Comparison of the prevalence of osteoporosis in people with spinal cord injury according to bone mineral density reference values for the diagnosis of osteoporosis: a retrospective, cross-sectional study.

BACKGROUND: Spinal cord injury (SCI) is a complex cause of rapid low bone mass that easily predisposes the affected individuals to osteoporosis-induced fractures. Several studies have investigated osteoporosis pathophysiology in SCI; however, those associated with its diagnosis in SCI are limited. Additionally, errors in osteoporosis diagnosis and its prevalence vary based on the bone mineral density (BMD) reference values (BMDRV), and no studies have reported BMDRV application for osteoporosis diagnosis in individuals with SCI. Therefore, this study aimed to compare the prevalence of osteoporosis among Korean adults aged ≥ 50 years with SCI according to BMDRV for diagnosing osteoporosis. METHODS: Overall, 855 patients with SCI who underwent BMD tests of the lumbar spine, femoral neck, and total hip at the National Rehabilitation Center (NRC) in Korea between 2010 and 2020 were included in this retrospective cross-sectional study. Osteoporosis was diagnosed in patients with SCI by comparing the differences in prevalence, diagnostic consistency, and risk factors according to the region-based BMDRV of the dual-energy x-ray absorptiometry (DXA) manufacturer and international BMDRV based on the Third National Health and Nutrition Examination Survey (NHANES III) data of females aged 20-29 years. RESULTS: The prevalence of osteoporosis according to the T-score provided by a single reference population of the NHANES III (TNHA) (PONHA) (males: 26.69%; females: 69.35%) was significantly higher in females and males than that according to the T-scores provided by the DXA manufacturer (TDXA) (PODXA) (males: 15.32%; females: 43.15%). The lumbar spine and femoral neck were major osteoporosis diagnosis sites for the PODXA and PONHA, respectively. Risk factors for osteoporosis differed based on the probability of osteoporosis (also known as the OZ ratio) according to the BMD criteria; however, the risk factors were similar according to old age, female sex, low body mass index (BMI), and long SCI period. No significant relationship was noted between the different SCI-related clinical factors (p > 0.05). CONCLUSIONS: The osteoporosis diagnostic site and prevalence in SCI differed according to the regional-based TDXA and international standards of the TNHA. Therefore, further studies on BMDRV are warranted to establish accurate diagnostic criteria for osteoporosis prevention in patients with SCI.

Trends in the high blood glucose and non-alcoholic fatty liver disease among Korean adolescents.

High blood glucose level and non-alcoholic fatty liver disease (NAFLD) in adolescents are long-term risk factors for cardiovascular diseases and poor prognosis. We investigated recent trends of high blood glucose levels and NAFLD among Korean adolescents aged 12-18 years. We conducted a cross-sectional analysis using data of 5,685 adolescents aged 12-18 years from the Korea National Health and Nutrition Examination Surveys (KNHANES), from 2007-2009 to 2016-2018. Linear trends in the prevalence of high blood glucose level, NAFLD, and associated factors were assessed using multivariable logistic regression analyses. During the study period, the odds ratios for high blood glucose level and NAFLD increased significantly in both sexes and in girls, respectively (p for trend <0.05). Over-consumption of total calories in boys and fat intake in boys and girls increased significantly (p for trend <0.05). In Korean adolescents, the prevalence of high blood glucose level and NAFLD has increased recently. Efforts to modify the associated factors and further research to determine the public health measures are warranted to prevent these metabolic abnormalities in adolescents.

Relationship of domain-specific quality of life with body mass index and waist circumference in a Korean elderly population.

BACKGROUND: Obesity affects health-related quality of life (QoL); however, their relationship among elderly Asians is not well known. AIMS: Relationship of domain-specific QoL with body mass index (BMI) and waist circumference and the sex differences were investigated using a nationally representative sample of elderly Korean population. METHODS: In the Korea National Health and Nutrition Examination Survey phase VII (2016-2018), 3659 adults aged ≥ 65 years (1551 men and 2108 women) participated. BMI and waist circumference were classified according to Asian- and Korean-specific criteria. QoL was evaluated using the European Quality of Life Scale-Five Dimensions (EQ-5D). Multivariable logistic regressions were used to examine the relationship of QoL with BMI and waist circumference. RESULTS: Men with BMI < 18.5 kg/m2 and ≥ 25.0 kg/m2 had a significant association with poor QoL in mobility and self-care, but no relationship was found with the other domains. Women with BMI ≥ 25.0 kg/m2 had poor QoL in mobility and self-care, and those with BMI ≥ 30.0 kg/m2 had poor QoL in usual activities and pain/discomfort. There was no significant association with anxiety/depression. Both elderly men and women with abdominal obesity had a significant association with poor QoL in mobility, self-care, usual activities, and pain/discomfort; however, there was no significant relationship with waist circumference and anxiety/depression. CONCLUSIONS: The association between QoL and BMI was different according to sex and the domains of QoL. Domain-specific QoL should be considered in the management of body weight of the elderly.

