• Journal of Animal Science and Technology
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• v.62 no.6
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• pp.777-789
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• 2020

Intense artificial selection has been imposed to Luzhong mutton sheep population in the past years. Improvements on growth and reproductive performance are two breeding goals in the present herd. Although some progresses were phenotypically observed possibly due to inbreeding induced by strong selection in terms of these traits, the genomic evaluation was poorly understood. Therefore, a high-density SNP array was used to characterize the pattern of runs of homozygosity (ROH), estimate inbreeding and inbreeding depressions on early growth performance and litter size based upon ROH, and scan positive selection signatures of recent population. Consequently, a low inbreeding level was observed which had negative effects on litter size, but not on early growth performance. And 160 genes were under selection, of which some were reported to be linked to several traits of sheep including body weight, litter size, carcass and meat quality, milk yield and composition, fiber quality and health, and the top genes were associated with growth (growth hormone [GH]- growth hormone receptor [GHR]- Insulin-like growth factor 1 [IGF1] axis) and litter size (bone morphogenic proteins [BMPs]-associated). The effectiveness of previous breeding measures was highlighted, but purging selection was proposed to alleviate the inbreeding depression on litter size, providing some genomic insights to breeding management of Luzhong mutton sheep.

• Clinical and Experimental Pediatrics
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• v.54 no.2
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• pp.51-54
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• 2011

Vitamin D is present in two forms, ergocalciferol (vitamin $D_2$) produced by plants and cholecalciferol (vitamin $D_3$) produced by animal tissues or by the action of ultraviolet light on 7-dehydrocholesterol in human skin. Both forms of vitamin D are biologically inactive pro-hormones that must undergo sequential hydroxylations in the liver and the kidney before they can bind to and activate the vitamin D receptor. The hormonally active form of vitamin D, 1,25-dihydroxyvitamin D3 $[1,25(OH)_2D]$, plays an essential role in calcium and phosphate metabolism, bone growth, and cellular differentiation. Renal synthesis of $1,25(OH)_2D$ from its endogenous precursor, 25-hydroxyvitamin D (25OHD), is the rate-limiting and is catalyzed by the $1{\alpha}$-hydroxylase. Vitamin D dependent rickets type I (VDDR-I), also referred to as vitamin D $1{\alpha}$-hydroxylase deficiency or pseudovitamin D deficiency rickets, is an autosomal recessive disorder characterized clinically by hypotonia, muscle weakness, growth failure, hypocalcemic seizures in early infancy, and radiographic findings of rickets. Characteristic laboratory features are hypocalcemia, increased serum concentrations of parathyroid hormone (PTH), and low or undetectable serum concentrations of $1,25(OH)_2D$ despite normal or increased concentrations of 25OHD. Recent advances have showed in the cloning of the human $1{\alpha}$-hydroxylase and revealed mutations in its gene that cause VDDR-I. This review presents the biology of vitamin D, and $1{\alpha}$-hydroxylase mutations with clinical findings.

• Asian-Australasian Journal of Animal Sciences
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• v.29 no.8
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• pp.1065-1074
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• 2016

Growth factors play an important role during early ovarian development and folliculogenesis, since they regulate the migration of germ cells to the gonadal ridge. They also act on follicle recruitment, proliferation/atresia of granulosa cells and theca, steroidogenesis, oocyte maturation, ovulation and luteinization. Among the growth factors, the growth differentiation factor 9 (GDF9) and the bone morphogenetic protein 15 (BMP15), belong to the transforming growth factor beta (TGF-${\beta}$) superfamily, have been implicated as essential for follicular development. The GDF9 and BMP15 participate in the evolution of the primordial follicle to primary follicle and play an important role in the later stages of follicular development and maturation, increasing the steroidogenic acute regulatory protein expression, plasminogen activator and luteinizing hormone receptor (LHR). These factors are also involved in the interconnections between the oocyte and surrounding cumulus cells, where they regulate absorption of amino acids, glycolysis and biosynthesis of cholesterol cumulus cells. Even though the mode of action has not been fully established, in vitro observations indicate that the factors GDF9 and BMP15 stimulate the growth of ovarian follicles and proliferation of cumulus cells through the induction of mitosis in cells and granulosa and theca expression of genes linked to follicular maturation. Thus, seeking greater understanding of the action of these growth factors on the development of oocytes, the role of GDF9 and BMP15 in ovarian function is summarized in this brief review.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3207-3210
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• 2014

