DNMT3A epigenetically regulates key microRNAs involved in epithelial-to-mesenchymal transition in prostate cancer.

Epithelial-to-mesenchymal transition (EMT) is involved in prostate cancer (PCa) metastatic progression, and its plasticity suggests epigenetic implications. Deregulation of DNA methyltransferases (DNMTs) and several microRNAs (miRNAs) plays a relevant role in EMT, but their interplay has not been clarified yet. In this study, we provide evidence that DNMT3A interaction with several miRNAs has a central role in an ex vivo EMT PCa model obtained via exposure of PC3 cells to conditioned media from cancer-associated fibroblasts. The analysis of the alterations of the miRNA profile shows that miR-200 family (miR-200a/200b/429, miR-200c/141), miR-205 and miR-203, known to modulate key EMT factors, are down-regulated and hyper-methylated at their promoters. DNMT3A (mainly isoform a) is recruited onto these miRNA promoters, coupled with the increase of H3K27me3/H3K9me3 and/or the decrease of H3K4me3/H3K36me3. Most interestingly, our results reveal the differential expression of two DNMT3A isoforms (a and b) during ex vivo EMT and a regulatory feedback loop between miR-429 and DNMT3A that can promote and sustain the transition towards a more mesenchymal phenotype. We demonstrate the ability of miR-429 to target DNMT3A 3'UTR and modulate the expression of EMT factors, in particular ZEB1. Survey of the PRAD-TCGA dataset shows that patients expressing an EMT-like signature are indeed characterized by down-regulation of the same miRNAs with a diffused hyper-methylation at miR-200c/141 and miR-200a/200b/429 promoters. Finally, we show that miR-1260a also targets DNMT3A, although it does not seem to be involved in EMT in PCa.

Ultrasonic Liposculpturing.

The author describes a revolutionary body contouring technique based on the surgical use of ultrasonic energy. It allows the selective destruction of only excess adipose tissue. The technique is based on three fundamental steps: (1) preparation of the areas to be treated with a large infiltration of a special solution, (2) treatment of the areas with ultrasonic energy through special titanium probes, (3) manual remodeling of the treated areas to eliminate the fluid from the bursted adipocytes (fatty acids). The advantages of this new technique are selective destruction of just the undesired tissues, elimination of the fluid from the adipose tissues, and the possibility of a real "lifting" of the skin of the treated areas, and a reduction of physical strain on the surgeon. The author has already treated more than 280 patients with excellent results and without contraindications or undesired side effects. The fundamental steps of ultrasonic liposculpturing, including a description of the physical principles on which the technique is based, are presented.

32 Years of Ultrasonic-Assisted Lipoplasty (U.A.L.): From Aesthetic to Obesity.

In this article, we tried to take stock of the state of the art in ultrasonic-assisted lipoplasty focusing on its most recent technologic advances and in the newest clinical applications, such as overweight, obesity, breast surgery and regenerative medicine. Great space was devoted to the analysis and clarification of the most common myths and legends related to this intriguing technique.

Retrospective analysis of the predictive factors associated with good surgical outcome in brachioplasty in massive weight loss patients.

BACKGROUND: Upper arm lift is a widespread body contouring procedure, but no globally accepted guidelines exist in selecting patients and, due to comorbidity and heterogeneity of them, it is difficult to identify predictive factors of good surgical outcome. The authors review the team's experience of 56 brachioplasty performed in massive weighs loss patients. METHODS: Data of 56 consecutive arm lifts were reviewed for preoperative, perioperative and postoperative variables and outcomes (complications, scarring, wound healing, revision surgery, need for blood transfusion, satisfaction, etc.). Surgical technique and postoperative care are described. A statistical analysis was performed to identify relationship between possible predictive factors and outcomes. Furthermore, an evaluation of different employed wound management devices was conducted. RESULTS: Follow-up ranged from 6 to 36 months (mean 20.1 months). Outcomes summary is reported (overall complication rate 50%, poor scarring rate 25%, delayed wound healing rate 26.8%, revision surgery rate 37.5%, need for blood transfusion rate 8.9%, satisfaction rate 71.4%) and statistical investigation evidenced the role of prior plastic surgery BMI and the associated change in BMI before and after weight loss, just prior brachioplasty, and the modality of weight loss. CONCLUSION: The authors' technique resulted in positive outcomes overall, considering the difficulty in dealing with the problems of MWL patients. Based on our results, we aim to suggest to perform brachioplasty in patient with the lower achievable BMI (preferably <30kg/m2) to reduce the negative effect of unmodifiable factors as diabetes, modality of weight loss, a wide ΔBMI, and other well-known negative predictive factors.

New perspectives in regenerative medicine and surgery: the bioactive composite therapies (BACTs).

