• Title/Summary/Keyword: IGF-Ⅰ

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Regulation of appetite-related neuropeptides by Panax ginseng: A novel approach for obesity treatment

  • Phung, Hung Manh;Jang, Dongyeop;Trinh, Tuy An;Lee, Donghun;Nguyen, Quynh Nhu;Kim, Chang-Eop;Kang, Ki Sung
    • Journal of Ginseng Research
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    • v.46 no.4
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    • pp.609-619
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    • 2022
  • Obesity is a primary factor provoking various chronic disorders, including cardiovascular disease, diabetes, and cancer, and causes the death of 2.8 million individuals each year. Diet, physical activity, medications, and surgery are the main therapies for overweightness and obesity. During weight loss therapy, a decrease in energy stores activates appetite signaling pathways under the regulation of neuropeptides, including anorexigenic [corticotropin-releasing hormone, proopiomelanocortin (POMC), cholecystokinin (CCK), and cocaine- and amphetamine-regulated transcript] and orexigenic [agoutirelated protein (AgRP), neuropeptide Y (NPY), and melanin-concentrating hormone] neuropeptides, which increase food intake and lead to failure in attaining weight loss goals. Ginseng and ginsenosides reverse these signaling pathways by suppressing orexigenic neuropeptides (NPY and AgRP) and provoking anorexigenic neuropeptides (CCK and POMC), which prevent the increase in food intake. Moreover, the results of network pharmacology analysis have revealed that constituents of ginseng radix, including campesterol, beta-elemene, ginsenoside Rb1, biotin, and pantothenic acid, are highly correlated with neuropeptide genes that regulate energy balance and food intake, including ADIPOQ, NAMPT, UBL5, NUCB2, LEP, CCK, GAST, IGF1, RLN1, PENK, PDYN, and POMC. Based on previous studies and network pharmacology analysis data, ginseng and its compounds may be a potent source for obesity treatment by regulating neuropeptides associated with appetite.

Gintonin-enriched fraction improves sarcopenia by maintaining immune homeostasis in 20- to 24-month-old C57BL/6J mice

  • Oh, Hyun-Ji;Jin, Heegu;Nah, Seung-Yeol;Lee, Boo-Yong
    • Journal of Ginseng Research
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    • v.45 no.6
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    • pp.744-753
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    • 2021
  • Background: Gintonin-enriched fraction (GEF) is a new non-saponin component glycolipoprotein isolated from ginseng root. This study examined the effect of GEF on age-related sarcopenia in old C57BL/6J mice. Methods: Young (3-6 months) and old (20-24 months) C57BL/6J mice received oral GEF (50 mg/kg/day or 150 mg/kg/day) daily for 5 weeks. During the oral administration period, body weight and grip strength were measured weekly. After sacrifice, muscles from the hindlimb were excised and used for hematoxylin and eosin staining and western blotting to determine the effects of GEF on sarcopenia. The thymus was photographed to compare size, and flow cytometry was performed to examine the effect of GEF on immune homeostasis in the thymus and spleen. Blood samples were collected, and the concentrations of pro-inflammatory cytokines and IGF-1 were measured. Results: GEF caused a significant increase in muscle strength, mass, and fiber size in old mice. GEF restored age-related disruption of immune homeostasis by maintaining T cell compartments and regulating inflammatory biomarkers. Thus, GEF reduced common low-grade chronic inflammatory parameters, which are the main cause of muscle loss. Conclusion: GEF maintained immune homeostasis and inhibited markers of chronic inflammation, resulting in anti-sarcopenia effects in aged C57BL/6J mice. Thus, GEF is a potential therapeutic agent that slows sarcopenia in the elderly.

Common and differential effects of docosahexaenoic acid and eicosapentaenoic acid on helper T-cell responses and associated pathways

