Melatonin Attenuates Methotrexate-Induced Reduction of Antioxidant Activity Related to Decreases of Neurogenesis in Adult Rat Hippocampus and Prefrontal Cortex
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Suwannakot, Kornrawee
[1
,2
]
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Sritawan, Nataya
[1
,2
]
Naewla, Salinee
论文数: 0引用数: 0
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机构:
Navamindradhiraj Univ, Fac Med Vajira Hosp, Dept Basic Med Sci, Bangkok, ThailandKhon Kaen Univ, Fac Med, Dept Anat, Khon Kaen 40002, Thailand
Naewla, Salinee
[3
]
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Aranarochana, Anusara
[1
,2
]
Sirichoat, Apiwat
论文数: 0引用数: 0
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Khon Kaen Univ, Fac Med, Dept Anat, Khon Kaen 40002, Thailand
Khon Kaen Univ, Fac Med, Dept Anat, Neurogenesis Res Grp, Khon Kaen 40002, ThailandKhon Kaen Univ, Fac Med, Dept Anat, Khon Kaen 40002, Thailand
Sirichoat, Apiwat
[1
,2
]
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Pannangrong, Wanassanun
[1
]
Wigmore, Peter
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Univ Nottingham, Sch Life Sci, Med Sch, Queens Med Ctr, Nottingham NG72RD, Notts, EnglandKhon Kaen Univ, Fac Med, Dept Anat, Khon Kaen 40002, Thailand
Wigmore, Peter
[4
]
Welbat, Jariya Umka
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Khon Kaen Univ, Fac Med, Dept Anat, Khon Kaen 40002, Thailand
Khon Kaen Univ, Fac Med, Dept Anat, Neurogenesis Res Grp, Khon Kaen 40002, ThailandKhon Kaen Univ, Fac Med, Dept Anat, Khon Kaen 40002, Thailand
Previous studies have revealed that the side effects of anticancer drugs induce a decrease of neurogenesis. Methotrexate (MTX), one of anticancer drugs, can induce lipid peroxidation as an indicator of oxidative stress in the brain. Melatonin has been presented as an antioxidant that can prevent oxidative stress-induced neuronal damage via the activation of antioxidant enzymes associated with the increase of neurogenesis. The aims of the present study are to examine the neuroprotective effect of melatonin on the neurotoxicity of MTX on neurogenesis and the changes of protein expression and antioxidant enzyme levels in adult rat hippocampus and prefrontal cortex (PFC). Male Sprague-Dawley rats were assigned into four groups: vehicle, MTX, melatonin, and melatonin+MTX groups. The vehicle group received saline solution and 10% ethanol solution, whereas the experimental groups received MTX (75 mg/kg, i.v.) and melatonin (8 mg/kg, i.p.) treatments. After the animal examination, the brains were removed for p21 immunofluorescence staining. The hippocampus and PFC were harvested for Western blot analysis and biochemical assessments of malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GPX), and superoxide dismutase (SOD). The immunofluorescence result showed that coadministration with melatonin diminished p21-positive cells in the hippocampal dentate gyrus, indicating a decrease of cell cycle arrest. Melatonin reduced the levels of MDA and prevented the decline of antioxidant enzyme activities in rats receiving MTX. In the melatonin+MTX group, the protein expression results showed that melatonin treatment significantly upregulated synaptic plasticity and an immature neuron marker through enhancing brain derived neurotrophic factor (BDNF) and doublecortin (DCX), respectively. Moreover, melatonin ameliorated the antioxidant defense system by improving the nuclear factor erythroid 2-related factor 2 (Nrf2) in rats receiving MTX. These findings suggested that the effects of melatonin can ameliorate MTX toxicity by several mechanisms, including an increase of endogenous antioxidants and neurogenesis in adult rat hippocampus and PFC.