Regenerative medicine and surgery is a rapidly expanding branch of translational research in tissue engineering, cellular and molecular biology. To date, the methods to improve cell intake, survival, and isolation need to comply with a complex and still unclear regulatory frame, becoming everyday more restrictive and often limiting the effectiveness and outcome of the therapeutic choices. Thus, the authors developed a novel 360° regenerative strategy based on the synergic action of several new components called the bioactive composite therapies (BACTs) to improve grafted cells intake, and survival in total compliance with the legal and ethical limits of the current regulatory frame. The rationale at the origin of this new technology is based on the evidence that cells need supportive substrate to survive in vitro and this observation, applying the concept of translational medicine, is true also in vivo. Bioactive composite mixtures (BACMs) are tailor-made bioactive mixtures containing several bioactive components that support cells' survival and induce a regenerative response in vivo by stimulating the recipient site to act as an in situ real bioreactor. Many different tissues have been used in the past for the isolation of cells, molecules, and growth factors, but the adipose tissue and its stromal vascular fraction (SVF) remains the most valuable, abundant, safe, and reliable source of regenerative components and particularly of adipose-derived stems cells (ADSCs). The role of plastic surgeons as the historical experts in all the most advanced techniques for harvesting, manipulating, and grafting adipose tissue is fundamental in this constant process of expansion of regenerative procedures. In this article, we analyze the main causes of cell death and the strategies for preventing it, and we present all the technical steps for preparing the main components of BACMs and the different mixing modalities to obtain the most efficient regenerative action on different clinical and pathological conditions. The second section of this work is dedicated to the logical and sequential evolution from simple bioactive composite grafts (BACGs) that distinguished our initial approach to regenerative medicine, to BACTs where many other fundamental technical steps are analyzed and integrated for supporting and enhancing the most efficient regenerative activity. Level of Evidence: Not gradable.

Complications after Breast Augmentation with Fat Grafting: A Systematic Review.

BACKGROUND: Breast augmentation with fat grafting is used as an alternative to breast implants. However, a systematic evaluation of the complication rates after fat grafting using only studies with consecutive patients has not previously been performed. In this study, the authors compiled studies reporting complication rates and radiologic changes in consecutive patients undergoing cosmetic breast augmentation with fat grafting. METHODS: Studies reporting on consecutive patients undergoing breast augmentation with fat grafting were included. Complication rates, radiologic changes, Breast Imaging Reporting and Data System assessments, and the number of patients undergoing revision surgery were extracted. Mean complication rates and radiologic changes were calculated with meta-analytical methods. RESULTS: Twenty-two studies with 2073 patients were included. The rates of major complications were low (hematoma, 0.5 percent; infection, 0.6 percent; and seroma, 0.1 percent). None of these patients needed revision surgery. The most frequent minor complication was palpable cysts in 2.0 percent of the patients; 67 percent of these were treated with aspiration. The radiologic changes in the patients after fat grafting were as follows: oil cysts, 6.5 percent; calcifications, 4.5 percent; and fat necrosis, 1.2 percent. The risk of being referred for additional radiologic imaging (e.g., to exclude malignant changes) was 16.4 percent, and the risk of being referred for biopsy was 3.2 percent. CONCLUSIONS: The complication rates after breast augmentation with fat grafting are low and support fat grafting as an alternative to breast augmentation with implants. The rates of radiologic changes are high after fat grafting, but the changes do not seem to have any therapeutic consequences for the patients.

The effects of the surgical removal of subcutaneous adipose tissue on energy expenditure and adipocytokine concentrations in obese women.

OBJECTIVE: To analyze the effects of the surgical removal of subcutaneous adipose tissue by ultrasound-assisted megalipoplasty (UAM) on energy expenditure and adipocytokine concentrations in obese women. METHODS: Fifteen premenopausal obese women with BMI 37.5+/-6.3 kg/m(2) (range: 30.7-53.6 kg/m(2)) underwent UAM. Body composition (by DEXA), resting metabolic rate (REE) by indirect calorimetry, insulin resistance (by the HOMA method), leptin, C-reactive protein, interleukin-6, resistin and adiponectin were measured before and 1, 3, 28 and 180 days after the procedure. RESULTS: UAM significantly reduced fat mass at day 3, without further changes in the following days. REE increased at day 3 after UAM, returned to baseline levels at day 28 and significantly declined at day 180. Leptin levels transiently increased after UAM and then declined according to fat mass reduction. C-reactive protein, interleukin-6 and resistin levels acutely increased after UAM and then returned to the baseline levels. Adiponectin levels acutely declined after the procedure and then stabilized to a plasma level slightly lower than at baseline. Insulin resistance deteriorated in the acute post-operative phase and then improved. CONCLUSION: The surgical removal of subcutaneous fat was associated to an acute inflammatory reaction with high REE and insulin-resistance. Later on, the metabolic effects of fat mass removal appeared, with a reduction of leptin levels and REE and an improvement of insulin resistance.