Depot-specific UCP1 expression in human white adipose tissue and its association with obesity-related markers.

BACKGROUND: This study investigated depot-specific mRNA expression of uncoupling protein 1 (UCP1) in human white adipose tissue (WAT) and its association with obesity-related markers. METHODS: We recruited 39 normal-weight, 41 nondiabetic obese, and 22 diabetic obese women. We measured UCP1 mRNA expression in abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), and investigated the associations between UCP1 mRNA expression in VAT and SAT, and obesity-related markers including mRNA expression of leptin, adiponectin, CCAAT-enhancer-binding protein homologous protein (CHOP), and positive regulatory domain-containing protein 16 (PRDM16). We also evaluated UCP1 mRNA expression in differentiated human white adipocytes after treatment with various stressors and metabolic improvement agents in vitro. RESULTS: UCP1 mRNA in VAT was significantly higher than in SAT in all groups. UCP1 mRNA in SAT was negatively correlated with BMI, total abdominal fat area, visceral fat area, blood pressure, fasting glucose, insulin, HOMA-IR score, triglyceride, hsCRP, fasting leptin levels, and adipocyte size. UCP1 mRNA in SAT was positively correlated with fasting adiponectin levels. UCP1 mRNA in VAT was negatively correlated with visceral-to-subcutaneous fat ratio (VSR), fasting glucose, and triglyceride levels. In SAT, UCP1 mRNA was negatively correlated with mRNA expression of leptin and CHOP, and positively correlated with mRNA expression of adiponectin. The expression of PRDM16 was positively correlated with UCP1 mRNA in both VAT and SAT. UCP1 mRNA expression in differentiated human white adipocytes was significantly reduced after incubation with thapsigargin, tunicamycin, homocysteine, TNF-α, or IL-ß, and significantly increased after incubation with exendin 4, dapagliflozin, and telmisartan. CONCLUSIONS: This study demonstrated depot-specific mRNA expression of UCP1 and its association with obesity-related markers in human WAT. UCP1 mRNA in human white adipocytes was suppressed by inflammatory agents and enhanced by metabolic improvement agents. UCP1 in human WAT might participate in the pathogenesis of obesity-related metabolic diseases.

Association of Alcohol Drinking Patterns With Presence of Impaired Fasting Glucose and Diabetes Mellitus Among South Korean Adults.

BACKGROUND: We aimed to investigate the association between alcohol drinking patterns and the presence of impaired fasting glucose (IFG) and diabetes mellitus (DM). METHODS: We used data from the Korean National Health and Nutrition Examination Survey, 2010-2014. The participants were aged ≥30 years and had no previous diagnosis of DM. High-risk drinking was defined as alcohol consumption of ≥7 glasses at a sitting for men, and ≥5 glasses for women. After adjusting for confounding factors, a polychotomous logistic regression analysis was performed to assess the association of drinking patterns with IFG and DM. RESULTS: For men, high-risk drinking was associated with higher odds ratios (ORs) of IFG (2-4/month, OR 1.51; 95% confidence interval [CI], 1.13-2.04; 2-3/week, OR 1.79; 95% CI, 1.38-2.33; and ≥4/week, OR 2.24; 95% CI, 1.65-3.03) and of DM (2-4/month, OR 2.12; 95% CI, 1.20-3.77; 2-3/week, OR 1.78; 95% CI, 1.05-3.03; and ≥4/week, OR 2.98; 95% CI, 1.72-5.17). For women, high-risk drinking was associated with higher risk of IFG (2-4/month, OR 1.51; 95% CI, 1.04-2.21; 2-3/week, OR 3.19; 95% CI, 2.20-4.64; and ≥4/week, OR 2.23; 95% CI, 1.23-4.06), but not of DM, compared with non-high-risk drinkers who consumed alcohol ≤1 day/month. Non-high-risk drinkers who consumed alcohol ≥4 days/week had higher ORs of DM in men, but lower ORs of DM in women compared with non-high risk drinkers who consumed alcohol ≤1 day/month. CONCLUSIONS: Compared with non-high-risk alcohol drinking, even occasional high-risk alcohol drinking was associated with a higher risk of IFG in men and women, and DM in men. Nearly daily non-high-risk alcohol drinking was associated with a higher risk of DM in men and lower risk of DM in women.

