• Experimental and Molecular Medicine
• /
• v.50 no.12
• /
• pp.3.1-3.14
• /
• 2018

Type 1 diabetes mellitus (T1DM) is a pathological condition associated with osteopenia. $WNT/{\beta}$-catenin signaling is implicated in this process. Trabecular and cortical bone respond differently to $WNT/{\beta}$-catenin signaling in healthy mice. We investigated whether this signaling has different effects on trabecular and cortical bone in T1DM. We first established a streptozotocin-induced T1DM mouse model and then constitutively activated ${\beta}$-catenin in osteoblasts in the setting of T1DM (T1-CA). The extent of bone loss was greater in trabecular bone than that in cortical bone in T1DM mice, and this difference was consistent with the reduction in the expression of ${\beta}$-catenin signaling in the two bone compartments. Further experiments demonstrated that in T1DM mice, trabecular bone showed lower levels of insulin-like growth factor-1 receptor (IGF-1R) than the levels in cortical bone, leading to lower $WNT/{\beta}$-catenin signaling activity through the inhibition of the IGF-1R/Akt/glycogen synthase kinase $3{\beta}$ ($GSK3{\beta}$) pathway. After ${\beta}$-catenin was activated in T1-CA mice, the bone mass and bone strength increased to substantially greater extents in trabecular bone than those in cortical bone. In addition, the cortical bone of the T1-CA mice displayed an unexpected increase in bone porosity, with increased bone resorption. The downregulated expression of WNT16 might be responsible for these cortical bone changes. In conclusion, we found that although the activation of $WNT/{\beta}$-catenin signaling increased the trabecular bone mass and bone strength in T1DM mice, it also increased the cortical bone porosity, impairing the bone strength. These findings should be considered in the future treatment of T1DM-related osteopenia.

• Psychiatry investigation
• /
• v.15 no.12
• /
• pp.1130-1134
• /
• 2018

Objective Trichotillomania is a relatively common illness whose neurobiology is poorly understood. One treatment for adult trichotillomania, n-acetyl cysteine (NAC), has antioxidative properties, as well as effects on central glutamatergic transmission. Preclinical models suggest that excessive oxidative stress may be involved in its pathophysiology. Methods Adults with trichotillomania provided a blood sample for analysis of compounds that may be influenced by oxidative stress [glutathione, angiotensin II, ferritin, iron, glucose, insulin and insulin growth factor 1 (IGF1), and hepcidin]. Participants were examined on symptom severity, disability, and impulsivity. The number of participants with out-of-reference range oxidative stress measures were compared against the null distribution. Correlations between oxidative stress markers and clinical measures were examined. Results Of 14 participants (mean age 31.2 years; 92.9% female), 35.7% (n=5) had total glutathione levels below the reference range (p=0.041). Other oxidative stress measures did not have significant proportions outside the reference ranges. Lower levels of glutathione correlated significantly with higher motor impulsiveness (Barratt Impulsiveness Scale sub-score) (r=0.97, p=0.001). Conclusion A third of patients with trichotillomania had low levels of glutathione, and lower levels of glutathione correlated significantly with higher motor impulsiveness. Because NAC is a precursor for cysteine, and cysteine is a rate limiting step for glutathione production, these results may shed light on the mechanisms through which NAC can have beneficial effects for impulsive symptoms. Confirmation of these results requires a suitable larger follow-up study, including an internal normative control group.

• Animal cells and systems
• /
• v.15 no.4
• /
• pp.310-314
• /
• 2011

The Banna miniature pig (BNMP) is a representative miniature pig breed in China. Even though BNMP dwarfism is obvious, its underlying causative mutations remain unknown. In this study, the BNMP and Large White pig (LWP) serum growth hormone (GH) and insulin-like growth factor (IGF-1) levels were detected by ELISA and compared. BNMP serum IGF-1 levels were significantly lower than LWP levels (P<0.05). The miniature condition may arise from mutations in the GH and GH receptor (GHR) genes. Therefore, GH and GHR cDNA from the BNMP were cloned into a pMD18-T vector by RT-PCR using the total RNA obtained from the BNMP's pituitary and liver tissues. Sequencing results indicated that the open reading frame of the BNMP GH gene is composed of a 26-residue signal peptide and a 191-residue mature peptide. The coding sequence of the BNMP GHR gene contained 639 amino acids, including a signal peptide that is 18 amino acids long. Two amino acid substitutions, A09V and R22Q, were found in the signal peptide of the GH gene. Additionally, the S104P mutation was found in the BNMP's mature GH protein. Four mutations in the cytoplasmic domain of GHR may influence the downstream signal transduction of GHR, which needs further experimental evidence.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.36 no.1
• /
• pp.39-42
• /
• 2010