Background: Inflammatory breast cancer (IBC) is an aggressive form of locally advanced breast cancer characterized by rapidly progressive breast erythema, pain and tenderness, oedema and paeu d'orange appearance. It accounts for 1-3% of all newly diagnosed cases of breast cancer in the west. Data on IBC from India are lacking. The aim of our study was to assess the clinical-pathological parameters and outcome of IBC at, All India Institute of Medical Sciences, a large tertiary care centre. Materials and Methods: We screened 3,650 breast cancer cases registered from January 2004 to December 2012 and found 41 cases of IBC. Data included demographics as well as clinical, radiological and histopathological characteristics, and were collected from clinical case records using the International Classification of Diseases code (C-50). Patients who presented with IBC as a recurrence, or who had a neglected and advanced breast cancer that simulated an IBC were excluded from this study. Results: The median age was 45 years (range 23-66). The median duration of symptoms was 5 months. The American Joint Committee on Cancer stage (AJCC) distribution was Stage III - 26 and IV - 15 patients. Estrogen receptor (ER), progesterone receptor (PR) positivity and human epidermal growth factor receptor 2 (HER2/neu) positivity were 50%, 46% and 60%, respectively. Triple negativity was found in 15% of the cases. All the non metastatic IBC patients received anthracycline and/ or taxane based chemotherapy followed by modified radical mastectomy, radiotherapy and hormonal therapy as indicated. Pathological complete remission rate was 15%. At a median follow-up of 30 months, the 3 year relapse free survival and overall survival were 30% and 40%respectively. Conclusion: IBC constituted 1.1% of all breast cancer patients at our centre. One third of these had metastatic disease at presentation. Hormone positivity and Her2 neu positivity were found in 50% and 60% of the cases, respectively.

• Journal of Pathology and Translational Medicine
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• v.52 no.6
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• pp.396-403
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• 2018

Background: In the current American Joint Committee on Cancer staging system of breast cancer, only tumor size determines T-category regardless of whether the tumor is single or multiple. This study evaluated if tumor multiplicity has prognostic value and can be used to subclassify breast cancer. Methods: We included 5,758 patients with invasive breast cancer who underwent surgery at Samsung Medical Center, Seoul, Korea, from 1995 to 2012. Results: Patients were divided into two groups according to multiplicity (single, n=4,744; multiple, n=1,014). Statistically significant differences in lymph node involvement and lymphatic invasion were found between the two groups (p<.001). Patients with multiple masses tended to have luminal A molecular subtype (p<.001). On Kaplan-Meier survival analysis, patients with multiple masses had significantly poorer disease-free survival (DFS) (p=.016). The prognostic significance of multiplicity was seen in patients with anatomic staging group I and prognostic staging group IA (p=.019 and p=.032, respectively). When targeting patients with T1-2 N0 M0, hormone receptor-positive, and human epidermal growth factor receptor 2 (HER2)-negative cancer, Kaplan-Meier survival analysis also revealed significantly reduced DFS with multiple cancer (p=.031). The multivariate analysis indicated that multiplicity was independently correlated with worse DFS (hazard ratio, 1.23; 95% confidence interval, 1.03 to 1.47; p=.025). The results of this study indicate that tumor multiplicity is frequently found in luminal A subtype, is associated with frequent lymph node metastasis, and is correlated with worse DFS. Conclusions: Tumor multiplicity has prognostic value and could be used to subclassify invasive breast cancer at early stages. Adjuvant chemotherapy would be necessary for multiple masses of T1-2 N0 M0, hormone-receptor-positive, and HER2-negative cancer.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.2
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• pp.383-387
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• 2006

