• Title/Summary/Keyword: transforming growth factor

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The Anti-Proliferation Effects and Its Mechanism of Bupleurum falcatum on Human Mesangial Cell (시호의 사구체 메산지움 세포 증식억제 효능 및 작용기전 연구)

  • Lee, Byung-Cheol;Ahn, Young-Min;Doo, Ho-Kyung;Ahn, Se-Young
    • The Journal of Internal Korean Medicine
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    • v.25 no.4
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    • pp.9-17
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    • 2004
  • Objective : Mesangial cell proliferation and excessive accumulation of extracellular matrix (ECM) proteins is the common pathologic feature of glomerulosclerosis, and platelet-derived growth factor (PDGF) BB-chain, transforming growth factor betal $(TGF-{\beta}1)$, cyclin dependent kinases (CDK) and CDK inhibitors mediated in these pathophysiological processes. Bupleurum falcatum which is one of the most widely used components in traditional oriental medicines, has multiple pharmacological effects, such as antipyretic, analgesic, immune modulating, anti-inflammatory, anti-allergic, anti-thrombotic, anti-atherosclerotic, and antitussive effects. Methods : In this study, we evaluated the influence of Bupleurum falcatum on mesangial cell proliferation, DNA synthesis and expression of PDGF-BB chain, $TGF-{\beta}1$, CDKI, CDK2, CDK4, p21 and p27 in fetal bovine serum (FBS)-activated human mesangial cell. Results : Bupleurum falcatum reduced the mesangial cell proliferation and DNA synthesis more than control and captopril. And in the ELISA analysis of $TGF-{\beta}1$, and RT-PCR of PDGF-BB chain, CDK1, CDK2, CDK4, p21, and p27, Bupleurum falcatum inhibited the expression of $TGF-{\beta}1$ protein and PDGF-BB, CDK1, CDK2 gene and promoted that of p21 gene in a dose-dependent manner in comparing with control and captopril. Conclusions: These results suggest that Bupleurum falcatum may inhibit the mesangial cell proliferation and DNA synthesis by regulation of PDGF-BB and $TGF-{\beta}1$ expressions, and by modulation of CDK1, CDK2 and p21 expression.

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Morphological Study on Differentiation of Hepatocytic Stem Cell by Intrasplenic Transplantation after Partial Hepatectomy (간부분 절제술 후 비장내 이식한 간세포화 줄기세포의 분화에 관한 형태학적 연구)

  • 양영철;박재홍;박중규;배기원
    • Journal of Life Science
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    • v.12 no.3
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    • pp.294-305
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    • 2002
  • This study was performed to evaluate regenerative effects of intrasplenic stem cell transplantation after partial hepatectomy. To evaluate the regenerative effects, Sprague Dawley rats were used. In vivo the embryonic stem cells of blastocysts were collected from superovulated rats on day 3.5 after the vaginal plug checked. The embryonic stem cells were cocultured with hepatocytes for 8 days, they were transplanted into the spleen. After the intrasplenic transplantation of cultured stem cells, they were initially distributed near the periarterial lymphatic sheath after transplantation in the hematoxylin-eosin staining. Their number were formely increased and their size enlarged at forming small lobules. The embryonic stem cells in the culture proliferated and initially proliferated around the periarterial lymphatic sheath and later they around the trabecula with blood vessels. After the transplantation of stem cells, their cell organelles were well developed rough endoplasmic reticulum at the 20th with prominent epidermal growth factor reaction, developed smooth endoplasmic reticulum at the 30th day, well differentiated bile canaliculi with increased transforming growth factor-$\beta$ and apoptosis reactions.