  • Lee, Jaeho;Choi, Yu Ri;Kim, Miso;Park, Jung Mi;Kang, Moonjong;Oh, Jaewon;Lee, Chan Joo;Park, Sungha;Kang, Seok-Min;Manabe, Ichiro;Ann, Soo-jin;Lee, Sang-Hak
    • BMB Reports
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    • v.54 no.5
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    • pp.278-283
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    • 2021
  • Our understanding of the differential effects between specific omega-3 fatty acids is incomplete. Here, we aimed to evaluate the effects of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on T-helper type 1 (Th1) cell responses and identify the pathways associated with these responses. Naïve CD4+ T cells were co-cultured with bone marrow-derived dendritic cells (DCs) in the presence or absence of palmitate (PA), DHA, or EPA. DHA or EPA treatment lowered the number of differentiated IFN-γ-positive cells and inhibited the secretion of IFN-γ, whereas only DHA increased IL-2 and reduced TNF-α secretion. There was reduced expression of MHC II on DCs after DHA or EPA treatment. In the DC-independent model, DHA and EPA reduced Th1 cell differentiation and lowered the cell number. DHA and EPA markedly inhibited IFN-γ secretion, while only EPA reduced TNF-α secretion. Microarray analysis identified pathways involved in inflammation, immunity, metabolism, and cell proliferation. Moreover, DHA and EPA inhibited Th1 cells through the regulation of diverse pathways and genes, including Igf1 and Cpt1a. Our results showed that DHA and EPA had largely comparable inhibitory effects on Th1 cell differentiation. However, each of the fatty acids also had distinct effects on specific cytokine secretion, particularly according to the presence of DCs.

Randomized, Double-blind, and Placebo-controlled Human Trial to Evaluate the Efficacy and Safety of Humulus japonicus Extract Powder on Child Height Growth: Study Protocol (소아 키 성장에 미치는 한삼덩굴추출분말의 유효성 및 안전성을 평가하기 위한 무작위배정, 이중눈가림, 위약 대조 인체적용시험: 인체적용시험 프로토콜)

  • Jang Subi;Choi Bom;Cheon Jin Hong;Kim Ki Bong
    • The Journal of Pediatrics of Korean Medicine
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    • v.37 no.3
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    • pp.121-132
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    • 2023
  • Objectives We aimed to confirm whether Humulus japonicus Extract Powder can enhance child height growth significantly and safely compared with a placebo. Methods A total of 150 children between the 3rd and 25th percentiles in height and between the ages of 6 and 9 years will be recruited to participate in this randomized, double-blind, placebo-controlled clinical trial. The participants will be randomly assigned to the treatment or placebo group. Participants in the treatment group will take one pack per day (700 mg of Humulus japonicus Extract Powder) for 24 weeks. Participants in the placebo group will take one package of placebo per day (0 mg of Humulus japonicus Extract Powder) for 24 weeks. The primary outcome will be a change in height after 12 weeks, and the secondary outcomes will be the height after 24 weeks, growth rate, height standard deviation, growth hormone, insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), bone alkaline phosphatase (BALP), and osteocalcin after 12 and 24 weeks. Results This protocol was approved by the Institutional Review Board (IRB) of the Korean Medicine Hospital of Busan University (IRB No. PNUKHIRB-2023-03-002). Research participants will be recruited from June 2023 to December 2023. Conclusions The results of this study provide clinical information regarding the effectiveness and safety of the Humulus japonicus Extract Powder in increasing child height.

Evaluation of the optimal dissolved oxygen level for rainbow trout (Oncorhynchus mykiss) in the recirculating aquaculture system (순환여과 양식시스템 내 무지개송어(Oncorhynchus mykiss)의 적정 용존산소 농도평가)

  • Kunhong PARK;Jinseo CHOI;Younghun LEE;Jeonghwan PARK
    • Journal of the Korean Society of Fisheries and Ocean Technology
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    • v.59 no.4
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    • pp.387-398
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    • 2023
  • Conventional aquaculture faces declining productivity, shifting to recirculating aquaculture system (RAS), known for minimizing water usage and maintaining consistent water temperatures for year-round fish growth. Rainbow trout (Oncorhynchus mykiss), a globally important cold-water species and the third most farmed fish in inland waters of Korea, valued for its fecundity and rapid growth. Dissolved oxygen, an important environmental factor affecting fish production and economics, highlights the need for smart aquaculture practices. Since 2018, the rise of intelligent aquaculture platforms, incorporating information and communications technology (ICT), emphasizes the essential role of RAS implementation. This eight-week study aimed to determine the optimal dissolved oxygen concentration for rainbow trout in RAS, utilizing a device for continuous monitoring, control and record. Dissolved oxygen concentrations were set at 5-6 mg/L, 9-10 mg/L, 14-15 mg/L and 17-18 mg/L. The growth rate significantly decreased at 5-6 mg/L, with no significant differences in other experimental groups. In hematological analysis, growth hormone (GH) was significantly highest at 5-6 mg/L, followed by 9-10 mg/L while Insulin-like growth factor-1 (IGF-1) was significantly lowest at 5-6 mg/L. In conclusion, the optimal dissolved oxygen concentration for rainbow trout in RAS is approximately 9-10 mg/L. Higher concentrations do not contribute to further growth or profitability.

