• Journal of Nutrition and Health
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• 제36권10호
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• pp.1030-1035
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• 2003

농업생명공학 산업의 발달과 더불어 유전자변형 농산물(GMO)이 개발 및 유통됨에 따라 농약, 노동력의 절감 및 식량난 해결에 도움을 줄 수 있는 반면, 독성, 알러지 유발, 항생제 내성 등 식품으로 섭취될 때 인체에 미치는 영향에 대한 문제가 국제적으로 논의되고 있다. 우리나라 농촌진흥청에서도 여러 유전자 변형 농산물이 개발되고 있으나 일반화에 앞서 그 안전성이 검토되어야 할 것으로 생각된다. 따라서 본 연구팀은 쌀이 우리의 주식인 점을 고려하여 우선 안전성이 검토되어야 할 시험재료로 선정하였고, 영양성분 측면에서의 실질적 동등성과 취약 계층에서의 안전성 검토를 위해 영양성분 분석 후 유전자 변형 쌀을 성장기 흰쥐에게 6주간 급여하였다. 특히 항생제 저항성 유전자마커가 현미에 있을 수 있다는 보고를 고려하여 유전자 변형 품종의 백미밥과 현미밥을 모종인 일품의 백미밥 및 현미밥으로 나누어 처리한 후 실험식이를 급여하였다. 그 결과 시험재료의 영양성분 함량에 큰 차이를 보이지 않았고, 실험식이를 급여하였을 때 모든 실험동물에서 임상적 증상, 조직의 외형이나 무게 및 혈중 영양성분 함량 등의 측면에 차이가 없었다. 그러므로 본 실험에 사용된 유전자 변형 품종(제초제 저항성)은 도정 정도에 상관없이 백미와 현미 모두 6주간 급여시 성장기 실험동물에 어떠한 부정적 영향도 미치지 않은 것으로 보인다. 그러나 유전자 변형 식품의 안전성에 대해 좀 더 보완된 in vivo 실험법의 확립과 1년 이상 장기간의 급여에 따른 영향 검토도 필요하고, 본 연구의 시험재료는 단지 제초제 저항성 품종의 백미와 현미에 대한 것으로 유전자 변형 목적 및 대상 식품의 다양성에 따른 안전성은 다시 검증되어야 할 것으로 생각된다.

• 한국식품영양과학회지
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• 제33권5호
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• pp.810-814
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• 2004

본 연구는 농촌진흥청에서 개발된 유전자 변형 식품의 영양적 안전성을 검토하기 위하여 수행되었다. 발이 우리의 주식인 점을 고려하여 우선 안전성 이 검토되어야 할 시험 재료로 선정하였고, 유전자 변형(제초제 저항성) 쌀의 실질적 동등성 구명을 위해 일반 및 미량 영양소의 함량을 분석하였으며, 대표적 취약 계층인 노령기 모델에서 유전자 변형 쌀을 가지고 안전성을 검토하였다. 특히 항생제 저항성 유전자 마커가 현미 에 있을 수 있고 열처리시 변화될 수 있음을 고려하여 유전자 변형 품종의 현미 및 현미밥과 모종인 일품의 현미 및 현미밥으로 배합한 실험식이를 8주간 급여하였다. 그 결과 시험재료의 영양성분 함량에 큰 차이를 보이지 않았고, 실험식이를 급여하였을 때 모든 실험 동물에서 임상적 증상, 조직의 외형이나 무게 및 혈청 생화학적 지표에 차이가 없었다. 그러므로 본 실험에 사용된 유전자 변형 품종(제초제 저항성 )의 현미와 현미밥 모두 노령기 실험동물에 어떠한 부정적 영향도 미치지 않은 것으로 보인다. 그러나 유전자 변형식품의 안전성에 대해 종 더 보완된 in uiuo 실험법의 확립과 장기간의 급여에 따른 영향검토가 필요하고, 본 연구의 시험재료는 단지 제초제 저항성 품종의 현미에 대한 것으로 다른 유전자 변형 식품의 안전성에 대해서는 계속적인 확인 실험이 있어야 할 것으로 생각된다.