Relationship between low handgrip strength and quality of life in Korean men and women.

PURPOSE: Handgrip strength is strongly related to muscle power in the extremities and is an important index for diagnosing sarcopenia. We evaluated the relationship between handgrip strength and quality of life (QoL) in Korean men and women. METHODS: We analyzed 4620 participants (2070 men and 2550 women) using data from the Korea National Health and Nutrition Examination Survey VI-3 (2015). Low handgrip strength was defined as the lower quartile of handgrip strength in the study population. QoL was evaluated according to the European Quality of Life Scale-Five Dimensions (EQ-5D). The relationship between handgrip strength and QoL was evaluated by multivariate logistic regression analyses. RESULTS: The odds ratios (ORs) for low handgrip strength significantly increased as age increased for both men and women. The ORs for low handgrip strength increased as body mass index decreased in men. In men with low handgrip strength, the OR for having problems in mobility (OR 1.93, 95% confidence interval (CI) 1.25-2.98) and having pain or discomfort (1.53, 1.04-2.24) significantly increased. In women with low handgrip strength, the OR for having problems in mobility (2.12, 1.02-2.87), problems in usual activities (2.04, 1.46-2.85), and having pain or discomfort (1.48, 1.15-1.90) significantly increased. CONCLUSION: Men with low handgrip strength had poor QoL on the mobility and pain/discomfort dimensions of EQ-5D, whereas women with low handgrip strength had poor QoL on mobility, usual activities, and pain/discomfort dimensions. Management to improve handgrip strength is necessary for achieving better QoL.

Wip1 directly dephosphorylates NLK and increases Wnt activity during germ cell development.

Mice null for wild-type p53-induced phosphatase 1 (WIP1) display defects in testis development and spermatogenesis, resulting in reduced fertility. However, the molecular mechanism underlying these abnormalities in the testis remains uncharacterized. We report that the phosphatase activity of WIP1 increases Wnt activity through Nemo-like kinase (NLK). WIP1 directly interacted with NLK, which is highly homologous to p38 MAPK, a WIP1 substrate, and dephosphorylated its activation site. The WIP1-mediated inhibition of NLK activity markedly decreased the phosphorylation of lymphoid enhancer-binding factor 1 (LEF1), enhancing its interaction with ß-catenin. Additionally, WIP1 depletion impaired germ cell development, as evidenced by the expression of Oct4 and the germ cell-specific markers Ddx4, Nanos3 and Dnd1 during the development of germ cells from Oct4-GFP transgenic (OG2) mouse embryonic stem cells (mESCs). The expression of WIP1, whose level was significantly lower after the differentiation of germ cells from mESCs, occurred in parallel with the expression of germ cell development markers and SRY-box 17 (Sox17), a downstream target of Wnt. These results indicate that WIP1 is essential for germ cell development, which is known to require Wnt activity.

Cystamine induces AIF-mediated apoptosis through glutathione depletion.

Cystamine and its reduced form cysteamine showed protective effects in various models of neurodegenerative disease, including Huntington's disease and Parkinson's disease. Other lines of evidence demonstrated the cytotoxic effect of cysteamine on duodenal mucosa leading to ulcer development. However, the mechanism for cystamine cytotoxicity remains poorly understood. Here, we report a new pathway in which cystamine induces apoptosis by targeting apoptosis-inducing factor (AIF). By screening of various cell lines, we observed that cystamine and cysteamine induce cell death in a cell type-specific manner. Comparison between cystamine-sensitive and cystamine-resistant cell lines revealed that cystamine cytotoxicity is not associated with unfolded protein response, reactive oxygen species generation and transglutaminase or caspase activity; rather, it is associated with the ability of cystamine to trigger AIF nuclear translocation. In cystamine-sensitive cells, cystamine suppresses the levels of intracellular glutathione by inhibiting γ-glutamylcysteine synthetase expression that triggers AIF translocation. Conversely, glutathione supplementation completely prevents cystamine-induced AIF translocation and apoptosis. In rats, cysteamine administration induces glutathione depletion and AIF translocation leading to apoptosis of duodenal epithelium. These results indicate that AIF translocation through glutathione depletion is the molecular mechanism of cystamine toxicity, and provide important implications for cystamine in the neurodegenerative disease therapeutics as well as in the regulation of AIF-mediated cell death.