Tracking of Stem Cells from Human Exfoliated Deciduous Teeth Labeled with Molday ION Rhodamine-B during Periodontal Bone Regeneration in Rats

  • Nan Zhang;Li Xu;Hao Song;Chunqing Bu;Jie Kang;Chuanchen Zhang;Xiaofei Yang;Fabin Han
    • International Journal of Stem Cells
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    • v.16 no.1
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    • pp.93-107
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    • 2023
  • Background and Objectives: Chronic periodontitis can lead to alveolar bone resorption and eventually tooth loss. Stem cells from exfoliated deciduous teeth (SHED) are appropriate bone regeneration seed cells. To track the survival, migration, and differentiation of the transplanted SHED, we used super paramagnetic iron oxide particles (SPIO) Molday ION Rhodamine-B (MIRB) to label and monitor the transplanted cells while repairing periodontal bone defects. Methods and Results: We determined an appropriate dose of MIRB for labeling SHED by examining the growth and osteogenic differentiation of labeled SHED. Finally, SHED was labeled with 25 ㎍ Fe/ml MIRB before being transplanted into rats. Magnetic resonance imaging was used to track SHED survival and migration in vivo due to a low-intensity signal artifact caused by MIRB. HE and immunohistochemical analyses revealed that both MIRB-labeled and unlabeled SHED could promote periodontal bone regeneration. The colocalization of hNUC and MIRB demonstrated that SHED transplanted into rats could survive in vivo. Furthermore, some MIRB-positive cells expressed the osteoblast and osteocyte markers OCN and DMP1, respectively. Enzyme-linked immunosorbent assay revealed that SHED could secrete protein factors, such as IGF-1, OCN, ALP, IL-4, VEGF, and bFGF, which promote bone regeneration. Immunofluorescence staining revealed that the transplanted SHED was surrounded by a large number of host-derived Runx2- and Col II-positive cells that played important roles in the bone healing process. Conclusions: SHED could promote periodontal bone regeneration in rats, and the survival of SHED could be tracked in vivo by labeling them with MIRB. SHED are likely to promote bone healing through both direct differentiation and paracrine mechanisms.

Experimental Studies on the Hair Growth Activity of Extracts of Pinelliae Rhizoma in Spontaneous Alopecia Model and Normal C57BL/6N Mice (반하추출물(半夏抽出物)이 자발적 원형탈모 생쥐와 정상 생쥐의 발모효과에 대한 실험적 연구)

  • Jeong, Il-Kook;Jo, Han-Young;Kim, Tae-Heon;Kim, Nam-Seok;Jeong, Han-Sol;Lee, Chang-Hyun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.23 no.1
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    • pp.84-92
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    • 2009
  • This experiment was investigated the effects of fresh and ginger processed Pinelliae Rhizoma extracts on hair growth activity, and its fractions(chloroform, ethyl acetate and water fractions) obtained from fresh Pinelliae Rhizoma on hair growth activity of the normal and spontaneous alopecia areata model of C57BL/6N mice for 16 days. The results were as follows: In fresh Pinelliae Rhizoma extracts treated group, hair growth effect was observed in whole skin area(100%) all the normal mice in whose hair had been clipped on 16th days. In ginger processed Pinelliae Rhizoma extracts treated group, hair growth effect was observed in whole skin area in 25% of normal mice in whose hair had been clipped on 16th days. But in control group, hair growth effect was observed in a part of whole skin area in 25% of normal mice. In fresh Pinelliae Rhizoma extracts treated group, hair follicles of middle stage of anagen phase was observed and it were grown down to subcutaneous tissue of skin in all the mice on 10th day. But in ginger processed Pinelliae Rhizoma extracts treated group and control group, Most of hair follicles of telogen phase was observed in skin. The treatment of extracts of fresh Pinelliae Rhizoma increased the expression of TGF-$\beta$(146%), IGF(107%), and prolactin(115%) in the skin of normal C57BL/6N mice compared to control group(100%). But expression of placenta lactogen(93%) was decreased in the skin of normal C57BL/6N mice compared to control group(100%). In spontaneous alopecia model, The hair growth activity of fresh Pinelliae Rhizoma extracts treated group(100%) was observed to be strong compared with the control group(20%) on 15th day. Hair growth activity on chloroform fractions of fresh Pinelliae Rhizoma extracts was observed in whole skin area in 75% of normal mice on the 9th day. In water and ethyl acetate fractions, hair growth activity was observed in a part of whole skin in 75% and 25% of normal mice, respectively. but hair growth activity of control group was not observed. After application of fractions of fresh Pinelliae Rhizoma extracts for 10 days, hair follicles of chloroform fraction treated group was observed middle stage of anagen phase and hair follicle were grown down to subcutaneous tissue of skin in all the mice. But hair follicles of initial stage of anagen phase were observed in water and ethyl acetate fractions. Most of hair follicles of telogen phase was observed in skin of control group. These experiments suggest that extracts of fresh Pinelliae Rhizoma may stimulate the topical hair growth activity and its chloroform fractions can be useful for treatment of alopecia areata.

