IGF-1 Genome-Edited Human MSCs Exhibit Robust Anti-Arthritogenicity in Collagen-Induced Arthritis.

Stem cell therapy stands out as a promising avenue for addressing arthritis treatment. However, its therapeutic efficacy requires further enhancement. In this study, we investigated the anti-arthritogenic potential of human amniotic mesenchymal stem cells (AMM) overexpressing insulin-like growth factor 1 (IGF-1) in a collagen-induced mouse model. The IGF-1 gene was introduced into the genome of AMM through transcription activator-like effector nucleases (TALENs). We assessed the in vitro immunomodulatory properties and in vivo anti-arthritogenic effects of IGF-1-overexpressing AMM (AMM/I). Co-culture of AMM/I with interleukin (IL)-1ß-treated synovial fibroblasts significantly suppressed NF-kB levels. Transplantation of AMM/I into mice with collagen-induced arthritis (CIA) led to significant attenuation of CIA progression. Furthermore, AMM/I administration resulted in the expansion of regulatory T-cell populations and suppression of T-helper-17 cell activation in CIA mice. In addition, AMM/I transplantation led to an increase in proteoglycan expression within cartilage and reduced infiltration by inflammatory cells and also levels of pro-inflammatory factors including cyclooxygenase-2 (COX-2), IL-1ß, NF-kB, and tumor necrosis factor (TNF)-α. In conclusion, our findings suggest that IGF-1 gene-edited human AMM represent a novel alternative therapeutic strategy for the treatment of arthritis.

Synergistic Therapeutic Potential of Dual 3D Mesenchymal Stem Cell Therapy in an Ischemic Hind Limb Mouse Model.

Three-dimensional (3D) culture systems have been widely used to promote the viability and metabolic activity of mesenchymal stem cells (MSCs). The aim of this study was to explore the synergistic benefits of using dual 3D MSC culture systems to promote vascular regeneration and enhance therapeutic potential. We used various experimental assays, including dual 3D cultures of human adipose MSCs (hASCs), quantitative reverse transcription polymerase chain reaction (qRT-PCR), in vitro cell migration, Matrigel tube network formation, Matrigel plug assay, therapeutic assays using an ischemic hind limb mouse model, and immunohistochemical analysis. Our qRT-PCR results revealed that fibroblast growth factor 2 (FGF-2), granulocyte chemotactic protein-2 (GCP-2), and vascular endothelial growth factor-A (VEGF-A) were highly upregulated in conventional 3D-cultured hASCs (ASC-3D) than in two-dimensional (2D)-cultured hASCs. Hepatocyte growth factor (HGF), insulin-like growth factor-1 (IGF-1), and stromal-cell-derived factor-1 (SDF-1) showed higher expression levels in cytokine-cocktail-based, 3D-cultured hASCs (ASC-3Dc). A conditioned medium (CM) mixture of dual 3D ASCs (D-3D; ASC-3D + ASC-3Dc) resulted in higher migration and Matrigel tube formation than the CM of single 3D ASCs (S-3D; ASC-3D). Matrigel plugs containing D-3D contained more red blood cells than those containing S-3D. D-3D transplantation into ischemic mouse hind limbs prevented limb loss and augmented blood perfusion when compared to S-3D transplantation. Transplanted D-3D also revealed a high capillary density and angiogenic cytokine levels and transdifferentiated into endothelial-like cells in the hind limb muscle. These findings highlight the benefits of using the dual 3D culture system to optimize stem-cell-based therapeutic strategies, thereby advancing the therapeutic strategy for ischemic vascular disease and tissue regeneration.

BMP-2 Genome-Edited Human MSCs Protect against Cartilage Degeneration via Suppression of IL-34 in Collagen-Induced Arthritis.

