Mechanical Stress Improves Fat Graft Survival by Promoting Adipose-Derived Stem Cells Proliferation.

Cell-assisted lipotransfer (CAL), defined as co-transplantation of aspirated fat with enrichment of adipose-derived stem cells (ASCs), is a novel technique for cosmetic and reconstructive surgery to overcome the low survival rate of traditional fat grafting. However, clinically approved techniques for increasing the potency of ASCs in CAL have not been developed yet. As a more clinically applicable method, we used mechanical stress to reinforce the potency of ASCs. Mechanical stress was applied to the inguinal fat pad by needling . Morphological and cellular changes in adipose tissues were examined by flow cytometric analysis 1, 3, 5, and 7 days after the procedure. The proliferation and adipogenesis potencies of ASCs were evaluated. CAL with ASCs treated with mechanical stress or sham control were performed, and engraftment was determined at 4 weeks post-operation. Flow cytometry analysis revealed that mechanical stress significantly increased the number as well as the frequency of ASC proliferation in fat. Proliferation assays and adipocyte-specific marker gene analysis revealed that mechanical stress promoted proliferation potential but did not affect the differentiation capacity of ASCs. Moreover, CAL with cells derived from mechanical stress-treated fat increased the engraftment. Our results indicate that mechanical stress may be a simple method for improving the efficacy of CAL by enhancing the proliferation potency of ASCs.

12-OAHSA is a component of olive oil and mitigates obesity-induced inflammation.

Fatty acid esters of hydroxyl fatty acids (FAHFAs) are a new family of endogenous lipids that exert anti-inflammatory action. Among the various FAHFA isomers, the dietary source of oleic acid-hydroxy stearic acid (OAHSA) and its anti-inflammatory functions are poorly understood. This study investigated the composition of OAHSA isomers in dietary oils and the impact of 12-OAHSA on obesity-induced inflammation. Liquid chromatography with tandem mass spectrometry analysis revealed that various dietary oils, including fish oil, corn oil, palm oil, soybean oil, and olive oil, present a wide variation in OAHSA profiles and amounts. The highest amounts of total OAHSAs are present in olive oil including 12-OAHSA. Compared to vehicle-treated obese mice, administration of 12-OAHSA significantly improved glucose homeostasis, independent of body weight. 12-OAHSA-treated mice displayed significantly reduced accumulation of CD11c+ adipose tissue macrophages, and CD4+/CD8+ adipose tissue T lymphocytes. Concomitantly, the expression of pro-inflammatory cytokine genes and the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway were significantly decreased in the 12-OAHSA-treated adipose tissue, while the expression of the anti-inflammatory gene Il10 was markedly increased. Moreover, in vitro cell culture experiments showed that 12-OAHSA significantly inhibited the lipopolysaccharides-induced inflammatory response in macrophages by suppressing the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway. Collectively, these results indicated that 12-OAHSA, as a component of olive oil, mitigates obesity-induced insulin resistance by regulating AT inflammation. Therefore, 12-OAHSA could be used as a novel nutritional intervention against obesity-associated metabolic dysregulation.

Adenosine-Prefabricated Adipose Tissue Improves Fat Graft Survival by Promoting VEGF-Dependent Angiogenesis.