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[11]
Chang CL, 2013, PLOS ONE, V8, DOI [10.1371/journal.pone.0072553, 10.1371/journal.pone.0062612]
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Wenzhou Med Univ, Inst Neurosci, Dept Histol & Embryol, Wenzhou 325035, Zhejiang, Peoples R ChinaWenzhou Med Univ, Inst Neurosci, Dept Histol & Embryol, Wenzhou 325035, Zhejiang, Peoples R China
Chen, Bai Hui
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Ahn, Ji Hyeon
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Park, Joon Ha
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Choi, Soo Young
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Lee, Yun Lyul
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Kang, Il Jun
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Hallym Univ, Dept Food Sci & Nutr, Chunchon 24252, South KoreaWenzhou Med Univ, Inst Neurosci, Dept Histol & Embryol, Wenzhou 325035, Zhejiang, Peoples R China
Kang, Il Jun
;
Hwang, In Koo
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Seoul Natl Univ, Dept Anat & Cell Biol, Coll Vet Med, Seoul 08826, South Korea
Seoul Natl Univ, Res Inst Vet Sci, Seoul 08826, South KoreaWenzhou Med Univ, Inst Neurosci, Dept Histol & Embryol, Wenzhou 325035, Zhejiang, Peoples R China
Hwang, In Koo
;
Lee, Tae-Kyeong
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Kangwon Natl Univ, Sch Med, Dept Neurobiol, Chunchon 24341, South KoreaWenzhou Med Univ, Inst Neurosci, Dept Histol & Embryol, Wenzhou 325035, Zhejiang, Peoples R China
Lee, Tae-Kyeong
;
Shin, Bich-Na
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Kangwon Natl Univ, Sch Med, Dept Neurobiol, Chunchon 24341, South KoreaWenzhou Med Univ, Inst Neurosci, Dept Histol & Embryol, Wenzhou 325035, Zhejiang, Peoples R China
Shin, Bich-Na
;
Lee, Jae-Chul
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Kangwon Natl Univ, Sch Med, Dept Neurobiol, Chunchon 24341, South KoreaWenzhou Med Univ, Inst Neurosci, Dept Histol & Embryol, Wenzhou 325035, Zhejiang, Peoples R China
Lee, Jae-Chul
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Hong, Seongkweon
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Kangwon Natl Univ, Sch Med, Dept Surg, Chunchon 24341, South KoreaWenzhou Med Univ, Inst Neurosci, Dept Histol & Embryol, Wenzhou 325035, Zhejiang, Peoples R China
Hong, Seongkweon
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Jeon, Yong Hwan
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Kangwon Natl Univ, Kangwon Natl Univ Hosp, Sch Med, Dept Radiol, Chunchon 24341, South KoreaWenzhou Med Univ, Inst Neurosci, Dept Histol & Embryol, Wenzhou 325035, Zhejiang, Peoples R China
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Shin, Myoung Cheol
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Kangwon Natl Univ, Dept Emergency Med, Chunchon 24341, South Korea
Kangwon Natl Univ, Kangwon Natl Univ Hosp, Sch Med, Inst Med Sci, Chunchon 24341, South KoreaWenzhou Med Univ, Inst Neurosci, Dept Histol & Embryol, Wenzhou 325035, Zhejiang, Peoples R China
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;
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Cho, Jun Hwi
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Won, Moo-Ho
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Kangwon Natl Univ, Sch Med, Dept Neurobiol, Chunchon 24341, South KoreaWenzhou Med Univ, Inst Neurosci, Dept Histol & Embryol, Wenzhou 325035, Zhejiang, Peoples R China
Won, Moo-Ho
;
Lee, Young Joo
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Sooncheonhyang Univ, Seoul Hosp, Dept Emergency Med, Coll Med, Seoul 04401, South KoreaWenzhou Med Univ, Inst Neurosci, Dept Histol & Embryol, Wenzhou 325035, Zhejiang, Peoples R China
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China Med Univ, Sch Publ Hlth, Dept Environm Hlth, Shenyang 110001, Liaoning, Peoples R ChinaChina Med Univ, Sch Publ Hlth, Dept Environm Hlth, Shenyang 110001, Liaoning, Peoples R China
Deng, Yu
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Zhu, Jiayu
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China Med Univ, Sch Publ Hlth, Dept Environm Hlth, Shenyang 110001, Liaoning, Peoples R ChinaChina Med Univ, Sch Publ Hlth, Dept Environm Hlth, Shenyang 110001, Liaoning, Peoples R China
Zhu, Jiayu
