• 생약학회지
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• 제49권1호
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• pp.28-39
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• 2018

This study investigated the effect of snail extract on the growth parameters of old female rats (27 weeks). Rats were administered orally with snail extract at a dose of 100 mg/kg, 200 mg/kg, chondroitin sulfate 10 mg/kg and 0.9% saline (control) for 8 weeks. Bone mineral density (BMD) and serum concentrations of insulin-like growth factor 1 (IGF-1) and insulinlike growth factor-binding protein 3 (IGFBP-3) were significantly higher in rats exposed to snail extract for 8 weeks. MG-63 cells (human osteoblast-like cells) were treated with snail extract for 48 h. Their differentiation and proliferation was investigated with Western blot and morphological changes observed via immunofluorescence staining of ${\beta}-catenin$. Treatment with snail extract significantly increased the levels of growth factors including ${\beta}-catenin$ and IGF-1. The snail extract affected osteoblast formation. Morphological changes in MG-63 cells were observed via immunofluorescence staining. Treatment with snail extract increased the expression of ${\beta}-catenin$ in MG-63 cells. Results suggest that the treatment of MG-63 cells with snail extract increased the longitudinal growth and growth factor levels. Snail extract may be pharmacologically effective in osteogenic differentiation in vitro and represents a potential therapeutic agent for bone formation.

• 한국식품영양학회지
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• 제34권6호
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• pp.568-575
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• 2021

The purpose of this study was to investigate the effects of extract mixture of C. wilfordii and P. umbrosa (IPLUS-CWPU) on bone growth in 4-week old young male SD rats. To confirm the effect of IPLUS-CWPU, we measured the length of bone growth plate, the ratio of proliferative zone to the length of growth plate and the expression level of insulin-like growth factor, IGF-1. The IPLUS-CWPU treatment shows a significant increase of tibial and femoral growth plate and the ratio of proliferative zone in growth plate. Especially, the length increased by 13.9% and 25.3% in the tibia and femur, respectively, in the high-dose group compared to the normal group. Moreover, the expression of IGF-1 gene in liver was upregulated in IPLUS-CWPU treated groups. These results indicated that IPLUS-CWPU administration could increase the proliferative zone of bone growth plate in early developmental stage by upregulation of IGF-1 gene.

• BMB Reports
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• 제54권9호
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• pp.470-475
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• 2021

Low-dose metronomic chemotherapy has been introduced as a less toxic and effective strategy to inhibit tumor angiogenesis, but its anti-angiogenic mechanism on endothelial progenitor cells (EPCs) has not been fully elucidated. Here, we investigated the functional role of regulated in development and DNA damage response 1 (REDD1), an endogenous inhibitor of mTORC1, in low-dose doxorubicin (DOX)-mediated dysregulation of EPC functions. DOX treatment induced REDD1 expression in bone marrow mononuclear cells (BMMNCs) and subsequently reduced mTORC1-dependent translation of endothelial growth factor (VEGF) receptor (Vegfr)-2 mRNA, but not that of the mRNA transcripts for Vegfr-1, epidermal growth factor receptor, and insulin-like growth factor-1 receptor. This selective event was a risk factor for the inhibition of BMMNC differentiation into EPCs and their angiogenic responses to VEGF-A, but was not observed in Redd1-deficient BMMNCs. Low-dose metronomic DOX treatment reduced the mobilization of circulating EPCs in B16 melanoma-bearing wild-type but not Redd1-deficient mice. However, REDD1 overexpression inhibited the differentiation and mobilization of EPCs in both wild-type and Redd1-deficient mice. These data suggest that REDD1 is crucial for metronomic DOX-mediated EPC dysfunction through the translational repression of Vegfr-2 transcript, providing REDD1 as a potential therapeutic target for the inhibition of tumor angiogenesis and tumor progression.

• Clinical and Experimental Reproductive Medicine
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• 제49권2호
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• pp.149-158
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• 2022

