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IRS-2 Partially Compensates for the Insulin Signal Defects in IRS-1-/- Mice Mediated by miR-33

  • Tang, Chen-Yi;Man, Xiao-Fei;Guo, Yue;Tang, Hao-Neng;Tang, Jun;Zhou, Ci-La;Tan, Shu-Wen;Wang, Min;Zhou, Hou-De
    • Molecules and Cells
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    • v.40 no.2
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    • pp.123-132
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    • 2017
  • Insulin signaling is coordinated by insulin receptor substrates (IRSs). Many insulin responses, especially for blood glucose metabolism, are mediated primarily through Irs-1 and Irs-2. Irs-1 knockout mice show growth retardation and insulin signaling defects, which can be compensated by other IRSs in vivo; however, the underlying mechanism is not clear. Here, we presented an Irs-1 truncated mutated mouse ($Irs-1^{-/-}$) with growth retardation and subcutaneous adipocyte atrophy. $Irs-1^{-/-}$ mice exhibited mild insulin resistance, as demonstrated by the insulin tolerance test. Phosphatidylinositol 3-kinase (PI3K) activity and phosphorylated Protein Kinase B (PKB/AKT) expression were elevated in liver, skeletal muscle, and subcutaneous adipocytes in Irs-1 deficiency. In addition, the expression of IRS-2 and its phosphorylated version were clearly elevated in liver and skeletal muscle. With miRNA microarray analysis, we found miR-33 was down-regulated in bone marrow stromal cells (BMSCs) of $Irs-1^{-/-}$ mice, while its target gene Irs-2 was up-regulated in vitro studies. In addition, miR-33 was down-regulated in the presence of Irs-1 and which was up-regulated in fasting status. What's more, miR-33 restored its expression in re-feeding status. Meanwhile, miR-33 levels decreased and Irs-2 levels increased in liver, skeletal muscle, and subcutaneous adipocytes of $Irs-1^{-/-}$ mice. In primary cultured liver cells transfected with an miR-33 inhibitor, the expression of IRS-2, PI3K, and phosphorylated-AKT (p-AKT) increased while the opposite results were observed in the presence of an miR-33 mimic. Therefore, decreased miR-33 levels can up-regulate IRS-2 expression, which appears to compensate for the defects of the insulin signaling pathway in Irs-1 deficient mice.

Anterior Vaginal Wall Sling for Female Stress Urinary Incontinence (여성 복압성 요실금에서 질전벽슬링수술의 효과)

  • Shin, Hong-Seok;Yoo, Jin-Wook;Jung, Hee-Chang;Park, Tong-Choon
    • Journal of Yeungnam Medical Science
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    • v.18 no.1
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    • pp.59-66
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    • 2001
  • Background: The purpose of this study was to determine the efficacy and safety of the anterior vaginal wall sling in the management of women with stress urinary incontinence. Materials and Methods: From January 1998 to December 1999, 42 patients(31 with genuine stress urinary incontinence and 11 with mixed urinary incontinence, 38 with anatomical incontinence and 4 with intrinsic sphincteric deficiency) underwent anterior vaginal wall sling at Yeungnam University Hospital were studied retrospectively. The mean age was 49.3 years(ranging from 34 to 66 years of age) and the mean follow-up period was 29.4 months(ranging from 16 to 40 months). Intra- and postoperative complication. success rate and patient's satisfaction were evaluated. Results: The mean operation time was 79 minutes(ranging from 65 to 124 minutes) and the mean hospital stay was 5.1 days(ranging from 4 to 10 days). Mean postoperative Foley catheter drainage was 2.1 days(ranging from 1 to 5 days). As a complication. bladder perforation occurred in one patient(2.4%). residual urine sensation developed in seven patients(16.7%), and suprapubic pain was complained in five patients(11.9%), which improved gradually. Vaginal epithelial inclusion cyst occurred in one patient(2.4%) at postoperative 31 months. Four(9.4%) patients with de novo instability were improved by anticholinergics medication. The success rate was 92.9% and 38 patients(90.5%) were satisfied with this procedure. Conclusion: We consider that the anterior vaginal wall sling to be a safe and effective surgical procedure for the treatment of female stress urinary incontinence, but a longer follow-up is necessary to determine long term effect.