Even though the regenerative potential of mesenchymal stem cells (MSCs) has been extensively studied, there is a debate regarding their minimal therapeutic properties. Bone morphogenetic proteins (BMP) are involved in cartilage metabolism, chondrogenesis, and bone healing. In this study, we aimed to analyze the role of genome-edited BMP-2 overexpressing amniotic mesenchymal stem cells (AMMs) in a mouse model of collagen-induced arthritis (CIA). The BMP-2 gene was synthesized and inserted into AMMs using transcription activator-like effector nucleases (TALENs), and BMP-2-overexpressing AMMs (AMM/B) were sorted and characterized using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The co-culture of AMM/B with tumor necrosis factor (TNF)-α-treated synovial fibroblasts significantly decreased the levels of interleukin (IL)-34. The therapeutic properties of AMM/B were evaluated using the CIA mouse model. The injection of AMM/B attenuated CIA progression and inhibited T helper (Th)17 cell activation in CIA mice. In addition, the AMM/B injection increased proteoglycan expression in cartilage and decreased the infiltration of inflammatory cells and factors, including IL-1ß, TNF-α, cyclooxygenase (COX)-2, and Nuclear factor kappa B (NF-kB) in the joint tissues. Therefore, editing the BMP-2 genome in MSCs might be an alternative strategy to enhance their therapeutic potential for treating cartilage degeneration in arthritic joints.

Dual CXCR4/IL-10 Gene-Edited Human Amniotic Mesenchymal Stem Cells Exhibit Robust Therapeutic Properties in Chronic Wound Healing.

Although stem cells have attracted attention as a novel therapeutic solution for tissue regeneration, their minimal efficacy remains controversial. In the present study, we aimed to investigate the enhanced therapeutic property of CXCR4/IL-10 dual angiogenic/anti-inflammatory gene knock-in amniotic mesenchymal stem cells (AMM) in a wound-healing model. Dual CXCR4 and IL-10 genes were inserted into the AMM genome using transcription-activator-like effector nuclease (TALEN). Matrigel tube formation and anti-inflammatory effects were assessed in vitro, and efficacy was tested in vivo in a diabetic wound-healing model. CXCR4/IL-10-expressing amniotic MSCs (AMM/CI) strongly expressed CXCR4 and IL-10 genes and robustly promoted tube formation and anti-inflammatory potential. AMM/CI transplantation resulted in accelerated wound healing, as well as high engraftment and re-epithelialization potential. Transplanted AMM/CI also exhibited high angiogenic and decreased pro-inflammatory gene expression in the wound tissue, indicating direct therapeutic effects on wound healing. Taken together, these data indicate that dual angiogenic/anti-inflammatory gene knock-in may be a novel approach to enhance the therapeutic effects of stem cells, and transplantation of AMM/CI can be an alternative therapeutic option in chronic wound healing.

Transfer learning based generalized framework for state of health estimation of Li-ion cells.

Estimating the state of health (SOH) of batteries powering electronic devices in real-time while in use is a necessity. The applicability of most of the existing methods is limited to the datasets that are used to train the models. In this work, we propose a generic method for SOH estimation with much wider applicability. The key problem is the identification of the right feature set which is derived from measurable voltage signals. In this work, relative rise in voltage drop across cell resistance with aging has been used as the feature. A base artificial neural network (ANN) model has been used to map the generic relation between voltage and SOH. The base ANN model has been trained using limited battery data. Blind testing has been done on long cycle in-house data and publicly available datasets. In-house data included both laboratory and on-device data generated using various charge profiles. Transfer learning has been used for public datasets as those batteries have different physical dimensions and cell chemistry. The mean absolute error in SOH estimation is well within 2% for all test cases. The model is robust across scenarios such as cell variability, charge profile difference, and limited variation in temperature.

SDF-1-edited human amniotic mesenchymal stem cells stimulate angiogenesis in treating hindlimb ischaemia.