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Mi, Chao
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Inst Shenyang Hlth Inspect, Dept Sch Hlth Supervis, Shenyang 110001, Liaoning, Peoples R ChinaChina Med Univ, Sch Publ Hlth, Dept Environm Hlth, Shenyang 110001, Liaoning, Peoples R China
Mi, Chao
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Xu, Bin
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China Med Univ, Sch Publ Hlth, Dept Environm Hlth, Shenyang 110001, Liaoning, Peoples R ChinaChina Med Univ, Sch Publ Hlth, Dept Environm Hlth, Shenyang 110001, Liaoning, Peoples R China
Xu, Bin
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Jiao, Congcong
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China Med Univ, Sch Publ Hlth, Dept Environm Hlth, Shenyang 110001, Liaoning, Peoples R ChinaChina Med Univ, Sch Publ Hlth, Dept Environm Hlth, Shenyang 110001, Liaoning, Peoples R China
Jiao, Congcong
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Li, Yuehui
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China Med Univ, Sch Publ Hlth, Dept Environm Hlth, Shenyang 110001, Liaoning, Peoples R ChinaChina Med Univ, Sch Publ Hlth, Dept Environm Hlth, Shenyang 110001, Liaoning, Peoples R China
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Xu, Donghui
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China Med Univ, Dept Pharm, Affiliated Hosp 1, Shenyang, Peoples R ChinaChina Med Univ, Sch Publ Hlth, Dept Environm Hlth, Shenyang 110001, Liaoning, Peoples R China
Xu, Donghui
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Liu, Wei
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China Med Univ, Sch Publ Hlth, Dept Environm Hlth, Shenyang 110001, Liaoning, Peoples R ChinaChina Med Univ, Sch Publ Hlth, Dept Environm Hlth, Shenyang 110001, Liaoning, Peoples R China
Liu, Wei
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Xu, Zhaofa
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China Med Univ, Sch Publ Hlth, Dept Environm Hlth, Shenyang 110001, Liaoning, Peoples R ChinaChina Med Univ, Sch Publ Hlth, Dept Environm Hlth, Shenyang 110001, Liaoning, Peoples R China
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Univ Calif Los Angeles, Dept Neurobiol, Los Angeles, CA 90095 USA
Univ Calif Los Angeles, Dept Psychiat & Psychol, Los Angeles, CA 90095 USA
Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USAUniv Calif Los Angeles, Dept Neurobiol, Los Angeles, CA 90095 USA
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Kempermann, Gerd
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Ctr Regenerat Therapies Dresden, D-01307 Dresden, GermanyUniv Calif Los Angeles, Dept Neurobiol, Los Angeles, CA 90095 USA
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Wenzhou Med Univ, Inst Neurosci, Dept Histol & Embryol, Wenzhou 325035, Zhejiang, Peoples R ChinaWenzhou Med Univ, Inst Neurosci, Dept Histol & Embryol, Wenzhou 325035, Zhejiang, Peoples R China
Chen, Bai Hui
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Ahn, Ji Hyeon
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Park, Joon Ha
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Choi, Soo Young
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Lee, Yun Lyul
;
Kang, Il Jun
论文数: 0引用数: 0
h-index: 0
机构:
Hallym Univ, Dept Food Sci & Nutr, Chunchon 24252, South KoreaWenzhou Med Univ, Inst Neurosci, Dept Histol & Embryol, Wenzhou 325035, Zhejiang, Peoples R China
Kang, Il Jun
;
Hwang, In Koo
论文数: 0引用数: 0
h-index: 0
机构:
Seoul Natl Univ, Dept Anat & Cell Biol, Coll Vet Med, Seoul 08826, South Korea
Seoul Natl Univ, Res Inst Vet Sci, Seoul 08826, South KoreaWenzhou Med Univ, Inst Neurosci, Dept Histol & Embryol, Wenzhou 325035, Zhejiang, Peoples R China
Hwang, In Koo
;
Lee, Tae-Kyeong
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Kangwon Natl Univ, Sch Med, Dept Neurobiol, Chunchon 24341, South KoreaWenzhou Med Univ, Inst Neurosci, Dept Histol & Embryol, Wenzhou 325035, Zhejiang, Peoples R China
Lee, Tae-Kyeong
;
Shin, Bich-Na
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Kangwon Natl Univ, Sch Med, Dept Neurobiol, Chunchon 24341, South KoreaWenzhou Med Univ, Inst Neurosci, Dept Histol & Embryol, Wenzhou 325035, Zhejiang, Peoples R China
Shin, Bich-Na
;
Lee, Jae-Chul