• Experimental and Molecular Medicine
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• 제50권12호
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• pp.12.1-12.14
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• 2018

Osteoporosis develops with high prevalence in both postmenopausal women and hypogonadal men. Osteoporosis results in significant morbidity, but no cure has been established. Mesenchymal stem cells (MSCs) critically contribute to bone homeostasis and possess potent immunomodulatory/anti-inflammatory capability. Here, we investigated the therapeutic efficacy of using an infusion of MSCs to treat sex hormone-deficient bone loss and its underlying mechanisms. In particular, we compared the impacts of MSC cytotherapy in the two genders with the aim of examining potential gender differences. Using the gonadectomy (GNX) model, we confirmed that the osteoporotic phenotypes were substantially consistent between female and male mice. Importantly, systemic MSC transplantation (MSCT) not only rescued trabecular bone loss in GNX mice but also restored cortical bone mass and bone quality. Unexpectedly, no differences were detected between the genders. Furthermore, MSCT demonstrated an equal efficiency in rectifying the bone remodeling balance in both genders of GNX animals, as proven by the comparable recovery of bone formation and parallel normalization of bone resorption. Mechanistically, using green fluorescent protein (GFP)-based cell-tracing, we demonstrated rapid engraftment but poor inhabitation of donor MSCs in the GNX recipient bone marrow of each gender. Alternatively, MSCT uniformly reduced the $CD3^+T$-cell population and suppressed the serum levels of inflammatory cytokines in reversing female and male GNX osteoporosis, which was attributed to the ability of the MSC to induce T-cell apoptosis. Immunosuppression in the microenvironment eventually led to functional recovery of endogenous MSCs, which resulted in restored osteogenesis and normalized behavior to modulate osteoclastogenesis. Collectively, these data revealed recipient sexually monomorphic responses to MSC therapy in gonadal steroid deficiency-induced osteoporosis via immunosuppression/anti-inflammation and resident stem cell recovery.

• Endocrinology and Metabolism
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• 제33권4호
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• pp.466-472
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• 2018

Background: Thyroid dysfunction is associated with negative neonatal and obstetric outcomes. Large differences in thyroid function reference intervals exist across different populations. These differences can be explained by population-specific factors, such as iodine status. Many countries in Latin America report iodine sufficiency, but relatively few countries have published up-to-date data on iodine levels and thyroid function in the overall population, and especially in pregnant women. We evaluated the iodine status of pregnant women in Chile and determined thyroid hormone reference ranges in this population. Methods: This was a prospective observational study of healthy Chilean women at their first prenatal visit before week 14. Thyroid-stimulating hormone (TSH), total thyroxine ($T_4$), free $T_4$, antithyroid peroxidase antibody (TPOAb), and iodine levels from spot urine samples were measured. Iodine status and the reference ranges for TSH were calculated. Results: A total of 1,022 pregnant women in the first trimester were selected. Urinary iodine levels were measured in 302 randomly-selected women. The median urinary iodine concentration was $173.45{\mu}g/L$ (interquartile range, 108.11 to 249.35).The reference ranges of TSH were calculated in 670 patients selected according to the National Academy of Clinical Biochemistry guidelines. The median TSH level was $1.88{\mu}IU/mL$ (2.5th percentile: 0.13 to 97.5th percentile: 5.37). Using the reference range in the 1,022 women, the prevalence of clinical hypothyroidism was 1.76%, and that of subclinical hypothyroidism was 3.92%. TPOAb positivity was more common in women with TSH levels above $3.5{\mu}IU/mL$. Conclusion: We found adequate iodine intake and a right-shifted distribution of serum TSH levels in pregnant women in Chile. The prevalence of hypothyroidism in our sample of pregnant women was higher than has been described in the literature.

• Experimental and Molecular Medicine
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• 제50권12호
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• pp.2.1-2.12
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• 2018

Glucagon-like peptide-1 (GLP-1) has a broad spectrum of biological activity by regulating metabolic processes via both the direct activation of the class B family of G protein-coupled receptors and indirect nonreceptor-mediated pathways. GLP-1 receptor (GLP-1R) agonists have significant therapeutic effects on non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) in animal models. However, clinical studies indicated that GLP-1 treatment had little effect on hepatic steatosis in some NAFLD patients, suggesting that GLP-1 resistance may occur in these patients. It is well-known that the gut metabolite sodium butyrate (NaB) could promote GLP-1 secretion from intestinal L cells. However, it is unclear whether NaB improves hepatic GLP-1 responsiveness in NAFLD. In the current study, we showed that the serum GLP-1 levels of NAFLD patients were similar to those of normal controls, but hepatic GLP-1R expression was significantly downregulated in NAFLD patients. Similarly, in the NAFLD mouse model, mice fed with a high-fat diet showed reduced hepatic GLP-1R expression, which was reversed by NaB treatment and accompanied by markedly alleviated liver steatosis. In addition, NaB treatment also upregulated the hepatic p-AMPK/p-ACC and insulin receptor/insulin receptor substrate-1 expression levels. Furthermore, NaB-enhanced GLP-1R expression in HepG2 cells by inhibiting histone deacetylase-2 independent of GPR43/GPR109a. These results indicate that NaB is able to prevent the progression of NAFL to NASH via promoting hepatic GLP-1R expression. NaB is a GLP-1 sensitizer and represents a potential therapeutic adjuvant to prevent NAFL progression to NASH.