Objective: Optimizing culture media for the incubation of immature oocytes is a vital strategy to increase the oocyte maturation rate during in vitro maturation (IVM) programs. This study evaluated the IVM and fertilization rates of human germinal vesicle (GV) and metaphase I (MI) oocytes using two different maturation media (commercial and homemade) with or without growth differentiation factor 9-β (GDF9-β). supplementation. Methods: Immature oocytes from intracytoplasmic sperm injection (ICSI) cycles were collected and assigned to one of two IVM culture media (commercial or homemade; cleavage-stage base). After maturation, MII oocytes were examined under an inverted microscope for the presence of the polar body, zona pellucida (ZP) birefringence, and meiotic spindle (MS) visualization after maturation in four conditions (commercial or homemade medium, with or without GDF9-β. ICSI was done for matured oocytes, and fertilization was confirmed by the visualization of two distinct pronuclei and two polar bodies. Results: No significant differences were found between the two culture media in terms of the time and rate of oocyte maturation or the rate of fertilization (p>0.05). Growth factor supplementation increased the 24-hour maturation rate for both GV and MI oocytes only in homemade medium. The maturation rate after 24 hours was higher for MI oocytes (p<0.05). Similar results were observed for MS visualization and ZP structure in both types of media (p>0.05). Conclusion: Higher rates of oocyte maturation and fertilization were observed after application of homemade medium supplemented with GDF9-β. Therefore, this combination may be recommended as an alternative for clinical IVM programs.

• Molecules and Cells
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• 제42권9호
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• pp.661-671
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• 2019

Adipose tissue-derived mesenchymal stem cells (ADSCs) are promising for regenerating degenerated intervertebral discs (IVDs), but the low efficiency of nucleus pulposus (NP)-specific differentiation limits their clinical applications. The Sonic hedgehog (Shh) signaling pathway is important in NP-specific differentiation of ADSCs, and Smoothened Agonist (SAG) is a highly specific and effective agonist of Shh signaling. In this study, we proposed a new differentiation strategy with the use of the small molecule SAG. The NP-specific differentiation and extracellular matrix (ECM) synthesis of ADSCs were measured in vitro, and the regenerative effects of SAG pretreated ADSCs in degenerated IVDs were verified in vivo. The results showed that the combination of SAG and transforming growth factor-${\beta}3$ ($TGF-{\beta}3$) is able to increase the ECM synthesis of ADSCs. In addition, the gene and protein expression levels of NP-specific markers were increased by treatment with SAG and $TGF-{\beta}3$. Furthermore, SAG pretreated ADSCs can also improve the disc height, water content, ECM content, and structure of degenerated IVDs in vivo. Our new differentiation scheme has high efficiency in inducing NP-specific differentiation of ADSCs and is promising for stem cell-based treatment of degenerated IVDs.

• The Korean Journal of Physiology and Pharmacology
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• 제20권1호
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• pp.53-62
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• 2016

Mesenchymal stem cells (MSCs) in the bone marrow and other somatic tissues reside in an environment with relative low oxygen tension. Cobalt chloride ($CoCl_2$) can mimic hypoxic conditions through transcriptional changes of some genes including hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) and vascular endothelial growth factor (VEGF). This study evaluated the potential role of $CoCl_2$ preconditioning on multi-lineage differentiation of C3H/10T1/2, a murine MSC line to understand its possible molecular mechanisms in vitro. $CoCl_2$ treatment of MSCs markedly increased HIF-$1{\alpha}$ and VEGF mRNA, and protein expression of HIF-$1{\alpha}$. Temporary preconditioning of MSCs with $CoCl_2$ induced up-regulation of osteogenic markers including alkaline phosphatase, osteocalcin, and type I collagen during osteogenic differentiation, followed by enhanced mineralization. $CoCl_2$ also increased chondrogenic markers including aggrecan, sox9, and type II collagen, and promoted chondrocyte differentiation. $CoCl_2$ suppressed the expression of adipogenic markers including $PPAR{\gamma}$, aP2, and $C/EBP{\alpha}$, and inhibited adipogenesis. Temporary preconditioning with $CoCl_2$ could affect the multi-lineage differentiation of MSCs.

• 한국양식학회지
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• 제1권1호
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• pp.53-66
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• 1988

틸라피아는 암수간에 성장차가 커 수컷 종묘만을 생산하여 양식함은 산업적으로 매우 중요시된다. 본 연구는 나일틸라피아의 암컷을 수컷으로 성전환시키기 위한 연구로써 본 종의 초기생식소 분화 및 여러 농도의 호르몬 처리에 의한 성전환율을 구한 후 호르몬이 성장에 미치는 효과를 조사하여 다음과 같은 결과를 얻었다. 나일틸라피아의 초기 생식소는 원생식세포의 점진적인 분열에 의해 부화후 9일째 형성되었으며, 난소와 정소로의 성 분화는 부화후 약 20일부터 조직학적으로 식별되었다. 17$\alpha$-mrthyltestosterone (MT)을 15, 30 및 60ppm의 농도로 10$\~$40일 동안 처리한 후 성전환율을 조사한 결과 모든 실험군에서 $95\%$ 이상의 수컷이 생산되었다. 특히 15ppm-40일, 30ppm-30일과 30ppm-40일 처리군에서는 $100\%$ 수컷이 유도되었다. 호르몬 처리에 의한 성장의 증가는 대조군에 비해 비교적 뚜렷하게 나타났으며, condition factor 역시 크게 나타나 MT는 틸라피아의 성장을 증가시킴은 물론 비만하게 함을 알 수 있었다.