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Gender-independent efficacy of mesenchymal stem cell therapy in sex hormone-deficient bone loss via immunosuppression and resident stem cell recovery

  • Sui, Bing-Dong;Chen, Ji;Zhang, Xin-Yi;He, Tao;Zhao, Pan;Zheng, Chen-Xi;Li, Meng;Hu, Cheng-Hu;Jin, Yan
    • Experimental and Molecular Medicine
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    • v.50 no.12
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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.

Protein Intake Recommendation for Korean Older Adults to Prevent Sarcopenia: Expert Consensus by the Korean Geriatric Society and the Korean Nutrition Society

  • Jung, Hee-Won;Kim, Sun-Wook;Kim, Il-Young;Lim, Jae-Young;Park, Hyoung-Su;Song, Wook;Yoo, Hyung Joon;Jang, HakChul;Kim, Kirang;Park, Yongsoon;Park, Yoon Jung;Yang, Soo Jin;Lee, Hae-Jeung;Won, Chang Won
    • Annals of Geriatric Medicine and Research
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    • v.22 no.4
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    • pp.167-175
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    • 2018
  • Sarcopenia, a common clinical syndrome in older adults, is defined as decreased muscle mass, strength, and physical performance. Since sarcopenia is associated with the incidence of functional decline, falls, and even mortality in older adults, researchers and health care providers have been keen to accumulate clinical evidence to advocate the screening and prevention of sarcopenia progression in older adults. The factors that may accelerate the loss of muscle mass and function include chronic diseases, inactivity, and deficiency in appropriate nutritional support. Among these, nutritional support is considered an initial step to delay the progression of muscle wasting and improve physical performance in community-dwelling older adults. However, a nationwide study suggested that most Korean older adults do not consume sufficient dietary protein to maintain their muscle mass. Furthermore, considering age-associated anabolic resistance to dietary protein, higher protein intake should be emphasized in older adults than in younger people. To develop a dietary protein recommendation for older adults in Korea, we reviewed the relevant literature, including interventional studies from Korea. From these, we recommend that older adults consume at least 1.2 g of protein per kg of body weight per day (g/kg/day) to delay the progression of muscle wasting. The amount we recommend (1.2 g/kg/day) is 31.4% higher than the previously suggested recommended daily allowance (i.e., 0.91 g/kg/day) for the general population of Korea. Also, evidence to date suggests that the combination of exercise and nutritional support may enhance the beneficial effects of protein intake in older adults in Korea. We found that the current studies are insufficient to build population-based guidelines for older adults, and we call for further researches in Korea.

Forecasting the Future Korean Society: A Big Data Analysis on 'Future Society'-related Keywords in News Articles and Academic Papers (빅데이터를 통해 본 한국사회의 미래: 언론사 뉴스기사와 사회과학 학술논문의 '미래사회' 관련 키워드 분석)

  • Kim, Mun-Cho;Lee, Wang-Won;Lee, Hye-Soo;Suh, Byung-Jo
    • Informatization Policy
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    • v.25 no.4
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    • pp.37-64
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    • 2018
  • This study aims to forecast the future of the Korean society via a big data analysis. Based upon two sets of database - a collection of 46,000,000 news on 127 media in Naver Portal operated by Naver Corporation and a collection of 70,000 academic papers of social sciences registered in KCI (Korea Citation Index of National Research Foundation) between 2005-2017, 40 most frequently occurring keywords were selected. Next, their temporal variations were traced and compared in terms of number and pattern of frequencies. In addition, core issues of the future were identified through keyword network analysis. In the case of the media news database, such issues as economy, polity or technology turned out to be the top ranked ones. As to the academic paper database, however, top ranking issues are those of feeling, working or living. Referring to the system and life-world conceptual framework suggested by $J{\ddot{u}}rgen$ Habermas, public interest of the future inclines to the matter of 'system' while professional interest of the future leans to that of 'life-world.' Given the disparity of future interest, a 'mismatch paradigm' is proposed as an alternative to social forecasting, which can substitute the existing paradigms based on the ideas of deficiency or deprivation.