Priming with ceramide-1 phosphate promotes the therapeutic effect of mesenchymal stem/stromal cells on pulmonary artery hypertension.

Some molecules enriched in damaged organs can contribute to tissue repair by stimulating the mobilization of stem cells. These so-called "priming" factors include bioactive lipids, complement components, and cationic peptides. However, their therapeutic significance remains to be determined. Here, we show that priming of mesenchymal stromal/stem cells (MSCs) with ceramide-1 phosphate (C1P), a bioactive lipid, enhances their therapeutic efficacy in pulmonary artery hypertension (PAH). Human bone marrow (BM)-derived MSCs treated with 100 or 200 µM C1P showed improved migration activity in Transwell assays compared with non-primed MSCs and concomitantly activated MAPK(p42/44) and AKT signaling cascades. Although C1P priming had little effect on cell surface marker phenotypes and the multipotency of MSCs, it potentiated their proliferative, colony-forming unit-fibroblast, and anti-inflammatory activities. In a monocrotaline-induced PAH animal model, a single administration of human MSCs primed with C1P significantly attenuated the PAH-related increase in right ventricular systolic pressure, right ventricular hypertrophy, and thickness of α-smooth muscle actin-positive cells around the vessel wall. Thus, this study shows that C1P priming increases the effects of MSC therapy by enhancing the migratory, self-renewal, and anti-inflammatory activity of MSCs and that MSC therapy optimized with priming protocols might be a promising option for the treatment of PAH patients.

Mycorrhizal Fungal Diversity Associated with Six Understudied Ectomycorrhizal Trees in the Republic of Korea.

Mycorrhizal fungi are key components of forest ecosystems and play essential roles in host health. The host specificity of mycorrhizal fungi is variable and the mycorrhizal fungi composition for the dominant tree species is largely known but remains unknown for the less common tree species. In this study, we collected soil samples from the roots of six understudied ectomycorrhizal tree species from a preserved natural park in the Republic of Korea over four seasons to investigate the host specificity of mycorrhizal fungi in multiple tree species, considering the abiotic factors. We evaluated the mycorrhizal fungal composition in each tree species using a metabarcoding approach. Our results revealed that each host tree species harbored unique mycorrhizal communities, despite close localization. Most mycorrhizal taxa belonged to ectomycorrhizal fungi, but a small proportion of ericoid mycorrhizal fungi and arbuscular mycorrhizal fungi were also detected. While common mycorrhizal fungi were shared between the plant species at the genus or higher taxonomic level, we found high host specificity at the species/OTU (operational taxonomic unit) level. Moreover, the effects of the seasons and soil properties on the mycorrhizal communities differed by tree species. Our results indicate that mycorrhizal fungi feature host-specificity at lower taxonomic levels.

Intracellular protein delivery by hollow mesoporous silica capsules with a large surface hole.

We prepared cell membrane-permeable hollow mesoporous silica capsules (HMSCs) by a simple new method. CTAB micellar assembly in cholesterol emulsion gave rise to a novel capsular morphology of the HMSC particles. The HMSCs consisted of mesostructured silica walls with a large surface hole (25-50 nm) and the average particle dimension was 100-300 nm. They exhibited high surface areas of up to 719.3 m(2) g(-1) and a mesoporous range of pores of 2.4-2.7 nm. The surface-functionalized HMSCs could also be prepared by a similar co-condensation method using tetraethoxysilane with various organoalkoxysilane precursors in the presence of cholesterol. These organically modified HMSCs could be further modified on demand. For example, a carboxy-functionalized HMSC could be surface-functionalized by a green fluorescent 5-aminofluorescein (AFL) through an amidation reaction to afford a fluorescent AFL-HMSC. The hollow capsular morphology of the HMSCs with a large surface hole enabled us to develop very efficient intracellular delivery systems for membrane-impermeable ions, molecules, and various functional proteins. Non-covalent sequestration and delivery of proteins as well as covalent linkage of fluorescent molecules on the silica surface are effective for this system. The highly negatively charged green fluorescent probe mag-fluo-4 could be intracellularly delivered into HeLa cells by HMSC without any difficulty. The HMSCs could also effectively transport large functional proteins such as antibodies into HeLa cells. The efficiency of protein delivery by HMSC seems to be 3-22-fold higher than that of mesoporous silica nanospheres (MSNs) based on confocal laser scanning microscopy (CLSM) analysis.