To investigate the effect of GyeongshinhaeGihwan 1(GGT1) frequently used as an anti-obesity herbal medicine in oriental medicine on the expression of obesity-related genes, we measured the changes in mRNA levels of these genes by GGT1 in human growth hormone transgenic (hGHTg) obese female rats, and these effects by GGT1 were compared with those of reductil (RD), an anti-obesity drug approved by FDA. Rats received once daily oral administrations of autoclaved water, RD, or GGT1 for 8 weeks. At the end of study, rats were sacrificed and tissues were harvested. Total RNA from adipose tissue, liver and kidney was prepared and the mRNA levels for LPL (lipoprotein lipase), $PPAR{\gamma}$ (peroxisome proliferator activated receptor-gamma), $PPAR{\delta}$ (peroxisome proliferator activated receptor-delta), leptin, $TNF{\alpha}$ (tumor necrosis factor-alpha), and internal standard G3PDH (glyceraldehyde-3-phosphate dehydrogenase) were analyzed by RT-PCR. Compared with control group, $PPAR{\gamma}$ mRNA levels of liver and kidney were decreased in both RD and GGT1 groups, and the effects were more prominent in GGT1 group than in RD group, suggesting that GGT1 is effective in the inhibition of lipid storage by decreasing the $PPAR{\gamma}$ expression. $PPAR{\delta}$ mRNA levels of adipose tissue were increased by RD and GGT1 compared with DW, and the magnitude of increase were higher in GGT1 group than in RD group, indicating that GGT1 stimulates fatty acid oxidation and energy metabolism by activating $PPAR{\delta}$ expression. GGT1 group had higher concentrations of serum leptin, a well-known inhibitor of appetite, than control and RD groups. However, The mRNA levels of leptin, LPL, and $TNF{\alpha}$ were not changed by GGT1. These results indicate that GGT1 can prevent obesity in hGHTg obese female rats by down-regulating and up-regulating the mRNA expression of $PPAR{\gamma}$ and $PPAR{\delta}$, respectively, and that this anti-obesity effects were more pronounced in GGT1 group compared with RD group. In addition, GGT1 seems to inhibit obesity by increasing the circulating leptin levels.

• Asian-Australasian Journal of Animal Sciences
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• v.14 no.3
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• pp.307-315
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• 2001

Litter size has been one of the important economic traits in porcine reproduction. The insulin-like growth factor (IGF) system has been shown to mediate actions of the steroid hormone or to synergize with other endocrine factors so that it consequently plays roles in reproductive processes, including ovulation, implantation, maintenance of pregnancy, and fetal development. However, the effect of the serum IGF system on porcine litter size has not been deeply studied. Therefore, this study was conducted to relate serum IFG-II concentration and IGF binding protein-3 (IGFBP-3) expression with porcine litter size. Moreover, the possible association of those with estrogen receptor (ER) as a candidate gene for litter size was investigated. Swine were separated into two groups showing high and low litter sizes, and sera were collected from sows in the estrous cycle to postnatal growth of their female progeny. Serum IFG-II concentration was measured by radioimmunoassay and IGFBP-3 expression was detected by Western ligand blotting. During the estrous cycle, IGFBP-3 expression in both groups decreased moderately from metestrus to estrus, but IFG-II concentration showed a reverse pattern. Also, IFG-II concentration and IGFBP-3 expression decreased gradually as pregnancy proceeded. Unlike IGFBP-3, IFG-II decreased moderately as newborn pigs grew. Significant differences in serum IFG-II amount between the two groups were detected at 60 (p<0.01), 75, 90, and 105 d (p<0.05) of pregnancy and at 60 (p<0.01), 45, and 105 d (p<0.05) of postnatal growth. Furthermore, based on ER genotypes, a high litter size group with genotypes AB and BB showed lower IFG-II concentration than a low litter size group with a genotype AA during pregnancy. Taken together, the results indicate that the serum IFG-II and IGFBP-3 are correlated with the litter size in pigs.

• Environmental Analysis Health and Toxicology
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• v.27
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• pp.10.1-10.7
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• 2012

Objectives: In recent years, a number of structurally diverse Histone deacetylase (HDAC) inhibitors have been identified and these HDAC inhibitors induce growth arrest, differentiation and/or apoptosis of cancer cells in vitro and in vivo. This study aimed at investigating the antitumor activity of newly synthesized HDAC inhibitor, 3-(4-dimethylamino phenyl)-N-hydroxy-2-propenamide (IN-2001) using human breast cancer cells. Methods: We have synthesized a new HDAC inhibitor, IN-2001, and cell proliferation inhibition assay with this chemical in estrogen receptor-positive human breast cancer MCF-7 cells. Cell cycle analysis on MCF-7 cells treated with IN-2001 was carried out by flow cytometry and gene expression was measured by RT-PCR. Results: In MCF-7 cells IN-2001 showed remarkable anti-proliferative effects in a dose- and time-dependent manner. In MCF-7 cells, IN-2001 showed a more potent growth inhibitory effect than that of suberoylanilide hydroxamic acid. These growth inhibitory effects were related to the cell cycle arrest and induction of apoptosis. IN-2001 showed accumulation of cells at $G_2$/M phase and of the sub-$G_1$ population in a time-dependent manner, representing apoptotic cells. IN-2001-mediated cell cycle arrest was associated with HDAC inhibitor-mediated induction of CDK inhibitor expression. In MCF-7 cells, IN-2001 significantly increased $p21^{WAF1}$ expression. Conclusions: In summary, cyclin-dependent kinase (CDK) induced growth inhibition, possibly through modulation of cell cycle and apoptosis regulatory proteins, such as CDK inhibitors, and cyclins. Taken together, these results provide an insight into the utility of HDAC inhibitors as a novel chemotherapeutic regime for hormone-sensitive and insensitive breast cancer.

