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  • MDPI AG  (15)
  • Lee, Hyesook  (15)
  • 1
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    Gamma Aminobutyric Acid-Enriched Fermented Oyster (Crassostrea gigas) Increases the Length of the Growth Plate on the Proximal Tibia Bone in Sprague-Dawley Rats
    MDPI AG ; 2020
    In:  Molecules Vol. 25, No. 19 ( 2020-09-23), p. 4375-
    Details
    In: Molecules, MDPI AG, Vol. 25, No. 19 ( 2020-09-23), p. 4375-
    Abstract: Bone growth during childhood and puberty determines an adult’s final stature. Although several prior studies have reported that fermented oyster (FO) consisting of a high amount of gamma aminobutyric acid can be attributed to bone health, there is no research on the efficacy of FO on growth regulation and the proximal tibial growth plate. Therefore, in this study, we investigated the effect of FO oral administration on hepatic and serum growth regulator levels and the development of the proximal tibial growth plate in young Sprague-Dawley rats. Both oral administration of FO (FO 100, 100 mg/kg FO and FO 200, 200 mg/kg FO) and subcutaneous injection of recombinant human growth hormone (rhGH, 200 μg/kg of rhGH) for two weeks showed no toxicity. Circulating levels of growth hormone (GH) significantly increased in the FO 200 group. The expression and secretion of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) were enhanced by FO administration. FO administration promoted the expression of bone morphogenic proteins IGF-1 and IGFBP-3 in the proximal tibial growth plate. This positive effect of FO resulted in incremental growth of the entire plate length by expanding the proliferating and hypertrophic zones in the proximal tibial growth plate. Collectively, our results suggested that oral administration of FO is beneficial for bone health, which may ultimately result in increased height.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules25194375
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2008644-1
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  • 2
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    Improvement of Immune and Hematopoietic Functions by Litsea japonica Fruit Extract in Cyclophosphamide-Treated BALB/c Mice
    MDPI AG ; 2022
    In:  Applied Sciences Vol. 13, No. 1 ( 2022-12-22), p. 145-
    Details
    In: Applied Sciences, MDPI AG, Vol. 13, No. 1 ( 2022-12-22), p. 145-
    Abstract: Loss of immunity is an important cause in the pathology of infectious disease. This study investigates the effect of Litsea japonica fruit extract (LJFE) as a potential functional food on immunity and hematopoietic function in immunosuppressed BALB/c mice. Immunity-stimulating activity was observed in mice supplemented with LJFE at low (25 mg/kg), medium (50 mg/kg), and high (100 mg/kg) dosage for seven days after administration of cyclophosphamide. LJFE treatment significantly improved spleen injury score (p 〈 0.001) and body weight (p 〈 0.02) by approximately two-fold with a high dosage of LJFE (100 mg/kg). Spleen-derived lymphocyte analysis demonstrated that the numbers of clusters of differentiation (CD)4+ and CD8+ T-cells were notably increased by approximately two-fold (p 〈 0.001) with a high dosage of LJFE (100 mg/kg). In mouse splenocytes differentiated into T- and B-lymphocytes, LJFE significantly induced proliferation up to approximately 90% of control for T- (p 〈 0.001) and B-lymphocytes (p 〈 0.01) with a high dosage of LJFE (100 mg/kg). Furthermore, LJFE significantly recovered the numbers of white blood cells, red blood cells, and platelets. Enzyme-linked immunosorbent assay revealed that serum levels of immune-related cytokines, such as tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-2, and interferon (IFN)-γ, were notably Increased. In addition, serum levels of immunoglobulin (Ig) A, IgM, and IgG were restored by LJFE treatment. This study provides a reference to use L. japonica as a functional food ingredient to improve immunity and hematological function in humans.