XAF1 destabilizes estrogen receptor α through the assembly of a BRCA1-mediated destruction complex and promotes estrogen-induced apoptosis.

X-linked inhibitor of apoptosis-associated factor 1 (XAF1) is a pro-apoptotic tumor suppressor that is frequently inactivated in multiple human cancers. However, its candidacy as a suppressor in the pathogenesis of breast cancer remains undefined. Here, we report that XAF1 acts as a molecular switch in estrogen (E2)-mediated cell-fate decisions favoring apoptosis over cell proliferation. XAF1 promoter hypermethylation is observed predominantly in estrogen receptor α (ERα)-positive versus ERα-negative tumor cells and associated with attenuated apoptotic response to E2. XAF1 is activated by E2 through a G protein-coupled estrogen receptor-mediated non-genomic pathway and induces ERα degradation and apoptosis while it is repressed by ERα for E2 stimulation of cell proliferation. The XAF1-ERα mutual antagonism dictates the outcomes of E2 signaling and its alteration is linked to the development of E2-resistant tumors. Mechanistically, XAF1 destabilizes ERα through the assembly of breast cancer-associated gene 1 (BRCA1)-mediated destruction complex. XAF1 interacts with ERα and BRCA1 via the zinc finger (ZF) domains 5/6 and 4, respectively, and the mutants lacking either of these domains fail to drive ERα ubiquitination and apoptosis. E2-induced regression of XAF1+/+ tumors is abolished by XAF1 depletion while XAF1-/- tumors recover E2 response by XAF1 restoration. XAF1 and ERα expression show an inverse correlation in primary breast tumors, and XAF1 expression is associated with the overall survival of patients with ERα-positive but not ERα-negative cancer. Together, this study uncovers an important role for the XAF1-ERα antagonism as a linchpin to govern E2-mediated cell-fate decisions, illuminating the mechanistic consequence of XAF1 alteration in breast tumorigenesis.

XAF1 drives apoptotic switch of endoplasmic reticulum stress response through destabilization of GRP78 and CHIP.

X-linked inhibitor of apoptosis-associated factor-1 (XAF1) is a stress-inducible tumor suppressor that is commonly inactivated in many human cancers. Despite accumulating evidence for the pro-apoptotic role for XAF1 under various stressful conditions, its involvement in endoplasmic reticulum (ER) stress response remains undefined. Here, we report that XAF1 increases cell sensitivity to ER stress and acts as a molecular switch in unfolded protein response (UPR)-mediated cell-fate decisions favoring apoptosis over adaptive autophagy. Mechanistically, XAF1 interacts with and destabilizes ER stress sensor GRP78 through the assembly of zinc finger protein 313 (ZNF313)-mediated destruction complex. Moreover, XAF1 expression is activated through PERK-Nrf2 signaling and destabilizes C-terminus of Hsc70-interacting protein (CHIP) ubiquitin E3 ligase, thereby blocking CHIP-mediated K63-linked ubiquitination and subsequent phosphorylation of inositol-required enzyme-1α (IRE1α) that is involved in in the adaptive ER stress response. In tumor xenograft assays, XAF1-/- tumors display substantially lower regression compared to XAF1+/+ tumors in response to cytotoxic dose of ER stress inducer. XAF1 and GRP78 expression show an inverse correlation in human cancer cell lines and primary breast carcinomas. Collectively this study uncovers an important role for XAF1 as a linchpin to govern the sensitivity to ER stress and the outcomes of UPR signaling, illuminating the mechanistic consequence of XAF1 inactivation in tumorigenesis.

XAF1 directs glioma response to temozolomide through apoptotic transition of autophagy by activation of ATM-AMPK signaling.

