Brn-3b and PPARy Nuclear Receptor Expression in Adipose Tissue of Human Subjects

Obesity rates have reached alarming heights globally, having more than doubled since the 1980's. Over 60% of diabetic patients are obese, and the increasing severity of the disease is associated with Type 2 Diabetes Mellitus (T2DM) incidence, which is reversible by weight loss could trigger the development of new medication, procedures and perhaps devices. Peroxisome proliferator-activated receptor gamma (PPARy) is a nuclear receptor expressed in adipose tissue and regulates the expression of genes involved in both adipocyte differenctiation and lipid metabolism. Another novel transcription factor, Brn-3b, known to be involved in neuronal development, has recently been shown to be expressed in murine adipose tissue and also in peripheral blood cells (PBCs) obtained from morbidly obese patients. Furthermore, the expression of Brn-3b was significantly reduced in PBCs of diabetic patients. The aim of this study was to investigate the expression of PPARy and Brn-3b in cells of the adipose tissue of obese patients undergoing weight-reducing sleeve gastrostomy. Anthropometric and biochemical data were collected for all patients. Samples from two abdominal adipose tissue depots (subcutaneous and omental) were also obtained from each patient. RNA was extracted and qPCR for PPARy and Brn-3b was performed. Our results showed that PPARy is highly expressed in the adipocytes of omental adipose tissue when compared to the adipocytes of the subcutaneous adipose tissue, while Brn-3b was not detectable in adipocytes, but exclusive expressed in the stromal vascular fraction, especially of the subcutaneous adipose tissue. The expression of Brn-3b increased the rising levels of systemic insulin and was also elevated in the SVF of patients with metabolic disease compared with those without. In conclusion our study indicated that there was a reciporacal relationship between the expression of PPARy and Brn-3b that needs further investigation, and raises questions concerning the implication of Brn-3b in the pathology of obesity and T2DM

Genetics and Acquired Hearing Loss

Hearing loss (HL) is a worldwide disease with substantial economic costs for the public health. Around 466 million people have disabling hearing loss and the WHO estimated that by 2050 over 900 million people will suffer hearing loss. Several factors including infections, noise-exposure, ototoxic medications or genetic disorders could cause hearing impairment. Hearing devices such as cochlear implants and aids are the current therapies. Although the prevalence of hearing loss is very high, alternative treatments as pharmaceutical agents are currently insufficient. Within the past years, increased knowledge on hearing loss etiology and physiopathology opened new opportunities for future research towards hearing loss treatment. Here we aim to review current bibliography on genetics factors involved in hearing loss

Targeting Wnt/EZH2/microRNA-708 signaling pathway inhibits neuroendocrine differentiation in prostate cancer

Prostate cancer (PC) castration resistance has been linked to the differentiation of PC luminal cells into hormone-refractory neuroendocrine (NE) cells. However, the molecular mechanisms controlling the emergence of lethal NE prostate cancer (NEPC) remain unclear. The present study aimed to investigate the mechanisms underlying the transition from prostate adenocarcinoma to NEPC. The microRNA miR-708 was involved in NE differentiation and was downregulated in NEPC cells and tumor specimens. miR-708 targeted Sestrin-3 to inhibit Forkhead Box O1 (FOXO1) phosphorylation, resulting in apoptosis of prostate adenocarcinoma cells and AKT-inactivated NEPC cells, the latter of which was consistent with the progression of tumor xenografts in mice under miR-708 treatment. In silico analysis of PC and NEPC tumor specimens suggested that the polycomb repressive complex subunit Enhancer of zeste homolog 2 (EZH2) was particularly overexpressed in NEPC. Notably, EZH2 bound to the miR-708 promoter and induced its silencing in NEPC. Inhibition of EZH2 prevented NE differentiation of PC cells. EZH2 expression was regulated by both Cyclin Dependent Kinase 1 (CDK1) and Wnt signaling. Silencing transcription factor 4 (TCF4), as a key protein in Wnt signaling, prevented NEPC formation. These results provide a molecular basis for the roles of miR-708 and EZH2 in NE differentiation in PC and highlight a new paradigm in NEPC formation and survival.Other Information Published in: Cell Death Discovery License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1038/s41420-019-0218-y</p