Although stem cells have extensively been studied as a novel vehicle for tissue repair, their sustained efficacy remains controversial. In this study, we aimed to investigate the angiogenic potency over time of stromal cell-derived factor-1 (SDF-1) gene-edited amniotic mesenchymal stem cells (AMM/S) in a hindlimb ischaemia model. An SDF-1 transgene was inserted into the AMM cell genome via transcription activator-like effector nuclease (TALEN) mediated knock-in, and cell migration, Matrigel tube formation, and in vivo Matrigel plug assays were performed. AMM/S were also transplanted into hindlimb ischaemia model mice. Blood perfusion, therapeutic potential, histology, capillary density and in vivo angiogenic assays were performed. AMM/S exhibited high expression of the SDF-1 gene, and robustly promoted migration, proliferation and microvascular formation. AMM/S transplantation significantly increased blood perfusion and limb loss prevention compared with AMM. AMM/S also significantly inhibited increased capillary density and expression of angiogenic factors in the ischaemic hindlimb. Our study demonstrated that AMM/S provides a significant therapeutic effect in ischaemic hindlimbs by enhancing angiogenesis.

Genome Edited Sirt1-Overexpressing Human Mesenchymal Stem Cells Exhibit Therapeutic Effects in Treating Collagen-Induced Arthritis.

Even though mesenchymal stem cells (MSCs) are known for cartilage regeneration, their therapeutic efficacy needs to be enhanced. In the present study, we produced genome-edited silent information regulator 2 type 1 (Sirt1)-overexpressing MSCs, and evaluated their therapeutic potential in a damaged cartilage mouse liver fibrosis model. The Sirt1 gene was successfully inserted into a 'safe harbor' genomic locus in amniotic mesenchymal stem cells (AMMs), and the chondrogenic properties of the Sirt1 gene overexpressing AMMs (AMM/S) were characterized using quantitative PCR and histology. Therapeutic potentials were investigated in a collagen-induced arthritis (CIA) mouse model. Chondrocyte-differentiated AMM/S expressed cartilage-specific genes and were positive for Safranin O staining. Transplantation of AMM/S attenuated CIA progression and suppressed T helper (Th)-17 cell activation while increasing the Treg cell population in CIA mice. Pro-inflammatory factors, such as interleukin (IL)-1ß, IL-6, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α were significantly decreased in AMM/S-injected joint tissues. In conclusion, genome-edited AMM/S may represent a safe and alternative therapeutic option for the treatment and repair of damaged cartilage, or in inflammatory joint arthritis.

Effects of education methods on self-efficacy of smoking cessation counseling among medical students.

BACKGROUND: Medical students need to receive training in providing smoking cessation counseling to provide effective smoking cessation interventions to smokers when they become doctors. This study examined the smoking cessation education curricula and factors affecting counseling self-efficacy (CSE) in smoking cessation treatment among medical students. METHODS: In a multicenter cross-sectional study, we obtained demographic information, personal history of tobacco use and intention to quit smoking, exposure to secondhand smoke in the school premises during the past week, the experience of learning about tobacco in each medical school, tobacco-related medical knowledge, and self-efficacy in smoking cessation counseling on medical students of four Korean medical schools. RESULTS: Among 1,416 medical students eligible, 313 (22.1%) students completed a self-administered questionnaire. Only 20.3% of the students reported positive CSE on smoking cessation. The factors affecting positive CSE were scores of ≥ 60 on tobacco-related medical knowledge, smoking experience, and blended learning (p = 0.014, 0.005, and 0.015, respectively). CONCLUSION: This study shows that high scores in tobacco-related medical knowledge and blended learning are correlated with positive CSE for smoking cessation counseling.

4-Methoxyphenyl (E)-3-(Furan-3-yl) Acrylate Inhibits Vascular Smooth Muscle Cell Proliferation.