Background: X-linked inhibitor of apoptosis-associated factor 1 (XAF1) is a tumor suppressor that is commonly inactivated in multiple human cancers. However, its role in the pathogenesis and therapeutic response of glioma is poorly characterized. Methods: XAF1 activation by temozolomide (TMZ) and its effect on TMZ cytotoxicity were defined using luciferase reporter, flow cytometry, and immunofluorescence assays. Signaling mechanism was analyzed using genetic and pharmacologic experiments. In vivo studies were performed in mice to validate the role of XAF1 in TMZ therapy. Results: Epigenetic alteration of XAF1 is frequent in cell lines and primary tumors and contributes to cancer cell growth. XAF1 transcription is activated by TMZ via JNK-IRF-1 signaling to promote apoptosis while it is impaired by promoter hypermethylation. In tumor cells expressing high O 6-methylguanine-DNA methyltransferase (MGMT), XAF1 response to TMZ is debilitated. XAF1 facilitates TMZ-mediated autophagic flux to direct an apoptotic transition of protective autophagy. Mechanistically, XAF1 is translocated into the mitochondria to stimulate reactive oxygen species (ROS) production and ataxia telangiectasia mutated (ATM)-AMP-activated protein kinase (AMPK) signaling. A mutant XAF1 lacking the zinc finger 6 domain fails to localize in the mitochondria and activate ROS-ATM-AMPK signaling and autophagy-mediated apoptosis. XAF1-restored xenograft tumors display a reduced growth rate and enhanced therapeutic response to TMZ, which is accompanied with activation of ATM-AMPK signaling. XAF1 expression is associated with overall survival of TMZ treatment patients, particularly with low MGMT cancer. Conclusions: This study uncovers an important role for the XAF1-ATM-AMPK axis as a linchpin to govern glioma response to TMZ therapy.

The CDK1/TFCP2L1/ID2 cascade offers a novel combination therapy strategy in a preclinical model of bladder cancer.

Aberrant activation of embryogenesis-related molecular programs in urothelial bladder cancer (BC) is associated with stemness features related to oncogenic dedifferentiation and tumor metastasis. Recently, we reported that overexpression of transcription factor CP2-like protein-1 (TFCP2L1) and its phosphorylation at Thr177 by cyclin-dependent kinase-1 (CDK1) play key roles in regulating bladder carcinogenesis. However, the clinical relevance and therapeutic potential of this novel CDK1-TFCP2L1 molecular network remain elusive. Here, we demonstrated that inhibitor of DNA binding-2 (ID2) functions as a crucial mediator by acting as a direct repressive target of TFCP2L1 to modulate the stemness features and survival of BC cells. Low ID2 and high CDK1 expression were significantly associated with unfavorable clinical characteristics. TFCP2L1 downregulated ID2 by directly binding to its promoter region. Consistent with these findings, ectopic expression of ID2 or treatment with apigenin, a chemical activator of ID2, triggered apoptosis and impaired the proliferation, suppressed the stemness features, and reduced the invasive capacity of BC cells. Combination treatment with the specific CDK1 inhibitor RO-3306 and apigenin significantly suppressed tumor growth in an orthotopic BC xenograft animal model. This study demonstrates the biological role and clinical utility of ID2 as a direct target of the CDK1-TFCP2L1 pathway for modulating the stemness features of BC cells.

Intravital imaging and single cell transcriptomic analysis for engraftment of mesenchymal stem cells in an animal model of interstitial cystitis/bladder pain syndrome.

Mesenchymal stem cell (MSC) therapy is a promising treatment for various intractable disorders including interstitial cystitis/bladder pain syndrome (IC/BPS). However, an analysis of fundamental characteristics driving in vivo behaviors of transplanted cells has not been performed, causing debates about rational use and efficacy of MSC therapy. Here, we implemented two-photon intravital imaging and single cell transcriptome analysis to evaluate the in vivo behaviors of engrafted multipotent MSCs (M-MSCs) derived from human embryonic stem cells (hESCs) in an acute IC/BPS animal model. Two-photon imaging analysis was performed to visualize the dynamic association between engrafted M-MSCs and bladder vasculature within live animals until 28 days after transplantation, demonstrating the progressive integration of transplanted M-MSCs into a perivascular-like structure. Single cell transcriptome analysis was performed in highly purified engrafted cells after a dual MACS-FACS sorting procedure and revealed expression changes in various pathways relating to pericyte cell adhesion and cellular stress. Particularly, FOS and cyclin dependent kinase-1 (CDK1) played a key role in modulating the migration, engraftment, and anti-inflammatory functions of M-MSCs, which determined their in vivo therapeutic potency. Collectively, this approach provides an overview of engrafted M-MSC behavior in vivo, which will advance our understanding of MSC therapeutic applications, efficacy, and safety.