• Biomedical Science Letters
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• v.13 no.3
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• pp.197-206
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• 2007

P2X receptors are membrane-bound ion channels that conduct $Na^+,\;K^+$, and $Ca^{2+}$ in response to ATP and its analogs. There are seven subunits identified so far ($P2X_1-P2X_7$). $P2X_2$ receptors are known to be expressed in a wide range of organs including brains and adrenal grands. PC12 cells are originated from adrenal grand and differentiated by nerve growth factor or pituitary adenylate cyclase activating poly peptide (PACAP). Previous studies indicate that $P2X_2$ receptor activation in PC12 cells couples to $Ca^{2+}-dependent$ release of catecholamine and ATP. It is known that acidic pH potentiates ATP currents at $P2X_2$ receptors. This leads to a hypothesis that $P2X_2$ receptors may play an important role in PC12 cell differentiation, one of the characteristics of which is neurite outgrowth, induced by the hormones under lower pH. In the present study, we isolated several clones which potentiate neurite outgrowth by PACAP in acidic pH (6.8), but not in alkaline pH (7.6). RT-PCR and electrophysiology data indicate that these clones express only functional $P2X_2$ receptors in the absence or presence of PACAP for 3 days. Potentiation of neurite outgrowth resulted from PACAP (100 nM) in acidic pH is inhibited by the two P2X receptor antagonists, suramin and PPADS ($100\;{\mu}M)$ each), and exogenous exprerssion of ATP-binding mutant $P2X_2$ receptor subunit ($P2X_2[K69A]$). However, acid sensing ion channels (ASICs) are not involved in PACAP-induced neurite outgrowth potentiation in lower pH since treatments of an inhibitor of ASICs, amyloride ($10\;{\mu}M$), did not give any effects to neurite extension. The vesicular proton pump ($H^+-ATPase$) inhibitor, bafilomycin (100 nM), reduced neurite extension indicating that ATP release resulted from $P2X_2$ receptor activation in PC12 cells is needed for neurite outgrowth. These were confirmed by activation of mitogen activated protein kinases, such as ERKs and p38. These results suggest roles of ATP and $P2X_2$ receptors in hormone-induced cell differentiation or neuronal synaptogenesis in local acidic environments.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10797-10801
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• 2015

Background: To explore the molecular mechanisms of metastatic osteosarcoma (OS) by using the microarray expression profiles of metastatic and non-metastatic OS samples. Materials and Methods: The gene expression profile GSE37552 was downloaded from Gene Expression Omnibus database, including 2 human metastatic OS cell line models and 2 two non-metastatic OS cell line models. The differentially expressed genes (DEGs) were identified by Multtest package in R language. In addition, functional enrichment analysis of the DEGs was performed by WebGestalt, and the protein-protein interaction (PPI) networks were constructed by Hitpredict, then the signal pathways of the genes involved in the networks were performed by Kyoto Encyclopaedia of Genes and Genomes (KEGG) automatic annotation server (KAAS). Results: A total of 237 genes were classified as DEGs in metastatic OS. The most significant up- and down-regulated genes were A2M (alpha-2-macroglobulin) and BCAN (brevican). The DEGs were significantly related to the response to hormone stimulus, and the PPI network of A2M contained IL1B (interleukin), LRP1 (low-density lipoprotein receptor-related protein 1) and PDGF (platelet-derived growth factor). Furthermore, the MAPK signaling pathway and focal adhesion were significantly enriched. Conclusions: A2M and its interactive proteins, such as IL1B, LRP1 and PDGF may be candidate target molecules to monitor, diagnose and treat metastatic OS. The response to hormone stimulus, MAPK signaling pathway and focal adhesion may play important roles in metastatic OS.