• 대한임상독성학회지
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• 제17권2호
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• pp.58-65
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• 2019

Purpose: Alpha-amanitin induces potent oxidative stress and apoptosis, and may play a significant role in the pathogenesis of hepatotoxicity. This study examined the mechanisms of α-amanitin-induced apoptosis in vitro, and whether green tea extract (GTE) offers protection against hepatic damage caused by α-amanitin (AMA) induced apoptosis in vivo. Methods: The effects of GTE and SIL on the cell viability of cultured murine hepatocytes induced by AMA were evaluated using an MTT assay. Apoptosis was assessed by an analysis of DNA fragmentation and caspase-3. In the in vivo protocol, mice were divided into the following four groups: control group (0.9% saline injection), AMA group (α-amanitin 0.6 mg/kg), AMA+SIL group (α-amanitin and silibinin 50 mg/kg), and AMA+GTE group (α-amanitin and green tea extract 25 mg/kg). After 48 hours of treatment, the hepatic aminotransferase and the extent of hepatonecrosis of each subject was evaluated. Results: In the hepatocytes exposed to AMA and the tested antidotes, the cell viability was significantly lower than the AMA only group. An analysis of DNA fragmentation showed distinctive cleavage of hepatocyte nuclear DNA in the cells exposed to AMA. In addition, the AMA and GTE or SIL groups showed more relief of the cleavage of the nuclear DNA ladder. Similarly, values of caspase-3 in the AMA+GTE and AMA+SIL groups were significantly lower than in the AMA group. The serum AST and ALT levels were significantly higher in the AMA group than in the control and significantly lower in the AMA+GTE group. In addition, AMA+GTE induced a significant decrease in hepatonecrosis compared to the controls when a histologic grading scale was used. Conclusion: GTE is effective against AMA-induced hepatotoxicity with its apoptosis regulatory properties under in vitro and in vivo conditions.

• BMB Reports
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• 제52권5호
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• pp.318-323
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• 2019

Mesenchymal stem cells (MSCs) are multipotent adult stem cells that present immunosuppressive effects in experimental and clinical trials targeting various rare diseases including inflammatory bowel disease (IBD). In addition, recent studies have reported tryptophanyl-tRNA synthetase (WRS) possesses uncanonical roles such as angiostatic and anti-inflammatory effects. However, little is known about the function of WRS in MSC-based therapy. In this study, we investigated if a novel factor, WRS, secreted from MSCs has a role in amelioration of IBD symptoms and determined a specific mechanism underlying MSC therapy. Experimental colitis was induced by administration of 3% DSS solution to 8-week-old mice and human umbilical cord blood-derived MSCs (hUCB-MSCs) were injected intraperitoneally. Secretion of WRS from hUCB-MSCs and direct effect of WRS on isolated $CD4^+$ T cells was determined via in vitro experiments and hUCB-MSCs showed significant therapeutic rescue against experimental colitis. Importantly, WRS level in serum of colitis induced mice decreased and recovered by administration of MSCs. Through in vitro examination, WRS expression of hUCB-MSCs increased when cells were treated with interferon-${\gamma}$ ($IFN-{\gamma}$). WRS was evaluated and revealed to have a role in inhibiting activated T cells by inducing apoptosis. In summary, $IFN-{\gamma}$-mediated secretion of WRS from MSCs has a role in suppressive effect on excessive inflammation and disease progression of IBD and brings new highlights in the immunomodulatory potency of hUCB-MSCs.

• 한국산학기술학회논문지
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• 제21권12호
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• pp.395-400
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• 2020