BACKGROUND: Angiogenesis plays an important role in determining the fat graft survival. However, clinical preconditioning techniques that target angiogenesis during fat grafting have not been established so far. Adenosine has emerged as a regulator of angiogenesis under hypoxic conditions; therefore, the aim of this study was to investigate the effects and underlying mechanisms of adenosine prefabrication on fat graft survival. METHODS: In the first animal study, a total of 32 mice were transplanted with fat prefabricated with vehicle (Control, N = 16) or adenosine (Adenosine, N = 16). In the second animal study, 24 mice were divided into three groups based on the type of fat graft: Control (N = 8), Adenosine (N = 8), and Axitinib (cotreatment of adenosine with axitinib, N = 8). At 1- and 4-weeks post-transplantation, grafts were evaluated by histopathological and biochemical assessment. Adenosine-induced vascular endothelial growth factor (VEGF) production and angiogenesis were determined using cell cultures. RESULTS: The retention volumes of fat grafts in the adenosine group were significantly increased until 4 weeks. Fat grafts from the adenosine group exhibited greater structural integrity, reduced fibrosis, and increased blood vessels. The expression levels of angiogenesis-related genes, Vegfa, Vegfr1, Vegfr2, and Vwf, were elevated in the adenosine group. Furthermore, adenosine upregulated VEGF production in preadipocytes, thereby enhancing the migration of endothelial cells. Treatment with the axitinib, VEGF receptor inhibitor, abrogated the adenosine-induced angiogenesis in the fat grafts. CONCLUSION: Adenosine prefabrication in fat improved the graft survival by enhancing angiogenesis through the VEGF/VEGFR axis in the preadipocytes and endothelial cells. Therefore, this method may be used as a novel strategy to increase the retention rate in fat grafts.

"Fasting: An Effective Preconditioning Method to Increase Fat Graft Survival".

BACKGROUND: Most preconditioning techniques before fat grafting require external manipulation. Since nutrition is the main factor maintaining the balance of lipogenesis and lipolysis, we hypothesized that fasting before undergoing autologous fat grafting may increase lipolysis and reduce adipocyte size, thereby improving the fat graft survival rate. METHODS: C57BL/6 mice were divided into 24 h starved or fed groups. Adipose tissue lipolysis, adipogenesis, and angiogenesis-related gene expression, in fat from both groups, were analyzed. The volume and weight of the grafted fat at 4-8 weeks postoperatively were measured using micro-computed tomography. Immunohistochemistry staining and mRNA expression analysis were also performed to evaluate the effect of fasting on fat graft survival. RESULTS: Fasting decreased adipocyte size by inducing adipose tissue lipolysis. Adipogenesis-related genes were remarkably downregulated while lipolysis-related genes and angiogenesis inducer genes were significantly upregulated in the starved adipose tissue. The mice grafted with the fat from the 24 h starved group had approximately 20% larger volumes and considerably heavier weights than those from the fed group. Increased viable adipocytes and vessels, and reduced macrophages in the fat grafts obtained from the 24 h starved group were also observed. CONCLUSIONS: Fasting for 24 h before harvesting fat increased the retention volume of fat graft by increasing angiogenesis via VEGF induction. Therefore, fasting would be a novel and reliable preconditioning strategy to improve graft survival in autologous fat grafting. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Favorable Crisscrossing Pattern With Polydioxanone: Barbed Thread Lifting in Constructing Fibrous Architecture.

BACKGROUND: The longevity of polydioxanone (PDO)-barbed lifting threads remains controversial. OBJECTIVES: The authors sought to assess the longevity extension effect of a crisscross implantation pattern in PDO-barbed thread lifting. METHODS: To acquire the desired outcome in PDO-barbed thread lifting, the authors suggested a paradigm shift to incorporate biochemical factors in enforcing the physico-mechanical lift. A nude mouse model was employed to evaluate their theory to compare the conventional fan-shaped protocols in barbed thread lifting with an architectural construction of intersections of fibrous capsule in a crisscross pattern. Three fragments of monofilament PDO-barbed-lifting threads were implanted in the dorsal skin of 12 nude mice. The pattern of implantation was fan-shaped in the control group and crisscross in the experimental group. Tissue specimens containing tangential areas of threads were harvested, fixed, and paraffin-embedded. Samples were horizontally cut and histologically analyzed employing hematoxylin and eosin, Massons' Trichrome, and Sirius red staining. Fibrotic areas and the width of fibrosis from the thread were also analyzed. RESULTS: Fibrous capsulations around the barbed area of the PDO-barbed lifting threads were threefold greater than those around the barb-free areas of the threads. In the crisscross implantation pattern, width and density of the fibrotic areas were fivefold greater than those of the fan-shaped areas. Induction of fibrous capsules around the PDO-barbed thread was markedly condensed in the crisscross areas. CONCLUSIONS: This study provides the basis for a more logical implantation pattern in PDO-barbed lifting threads for facial rejuvenation. By generating controlled multiple crisscross patterns, we can create more intense fibrogenesis, reduce tension applied on each barbed thread, and, therefore, extend the longevity of the result.

