• Journal of the Korea Academia-Industrial cooperation Society
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• v.20 no.9
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• pp.306-314
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• 2019

As dipeptidyl peptidase-4(DPP-4) inhibitors are used widely as a secondary treatment for type 2 diabetes because they tend to be well tolerated with minimal side effects, the human DPP-4(hDPP-4) gene was injected into a pig zygote through micro-injection, and 1-cell stage fertilized embryos were then transplanted surgically into the oviduct. Three pigs were fertilized with hDPP-4 genes and produced sixteen piglets, in which one male piglet was identified to be transgenic. Finally, transgenic pigs showing hDPP-4 gene expression in the tail were produced. Western blot and RT-PCR analysis confirmed that the hDPP-4 is expressed strongly in the membrane cells of the transgenic pig, and that the hDPP-4 gene appears in various tissues and tails. This suggests that the expression vector is normally expressed in transgenic pigs. These results are anticipated to be a model animal to check the endocrine function for insulin resistance that occurs in a hDPP-4 transgenic pig and to increase its value for use as a material in newly developed medicines.

• Journal of Life Science
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• v.29 no.8
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• pp.922-940
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• 2019

Obesity, represented by abnormal fat accumulation due to an imbalance between energy intake and expenditure, is a major public health issue worldwide, leading to multiple noncommunicable diseases, including atherosclerosis, hypertension, type 2 diabetes, and cancer. Diverse solutions have been proposed to combat obesity. Attention has focused on two types of adipose tissues as a promising therapeutic target in obesity: traditional brown and beige or brite. Unlike energy-storing white adipose (endocrine) tissue, traditional brown adipose tissue and beige adipose tissue have energy-dissipating thermogenic properties. Both types of tissue are present in adult humans and inducible through external stimuli, such as cold exposure, ${\beta}3$-adrenergic receptor agonists, and phytochemicals. Among these stimuli, microbiota present in the human intestinal tract participate in multiple metabolic activities. Modulation of gut microbiota may offer a potent and possibly curative strategy against various metabolic diseases. Numerous studies have focused on the effects of established antiobesity treatments on the gut microenvironment or brown-adipose-tissue activation. In this review, we focus mainly on stimuli known to alleviate obesity, weight gain, and metabolic diseases, in addition to known and possible inter-relations between gut microbiota modulation and similar interventions and adipose tissue browning. The findings may pave the way toward new strategies against obesity.

• Endocrinology and Metabolism
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• v.33 no.4
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• pp.459-465
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• 2018

Background: Differentiated thyroid carcinoma (DTC) shows a very good prognosis, but older patients have a higher recurrence rate and those show poor prognosis than younger patients. The aim of this study was to determine the clinical outcomes of thyroid cancer patients who experienced recurrence in old age according to the treatment strategy used. Methods: This retrospective observational cohort study was conducted at Asan Medical Center, Seoul, Korea. Among DTC patients with no evidence of disease after initial treatment, we enrolled 86 patients who experienced recurrence at an age >65 years from 1994 to 2012. Sixty-nine patients had local recurrence and 17 patients showed distant metastasis. Results: The mean age of patients at recurrence was 72 years. Patients were followed up for a median of 4.1 years after recurrence. Sixty-three of the 69 patients with local recurrence received additional treatment, while the other six received conservative care. The cancer-specific mortality rate was 15.5% in the local recurrence group. Airway problems were the main cause of death in patients who did not receive further treatment for local recurrence. Among the 17 patients with distant metastasis, 10 underwent specific treatment for metastasis and seven received only supportive management. Seven of those 17 patients died, and the cancer-specific mortality rate was 35% in the distant metastasis group. Conclusion: The overall cancer-specific mortality rate was 20% in DTC patients in whom recurrence was first detected at an age >65 years. Mortality due to uncontrolled local disease occurred frequently in patients who did not receive definitive management for recurrence.

• Korean Journal of Environmental Agriculture
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• v.39 no.4
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• pp.375-383
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• 2020