Body Shape Indices in Adolescents Based on the 2009-2012 Korea National Health and Nutrition Examination Survey.

A Body Shape Index (ABSI) is a recently proposed index for standardizing waist circumference (WC) for body mass index (BMI) and height in adults, using 2/3 and 1/2 as scaling exponents, respectively. However, ABSI has limited applicability to children and adolescents, as the relationship between height and weight changes with age and varies according to sex. This study aimed to investigate whether ABSI can be applied to adolescents and to analyze the relationships among BMI, WC, height, weight, and body shape index (BSI) in Korean adolescents. The data of 1023 adolescents aged 10-19 years from the 2009-2012 Korea National Health and Nutrition Examination Survey were collected. Body measurements (height, weight, WC, and BMI) were analyzed to estimate the BSI using log-linear regression. The scaling exponents for standardizing WC for weight and height were estimated according to age (per year) and sex. The scaling exponents for standardizing WC for weight and height were 0.698 and -1.090 for boys and 0.646 and -0.855 for girls, respectively. The exponents also differed according to age. BSI was negatively correlated with height, weight, and BMI in boys and girls, and these correlations differed in direction from those in adults. ABSI cannot be applied to adolescents. In adolescents, the BSI is dependent on age and sex and is associated with growth and puberty. Further studies are required to evaluate the association between BSI and other biomarkers, to improve its applicability as a parameter for predicting the risk of chronic diseases in adolescents.

Correlation between Serum Lipid Parameters and Interleukin-10 Concentration in Obese Individuals.

Background: The role of interleukin-10 (IL-10) in humans is controversial because IL-10 has been proposed to exhibit both pro- and anti-inflammatory effects. We aimed to determine the relationships between the changes in these parameters in obese individuals participating in a weight-reduction program. Methods: We measured cardiometabolic parameters including lipid profile and serum IL-10 concentration before and after completion of a 12-week weight-reduction program in 63 non-diabetic obese subjects with a body mass index ≥27 kg/m2 who had comorbid hypertension or dyslipidemia. All the participants were provided with individual intervention sessions designed to implement lifestyle modifications and administered 120 mg orlistat three times daily for 12 weeks. The relationships between changes in serum IL-10 concentration and changes in cardiometabolic risk factors were analyzed. Results: Changes in serum IL-10 concentration were significantly negatively correlated with changes in total cholesterol (r=-0.377), high-density lipoprotein cholesterol (HDL-C; r=-0.377), and low-density lipoprotein cholesterol (LDL-C; r=-0.278) concentrations. However, there were no correlations between changes in serum IL-10 concentration and changes in other cardiometabolic parameters. Conclusion: Serum IL-10 concentration can increase as serum total cholesterol decreases. Additional studies are needed to explore the mechanisms linking changes in serum IL-10 with serum LDL-C and HDL-C concentrations.

Forecasting of the COVID-19 pandemic situation of Korea.

For the novel coronavirus disease 2019 (COVID-19), predictive modeling, in the literature, uses broadly susceptible exposed infected recoverd (SEIR)/SIR, agent-based, curve-fitting models. Governments and legislative bodies rely on insights from prediction models to suggest new policies and to assess the effectiveness of enforced policies. Therefore, access to accurate outbreak prediction models is essential to obtain insights into the likely spread and consequences of infectious diseases. The objective of this study is to predict the future COVID-19 situation of Korea. Here, we employed 5 models for this analysis; SEIR, local linear regression (LLR), negative binomial (NB) regression, segment Poisson, deep-learning based long short-term memory models (LSTM) and tree based gradient boosting machine (GBM). After prediction, model performance comparison was evelauated using relative mean squared errors (RMSE) for two sets of train (January 20, 2020‒December 31, 2020 and January 20, 2020‒January 31, 2021) and testing data (January 1, 2021‒February 28, 2021 and February 1, 2021‒February 28, 2021) . Except for segmented Poisson model, the other models predicted a decline in the daily confirmed cases in the country for the coming future. RMSE values' comparison showed that LLR, GBM, SEIR, NB, and LSTM respectively, performed well in the forecasting of the pandemic situation of the country. A good understanding of the epidemic dynamics would greatly enhance the control and prevention of COVID-19 and other infectious diseases. Therefore, with increasing daily confirmed cases since this year, these results could help in the pandemic response by informing decisions about planning, resource allocation, and decision concerning social distancing policies.