    Type of Medium: Online Resource
    ISSN: 2076-3417
    URL: Article
    DOI: 10.3390/app13010145
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2704225-X
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  • 3
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    Protective Effect of Gamma Aminobutyric Acid against Aggravation of Renal Injury Caused by High Salt Intake in Cisplatin-Induced Nephrotoxicity
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 1 ( 2022-01-03), p. 502-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 1 ( 2022-01-03), p. 502-
    Abstract: Gamma-aminobutyric acid (GABA) is one of the inhibitory neurotransmitters. Several studies have suggested that GABA supplements can reduce blood pressure and modulate the renal immune system in vitro and in vivo. In the present study, we investigated the effect of GABA-enriched salt as an alternative to traditional salt on aggravated renal injury by high salt intake in cisplatin-induced nephrotoxicity mice. High salt intake accelerated the increase of biomarkers, such as blood urea nitrogen and serum creatinine levels for renal injury in cisplatin-induced nephrotoxicity mice. However, oral administration of GABA-contained salt notably suppressed serum BUN and creatinine levels. The efficacy of GABA salt was superior to lacto GABA salt and postbiotics GABA salt. Furthermore, GABA-enriched salt markedly restored histological symptoms of nephrotoxicity including renal hypertrophy, tubular dilation, hemorrhage, and collagen deposition aggravated by salt over-loading in cisplatin-exposed mice. Among them, GABA salt showed a higher protective effect against cisplatin-induced renal histological changes than lacto GABA salt and postbiotics GABA salt. In addition, administration of high salt significantly enhanced expression levels of apoptosis and inflammatory mediators in cisplatin-induced nephrotoxicity mice, while GABA-enriched salt greatly down-regulated the expression of these mediators. Taken together, these results demonstrate the protective effect of GABA against damage caused by high salt intake in cisplatin-induced renal toxicity. Its mechanism may be due to the suppression of hematological and biochemical toxicity, apoptosis, and inflammation. In conclusion, although the protective efficacy of GABA salt on renal injury is different depending on the sterilization and filtration process after fermentation with L. brevis BJ20 and L. plantarum BJ21, our findings suggest that GABA-enriched salt has a beneficial effect against immoderate high salt intake-mediated kidney injury in patients with cisplatin-induced nephrotoxicity.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23010502
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
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  • 4
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    ROS-Mediated Anti-Tumor Effect of Coptidis Rhizoma against Human Hepatocellular Carcinoma Hep3B Cells and Xenografts
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 9 ( 2021-04-30), p. 4797-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 9 ( 2021-04-30), p. 4797-
    Abstract: Coptidis Rhizoma is the dried rhizome from the Coptis chinensis Franch. that has been shown to have a number of beneficial pharmacological properties including antioxidant, anti-inflammatory, and anti-cancer effects. However, the anti-cancer effects of Coptidis Rhizoma on hepatocellular carcinoma (HCC) remain unclear. In this study, we investigated the anti-cancer properties of Coptidis Rhizoma ethanol extract (CR) in HCC Hep3B cells and in a xenograft mouse model. Our results showed that the CR significantly inhibited cell growth and induced apoptosis in Hep3B cells through increased expression of Bcl-2 associated x-protein (Bax) and cleavage of poly-ADP ribose polymerase (PARP), reduced expression of Bcl-2, and activated caspases. CR also increased the generation of intracellular reactive oxygen species (ROS), which caused a loss of mitochondrial membrane potential (MMP, ΔΨm) and activation of the mitochondria-mediated intrinsic apoptosis pathway. Moreover, N-acetylcysteine (NAC), a ROS inhibitor, markedly blocked the effects of CR on apoptotic pathways. CR also induced the expression of light chain 3 (LC3)-I/II, a key autophagy regulator, whereas CR-mediated autophagy was significantly suppressed by NAC. In addition, pre-treatment with NAC perfectly attenuated the inhibition of cell invasion and migration of CR-stimulated Hep3B cells. Furthermore, oral administration of CR suppressed Hep3B tumor growth in xenograft mice without toxicity, alterations to body weight, or changes in hematological and biochemical profiles. Taken together, our findings suggest that CR has anti-tumor effects that result from ROS generation, and may be a potential pharmacological intervention for HCC.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms22094797