The Cordyceps extract exhibits antiproliferative potential in vascular smooth muscle cells (SMCs) through the mitogen-activated protein kinase signaling pathway. In this study, we aimed to identify the active compounds in the Cordyceps extract and analyze their role in remodeling the arterial wall. On investigation, we discovered the following active compound: 4-methoxyphenyl (E)-3-(furan-3-yl) acrylate and synthesized it. We performed antiproliferation and antimigration assays in addition to an in vivo vessel wall remodeling experiment. Investigation of the mechanism adopted by the active compound to remodel the vessel was performed. The newly synthesized compound inhibited the proliferation and migration of SMCs. Treatment with the synthesized compound reduced neointima formation in the balloon-injured Sprague-Dawley rat model. In addition, this compound inhibited the activation of matrix metalloproteinase-2 and matrix metalloproteinase-9 in type I collagen-activated SMCs. Moreover, this compound suppressed the expression of cycloxygenase-2 (COX-2) in SMCs. Therefore, this compound can exert potential antiarteriosclerotic effects by modulating vessel wall remodeling. In conclusion, the newly synthesized 4-methoxyphenyl (E)-3-(furan-3-yl) acrylate might be an alternative therapeutic intervention for the treatment of atherosclerosis.

An Incremental Voltage Difference Based Technique for Online State of Health Estimation of Li-ion Batteries.

Accurate state of health (SOH) estimation of rechargeable batteries is important for the safe and reliable operation of electric vehicles (EVs), smart phones, and other battery operated systems. We propose a novel method for accurate SOH estimation which does not necessarily need full charging data. Using only partial charging data during normal usage, 10 derived voltage values ([Formula: see text]) are collected. The initial [Formula: see text] point is fixed and then for every 1.5% increase in the Coulomb counting, other points are selected. The difference between the [Formula: see text] values ([Formula: see text]) and the average temperature during the charging form the feature vector at different SOH levels. The training data set is prepared by extrapolating the charging voltage curves for the complete SOH range using initial 400 cycles of data. The trained artificial neural network (ANN) based on the feature vector and SOH values can be used in any battery management system (BMS) with a time complexity of only [Formula: see text]. Less than 1% mean absolute error (MAE) for the test cases has been achieved. The proposed method has a moderate training data requirement and does not need any knowledge of previous SOH, state of charge (SOC) vs. OCV relationship, and absolute SOC value.

Directly induced hepatogenic cells derived from human fibroblast ameliorate liver fibrosis.

Recently, reprogramming technology has emerged as a fascinating tool to generate specific tissue cells. In this study, we tested the hypothesis that ultrasound-directed cellular reprogramming can generate fibroblasts into hepatogenic cells. We directly induced human dermal fibroblasts (HDFs) into hepatocyte-like cells mediated by environmental transition-guided cellular reprogramming (h/entr) using ultrasound. We confirmed the characteristics of h/entr by the expression levels of hepatocyte specific RNA and proteins. The effects of h/entr on the activation of hepatic stellate cells were analyzed using conditioned medium (CM). h/entr were transplanted into mice with acute liver fibrosis and the therapeutic effects and mechanism of liver fibrosis were determined. h/entr exhibited high levels of hepatocyte specific genes, hepatogenic (hepatocyte growth factor [HGF], colony-stimulating factor 3 [CSF-3]) and anti-inflammatory (interleukin 10 [IL-10]) factors. h/entr CM suppressed the activation of hepatic stellate cells in vitro. Transplantation of h/entr significantly delayed liver fibrosis and improved liver function. Transplantation of h/entr accelerates liver regeneration, and human albumin expressing h/entr and human Alu gene were detected in the mouse livers. This report suggests that directly induced h/entr could be one of the highly effective therapeutic options for the treatment of liver cirrhotic disease.

Validation Study of Korean Translated Systemic Clinical Outcome Routine Evaluation-15 as Self-Report Family Assessment Measure: Focusing on Adolescent in Daegu and North Gyeongsang Province.