DENTAL TREATMENT IN A PATIENT WITH CONGENITAL PANHYPOPITUITARISM UNDER GENERAL ANESTHESIA (선천성 범뇌하수체저하증(Congenital panhypopituitarism) 환자의 전신마취 하 치과치료)

  • Kim, Hyuntae;Song, Ji-Soo;Hyun, Hong-Keun;Kim, Young-Jae;Kim, Jung-Wook;Jang, Ki-Taeg;Lee, Sang-Hoon;Shin, Teo Jeon
    • The Journal of Korea Assosiation for Disability and Oral Health
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    • v.15 no.1
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    • pp.70-73
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    • 2019
  • Congenital panhypopituitarism is an uncommon condition, present from birth, characterized by the decreased secretion of most of the hormones produced by the pituitary. The purpose of this case report is to present a case about caries treatment of a 26-month-old female patient with congenital panhypopituitarism under general anesthesia. A 26-month-old girl with congenital panhypopituitarism visited Seoul National University Dental Hospital for caries treatment of anterior primary teeth. Because of the child's age and underlying systemic disease, dental treatment under general anesthesia was considered. Prior to the dental procedure, 30mg of cortisol was administered intravenously in order to prevent possible adrenal crisis by stressful events. The dental procedure was successfully performed under general anesthesia. This case report suggests that general anesthesia may be useful for the dental treatment with congenital panhypopituitarism. Hormone deficiency should be assessed prior to dental procedure and, if necessary, stress hormone replacement therapy should be considered.

vfr, A Global Regulatory Gene, is Required for Pyrrolnitrin but not for Phenazine-1-carboxylic Acid Biosynthesis in Pseudomonas chlororaphis G05

  • Wu, Xia;Chi, Xiaoyan;Wang, Yanhua;Zhang, Kailu;Kai, Le;He, Qiuning;Tang, Jinxiu;Wang, Kewen;Sun, Longshuo;Hao, Xiuying;Xie, Weihai;Ge, Yihe
    • The Plant Pathology Journal
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    • v.35 no.4
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    • pp.351-361
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    • 2019
  • In our previous study, pyrrolnitrin produced in Pseudomonas chlororaphis G05 plays more critical role in suppression of mycelial growth of some fungal pathogens that cause plant diseases in agriculture. Although some regulators for pyrrolnitrin biosynthesis were identified, the pyrrolnitrin regulation pathway was not fully constructed. During our screening novel regulator candidates, we obtained a white conjugant G05W02 while transposon mutagenesis was carried out between a fusion mutant $G05{\Delta}phz{\Delta}prn::lacZ$ and E. coli S17-1 (pUT/mini-Tn5Kan). By cloning and sequencing of the transposon-flanking DNA fragment, we found that a vfr gene in the conjugant G05W02 was disrupted with mini-Tn5Kan. In one other previous study on P. fluorescens, however, it was reported that the deletion of the vfr caused increased production of pyrrolnitrin and other antifungal metabolites. To confirm its regulatory function, we constructed the vfr-knockout mutant $G05{\Delta}vfr$ and $G05{\Delta}phz{\Delta}prn::lacZ{\Delta}vfr$. By quantifying ${\beta}-galactosidase$ activities, we found that deletion of the vfr decreased the prn operon expression dramatically. Meanwhile, by quantifying pyrrolnitrin production in the mutant $G05{\Delta}vfr$, we found that deficiency of the Vfr caused decreased pyrrolnitrin production. However, production of phenazine-1-carboxylic acid was same to that in the wild-type strain G05. Taken together, Vfr is required for pyrrolnitrin but not for phenazine-1-carboxylic acid biosynthesis in P. chlororaphis G05.