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
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  • 5
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    Spermidine Attenuates Oxidative Stress-Induced Apoptosis via Blocking Ca2+ Overload in Retinal Pigment Epithelial Cells Independently of ROS
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 3 ( 2021-01-29), p. 1361-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 3 ( 2021-01-29), p. 1361-
    Abstract: Retinal pigment epithelial (RPE) cells occupy the outer layer of the retina and perform various biological functions. Oxidative damage to RPE cells is a major risk factor for retinal degeneration that ultimately leads to vision loss. In this study, we investigated the role of spermidine in a hydrogen peroxide (H2O2)-induced oxidative stress model using human RPE cells. Our findings showed that 300 μM H2O2 increased cytotoxicity, apoptosis, and cell cycle arrest in the G2/M phase, whereas these effects were markedly suppressed by 10 μM spermidine. Furthermore, spermidine significantly reduced H2O2-induced mitochondrial dysfunction including mitochondrial membrane potential and mitochondrial activity. Although spermidine displays antioxidant properties, the generation of intracellular reactive oxygen species (ROS) upon H2O2 insult was not regulated by spermidine. Spermidine did suppress the increase in cytosolic Ca2+ levels resulting from endoplasmic reticulum stress in H2O2-stimulated human RPE cells. Treatment with a cytosolic Ca2+ chelator markedly reversed H2O2-induced cellular dysfunction. Overall, spermidine protected against H2O2-induced cellular damage by blocking the increase of intracellular Ca2+ independently of ROS. These results suggest that spermidine protects RPE cells from oxidative stress, which could be a useful treatment for retinal diseases.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms22031361
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
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  • 6
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    The Protective Effect of Topical Spermidine on Dry Eye Disease with Retinal Damage Induced by Diesel Particulate Matter2.5
    MDPI AG ; 2021
    In:  Pharmaceutics Vol. 13, No. 9 ( 2021-09-10), p. 1439-
    Details
    In: Pharmaceutics, MDPI AG, Vol. 13, No. 9 ( 2021-09-10), p. 1439-
    Abstract: Air pollutants, especially ambient fine particulate matter2.5, may contribute to various ocular surface disorders, including dry eye disease, keratitis and conjunctivitis. A natural polyamine spermidine has a protective effect on the retina and optic nerve; however, no study has been conducted on the application of spermidine in particulate matter2.5-induced dry eye disease. In the present study, we investigated the effect of spermidine eye drops in topically exposed particulate matter2.5-induced dry eye models of Sprague-Dawley rats, by hematological, biochemical and histological evaluation. Spermidine eye drops attenuated the particulate matter2.5 exposure-induced reduction of tear secretion and corneal epithelial damage. Furthermore, spermidine protected against conjunctival goblet cell loss and retinal ganglion cell loss induced by particulate matter2.5. Additionally, spermidine markedly prevented particulate matter2.5-induced infiltration of cluster of differentiation3+ and cluster of differentiation4+ T lymphocytes and F4/80+ macrophages on lacrimal gland. Moreover, over expression of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-6 and interleukin-17 in the lacrimal gland and cornea. Meanwhile, the levels of serum total cholesterol and low-density lipoprotein cholesterol were markedly increased by topical exposure to particulate matter2.5, but this change in the lipid profile was decreased by spermidine. Taken together, spermidine may have protective effects against particulate matter2.5-induced dry eye symptoms via stabilization of the tear film and suppression of inflammation and may in part contribute to improving retinal function and lipid metabolism disorder.