BACKGROUND: Systemic Clinic Outcome and Routine Evaluation (SCORE-15) is a compact scale that contains the most critical family function assessment tools including assessments of the strengths, adaptability, and communication among family members. It has been translated into other languages in the United States and Europe. This study aimed to verify the reliability and validity of SCORE-15 with a small research population and justify its applicability in Korea. METHODS: SCORE-15 is a self-reporting family function measurement tool for each family member over the age of 11 years. This study used the Family Communication Scale (FCS) included in the Family Adaptability and Cohesion Evaluation Scales (FACES) IV package and FACES in FACES-III to verify the validity of the Korean-translated SCORE-15. Cronbach's α value was calculated to check the reliability of SCORE-15. Data were analyzed using STATA ver. 15.0 (Stata Corp., College Station, TX, USA). RESULTS: The study analyzed the correlation between FACES-III and SCORE-15 and FCS and SCORE-15 so that there was a significant static correlation in both comparisons (r=0.72 and r=0.81, respectively). Also, the research compared each subscale to analyze the correlation and the range was 0.47 to 0.95. The total SCORE-15 Cronbach's α value was 0.92 and those values of the subscales for family strengths, family communication, and family difficulty were 0.89, 0.73, and 0.87, respectively (P<0.001). CONCLUSION: Our study was the first to validate the Korean SCORE-15, which can be used as an appropriate shortform indicator for evaluating family function and changes in detecting therapeutic improvements in Korea.

Minicircle-based GCP-2 ex vivo gene therapy enhanced the reepithelialization and angiogenic capacity.

Recently, minicircle (MC)-based cell therapy has been emerging as a novel technology for nonviral genetic modification. In this study, we investigated the characteristics of granulocyte chemotactic protein-2 (GCP-2)-overexpressing fibroblasts (GCP-2/MC) using MC microporation technology, as well as its therapeutic mechanism in wound healing. GCP-2 parent plasmid and MC containing GCP-2 were generated. Human dermal fibroblasts (HDF) were transfected with MC containing GCP-2. Quantitative reverse transcription polymerase chain reaction (qRT-PCR), scratch wound assay, and in vivo wound healing assay were performed. Gene and protein expression analysis revealed that GCP-2/MC highly expressed epithelialization growth factor, epidermal growth factor (EGF), chemokines, GCP-2, interleukin (IL)-8, as well as wound healing-associated genes such as insulin growth factor (IGF)-1 and hepatocyte growth factor (HGF). An in vitro scratch wound closure and matrigel tube formation assays demonstrated that the culture medium derived from GCP-2/MC substantially accelerated the wound closure and matrigel network formation. Wounds in nude mice were created by skin excisions followed by injections of GCP-2/MC. Results showed high cell survival potential and that GCP-2/MC transplantation highly accelerated skin wound closure by increasing reepithelialization, capillary density, and enhancing angiogenic factors, suggesting direct benefits for cutaneous closure. Taken together, these data suggest that MC-based GCP-2 overexpression could be a promising alternative strategy for promoting wound healing.

Internal short circuit detection in Li-ion batteries using supervised machine learning.

With the proliferation of Li-ion batteries in smart phones, safety is the main concern and an on-line detection of battery faults is much wanting. Internal short circuit is a very critical issue that is often ascribed to be a cause of many accidents involving Li-ion batteries. A novel method that can detect the Internal short circuit in real time based on an advanced machine leaning approach, is proposed. Based on an equivalent electric circuit model, a set of features encompassing the physics of Li-ion cell with short circuit fault are identified and extracted from each charge-discharge cycle. The training feature set is generated with and without an external short-circuit resistance across the battery terminals. To emulate a real user scenario, internal short is induced by mechanical abuse. The testing feature set is generated from the battery charge-discharge data before and after the abuse. A random forest classifier is trained with the training feature set. The fault detection accuracy for the testing dataset is found to be more than 97%. The proposed algorithm does not interfere with the normal usage of the device, and the trained model can be implemented in any device for online fault detection.

Interleukin 10-Secreting MSCs via TALEN-Mediated Gene Editing Attenuates Left Ventricular Remodeling after Myocardial Infarction.

