Bisphenol A and 2,3,7,8-tetrachlorodibenzo-p-dioxin at non-cytotoxic doses alter the differentiation potential and cell function of rat adipose-stem cells.

The possibility of chemical contamination is an important issue to consider when designing a cell therapy strategy. Both bisphenol A (BPA) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are among the most environmentally relevant endocrine disrupting chemicals (EDCs, compounds with a high affinity for adipose tissue) recently studied. Adipose-derived stem cells (ASCs) are mesenchymal stromal cells (MSCs) obtained from adipose tissue widely used in regenerative medicine to prevent and treat diseases in several tissues and organs. Although the experimental use of tissue-engineered constructs requires careful analysis for approval and implantation, there has been a recent increase in the number of approved clinical trials for this promising strategy. This study aimed to evaluate cell viability, apoptosis, DNA damage, and the adipogenic or osteogenic differentiation potential of rat adipose-derived stem cells (rASCs) exposed to previously established non-cytotoxic doses of BPA and TCDD in vitro. Results demonstrated that 10 µM of BPA and 10 nM of TCDD were able to significantly reduce cell viability, while all exposure levels resulted in DNA damage, although did not increase the apoptosis rate. According to the analysis of adipogenic differentiation, 1 µM of BPA induced the significant formation of oil droplets, suggesting an increased adipocyte differentiation, while both 10 µM of BPA and 10 nM of TCDD decreased adipocyte differentiation. Osteogenic differentiation did not differ among the treatments. As such, BPA and TCDD in the concentrations tested can modify important processes in rASCs such as cell viability, adipogenic differentiation, and DNA damage. Together, these findings prove that EDCs play an important role as contaminants, putatively interfering in cell differentiation and thus impairing the therapeutic use of ASCs.

Fibrillar collagen genes are not coordinately upregulated with TGF ß1 expression in finasteride-treated prostate.

Benign prostatic hyperplasia (BPH) is the most common cause of lower urinary tract symptoms (LUTS) in older men. In this regard, recent studies have attempted to define the relationships between prostatic fibrosis, LUTS, and increased expression of transforming growth factor ß1 (TGF ß1) in BHP. Therapeutic approaches for BPH such as 5-α-reductase inhibitors and alpha-adrenergic blocking agents increase TGF ß1 expression in the prostatic tissue. Here, we investigated the effects of the 5-α-reductase inhibitor-finasteride-on rat ventral prostate tissue, especially with regard to the tissue distribution and gene expression of fibrillar collagens. Adult Wistar rats (n = 15) were treated with finasteride (25 mg/kg/day) by subcutaneous injection for 7 and 30 days. Age-matched, vehicle-treated (n = 15) adult Wistar rats were used as control. Finasteride treatment reduced prostate size and increased the area of types I and III collagen fibers in the prostatic stroma. As expected, TGF ß1 mRNA expression was upregulated by finasteride treatment. However, COL1A1 and COL3A1 mRNA expressions decreased after both 7 and 30 days of finasteride treatment, suggesting that finasteride treatment promotes prostate parenchyma and stroma changes, which lead to the observed types I and III collagen remodeling without de novo collagen synthesis. The upregulation of TGF ß1 mRNA and protein associated with the 5-α-reductase inhibitor is more closely related to epithelial and stromal cell death pathways than to prostatic fibrosis.

Zygomatic Muscle Neurotization with Nerve Grafts and End-to-Side Neurorrhaphies: A New Technique for Facial Palsy.

Moebius syndrome is a rare congenital facial palsy that can generate serious emotional repercussions, mainly due to the inability to smile. Currently, no treatment is available; however, surgery can restore muscle function. This case report introduces a new technique for the treatment of Moebius syndrome with zygomatic muscle neurotization using nerve grafts and end-to-side neurorrhaphies, in a 3-year-old girl diagnosed with bilateral Moebius syndrome who was unable to smile on the left side. After 4 years, the patient presented with full smile restoration on the left side, with right and left independent movements and complete symmetry.