Maxillary sinus lift and bone graft are used to reconstruct atrophic maxilla molar area for endosseous dental implants. Many different grafting materials and techniques can be used for maxillary sinus bone graft. Bio-$Oss^{(R)}$ has been proposed as bone substitute and successfully utilized as osteoconductive filler. Platelet rich plasma (PRP) is an autologous material with many growth factors, such as PDGF, TGF-$\beta$, IGF, VEGF, facilitating bone healing process. And Platelet poor plasma (PPP) is the by-product in procedure of producing PRP. Six rabbits were used as experimental animal. Both maxillary sinus were grafted with Bio-$Oss^{(R)}$ and PRP, and Bio-$Oss^{(R)}$ and PPP. Rabbits were sacrificed at 4, 8 and 12 weeks. The grafting sites were evaluated by histomorphometric analysis. As a result, using PRP showed excellent bone formation in the early stage, but no further significant effect after that. In late stage, the ability of bone formation of using PRP was even worse than using PPP. The further studies need to be considered in this case.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.37 no.12
• /
• pp.1576-1582
• /
• 2008

This study was conducted to investigate the effect of administration of calcium supplementary food containing fermented product of Bacillus subtilis SE4 highly producing poly-$\gamma$-glutamic acid on the growthparameters of adolescent male rats. Four-week old male Sprague-Dawley (SD) rats were fed for 4 weeks and assigned to the following 4 groups: two groups administered orally with new calcium supplementary food (such as 150 mg/kg and 300 mg/kg) containing fermented product of B. subtilis SE4, one group administered with conventional calcium supplementary food product (150 mg/kg) and one saline group as control. Daily weight gain and daily food intake in the two new food product groups were higher than those of conventional food product group and control group. Especially, the content of serum IGF-I in the two new food product groups were significantly higher than those in conventional food product group and in control group (p<0.05). In addition, length and weight of longitudinal bone in the two new food product groups were longer and heavier than those of conventional food product group and control group. Therefore, the addition of fermented food product of B. subtilis SE4 into the conventional calcium supplementary food increased all the parameters examined for the growth of the adolescent male rats.

• Proceedings of the Korean Society of Toxicology Conference
• /
• 2001.10a
• /
• pp.203-204
• /
• 2001

Background and Aim: Transitional cell carcinoma (TCC) of the bladder represents the fifth most prevalent malignancy in Western population, with peak incidence found in males of the 50- to 70-year-old age group. A major problem in the management of bladder cancer is the low sensitivity of a large proportion (approximately 40%) among bladder tumors to chemotherapy and the high risk for recurrence of bladder tumors after transurethral resection.(omitted)

• Molecules and Cells
• /
• v.25 no.2
• /
• pp.211-215
• /
• 2008

To gain a better understanding of the methylation imprinting changes associated with heat stress in early development, we used bisulfite sequencing and bisulfite restriction analysis to examine the DNA methylation status of imprinted genes in early embryos (blastocysts). The paternal imprinted genes, H19 and Igf-2r, had lower methylation levels in heat-stressed embryos than in control embryos, whereas the maternal imprinted genes, Peg3 and Peg1, had similar methylation pattern in heat-stressed embryos and in control embryos. Our results indicate that heat stress may induce aberrant methylation imprinting, which results in developmental failure of mouse embryos, and that the effects of heat shock on methylation imprinting may be gene-specific.

• Journal of Animal Science and Technology
• /
• v.48 no.5
• /
• pp.663-670
• /
• 2006

The present study was performed to investigate the effect of plant type recombinant porcine somatotropin (pST) adminstration on growth performance and blood profile of finishing pigs. Forty-eight Landrace barrows weighing 78 kg were employed for six week growth trial. Twelve barrows were allocated into various rpST types ; the control (CONT), the 4:1 type rpST (TRT 1), the 1:1 type rpST (TRT 2); and the 4:1 type rpST group(TRT 3) respectively. CONT group were not planted rpST. TRT 1 group was treated with rpST once a week for 6 weeks. Each dose contained the rpST equivalent to 100mg from initial to two weeks and 125mg from three weeks to finial week. TRT 2 and TRT 3 groups were planted rpST four times contained the rpST equivalent to 100mg during trial period from initial to two weeks, and 125 mg from three weeks, to four weeks, respectively. All pigs were fed a commercial feed containing 0.9% lysine ad lib. Daily gain increased by 19.4% in TRT 1(p<0.05) compared to the CONT. rpST improved feed/gain by 13.4～28.9% in all treatment groups(p<0.05). Back fat thickness of the all rpST treated groups were 23.3～29.2% thinner than that of the CONT. These results indicated that the rpST stimulated growth performance in finishing pigs and plant type rpST could be used as a growth stimulant for finishing pigs.