Role of Expression of Inflammatory Mediators in Primary and Recurrent Lumbar Disc Herniation

  • Dagistan, Yasar;Cukur, Selma;Dagistan, Emine;Gezici, Ali Riza
    • Journal of Korean Neurosurgical Society
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    • v.60 no.1
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    • pp.40-46
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    • 2017
  • Objective: To assess role of some inflammatory mediators in patients with primary and recurrent lumbar disc herniation. Expression of IL-6, transforming growth factor (TGF)-1, insulin-like growth factor (IGF)-1, and Bcl-2-associated X protein (BAX) have been shown to be more intense in the primary group than the recurrent goup, but this mediators may be important aspects prognostic. Methods: 19 patients underwent primary and revision operations between June 1, 2009 and June 1, 2014, and they were included in this study. The 19 patients' intervertebral disc specimens obtained from the primary procedures and reoperations were evaluated. Expression of IL-6, TGF-1, IGF-1, and BAX were examined immunohistochemically in the 38 biopsy tissues obtained from the primary and recurrent herniated intervertebral discs during the operation. Results: For IL-6 expression in the intervertebral disc specimens, there was no difference between the groups. The immunohistochemical study showed that the intervertebral disc specimens in the primary group were stained intensely by TGF-1 compared with the recurrent group. Expression of IGF-1 in the primary group was found moderate. In contrast, in the recurrent group of patients was mild expression of IGF-1. The primary group intervertebral disc specimens were stained moderately by BAX compared with the recurrent group. Conclusion: The results of our prognostic evaluation of patients in the recurrent group who were operated due to disc herniation suggest that mediators may be important parameters.

Alteration of TGFB1, GDF9, and BMPR2 gene expression in preantral follicles of an estradiol valerate-induced polycystic ovary mouse model can lead to anovulation, polycystic morphology, obesity, and absence of hyperandrogenism

  • Asghari, Reza;Shokri-Asl, Vahid;Rezaei, Hanieh;Tavallaie, Mahmood;Khafaei, Mostafa;Abdolmaleki, Amir;Seghinsara, Abbas Majdi
    • Clinical and Experimental Reproductive Medicine
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    • v.48 no.3
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    • pp.245-254
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    • 2021
  • Objective: In humans, polycystic ovary syndrome (PCOS) is an androgen-dependent ovarian disorder. Aberrant gene expression in folliculogenesis can arrest the transition of preantral to antral follicles, leading to PCOS. We explored the possible role of altered gene expression in preantral follicles of estradiol valerate (EV) induced polycystic ovaries (PCO) in a mouse model. Methods: Twenty female balb/c mice (8 weeks, 20.0±1.5 g) were grouped into control and PCO groups. PCO was induced by intramuscular EV injection. After 8 weeks, the animals were killed by cervical dislocation. Blood serum (for hormonal assessments using the enzyme-linked immunosorbent assay technique) was aspirated, and ovaries (the right ovary for histological examinations and the left for quantitative real-time polymerase) were dissected. Results: Compared to the control group, the PCO group showed significantly lower values for the mean body weight, number of preantral and antral follicles, serum levels of estradiol, luteinizing hormone, testosterone, and follicle-stimulating hormone, and gene expression of TGFB1, GDF9 and BMPR2 (p<0.05). Serum progesterone levels were significantly higher in the PCO animals than in the control group (p<0.05). No significant between-group differences (p>0.05) were found in BMP6 or BMP15 expression. Conclusion: In animals with EV-induced PCO, the preantral follicles did not develop into antral follicles. In this mouse model, the gene expression of TGFB1, GDF9, and BMPR2 was lower in preantral follicles, which is probably related to the pathologic conditions of PCO. Hypoandrogenism was also detected in this EV-induced murine PCO model.

