Nandrolone Decanoate supplementation promotes AMPK activation and divergent brain connectivity rearrangements in adult and aged mice.

Abnormalities in energetic and proteic homeostasis during ageing relate to neurodegenerative diseases. The mitochondria are a hub of oxidative metabolism, influencing autophagic flux. Ageing can lead to a functional disruption of these systems, leading to neuroenergetic and proteotoxic imbalance. Lower levels of testosterone have been proposed as a mechanism accelerating functional decline during ageing. In this study we investigated whether nandrolone decanoate (ND), an analog of testosterone, in aged animals improves mitochondrial bioenergetics and autophagy. Albino CF1 mice of 3 and 18 months of age, were separated in 4 groups that received daily subcutaneous injections for 15 days of either ND (15mg/kg), or vehicle. Were performed baseline and 14th day 18FDG uptake analysis, through positron emission tomography scan. High resolution respirometry was performed to assess functionally mitochondrial respiratory states and respiratory control ratio (RCR) in synaptossomes fractions. Also, hypothalamic immunocontent of AMPK, pAMPKT172, Beclin-1 and BCL-2 LC3 was assessed. Results demonstrate that aged animals did not display alterations nor in 18FDG uptake, neither in mitochondrial respiratory states. Also, aged mice displayed reduced pAMPKT172/ AMPK ratio, and increased LC3-II compared to adult controls. Curiously, ND in aged mice did neither increase 18FDG uptake, nor alter mitochondrial states. Albeit, ND increased pAMPKT172/ AMPK ratio, LC3-II turnover, as well as increased RCR. This suggest that ageing does not culminate necessarily in bioenergetics alterations in brain, although biomarkers of energetic status and autophagy are reduced. ND improved bioenergetic efficiency and autophagy in aged mice. These benefits are probably mediated by reprogramation of AMPK signalling.

PSMA expression in differentiated thyroid cancer: association with radioiodine, 18FDG uptake, and patient outcome

Context Little is known about prostate-specific membrane antigen (PSMA) expression in patients with cervical involvement of differentiated thyroid cancer (DTC). Objective We investigated PSMA expression in neck persistent/recurrent disease (PRD) using immunohistochemistry and the association with radioiodine (RAI) or 18Fluorodeoxyglucose ( 18FDG) uptake, and patient outcome. Design, setting and patients Data from 44 consecutive DTC patients who underwent neck reoperation from 2006 to 2018 in a comprehensive cancer center. Main outcome measure(s) Immunostaining was performed with vascular endothelial marker CD31 and PSMA. PSMA expression was quantified using the immunoreactive score (IRS). RAI and 18FDG uptake were assessed before surgery using post-therapeutic RAI scintigraphy and 18FDG PET/CT. Mean follow-up after re-intervention was 6.5 ±3.7 years. Results Thirty patients (68%) showed at least one PSMA-positive lesion (IRS≥2) with similar proportions in RAI-positive and RAI-negative patients (75% vs. 66%). In RAI-negative patients, however, the proportion of PSMA-positive disease (79% vs. 25%, p<0.01) and the mean IRS (4.0 vs. 1.0, p=0.01) were higher in 18FDG-positive than in 18FDG-negative patients. Furthermore, mean IRS was higher in patients ≥55 years, large primary tumors (>40 mm) or aggressive subtypes, and was correlated with structural disease at last follow-up. Strong PSMA expression (IRS≥9) was associated with shorter progression-free survival (PFS). Conclusions Our findings show that PSMA expression was present in two-thirds of patients with neck PRD, that it was related to poor prognostic factors and that very high expression was associated with poorer PFS. This preliminary study may offer new perspectives for the management of RAI-refractory DTC.

Natural Compound Methyl Protodioscin Suppresses Proliferation and Inhibits Glycolysis in Pancreatic Cancer

Methyl protodioscin (MPD) is one of the main bioactive components in the plant of Dioscoreaceae. MPD has been demonstrated to possess antitumor activities. However, its role in pancreatic cancer and the underlying molecular mechanisms are poorly defined. In the present study, we demonstrated that MPD inhibited proliferation and promoted apoptosis of pancreatic cancer. Furthermore, our results demonstrated that MPD decreased oncogene c-Myc in protein level and resulted in concomitant reduction in glycolysis. In vivo assays with xenograft mouse model further confirmed the in vitro observations, which indicated that MPD inhibited 18FDG uptake in tumors formed by subcutaneously injection of MIA PaCa-2 cells. Collectively, our present study uncovered novel antitumor functions of MPD in pancreatic cancer and provided the possible molecular mechanism.