Corrosive Esophageal Injury due to a Commercial Vinegar Beverage in an Adolescent.

Although gastroesophageal damage is commonly induced by accidental drinking of a strong acid or alkali, damage due to the consumption of a vinegar beverage is not well known. We report a case of corrosive esophageal ulcer found in an adolescent consuming a vinegar drink daily. A 15-year-old male visited the emergency room presenting with hematemesis and severe epigastric pain. Multiple longitudinal ulcers, concurrent mucosal hemorrhage, and denuded mucosa were noted in the whole of the esophagus via an endoscopic examination. He had been drinking a vinegar beverage daily without sufficient dilution. The patient was treated with corticosteroid, antibiotic therapy, and mucosa protecting alginate medication and was asked to fast for a week. The follow-up endoscopy showed improvement of the esophageal injuries. Overall, continuous consumption of a vinegar beverage can result in acidic burns and destruction of the surface of the upper gastrointestinal tract. Therefore, vinegar beverages should be considered as corrosive agents.

Carboxytherapy-Induced Fat loss is Associated with VEGF-Mediated Vascularization.

BACKGROUND: Carboxytherapy is the transcutaneous administration of CO2 gas for therapeutic purposes. Although this non-surgical procedure has been widely used for reducing localized adiposity, its effectiveness on fat loss in obese patients and its underlying mechanisms remain unclear. METHODS: C57BL/6 mice were fed with a high-fat diet for 8 weeks to generate obese animal models. Obese mice were randomly assigned to two groups: One group was administered air to both inguinal fat pads (air/air), and the other group was treated with air to the left inguinal fat pad and with CO2 to the right inguinal fat pad (air/CO2). Each group was treated every other day for 2 weeks. Morphological changes and expression levels of genes associated with lipogenesis and vascularization in fat were determined by histological and qRT-PCR analyses. RESULTS: Mice treated with air/CO2 showed lower body weights and blood glucose levels compared to air/air-treated mice. Paired comparison analysis revealed that CO2 administration significantly decreased adipose tissue weights and adipocyte sizes compared to air treatment. Additionally, CO2 treatment markedly increased vessel numbers and expressions of Vegfa and Fgf1 genes in adipose tissues. The expressions of Fasn and Fabp4 genes were also modestly reduced in CO2-treated adipose tissue. Moreover, Ucp1 expression, the target gene of VEGF and a key regulator in energy expenditure, was significantly increased in CO2-treated adipose tissue. CONCLUSIONS: Carboxytherapy is effective in the reduction of localized fat in obese patients which is mechanistically associated with alteration of the vasculature involved in VEGF. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Incidentally Discovered Solitary Gastrointestinal Polyp with Pathological Significance in Children: Four Case Reports.

Most solitary gastrointestinal (GI) polyps in children are either inflammatory or hamartomatous. Solitary hyperplastic polyp, sentinel polyp and solitary adenomatous polyp have been occasionally diagnosed in adults, but very rarely reported in Korean children. We recently came across a case with adenomatous polyp in the colon, a case with hyperplastic polyp beneath the gastroesophageal junction, a case with hyperplastic polyp in the prepyloric area, and a case with sentinel polyp in the distal esophagus, which are unusual pathologic types in children. These mucosal lesions were diagnosed incidentally during elective endoscopic examinations for GI symptoms. Most polyps do not cause significant symptoms, so the diagnosis might be delayed, especially in children, in whom GI endoscopy is not commonly performed for screening purpose as in the adults.