Use of adipose-derived stem cells in lymphatic tissue engineering and regeneration

  • Forte, Antonio Jorge;Boczar, Daniel;Sarabia-Estrada, Rachel;Huayllani, Maria T.;Avila, Francisco R.;Torres, Ricardo A.;Guliyeva, Gunel;Aung, Thiha;Quinones-Hinojosa, Alfredo
    • Archives of Plastic Surgery
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    • v.48 no.5
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    • pp.559-567
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    • 2021
  • The potential to differentiate into different cell lines, added to the easy and cost-effective method of extraction, makes adipose-derived stem cells (ADSCs) an object of interest in lymphedema treatment. Our study's goal was to conduct a comprehensive systematic review of the use of ADSCs in lymphatic tissue engineering and regeneration. On July 23, 2019, using PubMed/MEDLINE, Cochrane Clinical Answers, Cochrane Central Register of Controlled Trials, and Embase databases, we conducted a systematic review of published literature on the use of ADSCs in lymphatic tissue engineering and regeneration. There were no language or time frame limitations, and the following search strategy was applied: ((Adipose stem cell) OR Adipose-derived stem cell)) AND ((Lymphedema) OR Breast Cancer Lymphedema). Only original research manuscripts were included. Fourteen studies fulfilled the inclusion criteria. Eleven studies were experimental (in vitro or in vivo in animals), and only three were clinical. Publications on the topic demonstrated that ADSCs promote lymphangiogenesis, and its effect could be enhanced by modulation of vascular endothelial growth factor-C, interleukin-7, prospero homeobox protein 1, and transforming growth factor-β1. Pilot clinical studies included 11 patients with breast cancer-related lymphedema, and no significant side effects were present at 12-month follow-up. Literature on the use of ADSCs in lymphatic tissue engineering and regeneration demonstrated promising data. Clinical evidence is still in its infancy, but the scientific community agrees that ADSCs can be useful in regenerative lymphangiogenesis. Data collected in this review indicate that unprecedented advances in lymphedema treatment can be anticipated in the upcoming years.

The effect of Korean Red Ginseng on full-thickness skin wound healing in rats

  • Park, Ki-Soo;Park, Dae-Hwan
    • Journal of Ginseng Research
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    • v.43 no.2
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    • pp.226-235
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    • 2019
  • Background: Panax ginseng is regarded as one of the best compounds for promoting health, and it has been used traditionally as a medicinal herb. Recently, Korean Red Ginseng (RG) has been shown to protect skin from aging and wrinkling; it can also relieve atopic dermatitis and allergy symptoms. This study aimed to evaluate RG's effects on the regeneration of the full-thickness skin wounds in rat. Methods: Full-thickness skin wounds were generated in rats, and then RG was administered either orally or topically. The wound-healing effects of RG were investigated by assessing wound size, mRNA expression patterns of genes related to wound healing, histological staining, and measurements of lipid, moisture, and elasticity in skin tissues. Results: The wound size was smaller, and tissue regeneration rate was faster in the RG-treated group than that in the control group on days 15 and 20 after initiating treatment. On postoperative day 20, skin lipid and moisture content had increased significantly in the RG-treated group. Significant increases in the gene expression levels of transforming growth $factor-{\beta}1$ and vascular endothelial growth factor were found in the RG group during the early stages of wound healing. Matrix metalloproteinase-1 and matrix metalloproteinase-9 showed significant increases in gene expression levels on day 20. Conclusion: The results suggested that RG may promote healing of full-thickness skin wounds in rats. They also provided basic insights into the effects of RG on skin regeneration, supporting its use as a dressing material for wound treatment and its development as a functional food.

Micro-CT Analysis of Cranial Bone and Tooth Density in Mice Deficient for GDF11 or Myostatin