BACKGROUND: Bisphenol A (BPA) is a chemical widely used in polycarbonate plastics, epoxy resins. BPA is an endocrine disruptor. Residue of BPA in agricultural environments is a major concern. The objective of this study was to understand the characteristics of the uptake and distribution of BPA and its metabolites introduced into the agricultural environment to crops, and to use it as basic data for further research on reduction of BPA in agricultural products. METHODS AND RESULTS: This study established the analysis method of BPA and its metabolites in soil and crops, and estimated the intake of BPA and its metabolites from lettuce (Lactuca sativa) grown in sandy loam and loam soil, which are representative soils in Korea. The two major metabolites of BPA were 4-hydroxyacetophenone (4-HAP) and 4-hydroxybenzoic acid (4-HBA). BPA, 4-HAP and 4-HBA have been analyzed by using liquid chromatography tandem mass spectrometry (LC-MS/MS). These substances were detected in sandy loam and loam soil, indicating that certain portions of BPA were converted to 4-HAP and 4-HBA in the soil; however, it was observed that only 4-HBA migrated to lettuce through the roots into crops. CONCLUSION: The uptake residues showed the BPA and 4-HAP were not detected in lettuces grown on sandy loam (SL) and loam (L) soil treatments that were applied with of 10 ng/g, 50 ng/kg and 500 ng/g of BPA. However, the 4-HBA was detected at the level of 7 ng/g and 11 ng/g in the lettuce grown in sandy loam and loam soil that were treated with the 500 ng/g of BPA, respectively, while the 8 ng/g of 4-HBA was measured in the lettuce cultivated in the loam that was treated with 100 ng/g of BPA. This result presents that the BPA persisting in the soil of the pot was absorbed through the lettuce roots and then distributed in the lettuce leaves at the converted form of 4-HBA, what is the oxidative metabolite of BPA.

• Journal of Animal Reproduction and Biotechnology
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• v.35 no.4
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• pp.329-337
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• 2020

Cytochrome P450 1A2 (CYP1A2) is a member of the cytochrome P450 superfamily enzymes in mammals and plays a major role in metabolizing endogenous hormones in the liver. In recent days, CYP1A2 expression has been found in not only the liver but also other tissues including the pancreas and lung. However, little information is available regarding the expression of CYP1A2 in the ovary, in spite of the facts that the ovarian follicle growth and atresia are tightly associated with controls of endocrine hormonal networks. Therefore, the expression of CYP1A2 in the ovaries of prepubertal and pubertal rats was investigated to assess its expression pattern and puberty-related alteration. It was demonstrated that the expression level of CYP1A2 was significantly (p < 0.01) higher in the pubertal ovaries than prepubertal counterparts. At the ovarian follicle level in both groups, whereas CYP1A2 expression was less detectable in the primordial, primary and secondary follicles, the strongly positive expression of CYP1A2 was localized in the granulosa cell layers in the antral and pre-ovulatory follicles. However, the ratio of CYP1A2-positive ovarian follicle was significantly (p < 0.01) higher in the ovary of pubertal group (73.1 ± 3.1%) than prepubertal one (41.0 ± 10.5%). During the Immunofluorescence, expression of CYP1A2 was mainly localized in Fas-positive follicles, indicating the atretic follicles. In conclusion, these results suggested that CYP1A2 expression was mainly localized at the atretic follicular cells and affected by the onset of puberty. Further study is still necessary but we hypothesize that CYP1A2 expresses in the atretic follicles to metabolize residue of the reproductive hormones. These findings may have important implications for the fields of reproductive biology of animals.

• Journal of Korean Medical Ki-Gong Academy
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• v.20 no.1
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• pp.85-103
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• 2020

Objective : A common treatment for hypothyroidism is to supplement the deficient hormones. However, taking hormone medication does not improve clinical symptoms or side effects, so it is necessary to develop other improved treatments. The purpose of this study is to report that the Korean medicine treatment along with Whidam's Gokgol(CV2) Sugi therapy has improved symptoms of hypothyroidism and related the level of TSH, free T4 after halting the use of levothyroxine. Methods : We employed Korean medicine treatment; herbal-medication(延齡固本丹 and 加減平胃散), acupuncture, and cupping therapy, and so forth. At the same time, we treated the patient with Whidam's Sugi therapy(especially, Gokgol Sugi therapy). We treated the patient more than five times a week for the first month and treated more than three times a week for the next three months. Since then, we have treated the patient once or twice a week. The patient took a total of four blood tests during her treatment in 2012 and 2017. Results : 1. Both TSH and free T4 levels and clinical symptoms were normalized for patient with hypothyroidism who stopped taking levothyroxine by treating the patient with Korean medicine treatment and Whidam's Sugi therapy. 2. The combination of Korean medicine treatment and Whidam's Sugi therapy was also used in the case of subclinical hypothyroidism patient. 3. The combination of Korean medicine treatment and Whidam's Sugi therapy for hypothyroidism lasted for five years, not just for a short period of time. Conclusions : The combination of Korean medicine treatment and Whidam's Sugi therapy(especially, Gokgol Sugi therapy) was effective in the treatment of hypothyroidism and it helped to normalize the level of TSH, free T4. It is hoped that further clinical research will continue in the future so that it can be used not only for hypothyroidism but also for other endocrine diseases.