Nebulized enriched heparin to treat no critical patients with Sars-Cov-2: Triple-blind clinical trial.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a viral respiratory disease that spreads rapidly, reaching pandemic status, causing the collapse of numerous health systems, and a strong economic and social impact. The treatment so far has not been well established and there are several clinical trials testing known drugs that have antiviral activity, due to the urgency that the global situation imposes. Drugs with specific mechanisms of action can take years to be discovered, while vaccines may also take a long time to be widely distributed while new virus variants emerge. Thus, drug repositioning has been shown to be a good strategy for defining new therapeutic approaches. Studies of the effect of enriched heparin in the replication of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) in vitro assays justify the advance for clinical tests. METHODS AND ANALYSIS: A phase I/II triple-blind parallel clinical trial will be conducted. Fifty participants with radiological diagnosis of grade IIA pneumonia will be selected, which will be allocated in 2 arms. Participants allocated in Group 1 (placebo) will receive nebulized 0.9% saline. Participants allocated in Group 2 (intervention) will receive nebulized enriched heparin (2.5 mg/mL 0.9% saline). Both groups will receive the respective solutions on a 4/4 hour basis, for 7 days. The main outcomes of interest will be safety (absence of serious adverse events) and efficacy (measured by the viral load).Protocols will be filled on a daily basis, ranging from day 0 (diagnosis) until day 8.

Enxerto de gordura: lipofragmentado x lipoaspirado / Fat grafting: Lipofragmentation x Liposuction

Introdução: Com o objetivo de obter lipoenxerto autógeno e injetável de tecido ressecado em dermolipectomias, este estudo propõe um novo método para colheita e processamento do tecido adiposo, através de um dispositivo fragmentador específico. O principal objetivo foi estabelecer uma análise comparativa das características de qualidade e viabilidade do novo lipofragmentado em relação ao já conhecido lipoaspirado, amplamente aceito como fonte viável de lipoenxerto. Ensaios in vivo e in vitro foram delineados para avaliar o comportamento biológico das amostras, a fim de orientar novos e possíveis estudos em humanos com aplicações clínicas. Métodos: Uma paciente pós-bariátrica que foi submetida a dermolipectomia abdominal teve sua peça cirúrgica ressecada e dividida em quatro partes que foram submetidas a Lipoaspiração e Lipofragmentação, sem e com infiltração prévia. Todas as amostras foram submetidas a centrifugação e então distribuídas para os ensaios que envolveram avaliação histológica, imunohistoquímica, citometria de fluxo, cultura celular e ainda a injeção de xenoenxerto no dorso de 10 ratos Wistar, retirados após seis semanas para avaliação de massa, volume e características histológicas. Resultados: As amostras de gordura fragmentada, seca e infiltrada, mostraram características estruturais e comportamento biológico semelhantes aos das amostras de lipoaspirado. Conclusões: A fragmentação da gordura transformou o tecido celular subcutâneo das dermolipectomias em uma nova variante de lipoenxerto injetável e viável, com características biológicas semelhantes àquelas do lipoaspirado tradicional. Embora ainda preliminares, nossos resultados embasam a realização de novas investigações buscando otimizar a técnica com vistas ao aprimoramento da enxertia gordurosa e suas possíveis aplicações na medicina regenerativa.

Introduction: Aiming to obtain autogenous and injectable lipografts from resected tissues in dermolipectomies, this study proposes a new method for harvesting and processing adipose tissue through a specific fragmenting device. The main objective was to establish a comparative analysis of the quality and viability characteristics of the new lipofragmentation technique and those of the well-known liposuction technique, widely accepted as a viable source of fat grafting. In vivo and in vitro assays were designed to evaluate the biological behavior of the samples to guide new and possible human studies with clinical applications. Methods: A post-bariatric patient who underwent abdominal dermolipectomy had her surgical specimen resected, which was divided into four parts that underwent liposuction and lipofragmentation, with and without prior infiltration. All samples were centrifuged and distributed for assays with assessments involving histological analysis, immunohistochemistry, flow cytometry, cell culture, and xenograft injection on the back of 10 Wistar rats, which was evaluated after six weeks for mass, volume, and histological features. Results: The structural characteristics and biological behaviors of fragmented, dry, and infiltrated fat samples were similar to those of liposuction samples. Conclusions: Fat fragmentation transformed the subcutaneous cellular tissue of dermolipectomies into a new, viable injectable lipograft variant, with biological characteristics similar to those of traditional liposuction. Although still preliminary, our results support further investigations to optimize the technique and improve fat grafting and its possible applications in regenerative medicine.