BACKGROUND/AIMS: Stem cells or progenitor cells have been demonstrated as a novel alternative for cell therapy; however, their sustained efficacy is still debated. This study aimed to evaluate whether interleukin 10 (IL-10) gene-edited amniotic mesenchymal stem cells (AMM/I) contribute to left ventricular (LV) function and remodeling after acute myocardial infarction (AMI). METHODS: The IL-10 gene was integrated into the genomic locus of AMM via transcription activator-like effector nucleases (TALEN) and AMM/I were intramyocardially transplanted into AMI mice models. Cardiac function, quantitative polymerase chain reaction, histology, capillary density, and apoptosis assays were performed. RESULTS: AMM/I transplantation significantly suppressed infiltrated CD68 positive or F4/80 positive inflammatory cells and reduced the expression of pro-inflammatory factors in the infarcted myocardium. In addition, significantly improved LV function and reduced infarct size was noted in mice model with AMM/I transplantation than in those given AMM. Moreover, AMM/I highly inhibited cell apoptosis and increased capillary density in the infarcted myocardium. CONCLUSION: Our study demonstrated that AMM/I recruitment played favorable roles in the early restoration of LV function and remodeling by suppressing inflammation and enhancing cardiac protection and capillary density.

Human adipose mesenchymal stem cells overexpressing dual chemotactic gene showed enhanced angiogenic capacity in ischaemic hindlimb model.

Aims: In present study, we sought to characterize the angio-vasculogenic property of human adipose mesenchymal stem cells (ASCs) overexpressing dual chemokine GCP-2 and SDF-1α (ASC-G/S) and to determine the therapeutic potential of ASC-G/S in the context of experimental ischaemia. Methods and results: We generated ASC-G/S line and performed flow cytometry, quantitative (q)-PCR, Matrigel tube formation, Matrigel plug assays, and in vivo therapeutic assays using hind limb ischaemia mouse model. Q-PCR results showed that the representative pro-angiogenic factors were highly upregulated in ASC-G/S compared with ASCs single chemokine overexpressing GCP-2 (ASC-G). In addition, ASC-G/S exhibited high expression of endothelium-specific genes shch as vWF and Flk-1 and showed robust in vitro micro-vascular formation. ASC-G/S was transplanted into ischaemic mouse hind limbs and compared with control groups. ASC-G/S injection prevented limb loss and augmented blood perfusion, suggesting that ASC-G/S enhances neovascularization in hind limb ischaemia. In addition, transplanted ASC-G/S revealed high vasculogenic potential in vivo compared with transplanted ASC-G. Conclusion: Our data suggest that ASC-G/S has high therapeutic effects on hind limb ischaemia via robust angiogenic and vasculogenic action.

NOVA1 acts as an oncogene in osteosarcoma.

Osteosarcoma is one of the most common bone tumors in young patients. NOVA1 (neuro-oncological ventral antigen 1) is a neuron-specific RNA binding-protein and belongs to the Nova family. Previous studies showed that NOVA1 played crucial roles in the development of several tumors. The objective of our study was to study the role of NOVA1 in the osteosarcoma. In our study, we showed that NOVA1 expression was upregulated in osteosarcoma cell lines and tissues. The expression of NOVA1 was upregulated in 22 (22/30; 73%) osteosarcoma cases compared to that in the adjacent tissues. Overexpression of NOVA1 promoted osteosarcoma cell viability, colony formation and invasion. Furthermore, knockdown of NOVA1 suppressed osteosarcoma cell viability, colony formation and invasion. These data suggested that NOVA1 acted as an oncogene in the development of osteosarcoma.

Stromal vascular fraction shows robust wound healing through high chemotactic and epithelialization property.

BACKGROUND: Although human stromal vascular fraction (SVF) has been regarded as an attractive stem cell source, its therapeutic mechanism in wound healing has not been fully elucidated. AIMS: In this study, we investigated the molecular characteristics and therapeutic property of SVF for wound healing. METHODS: Microarray data showed that SVF cells are enriched with a higher level of wound healing or epithelium development-related genes and micro RNA. RESULTS: Quantitative polymerase chain reaction (PCR) and reverse transcriptase PCR results revealed that the epithelialization growth factor, epidermal growth factor (EGF), chemokines, stromal cell-derived factor (SDF-1 or CXCL12), neutrophil-activating protein-2 (NAP-2 or CXCL7), chemokine receptors (CXCR1, CCR2 and CCR3) and wound healing genes were up-regulated in SVF compared with those in adipose-derived mesenchymal stem cells (ASCs). An in vitro scratch wound closure experiment demonstrated that co-culture with SVF substantially accelerated the wound closure of fibroblasts. Wounds in nude mice were created by skin excisions followed by injections of SVF with Pluronic hydrogel. SVF implantation highly accelerated wound closure and increased cellularity and re-epithelialization. In addition, the transplanted SVF exhibited high engraftment rates in the wound area, suggesting direct benefits for cutaneous closure. CONCLUSIONS: Taken together, these data suggest that SVF possesses high therapeutic capability for wound healing via the secretion of epithelialization and chemotactic growth factors and enhanced engraftment properties.