  • Suh, Joonho;Kim, Na-Kyung;Lee, Yun-Sil
    • Journal of Oral Medicine and Pain
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    • v.45 no.4
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    • pp.83-88
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    • 2020
  • Purpose: Growth differentiation factor 11 (GDF11) and myostatin (MSTN) are closely-related transforming growth factor β family members reported to play crucial roles in bone formation. We previously reported that, in contrast to MSTN, GDF11 promotes osteogenesis of vertebrae and limbs. GDF11 has been also reported as an important regulator in tooth development by inducing differentiation of pulp stem cells into odontoblasts for reparative dentin formation. The goal of this study was to investigate the differential roles of GDF11 and MSTN in dental and cranial bone formation. Methods: Micro-computed tomography analysis was performed on cranial bones, including frontal, parietal, and interparietal bones, and lower incisors of wild-type, Gdf11 knockout (Gdf11-/-), and Mstn knockout (Mstn-/-) mice. Tissue volume, thickness, and mineral density were evaluated for both cranial bone and lower incisors. Lower incisor lengths were also measured. Because Gdf11-/- mice die shortly after birth, analysis was performed on newborn (P0) mice. Results: Compared to those of Mstn-/- mice, cranial bone volume, thickness, and mineral density levels were all significantly diminished in Gdf11-/- mice. Tissue mineral density of Gdf11-/- mice were also significantly decreased compared to wild-type mice. Likewise, lower incisor length, tissue volume, thickness, and mineral density levels were all significantly reduced in Gdf11-/- mice compared to Mstn-/- mice. Incisor length was also significantly decreased in Gdf11-/- mice compared to wild-type mice. Mstn-/- mice exhibited mildly increased levels of tissue volume, thickness, and density in cranial bone and lower incisor compared to wild-type mice although statistically not significant. Conclusions: Our findings suggest that GDF11, unlike MSTN, endogenously promotes cranial bone and tooth development.

Effects of dietary inactivated probiotics on growth performance and immune responses of weaned pigs

  • Kang, Joowon;Lee, Jeong Jae;Cho, Jin Ho;Choe, Jeehwan;Kyoung, Hyunjin;Kim, Sung Hun;Kim, Hyeun Bum;Song, Minho
    • Journal of Animal Science and Technology
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    • v.63 no.3
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    • pp.520-530
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    • 2021
  • This experiment was performed to verify whether dietary heat-killed Lactobacillus rhamnosus (LR) improves growth performance and modulates immune responses of weaned pigs. Ninety-six weaned pigs ([Landrace × Yorkshire] × Duroc; 6.95 ± 0.25 kg body weight [BW]; 28 d old) were randomly allocated to four treatments: 1) a basal diet without heat-killed LR (CON), 2) T1 (CON with 0.1% heat-killed LR), 3) T2 (CON with 0.2% heat-killed LR), and 4) T3 (CON with 0.4% heat-killed LR). Each treatment had six pens with four pigs (6 replicates per treatment) in a randomized completely block design. The heat-killed LR used in this study contained 1 × 109 FU/g of LR in a commercial product. Pigs were fed each treatment for four weeks using a two-phase feeding program to measure growth performance and frequency of diarrhea. During the last week of this study, all diets contained 0.2% chromic oxide as an indigestible marker. Fecal sampling was performed through rectal palpation for the consecutive three days after the four adaptation days to measure apparent total tract digestibility (ATTD) of dry matter, crude protein, and gross energy (GE). Blood sampling was also performed on day 1, 3, 7, and 14 after weaning to measure immune responses such as serum tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), C-reactive protein (CRP), and cortisol. The heat-killed LR increased (p < 0.05) growth rate, feed efficiency, and ATTD of GE for overall experimental period compared with CON, but reduced (p < 0.05) post-weaning diarrhea. In addition, pigs fed diets contained heat-killed had lower concentrations of serum TNF-α (d 7; p < 0.05), TGF-β1 (d 7; p < 0.10), and cortisol (d 3 and 7; p < 0.05) than pigs fed CON. In conclusion, dietary heat-killed LR improved growth rate, modified immune responses of weaned pigs, and alleviated post-weaning diarrhea.