해부학적, 생리학적으로 인간과 유사한 특성을 지닌 돼지를 이용한 실험은 의학적 분야에서 폭넓게 이용되고 있다. 돼지에서 혈액의 일반적인 성상과 이화학적 수치는 의학적 연구 및 수의학적 치료에서도 중요한 부분으로 인정되고 있으나, 형질전환 돼지에 대한 연구는 미비한 실정이다. 따라서, 본 연구에서는 htPA 형질전환 돼지의 혈액을 이용한 일반성상 및 이화학적 성상을 비교 분석하여 형질전환 돼지에 대한 기초 자료로 활용하고자 조사하였다. 일반돼지 7(LY)두와 형질전환 돼지 8(LY)두의 혈액을 각각 분석하였다. 혈액의 일반 성상은 16종을 분석하였으며, 혈청을 이용한 이화학 분석의 경우 15종 항목을 조사하였다. 그 결과 혈액의 일반 성상 분석에서는 적혈구(RBC), 평균적혈구 혈색소량(MCH)과 임파구(LYM)에서 두 그룹간 유의적 차이를 나타내었다. 이화학적 성상 분석에서는 혈중뇨소질소(BUN), 총단백질(TP), 콜레스테롤(CHOL), (ALT), 크레아틴(CREA), 감마글루타밀전이효소(GGT), 글로빈(GOB) 그리고 아밀라아제(AMYL)가 두 그룹간 유의적 차이를 나타내었다. 앞으로 지속적인 형질전환 돼지에 대한 생체정보를 조사함으로써, 기초 자료로 이용할 수 있을 뿐만 아니라, 더 나아가 의학적 연구 분야에 적용 시 참고할 수 있을 것으로 여겨진다.

• 대한본초학회지
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• 제36권6호
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• pp.27-37
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• 2021

Objectives : In the current study, we performed the 13-week repeated oral dose toxicity test and a 4-week recovery test of standardized Cornus officinalis Sieb. et Zucc. and Psoralea corylifolia L. 30 % ethanol extract (SCP) in Sprague-Dawley (SD) rats owing to aims for verifying no observed adverse effect level (NOAEL). Methods : The animal study was performed according to OECD guidelines for the testing of chemicals section 4 health effects test No.408 repeated dose 90-day oral toxicity study in rodents (03 October 2008). In the repeated dose toxicity study, SCP was orally administered to female and male rats at dose levels of 1,000, 2,000, and 4,000 mg/kg/day for 13-week. The control group and high dose (4,000 mg/kg/day) group were then monitored for 4 extra weeks to determine recovery time after the study period. 1) Results : Compared with the control group, there were no treatment-related adverse effects in clinical signs, body weight, hematology, serum biochemistry (Aspartate aminotransferase, Alanine aminotransferase, Alkaline phosphatase, 𝛾-Glutamyl transpeptidase, Blood urea nitrogen, Creatinine, Glucose, Total cholesterol, Total protein, Creatine phosphokinase, Albumin, Total bilirubin, Triglyceride, Inorganic phosphorus, Albumin/Globulin ratio, Calcium ion, Sodium ion, Potassium ion, Chloride ion), necropsy findings and organ weight (Ovary, Adrenal gland, Pituitary, Thymus, Prostate, Testis, Epididymis, Spleen, Kidney, Heart, Lung, Brain, Liver) at any dose tested. Conclusions : Taken together, these results suggest that the NOAEL of SCP in both genders was considered as over 4,000 mg/kg. Results from this study provide scientific evidence for the safety of SCP.

• Nutrition Research and Practice
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• 제16권5호
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• pp.589-603
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• 2022

BACKGROUND/OBJECTIVES: Previous studies have reported that protein supplementation contributes to the attenuation of inflammation. Serious trauma such as burn injury usually results in the excessive release of inflammatory factors and organs dysfunction. However, a few reports continued to focus on the function of protein ingestion in regulating burn-induced inflammation and organ dysfunction. MATERIALS/METHODS: This study established the rat model of 30% total body surface area burn injury, and evaluated the function of blended protein (mixture of whey and soybean proteins). Blood routine examination, inflammatory factors, blood biochemistry, and immunohistochemical assays were employed to analyze the samples from different treatment groups. RESULTS: Our results indicated a decrease in the numbers of white blood cells, monocytes, and neutrophils in the burn injury group administered with the blended protein nutritional support (Burn+BP), as compared to the burn injury group administered normal saline supplementation (Burn+S). Expressions of the pro-inflammatory factors (tumor necrosis factor-α and interleukin-6 [IL-6]) and chemokines (macrophage chemoattractant protein-1, regulated upon activation normal T cell expressed and secreted factor, and C-C motif chemokine 11) were dramatically decreased, whereas anti-inflammatory factors (IL-4, IL-10, and IL-13) were significantly increased in the Burn+BP group. Kidney function related markers blood urea nitrogen and serum creatinine, and the liver function related markers alanine transaminase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase were remarkably reduced, whereas albumin levels were elevated in the Burn+BP group as compared to levels obtained in the Burn+S group. Furthermore, inflammatory cells infiltration of the kidney and liver was also attenuated after burn injury administered with blended protein supplementation. CONCLUSIONS: In summary, nutritional support with blended proteins dramatically attenuates the burn-induced inflammatory reaction and protects organ functions. We believe this is a new insight into a potential therapeutic strategy for nutritional support of burn patients.