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Kangwon Natl Univ, Sch Med, Dept Neurobiol, Chunchon 24341, South KoreaWenzhou Med Univ, Inst Neurosci, Dept Histol & Embryol, Wenzhou 325035, Zhejiang, Peoples R China
Lee, Jae-Chul
;
Hong, Seongkweon
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Kangwon Natl Univ, Sch Med, Dept Surg, Chunchon 24341, South KoreaWenzhou Med Univ, Inst Neurosci, Dept Histol & Embryol, Wenzhou 325035, Zhejiang, Peoples R China
Hong, Seongkweon
;
Jeon, Yong Hwan
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Kangwon Natl Univ, Kangwon Natl Univ Hosp, Sch Med, Dept Radiol, Chunchon 24341, South KoreaWenzhou Med Univ, Inst Neurosci, Dept Histol & Embryol, Wenzhou 325035, Zhejiang, Peoples R China
Jeon, Yong Hwan
;
Shin, Myoung Cheol
论文数: 0引用数: 0
h-index: 0
机构:
Kangwon Natl Univ, Dept Emergency Med, Chunchon 24341, South Korea
Kangwon Natl Univ, Kangwon Natl Univ Hosp, Sch Med, Inst Med Sci, Chunchon 24341, South KoreaWenzhou Med Univ, Inst Neurosci, Dept Histol & Embryol, Wenzhou 325035, Zhejiang, Peoples R China
Shin, Myoung Cheol
;
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Cho, Jun Hwi
;
Won, Moo-Ho
论文数: 0引用数: 0
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Kangwon Natl Univ, Sch Med, Dept Neurobiol, Chunchon 24341, South KoreaWenzhou Med Univ, Inst Neurosci, Dept Histol & Embryol, Wenzhou 325035, Zhejiang, Peoples R China
Won, Moo-Ho
;
Lee, Young Joo
论文数: 0引用数: 0
h-index: 0
机构:
Sooncheonhyang Univ, Seoul Hosp, Dept Emergency Med, Coll Med, Seoul 04401, South KoreaWenzhou Med Univ, Inst Neurosci, Dept Histol & Embryol, Wenzhou 325035, Zhejiang, Peoples R China
机构:
China Med Univ, Sch Publ Hlth, Dept Environm Hlth, Shenyang 110001, Liaoning, Peoples R ChinaChina Med Univ, Sch Publ Hlth, Dept Environm Hlth, Shenyang 110001, Liaoning, Peoples R China
Deng, Yu
;
Zhu, Jiayu
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h-index: 0
机构:
China Med Univ, Sch Publ Hlth, Dept Environm Hlth, Shenyang 110001, Liaoning, Peoples R ChinaChina Med Univ, Sch Publ Hlth, Dept Environm Hlth, Shenyang 110001, Liaoning, Peoples R China
Zhu, Jiayu
;
Mi, Chao
论文数: 0引用数: 0
h-index: 0
机构:
Inst Shenyang Hlth Inspect, Dept Sch Hlth Supervis, Shenyang 110001, Liaoning, Peoples R ChinaChina Med Univ, Sch Publ Hlth, Dept Environm Hlth, Shenyang 110001, Liaoning, Peoples R China
Mi, Chao
;
Xu, Bin
论文数: 0引用数: 0
h-index: 0
机构:
China Med Univ, Sch Publ Hlth, Dept Environm Hlth, Shenyang 110001, Liaoning, Peoples R ChinaChina Med Univ, Sch Publ Hlth, Dept Environm Hlth, Shenyang 110001, Liaoning, Peoples R China
Xu, Bin
;
Jiao, Congcong
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h-index: 0
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China Med Univ, Sch Publ Hlth, Dept Environm Hlth, Shenyang 110001, Liaoning, Peoples R ChinaChina Med Univ, Sch Publ Hlth, Dept Environm Hlth, Shenyang 110001, Liaoning, Peoples R China
Jiao, Congcong
;
Li, Yuehui
论文数: 0引用数: 0
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China Med Univ, Sch Publ Hlth, Dept Environm Hlth, Shenyang 110001, Liaoning, Peoples R ChinaChina Med Univ, Sch Publ Hlth, Dept Environm Hlth, Shenyang 110001, Liaoning, Peoples R China
Li, Yuehui
;
Xu, Donghui
论文数: 0引用数: 0
h-index: 0
机构:
China Med Univ, Dept Pharm, Affiliated Hosp 1, Shenyang, Peoples R ChinaChina Med Univ, Sch Publ Hlth, Dept Environm Hlth, Shenyang 110001, Liaoning, Peoples R China
Xu, Donghui
;
Liu, Wei
论文数: 0引用数: 0
h-index: 0
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China Med Univ, Sch Publ Hlth, Dept Environm Hlth, Shenyang 110001, Liaoning, Peoples R ChinaChina Med Univ, Sch Publ Hlth, Dept Environm Hlth, Shenyang 110001, Liaoning, Peoples R China
Liu, Wei
;
Xu, Zhaofa
论文数: 0引用数: 0
h-index: 0
机构:
China Med Univ, Sch Publ Hlth, Dept Environm Hlth, Shenyang 110001, Liaoning, Peoples R ChinaChina Med Univ, Sch Publ Hlth, Dept Environm Hlth, Shenyang 110001, Liaoning, Peoples R China
机构:
Univ Calif Los Angeles, Dept Neurobiol, Los Angeles, CA 90095 USA
Univ Calif Los Angeles, Dept Psychiat & Psychol, Los Angeles, CA 90095 USA
Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USAUniv Calif Los Angeles, Dept Neurobiol, Los Angeles, CA 90095 USA
Ehninger, Dan
;
Kempermann, Gerd
论文数: 0引用数: 0
h-index: 0
机构:
Ctr Regenerat Therapies Dresden, D-01307 Dresden, GermanyUniv Calif Los Angeles, Dept Neurobiol, Los Angeles, CA 90095 USA