• Animal Bioscience
• /
• v.35 no.7
• /
• pp.989-998
• /
• 2022

Objective: This study investigated the effects of intrauterine growth restriction (IUGR) during late pregnancy on the cell growth, proliferation, and differentiation in ovine fetal thymuses. Methods: Eighteen time-mated Mongolian ewes with singleton fetuses were allocated to three groups at d 90 of pregnancy: restricted group 1 (RG1, 0.18 MJ ME/body weight [BW]^0.75/d, n = 6), restricted group 2 (RG2, 0.33 MJ ME/BW^0.75/d, n = 6) and control group (CG, ad libitum, 0.67 MJ ME/BW^0.75/d, n = 6). Fetuses were recovered at slaughter on d 140. Results: The G0/G1 phase cell number in fetal thymus of the RG1 group was increased but the proliferation index and the expression of proliferating cell nuclear antigen (PCNA) were reduced compared with the CG group (p<0.05). Fetuses in the RG1 group exhibited decreased growth hormone receptor (GHR), insulin-like growth factor 2 receptor (IGF-2R), and their mRNA expressions (p<0.05). For the RG2 fetuses, there were no differences in the proliferation index and PCNA expression (p>0.05), but growth hormone (GH) and the mRNA expression of GHR were lower than those of the CG group (p<0.05). The thymic mRNA expressions of cyclin-dependent protein kinases (CDKs including CDK1, CDK2, and CDK4), CCNE, E2-factors (E2F1, E2F2, and E2F5) were reduced in the RG1 and RG2 groups (p<0.05), and decreased mRNA expressions of E2F4, CCNA, CCNB, and CCND were occurred in the RG1 fetuses (p<0.05). The decreased E-cadherin (E-cad) as a marker for epithelial-mesenchymal transition (EMT) was found in the RG1 and RG2 groups (p<0.05), but the OB-cadherin which is a marker for activated fibroblasts was increased in fetal thymus of the RG1 group (p<0.05). Conclusion: These results indicate that weakened GH/IGF signaling system repressed the cell cycle progression in G0/G1 phase in IUGR fetal thymus, but the switch from reduced E-cad to increased OB-cadherin suggests that transdifferentiation process of EMT associated with fibrogenesis was strengthened. The impaired cell growth, retarded proliferation and modified differentiation were responsible for impaired maturation of IUGR fetal thymus.

• Journal of Biosystems Engineering
• /
• v.38 no.2
• /
• pp.129-137
• /
• 2013

Purpose: Modeling has been used for elucidating the mechanism of complex biosystems. In spite of importance and uniqueness of adolescent calcium (Ca) metabolism characterized by a threshold Ca intake, its regulatory mechanism has not been covered and even not proposed. Hence, this study aims at model-based proposing potential mechanisms regulating adolescent Ca metabolism. Methods: Two different hypothetic mechanisms were proposed. The main mechanism is conceived based on Ca-protein binding which induces renal Ca filtration, while additional mechanism assumed that active renal Ca re-absorption regulated Ca metabolism in adolescents. Mathematical models were developed to represent the proposed mechanism and simulated them whether they could produce adolescent Ca profiles in serum and urine. Results: Simulation showed that both mechanisms resulted in the unique behavior of Ca metabolism in adolescents. Based on the simulation insulin-like growth factor-1 (IGF-1) is suggested as a potential regulator because it is related to both growth, a remarkable characteristic of adolescence, and Ca metabolism including absorption and bone accretion. Then, descriptive modeling is employed to conceptualize the hypothesized mechanisms governing adolescent Ca metabolism. Conclusions: This study demonstrated that modeling is a powerful tool for elucidating an unknown mechanism by simulating potential regulatory mechanisms in adolescent Ca metabolism. It is expected that various analytic applications would be plausible in the study of biosystems, particularly with combination of experimental and modeling approaches.