Affecting On Growth Of In Vitro And Ex Vitro Of A. Formosanus Hay

  • Ket, Nguyen-Van;Paek, Kee-Yoeup
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2002.11a
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    • pp.29-30
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    • 2002
  • The goal of this research was to develop the effectiveness of in vitro culture method for A. formosanus and study the environment in vitro conditions affecting on growth. The first series of experiments were examined to investigate the response of three different basal media, MS (Murashige and Skoog, 1962), Knudson (KC; Knudson, 1946) and modified hyponex on growth and multiplication during in vitro culture. Multiple shoot proliferation was induced in shoot tip explants on Hyponex (H3) media supplemented with BA (1 mg1$\^$-1/) or TDZ (1-2 mg1$\^$-1/). Addition of activated charcoal (1%) to the TDZ containing medium promoted rapid shoot tip proliferation (11.1 shoots per explant) but the same medium had an opposite effect resulting in poor proliferation in the nodal explants. However, the regenerated shoots had slow growth rate and failed to elongate. This problem was overcome by transferring the shoot clumps to a hormone free H3 media supplemented with 2% sucrose and 0.5% activated charcoal. Using bioreactor culture for scaling up was also shown the best way for multiple shoot induction and growth of this plant. The second series of experiments was studied to investigate the effect of physical environment factors on growth of in vitro plantlets. The Anoectochilus formosanus plantlets were cultured under different air exchange rate (0.1, 0.9, 1.2h$\^$-1/), without sucrose or supplement 20g.1$\^$-1/ (photoautotrophic or photomixotrophic, respectively), and different photosynthesis photon flux (40, 80, 120 ,${\mu}$mol.m$^2$.s$\^$-1/- PPF). Under non-enrichment CO$_2$ treatment, slow growth was observed in photoautotrophical condition as compared with photomixotrophical condition on shoot height, fresh weigh and dry weight parameters; High air exchange (1.2.h-l) was found to be inadequate for plant growth in photomixotrophical condition. On the contrary, under CO$_2$, enrichment treatment, the plant growth parameters were sharply (visibly) improved on photoautotrophic treatments, especially on the treatment with air exchange rate of 0.9.h-1. The growth of plant in photoautotrophic condition was not inferior compared with photomixotrophic, and the best growth of plantlet was observed in treatment with low air exchange rate (0.9.h-1). Raising the PPF level from 80 to 120${\mu}$mol.m$\^$-2/.s$\^$-1/ decreased the plant height, particularly at 120${\mu}$mol.m$\^$-2/.s$\^$-1/ in photoautotrophic condition, fresh weight and dry weight declined noticeably. At the PPF of 120${\mu}$mol.m$\^$-2/,s$\^$-1/, chlorophyll contents lowed compared to those grown under low PPF but time courses of net photosynthesis rate was decreased noticeably. Light quality mainly affected morphological variables, changes of light quality also positively affected biomass production via changes in leaf area, stem elongation, chlorophyll content. Plant biomass was reduced when A. formosanus were grown under red LEDs in the absence of blue wavelengths compare to plants grown under supplemental blue light or under fluorescent light. Stem elongation was observed under red and blue light in the present experiment. Smaller leaf area has found under blue light than with other lighting treatments. Chlorophyll degradation was more pronounced in red and blue light compared with white light or red plus blue light which consequent affected the photosynthetic capacity of the plant. The third series of experiment were studied to investigate the effect of physical environment factors on growth of ex vitro plants including photosynthesis photon flux (PPF), light quality, growing substrates, electrical conductivity (EC) and humidity conditions. In the present experiments, response of plant on PPF and light quality was similar in vitro plants under photosynthesis photon flux 40${\mu}$mol.m,$\^$-2/.s$\^$-1/ and white light or blue plus red lights were the best growth. Substrates testing results were indicated cocopeat or peat moss were good substrates for A. formosanus growth under the greenhouse conditions. In case of A. formosanus plants, EC is generally maintained in the range 0.7 to 1.5 dS.m-1 was shown best results in growth of this plant. Keeping high humidity over 70% under low radiation enhanced growth rate and mass production.

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