Effects of Achyranthes Bidentata Polysaccharide on Growth Performance, Immunological, Adrenal, and Somatotropic Responses of Weaned Pigs Challenged with Escherichia coli Lipopolysaccharide

  • Guo, Guanglun;Liu, Yulan;Fan, Wei;Han, Jie;Hou, Yongqing;Yin, Yulong;Zhu, Huiling;Ding, Binying;Shi, Junxia;Lu, Jing;Wang, Huirong;Chao, Jin;Qu, Yonghua
    • Asian-Australasian Journal of Animal Sciences
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    • v.21 no.8
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    • pp.1189-1195
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    • 2008
  • A study was conducted with 48 weaned barrows ($28{\pm}3d$, $8.45{\pm}0.14kg$) to determine the effect of Achyranthes bidentata polysaccharide (ABPS) supplementation on pig performance, immunological, adrenal and somatotropic responses following Escherichia coli lipopolysaccharide (LPS) challenge. The experiment was a $2{\times}2$ factorial design; the main factors included diet (supplementation with 0 or 500 mg/kg ABPS) and immunological challenge (LPS or saline). On d 14 and 21 of the trial, pigs were given an intraperitoneal injection with either $100{\mu}g/kg$ BW of LPS or an equivalent amount of sterile saline. Blood samples were obtained 3 h after injection for analysis of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), prostaglandin $E_2$ ($PGE_2$), cortisol, growth hormone (GH), insulin-like growth factor (IGF)-I and immunoglobulin G (IgG). On d 2 after LPS challenge, peripheral blood lymphocyte proliferation (PBLP) was measured. LPS administration decreased average daily feed intake (ADFI) (p<0.05), had a tendency to decrease average daily gain (ADG) (p<0.10) during both the first and second challenge periods and increased (p<0.05) feed:gain ratio only during the first challenge period. ABPS tended to improve ADG (p<0.10) during the first challenge period, and improved ADG (p<0.05) and tended to improve ADFI (p<0.10) during the second challenge period. ABPS did not affect feed:gain ratio. An interaction (p<0.05) between LPS challenge and diet was observed for the plasma concentrations of TNF-${\alpha}$, $PGE_2$ and cortisol after both LPS challenges such that, among LPS-treated pigs, pigs fed the ABPS diet were lower for these indices than those receiving the control diet. In contrast, pigs fed the ABPS diet had higher IGF-I (p<0.05) compared with those fed the control diet. No effect of diet, LPS challenge or both on GH and IgG was observed after both LPS administrations. LPS challenge increased PBLP when these cells were incubated with $8{\mu}g/ml$ of LPS during both the challenge periods, and did likewise when incubated with $8{\mu}g/ml$ of concanavalin A only after the first challenge. ABPS had no effect on PBLP. These data demonstrate that ABPS alters the release of pro-inflammatory cytokines following an immunological challenge, which might enable pigs to achieve better performance.