Macrophage Lamin A/C Regulates Inflammation and the Development of Obesity-Induced Insulin Resistance.

Obesity-induced chronic low-grade inflammation, in particular in adipose tissue, contributes to the development of insulin resistance and type 2 diabetes. However, the mechanism by which obesity induces adipose tissue inflammation has not been completely elucidated. Recent studies suggest that alteration of the nuclear lamina is associated with age-associated chronic inflammation in humans and fly. These findings led us to investigate whether the nuclear lamina regulates obesity-mediated chronic inflammation. In this study, we show that lamin A/C mediates inflammation in macrophages. The gene and protein expression levels of lamin A/C are significantly increased in epididymal adipose tissues from obese rodent models and omental fat from obese human subjects compared to their lean controls. Flow cytometry and gene expression analyses reveal that the protein and gene expression levels of lamin A/C are increased in adipose tissue macrophages (ATMs) by obesity. We further show that ectopic overexpression of lamin A/C in macrophages spontaneously activates NF-κB, and increases the gene expression levels of proinflammatory genes, such as Il6, Tnf, Ccl2, and Nos2. Conversely, deletion of lamin A/C in macrophages reduces LPS-induced expression of these proinflammatory genes. Importantly, we find that myeloid cell-specific lamin A/C deficiency ameliorates obesity-induced insulin resistance and adipose tissue inflammation. Thus, our data suggest that lamin A/C mediates the activation of ATM inflammation by regulating NF-κB, thereby contributing to the development of obesity-induced insulin resistance.

Telmisartan mitigates hyperglycemia-induced vascular inflammation by increasing GSK3ß-Ser9 phosphorylation in endothelial cells and mouse aortas.

Telmisartan, an angiotensin II type 1 receptor blocker (ARB), attenuates hyperglycemia-aggravated vascular inflammation by decreasing IκB kinase ß (IKKß) expression in endothelial cells. Because glycogen synthase 3ß (GSK3ß) is involved in inflammatory process by regulating nuclear factor-κB (NF-κB) activity, we investigated whether GSK3ß mediates telmisartan-ameliorated vascular inflammation in hyperglycemia-treated endothelial cells and high-fat diet (HFD)-fed mice. Telmisartan remarkably induced GSK3ß-Ser9 phosphorylation in hyperglycemia-treated endothelial cells that accompanied a decrease in hyperglycemia-induced NF-κB p65-Ser536 phosphorylation, vascular cell adhesion molecule-1 (VCAM-1) expression, and THP-1 monocyte adhesion. Ectopic expression of GSK3ß-S9A, a constitutively active mutant of GSK3ß, significantly restored complete telmisartan-inhibited NF-κB p65-Ser536 phosphorylation, VCAM-1 expression, and THP-1 monocyte adhesion. In addition, it reversed telmisartan-repressed IKKß expression. Among the ARB, including losartan and fimasartan, only telmisartan increased GSK3ß-Ser9 phosphorylation, and telmisartan-induced GSK3ß-Ser9 phosphorylation remained unchanged by pretreatment with GW9662, a specific and irreversible peroxisome proliferator-activated receptor γ (PPARγ) antagonist. Finally, in the aortas of HFD-fed mice, telmisartan treatment significantly attenuated HFD-induced upregulation of NF-κB p65-Ser536 phosphorylation, VCAM-1 expression, and IKKß expression and downregulation of GSK3ß-Ser9 phosphorylation. Taken together, our findings demonstrated that telmisartan ameliorates hyperglycemia-exacerbated vascular inflammation, at least in part, by inducing GSK3ß-Ser9 phosphorylation, which consequently inhibits IKKß expression, NF-κB p65-Ser536 phosphorylation, and VCAM-1 expression in a PPARγ-independent manner.