SA-ANP

Magnesium oxide nanostructured particles (NP) were prepared using a simple solution combustion technique using different leaf extracts such as Mangifera indica (Mango - Ma), Azadirachta indica (Neem-Ne), and Carica papaya (Papaya-Pa) as surfactants. The highly crystalline phase of MgO nanostructures was confirmed by PXRD and FTIR studies for 2 h 500°C calcined samples. To analyze the characteristics of obtained material-MaNP, NeNP, and PaNP for dosimetry applications, thermoluminescence (TL) studies were carried out for Co-60 gamma rays irradiated samples in the dose range 10-50 KGy; PaNP and NeNP exhibited well-defined glow curve when compared with MaNP samples. In addition, it was observed that the TL intensity decreases, with increase in gamma dose and the glow peak temperature is shifted towards the higher temperature with the increase in heating rate. The glow peak was segregated using glow curve deconvolution and thermal cleaning method. Kinetic parameters estimated using Chen's method, trap depth (E), and frequency factor (s) were found to be 0.699, 7.408, 0.4929, and 38.71, 11.008, and 10.71 for PaNP, NeNP, and MaNP respectively. The well-resolved glow curve, good linear behavior in the dose range of 10-50, KGy, and less fading were observed in PaNP as compared with MaNP and NeNP. Further, the antibacterial activity was checked against human pathogens such as Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. A visible zone of clearance was observed at 200 and 100 μg/mL by the PaNP and NeNP, indicating the death of colonies by the nanoparticles. Therefore, PaNP nanomaterial is a potential phosphor material for dosimetry and antibacterial application compared to NeNP and MaNP.

Aldosterone is a critical pathological driver for cardiac and renal diseases. We recently discovered that mutant atrial natriuretic peptide (MANP), a novel atrial natriuretic peptide (ANP) analog, possessed more potent aldosterone inhibitory action than ANP in vivo. MANP and natriuretic peptide (NP)-augmenting therapy sacubitril/valsartan are under investigations for human hypertension treatment. Understanding the elusive mechanism of aldosterone inhibition by NPs remains to be a priority. Conflicting results were reported on the roles of the pGC-A (particulate guanylyl cyclase A receptor) and NP clearance receptor in aldosterone inhibition. Furthermore, the function of PKG (protein kinase G) and PDEs (phosphodiesterases) on aldosterone regulation are not clear.

In the present study, we investigated the molecular mechanism of aldosterone regulation in a human adrenocortical cell line H295R and in mice.

We first provided evidence to show that pGC-A, not NP clearance receptor, mediates aldosterone inhibition. Next, we confirmed that MANP inhibits aldosterone via PDE2 (phosphodiesterase 2) not PKG, with specific agonists, antagonists, siRNA silencing, and fluorescence resonance energy transfer experiments. Further, the inhibitory effect is mediated by a reduction of intracellular Ca2+ levels. We then illustrated that MANP directly reduces aldosterone synthase CYP11B2 (cytochrome p450 family 11 subfamily b member 2) expression via PDE2. Last, in PDE2 knockout mice, consistent with in vitro findings, embryonic adrenal CYP11B2 is markedly increased.

Our results innovatively explore and expand the NP/pGC-A/3',5', cyclic guanosine monophosphate (cGMP)/PDE2 pathway for aldosterone inhibition by MANP in vitro and in vivo. In addition, our data also support the development of MANP as a novel ANP analog drug for aldosterone excess treatment.