MiR-126-3p inhibits apoptosis and promotes proliferation by targeting phosphatidylinositol 3-kinase regulatory subunit 2 in porcine ovarian granulosa cells

  • Zhou, Xiaofeng;He, Yingting;Jiang, Yao;He, Bo;Deng, Xi;Zhang, Zhe;Yuan, Xiaolong;Li, Jiaqi
    • Asian-Australasian Journal of Animal Sciences
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    • v.33 no.6
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    • pp.879-887
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    • 2020
  • Objective: Numerous studies have indicated that the apoptosis and proliferation of granulosa cells (GCs) are closely related to the normal growth and development of follicles and ovaries. Previous evidence has suggested that miR-126-3p might get involved in the apoptosis and proliferation of GCs, and phosphatidylinositol 3-kinase regulatory subunit 2 (PIK3R2) gene has been predicted as one target of miR-126-3p. However, the molecular regulation of miR-126-3p on PIK3R2 and the effects of PIK3R2 on porcine GCs apoptosis and proliferation remain virtually unexplored. Methods: In this study, using porcine GCs as a cellular model, luciferase report assay, mutation and deletion were applied to verify the targeting relationship between miR-126-3p and PIK3R2. Annexin-V/PI staining and 5-ethynyl-2'-deoxyuridine assay were applied to explore the effect of PIK3R2 on GCs apoptosis and proliferation, respectively. Real-time quantitative polymerase chain reaction and Western Blot were applied to explore the regulation of miR-126-3p on PIK3R2 expression. Results: We found that miR-126-3p targeted at PIK3R2 and inhibited its mRNA and protein expression. Knockdown of PIK3R2 significantly inhibited the apoptosis and promoted the proliferation of porcine GCs, and significantly down-regulated the mRNA expression of several key genes of PI3K pathway such as insulin-like growth factor 1 receptor (IGF1R), insulin receptor (INSR), pyruvate dehydrogenase kinase 1 (PDK1), and serine/threonine kinase 1 (AKT1). Conclusion: MiR-126-3p might target and inhibit the mRNA and protein expressions of PIK3R2, thereby inhibiting GC apoptosis and promoting GC proliferation by down-regulating several key genes of the PI3K pathway, IGF1R, INSR, PDK1, and AKT1. These findings would provide great insight into further exploring the molecular regulation of miR-126-3p and PIK3R2 on the functions of GCs during the folliculogenesis in female mammals.

Synergism Induced by Combination of Farnesyl Transferase Inhibitor SCH66336 and Insulin like-Growth Factor Binding Protein-3 in apoptosis of Non-Small Cell Lung Cancer Cell lines (비소세포성 폐암 세포주에서 Farnesyl Transferase Inhibitor SCH66336과 인슐린양 성장 인자 결합 단백-3의 병용처리에 의한 세포고사 상승 작용)

  • Kim, Young;Kim, Se Kyu;Kim, Hyung Jung;Chang, Joon;Ahn, Chul Min;Kim, Sung Kyu;Chang, Yoon Soo
    • Tuberculosis and Respiratory Diseases
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    • v.58 no.2
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    • pp.120-128
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    • 2005
  • Background : Insulin-like growth factor binding protein (IGFBP)-3 regulates non-small cell lung cancer(NSCLC) cell proliferation in vitro and in vivo by inhibiting IGF-mediated signaling pathways. To have better strategies for the treatment of lung cancer, we analyzed the combining effects of adenovirus expressing IGFBP-3 (Ad5CMV-BP3) and SCH66336, a farnesyl transferase inhibitor (FTI) designed to block Ras-mediated proliferative signaling pathways. Methods : To measure the combining effects of Ad5CMV-BP3 and SCH66336 on the proliferation of NSCLC cells, human NSCLC cell lines (H1299, H596, A549, H460, and H358), SCH66336, recombinant adenovirus expressing IGFBP-3 (Ad5CMV-BP3) and athymic nude mice were used in these experiments. Results : The combination of Ad5CMV-BP3 and SCH66336 produced a synergistic enhancement in antiproliferative effects over a range of clinically achievable concentrations in a variety of NSCLC cell lines. Furthermore, we observed a significant reduction in growth of NSCLC xenograft induced in athymic nude mice. Conclusion : In conclusion, this study demonstrated for the first time that the FTI SCH66336 synergizes with IGFBP-3 and enhances its apoptotic activity in NSCLC cells in vitro and in vivo. The combined treatment of Ad5CMV-BP3 and SCH66336 raises the possibility of using this regimen in clinic for the treatment of NSCLC.