• Clinical and Experimental Reproductive Medicine
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• 제46권4호
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• pp.166-172
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• 2019

Objective: In vitro maturation (IVM) of immature oocytes can be useful for some infertile patients. In IVM programs, the rates of embryo formation and pregnancy are low. Therefore, it is essential to recognize the main factors involved in regulating oocyte maturation in vitro. The purpose of this study was to investigate the effects of growth differentiation factor 9 (GDF9) and cumulus cell (CC) supplementation in IVM medium on the rates of embryo formation and viability of human blastocysts. Methods: A total of 80 germinal vesicle oocytes from stimulated cycles underwent an IVM program. The oocytes were divided into four groups, where group I consisted of IVM media only and served as the control, group II consisted of IVM+CCs, group III consisted of IVM+GDF9 (200 ng/mL), and group IV consisted of IVM+CCs+GDF9 (200 ng/mL). Intracytoplasmic sperm injection was performed on the IVM oocytes, and the cleavage embryos that were generated were vitrified. Following thawing, the embryos were cultured for 3 additional days, and the viability rates of the developed blastocysts were determined. Results: The maturation rate of the oocytes did not differ significantly across the four groups. The fertilization rate in group II was significantly higher than that in the control group (76.5% vs. 46.2%). Embryo formation was significantly more frequent in all experimental groups than in the control group, while blastocyst formation did not show significant differences in the three experimental groups compared to the control. The mean viability rates in groups II, III, and IV were 58.16%, 55.91%, and 55.95%, respectively, versus 37.78% in the control group (p< 0.05). Conclusion: Supplementation of IVM culture media with GDF9 and CCs enhanced the fertilization, embryo formation, and viability rates of blastocysts generated from vitrified cleavage embryos.

• Biomolecules & Therapeutics
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• 제23권4호
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• pp.313-319
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• 2015

P7C3 and its derivatives, 1-(3,6-dibromo-9H-carbazol-9-yl)-3-(p-tolylamino)propan-2-ol (1) and N-(3-(3,6-dibromo-9H-carbazol-9-yl)-2-hydroxypropyl)-N-(3-methoxyphenyl)-4-methylbenzenesulfonamide (2), were previously reported to increase neurogenesis in rat neural stem cells (NSCs). Although P7C3 is known to increase neurogenesis by protecting newborn neurons, it is not known whether its derivatives also have protective effects to increase neurogenesis. In the current study, we examined how 1 induces neurogenesis. The treatment of 1 in NSCs increased numbers of cells in the absence of epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF2), while not affecting those in the presence of growth factors. Compound 1 did not induce astrocytogenesis during NSC differentiation. 5-Bromo-2'-deoxyuridine (BrdU) pulsing experiments showed that 1 significantly enhanced BrdU-positive neurons. Taken together, our data suggest that 1 promotes neurogenesis by the induction of final cell division during NSC differentiation.

• Asian-Australasian Journal of Animal Sciences
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• 제15권9호
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• pp.1364-1370
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• 2002

The objective of this study was to examine the effect of compensatory growth nutritional regimen on mammary gland growth and lactation. One hundred twenty-two Sprague Dawley female rats (35 days of age) were randomly assigned to either a control or a stair-step compensatory nutrition (SSCN) feeding regimen or an alternating 2-2-3-3-week schedule beginning with 40% energy restriction for 2 weeks followed by re-alimentation (control diet) for 2 weeks. Pup weight gain and milk yield were improved 8% and 8 to 15%, respectively, by the SSCN regimen. The gene expression of $\beta$-casein was 2.3-fold greater in the SSCN group than in the control group during early lactation, but they were greater at all stages of the second lactation. The gene expression of insulin-like growth factor-I was 40% lower in the SSCN group than in the control group during early lactation of the second lactation, but during late lactation it was 80% greater than in the control group. The concentration of serum corticosterone tended to be higher in the SSCN group during the late stage of the first lactation. These results suggest that the stair-step compensatory nutrition regimen improves lactation performance and persistency by modulation of cell differentiation and apoptotic cell death.