• Journal of Environmental Health Sciences
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• v.47 no.3
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• pp.245-258
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• 2021

Objectives: In many previous studies, endocrine disruptors (EDCs) have been found to affect delays in puberty. Various EDCs have been reported on, but there have been only limited epidemiologic studies on the effects of exposure to environmental heavy metals and pyrethroid pesticides on puberty delay. Therefore, the aim of this study was to investigate the association of exposure to environmental mercury, cadmium, and pyrethroid pesticides with delayed puberty in children based on national survey data that represents Korean children. Methods: We selected 450 children at the ages of 9-11 years old from the third Korean National Environmental Health Survey (3rd KoNEHS). The relations of urinary Hg, Cd, and 3-PBA with pubertal development were evaluated using multiple logistic regression analyses. Results: Urinary Hg levels were significantly associated with delayed puberty in boys [testicle development: OR=0.41 (95% CI: 0.20, 0.84); genitalia development: OR=0.35 (95% CI: 0.15, 0.81)]. Girls with higher Hg levels were more likely to experience delayed menarche [OR=0.23 (95% CI: 0.06, 0.90)]. We observed a significant 49% reduction in odds for menarche per increasing unit of urinary cadmium levels [OR=0.51 (95% CI: 0.24, 1.01)]. In addition, urinary 3-PBA showed a negative association with genitalia development in boys and menarche in girls [genitalia development: OR=0.73 (95% CI: 0.55, 0.96); menarche: OR=0.56 (95% CI: 0.32, 1.00)]. Conclusions: The results of this study support the hypothesis that exposure to environmental mercury, cadmium and pyrethroid pesticides may affect puberty delays. Additional evidence needs to be obtained through further prospective studies.

• Development and Reproduction
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• v.25 no.1
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• pp.15-24
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• 2021

Benzo[a]pyrene (B[a]P) is a potent carcinogen and is classified as an endocrine-disrupting chemical. In mammalian testes, Sertoli cells support spermatogenesis. Therefore, if these cells are negatively affected by exposure to xenotoxic chemicals, spermatogenesis can be seriously disrupted. In this context, we evaluated whether mouse testicular TM4 Sertoli cells are susceptible to the induction of cytotoxicity-mediated cell death after exposure to B[a] P in vitro. In the present study, while B[a]P and B[a]P-7,8-diol were not able to induce cell death, exposure to BPDE resulted in cell death. BPDE-induced cell death is accompanied by the activation of caspase-3 and caspase-7. Depolarization of the mitochondrial membrane and cytochrome c release from mitochondria were observed in benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE)-treated cells. These results indicate that TM4 cells are susceptible to apoptosis in a caspase-dependent manner. Western blot and reverse transcription-polymerase chain reaction (RT-PCR) analyses showed that aryl hydrocarbon receptor (AhR) expression was almost undetectable in TM4 cells and that its expression was not altered after B[a]P treatment. This indicates that TM4 cells are nearly AhR-deficient. In TM4 cells, the CYP1A1 protein and its activity were not present. From these results, it is clear that AhR may be a prerequisite for CYP1A1 expression in TM4 cells. Therefore, TM4 cells can be referred to as CYP1A1-deficient cells. Thus, TM4 Sertoli cells are believed to have a rigid and protective cellular machinery against genotoxic agents. In conclusion, it is suggested that tolerance to B[a]P cytotoxicity is associated with insufficient AhR and CYP1A1 expression in testicular Sertoli cells.

• Biomolecules & Therapeutics
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• v.29 no.5
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• pp.551-561
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• 2021

Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.

• Journal of Pharmacopuncture
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• v.25 no.2
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• pp.106-113
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• 2022

Objectives: Herbal medicine is a worldwide health topic. Vitex agnus-castus L. (VAC) is a popular plant used for gynecologic problems due to its hormonal effects. The aim of this study is to reveal VAC extract effect on fetus when this herb is used started from antenatal period or during pregnancy. Methods: Performed from starting day of January 2019 till February 2019, 48 rats were assigned in randomly divided eight-member six groups: control (C1), treated group with 365 mg/kg VAC from initiation of insemination (T1) and 30 days prior to pregnancy (T2), control that underwent caesarean section on 15^th day of gestational age (C2) and treated group with 365 mg/kg VAC from initiation of insemination (T3) and 30 days prior to pregnancy (T4) that underwent caesarean section. Weight, sex and number of fetuses, abortion and still birth rate and estradiol level were evaluated using t-test by SPSS software. Results: We showed increased weight among T1 group considering totally and sex-dependent which is significant (all p-value < 0.05). We also detected significantly decreased weight in T2 in total (p-value < 0.0001) and when considering female fetuses (0.043) but not males (0.17). Although the results showed slightly non-significant increased weight among fetuses of T3 (totally or based on the fetus sex) compared to the control group (C2), T4 group had statistically decreased weight compared to control group. Pregnancy rate and pregnancy outcome were affected by VAC usage. The time of VAC initiation also affected live birth and abortion rates. Conclusion: VAC extract may affect pregnancy rate, live birth rate, abortion and stillbirth rates. Its effect on the weight and the sex showed dual pattern depends on the time of initiation and pregnancy trimester of evaluation. Prescribing this medicinal plant for patients being prone to pregnancy should be with caution. Further study is recommended.