The Effect of Sintongchukea-tang (Shentongzhuyu-tang) on Bone Fusion in Rib Fractured Rats (신통축어탕(身痛逐瘀湯)이 늑골골절 유발 Rat의 골유합에 미치는 영향)

  • Nam, Dae-Jin;Oh, Min-Seok
    • Journal of Korean Medicine Rehabilitation
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    • v.30 no.3
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    • pp.1-21
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    • 2020
  • Objectives This study was designed to evaluate the bone regeneration effects of Sintongchukea-tang (SC) on rib fractured rats. Methods Rats were randomly divided into 5 groups (normal, control, positive control, SC low [SC-L] and SC high [SC-H]). All groups were subject to fractured rib except normal group. Normal group received no treatment at all. Control group was orally fed with phosphate buffered saline, and positive control group was medicated with tramadol (20 mg/kg). SC group was orally medicated with SC (50 mg/kg, 100 mg/kg) once a day for 14 days. The fracture healing process was observed by x-ray, micro CT and fracture tissue slide was observed by immunohistochemical staining. We analysed levels of transforming growth factor-β1, Ki67, alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), receptor activator of nuclear factor kappa-β, tartrate resistant acid phosphatase (TRAP) and analysed levels of Osteocalcin in plasma. We measured levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), ALP, blood urea nitrogen (BUN) and creatinine in plasma, for hepatotoxicity and nephrotoxicity of SC. Results Though X-ray and micro-computed tomography, more callus formation was observed and bone union was progressing. Through Hematoxylin and Eosin, callus formation was increased compared to the control group. Runx2 level at SC-H was significantly increased and TRAP level at SC-L was significantly decreased compared with the control group. AST, ALT, ALP, BUN and creatinine were not statistically different from the control group. Conclusions As described above, SC promoted fracture healing by stimulating the bone regeneration factor. And SC shows no hepatotoxicity and nephrotoxicity. In conclusion, it seems that SC helps to promote fracture regeneration and it can be used clinically to patients with fracture.

The Healing Effect of Jinmu-tang (Zhenwu-tang) in Femur Fractured Rats (진무탕(眞武湯)이 흰쥐의 대퇴골 골절 치유에 미치는 실험적 연구)

  • Park, Jung-Oh;Oh, Min-Seok
    • Journal of Korean Medicine Rehabilitation
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    • v.30 no.2
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    • pp.19-35
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    • 2020
  • Objectives The aim of this study is to evaluate the fracture healing effect of Jinmu-tang (JM) on femur fractured rats. Methods Rats were randomly divided into 5 groups (normal, control, positive control, JM extract with low concentration and JM extract with high concentration). All group except normal group went through both femur fracture. Normal and control group received no treatment at all. Positive control group were medicated with tramadol (20 mg/kg) once a day for 14 days. Experimental group was orally medicated with JM extract (10 mg/kg for low concentration, 50 mg/kg for high concentration) once a day for 14 days. In order to investigate fracture healing process, plasma and serum were obtained. Also, micro-computed tomography was conducted to see the frature site visually. Immunohistochemistry for transforming growth factor-β1, Ki67, alkaline phosphatase, runt-related transcription factor 2, receptor activator of nuclear factor kappa-β, tartrate resistant acid phosphatase was conducted to observe bone healing progress after 14 days since fracture occured. Aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen and creatinine levels were measured in plasma, for hepatotoxicity and nephrotoxicity of JM extract. Osteocalcin was measured to observe activity of osteoblast. Results Through Micro-CT, more fracture healing was observed on both experimental group than control and positive control group. Through Hematoxylin & Eosin and safranin O staining showed bone cell proliferation and bone formation in the experimental group. RANK was significantly increased in the experimental groups. JM with high concentration showed statistically significant of TGF-β and Osteocalcin. NO, TRAP and ALP were not significantly changed. Liver toxicity was not significantly observed. Creatinine significantly increased in both experimental groups after 28 days. Conclusions As described above, JM extract showed anti-inflammatory effect, promoted fracture healing by stimulating the bone regeneration factor, and showed little hepatotoxicity and nephrotoxicity. In conclusion, JM extract can promote fracture healing and it can be used clinically to patients with fracture.