    Type of Medium: Online Resource
    ISSN: 1999-4923
    URL: Article
    DOI: 10.3390/pharmaceutics13091439
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527217-2
    SSG: 15,3
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  • 7
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    Induction of Apoptosis by Isoalantolactone in Human Hepatocellular Carcinoma Hep3B Cells through Activation of the ROS-Dependent JNK Signaling Pathway
    MDPI AG ; 2021
    In:  Pharmaceutics Vol. 13, No. 10 ( 2021-10-06), p. 1627-
    Details
    In: Pharmaceutics, MDPI AG, Vol. 13, No. 10 ( 2021-10-06), p. 1627-
    Abstract: Isoalantolactone (IALT) is one of the isomeric sesquiterpene lactones isolated from the roots of Inula helenium L. IALT is known to possess various biological and pharmacological activities, but its anti-cancer mechanisms are not well understood. The aim of the present study was to investigate the anti-proliferative effects of IALT in human hepatocellular carcinoma (HCC) cells and to evaluate the potential anti-cancer mechanisms. Our results demonstrated that IALT treatment concentration-dependently suppressed the cell survival of HCC Hep3B cells, which was associated with the induction of apoptosis. IALT increased the expression of death-receptor-related proteins, activated caspases, and induced Bid truncation, subsequently leading to cleavage of poly (ADP-ribose) polymerase. In addition, IALT contributed to the cytosolic release of cytochrome c by destroying mitochondrial integrity, following an increase in the Bax/Bcl-2 expression ratio. However, IALT-mediated growth inhibition and apoptosis were significantly attenuated in the presence of a pan-caspase inhibitor, suggesting that IALT induced caspase-dependent apoptosis in Hep3B cells. Moreover, IALT activated the mitogen-activated protein kinases signaling pathway, and the anti-cancer effect of IALT was significantly diminished in the presence of a potent c-Jun N-terminal kinase (JNK) inhibitor. IALT also improved the generation of intracellular reactive oxygen species (ROS), whereas the ROS inhibitor significantly abrogated IALT-induced growth reduction, apoptosis, and JNK activation. Furthermore, ROS-dependent apoptosis was revealed as a mechanism involved in the anti-cancer activity of IALT in a 3D multicellular tumor spheroid model of Hep3B cells. Taken together, our findings indicate that IALT exhibited anti-cancer activity in HCC Hep3B cells by inducing ROS-dependent activation of the JNK signaling pathway.
    Type of Medium: Online Resource
    ISSN: 1999-4923
    URL: Article
    DOI: 10.3390/pharmaceutics13101627
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527217-2
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  • 8
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    Anti-Inflammatory Effect of Auranofin on Palmitic Acid and LPS-Induced Inflammatory Response by Modulating TLR4 and NOX4-Mediated NF-κB Signaling Pathway in RAW264.7 Macrophages
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 11 ( 2021-05-31), p. 5920-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 11 ( 2021-05-31), p. 5920-
    Abstract: Chronic inflammation, which is promoted by the production and secretion of inflammatory mediators and cytokines in activated macrophages, is responsible for the development of many diseases. Auranofin is a Food and Drug Administration-approved gold-based compound for the treatment of rheumatoid arthritis, and evidence suggests that auranofin could be a potential therapeutic agent for inflammation. In this study, to demonstrate the inhibitory effect of auranofin on chronic inflammation, a saturated fatty acid, palmitic acid (PA), and a low concentration of lipopolysaccharide (LPS) were used to activate RAW264.7 macrophages. The results show that PA amplified LPS signals to produce nitric oxide (NO) and various cytokines. However, auranofin significantly inhibited the levels of NO, monocyte chemoattractant protein-1, and pro-inflammatory cytokines, such as interleukin (IL)-1β, tumor necrosis factor-α, and IL-6, which had been increased by co-treatment with PA and LPS. Moreover, the expression of inducible NO synthase, IL-1β, and IL-6 mRNA and protein levels increased by PA and LPS were reduced by auranofin. In particular, the upregulation of NADPH oxidase (NOX) 4 and the translocation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) induced by PA and LPS were suppressed by auranofin. The binding between the toll-like receptor (TLR) 4 and auranofin was also predicted, and the release of NO and cytokines was reduced more by simultaneous treatment with auranofin and TLR4 inhibitor than by auranofin alone. In conclusion, all these findings suggested that auranofin had anti-inflammatory effects in PA and LPS-induced macrophages by interacting with TLR4 and downregulating the NOX4-mediated NF-κB signaling pathway.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms22115920
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
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  • 9