A Study on the Changing and Influence Factors in East Asia Wetland through Literature Analysis (문헌분석을 통한 동아시아 습지 변화 요인 및 영향 분석 연구)

  • Yoo, Younghoon;Necesito, Imee V.;Lee, Haneul;Kim, Kyunghun;Lee, Junhyeong;Kim, Hung Soo
    • Journal of Wetlands Research
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    • v.23 no.3
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    • pp.260-276
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    • 2021
  • Wetlands are constantly affected by internal and external environments that make up the wetlands, and these effects make wetlands change. East Asia countries where about 15% of Ramsar's registered wetlands are located, is valuable conservation area due to various wetland types and biodiversity. However, due to climate change and other factors, the total area of wetlands has been reduced and biodiversity have been damaged. To mitigate these problems and to manage wetlands efficiently, it is important to identify the factors that change wetlands and to identify how each factor affects them. In this study, we conducted a wetland-related literature analysis in East Asia to derive factors that affect the changes in wetlands, and analyzed the relationships among the factors. Finally we presented research directions considering wetland change factors. In most of the East Asia countries, it was found that there is deficiency in research studies about extraction in direct factors and water-energy infrastructure, tourism & recreation in indirect factors. Also, we presented the necessity for future research using the result between connectivity & relationship analysis and indirect drivers of change and their influence on direct drivers of change. The results of this study could contribute to the establishment of an R&D cooperation system in East Asia region and strengthen wetland management.

Vitamin D in autoimmune, allergic, and infectious diseases (비타민 D의 자가면역, 알레르기, 감염질환에서의 역할)

  • Shim, Chae-Hyeon;Choi, Je-Min
    • Food Science and Industry
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    • v.55 no.3
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    • pp.276-283
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    • 2022
  • Vitamin D is a fat-soluble vitamin helps to retain calcium and phosphorus but also has shown to affect immune regulation and homeostasis. In humans, vitamin D3 and vitamin D2 and their metabolite has intensively studied in both innate and adaptive immune system that they are important to regulate overwhelmed inflammation. The vitamin D receptor is a nuclear hormone receptor which regulate various downstream target gene expressions as a transcription factor related to metabolism, immune regulation, etc. Vitamin D deficiency is a high-risk factor for inflammatory diseases like autoimmune disease and allergy. In addition, reduced vitamin D seem to correlate with susceptibility to the virus infection such as HIV and COVID-19. In this review, we will summarize up-to-date vitamin D's role in various immune cells, immune regulatory functions during autoimmune, allergic, and infectious diseases. We will also discuss about vitamin D supplement effects in human trial studies for COVID-19.

The Effects of Middle School Students' Belongingness Orientation on their Psychological Adaptation and Friend Networks: A Short-term Longitudinal Social Network Analysis (중학생의 소속감 지향성이 심리적 적응 및 친구 네트워크에 미치는 영향력 비교: 소셜 네트워크 분석을 활용한 단기-종단적 분석)

  • Lee, Seungjin;Ko, Young-gun
    • Korean Journal of School Psychology
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    • v.18 no.2
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    • pp.175-195
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    • 2021
  • Intimate friendships and a sense of belonging have positive effects on adolescent's psychological adaptation. Belongingness orientation is the motivation to belong. It is divided into growth orientation and deficit-reduction orientation, both of which have different effects on psychological adaptation and interpersonal characteristics. This study was conducted to determine how adolescents' belongingness orientation affected their psychological adaptation and friend networks. Students in their second year of middle school were surveyed both at the beginning and end of the spring semester. Friend networks were measured through network centrality analysis. Multilevel regression analysis produced three major results. The first major result was that the correlations between growth orientation and loneliness and between growth orientation and stress at the beginning of the spring semester was statistically significant even when friend network centrality was included in the analysis model, but the correlation between deficit-reduction orientation and loneliness and between deficit-reduction orientation and stress were not statistically significant. The second major result was that growth orientation significantly predicted friend network centrality at the end of the spring semester. This effect was significant even when friend network centrality at the beginning of the semester and psychological adaptation level at the end of the spring semester were added to the analysis model. The third major result was that the correlation between friend network centrality at the end of the semester and psychological adaptation level was statistically significant even when psychological adaptation levels at the beginning and the end of the semester were included in the analysis model. This study is meaningful in that it had a short-term longitudinal design and empirically demonstrated the relationship between belongingness orientation and psychological adaptation level of adolescents and between belongingness orientation and the development of friend networks. Lastly, we discussed limitations of this study and provided suggestions for future research.