The relationship between circulating neutrophil gelatinase-associated lipocalin and early alteration of metabolic parameters is associated with dietary saturated fat intake in non-diabetic Korean women.

Circulating neutrophil gelatinase-associated lipocalin (NGAL) is associated with obesity-related metabolic disorders. This study investigated the relationship between serum NGAL and early alteration of metabolic parameters in non-diabetic Korean women, particularly with respect to saturated fat (SFA) intake. Anthropometric parameters, fasting glycemic status, and levels of lipids, oxidative stress/inflammatory markers, and NGAL were measured in 82 non-diabetic Korean women [Super-healthy group (n=57) with 0 metabolic syndrome risk factor (MetS RF) and MetS-risk group (n=25) with MetS RF≥1]. Age, weight, waist circumference, blood pressure, fasting glucose, HbA1C, triglyceride, LDL and total-cholesterol, and NGAL levels were higher, and HDL-cholesterol was lower in the MetS-risk group than in the Super-healthy group. Age-adjusted serum NGAL levels were higher in the MetS-risk group than in the Super-healthy group. NGAL increased proportionally with increase in MetS RFs (p=0.038) and correlated positively with BMI, triglycerides, LDL- and total-cholesterol, interleukin-6, white blood cell count, and neutrophil%, and negatively with HDL-cholesterol and superoxide dismutase activity. Serum NGAL levels positively correlated with SFA intake before and after adjustment (age and BMI). Serum NGAL levels were higher in high-SFA consumers [≥7g/day, ≥7% of total calorie intake (TCI)] than in low-SFA consumers (<7g/day, <7% of TCI). Serum NGAL levels were highest in the MetS-risk group consuming higher SFA and lowest in the Super-healthy group consuming lower SFA. However, serum NGAL did not significantly differ between the low-SFA consuming MetS-risk and Super-healthy groups. The relationship between circulating NGAL and early alteration of metabolic parameters is associated with dietary SFA intake in non-diabetic Korean women.

Angio-Vasculogenic Properties of Endothelial-Induced Mesenchymal Stem Cells Derived From Human Adipose Tissue.

BACKGROUND: Although stem cells have been regarded as a promising therapeutic option, the marginal therapeutic effects of stem cells are limitations that must be overcome for the development of effective cell therapy. This study sought to identify the angio-vasculogenic properties of endothelial differentiated mesenchymal stem cells (MSCs) and to determine whether these cells are effective for vascular repair. METHODS AND RESULTS: Adipose MSCs were cultured for 10 days under endothelial cell (EC) culture conditions. These endothelial cell differentiated adipose MSCs (EA) and undifferentiated adipose MSCs (UA) were characterized via angiogenesis and adhesion assays. These cells were transplanted into a hindlimb ischemia (HLI) model to determine therapeutic effects and their underlying mechanisms. EA displayed low adhesion and angiogenic properties in vitro compared with UA. When implanted into mouse HLI models, EA exhibited the decreased recovery of blood perfusion in limb ischemia than uncultured UA. Histology data showed that injected EA exhibited lower retention, angiogenic cytokine levels, and neovascularization in vivo than did UA. Short-term differentiated EA display less cell engraftment and angio-vasculogenic potential, and are less effective for peripheral vascular repair than UA. CONCLUSIONS: EC differentiation of MSCs may not present an effective strategy for the promotion of therapeutic neovascularization.