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    The Protective Effect of Oral Application of Corni Fructus on the Disorders of the Cornea, Conjunctiva, Lacrimal Gland and Retina by Topical Particulate Matter 2.5
    MDPI AG ; 2021
    In:  Nutrients Vol. 13, No. 9 ( 2021-08-27), p. 2986-
    Details
    In: Nutrients, MDPI AG, Vol. 13, No. 9 ( 2021-08-27), p. 2986-
    Abstract: Particulate matter 2.5 (PM2.5) may aggravate dry eye disease (DED). Corni Fructus (CF), which is fruit of Cornus officinalis Sieb. et Zucc., has been reported to have various beneficial pharmacological effects, whereas the effect of CF on the eye is still unknown. Therefore, in this study, we investigated the effect of oral administration of water extract of CF (CFW) on the eye, hematology, and biochemistry in a DED model induced by topical exposure to PM2.5. Furthermore, the efficacy of CFW compared with cyclosporine (CsA), an anti-inflammatory agent, and lutein, the posterior eye-protective agent. Sprague-Dawley rats were topically administered 5 mg/mL PM2.5 in both eyes four times daily for 14 days. During the same period, CFW (200 mg/kg and 400 mg/kg) and lutein (4.1 mg/kg) were orally administered once a day. All eyes of rats in the 0.05% cyclosporine A (CsA)-treated group were topically exposed to 20 μL of CsA, twice daily for 14 days. Oral administration of CFW attenuated the PM2.5-induced reduction of tear secretion and corneal epithelial damage. In addition, CFW protected against goblet cell loss in conjunctiva and overexpression of inflammatory factors in the lacrimal gland following topical exposure to PM2.5. Furthermore, CFW markedly prevented PM2.5-induced ganglion cell loss and recovered the thickness of inner plexiform layer. Meanwhile, CFW treatment decreased the levels of total cholesterol and low-density lipoprotein cholesterol in serum induced by PM2.5. Importantly, the efficacy of CFW was superior or similar to that of CsA and lutein. Taken together, oral administration of CFW may have protective effects against PM2.5-induced DED symptoms via stabilization of the tear film and suppression of inflammation. Furthermore, CFW may in part contribute to improving retinal function and lipid metabolism disorder.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    URL: Article
    DOI: 10.3390/nu13092986
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2518386-2
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  • 10
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    Betulinic Acid Restricts Human Bladder Cancer Cell Proliferation In Vitro by Inducing Caspase-Dependent Cell Death and Cell Cycle Arrest, and Decreasing Metastatic Potential
    MDPI AG ; 2021
    In:  Molecules Vol. 26, No. 5 ( 2021-03-04), p. 1381-
    Details
    In: Molecules, MDPI AG, Vol. 26, No. 5 ( 2021-03-04), p. 1381-
    Abstract: Betulinic acid (BA) is a naturally occurring pentacyclic triterpenoid and generally found in the bark of birch trees (Betula sp.). Although several studies have been reported that BA has diverse biological activities, including anti-tumor effects, the underlying anti-cancer mechanism in bladder cancer cells is still lacking. Therefore, this study aims to investigate the anti-proliferative effect of BA in human bladder cancer cell lines T-24, UMUC-3, and 5637, and identify the underlying mechanism. Our results showed that BA induced cell death in bladder cancer cells and that are accompanied by apoptosis, necrosis, and cell cycle arrest. Furthermore, BA decreased the expression of cell cycle regulators, such as cyclin B1, cyclin A, cyclin-dependent kinase (Cdk) 2, cell division cycle (Cdc) 2, and Cdc25c. In addition, BA-induced apoptosis was associated with mitochondrial dysfunction that is caused by loss of mitochondrial membrane potential, which led to the activation of mitochondrial-mediated intrinsic pathway. BA up-regulated the expression of Bcl-2-accociated X protein (Bax) and cleaved poly-ADP ribose polymerase (PARP), and subsequently activated caspase-3, -8, and -9. However, pre-treatment of pan-caspase inhibitor markedly suppressed BA-induced apoptosis. Meanwhile, BA did not affect the levels of intracellular reactive oxygen species (ROS), indicating BA-mediated apoptosis was ROS-independent. Furthermore, we found that BA suppressed the wound healing and invasion ability, and decreased the expression of Snail and Slug in T24 and 5637 cells, and matrix metalloproteinase (MMP)-9 in UMUC-3 cells. Taken together, this is the first study showing that BA suppresses the proliferation of human bladder cancer cells, which is due to induction of apoptosis, necrosis, and cell cycle arrest, and decrease of migration and invasion. Furthermore, BA-induced apoptosis is regulated by caspase-dependent and ROS-independent pathways, and these results provide the underlying anti-proliferative molecular mechanism of BA in human bladder cancer cells.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules26051381
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2008644-1
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