Jowl Reduction With Deoxycholic Acid.

BACKGROUND: The study proposes a novel protocol for targeting the jowls using deoxycholic acid (DCA) injections, with emphasis on safety and feasibility of the procedure. METHODS: This prospective study was conducted at a cosmetic practice between June 2016 and May 2017. Twelve consecutive patients seeking reduction/improvement in mild/moderate jowl fat were injected with DCA subcutaneously in a predefined circular area 1.0 cm above the mandibular border. Treatment response was assessed using physician-evaluated Global Aesthetic Improvement Scale (GAIS) and Subject GAIS. RESULTS: Twelve patients (11 women and 1 man) with mild (n = 8) or moderate (n = 4) jowls were treated. After the first treatment, GAIS responses for 24 jowls showed 5 jowls with vast improvement, 15 with moderate improvement, and 4 with no change. After the second session for 5 jowls in 3 patients, GAIS responses showed vast improvement in 4 jowls and moderate improvement in 1. Adverse events included induration (n = 4), bruising (n = 6), numbness (n = 2), pain (n = 5), redness (n = 3), edema (n = 9), and dysphagia (n = 1). CONCLUSION: Results of this early experience showed that DCA injections were safe and effective for nonsurgical jowl reduction.

Novel mechanism of the vascular protector prostacyclin: regulating microRNA expression.

Prostacyclin (PGI(2)) is a key vascular protector, metabolized from endogenous arachidonic acid (AA). Its actions are mediated through the PGI(2) receptor (IP) and nuclear receptor, peroxisome proliferator-activated receptor γ (PPARγ). Here, we found that PGI(2) is involved in regulating cellular microRNA (miRNA) expression through its receptors in a mouse adipose tissue-derived primary culture cell line expressing a novel hybrid enzyme gene (COX-1-10aa-PGIS), cyclooxygenase-1 (COX-1) and PGI(2) synthase (PGIS) linked with a 10-amino acid linker. The triple catalytic functions of the hybrid enzyme in these cells successfully redirected the endogenous AA metabolism toward a stable and dominant production of PGI(2). The miRNA microarray analysis of the cell line with upregulated PGI(2) revealed a significant upregulation (711, 148b, and 744) and downregulation of miRNAs of interest, which were reversed by antagonists of the IP and PPARγ receptors. Furthermore, we also found that the insulin-mediated lipid deposition was inhibited in the PGI(2)-upregulated adipocytes. The study also initiated a discussion that suggested that the endogenous PGI(2) inhibition of lipid deposition in adipocytes could involve miRNA-mediated inhibition of expression of the targeted genes. This indicated that PGI(2)-miRNA regulation could exist in broad pathophysiological processes involving PGI(2) (i.e., apoptosis, vascular inflammation, cancer, embryo implantation, and obesity).

Renal proximal tubules from old Fischer 344 rats grow into epithelial cells in cultures and exhibit increased oxidative stress and reduced D1 receptor function.

Earlier we reported defects in D1 receptor function in renal proximal tubules (RPTs) of aged Fischer 344 (F344) and obese Zucker rats. However, the defects in the receptor function in RPTs of obese Zucker rats do not pass onto primary cultures of RPTs from these animals. Here, we determined whether the defects in D1 receptor function in RPTs of aged F344 rats pass onto the primary cultures. RPTs from aged (24-mo) and adult (6-mo) F344 rats were grown into primary cultures. The microscopic studies showed that cells in cultures from adult and old rats were healthy as determined by the shape and size of the cells and nuclei. D1 receptor agonist SKF-38393 produced inhibition of (86)Rb (rubidium) uptake, index of Na-K-ATPase activity, in cells from adult rats, but this was reduced in old rats. Also, SKF-38393 increased the [(35)S]GTPgammaS binding, index of receptor activation, in the membranes of cells from adult rats but to a lesser extent from old rats. Furthermore, there was a downward trend in the levels of D1 receptor numbers and in the receptor proteins in old rats. Interestingly, gp(91phox) subunit of NADPH oxidase and cellular protein carbonyl levels (oxidative stress marker) were higher in cultures from old rats. These results show that RPTs from adult and old F344 rats grow into epithelial cells in cultures. Furthermore, cells in cultures from old rats are at a higher level of oxidative stress, which may be contributing to the reduced D1 receptor function in the cells from old compared with adult rats.

Involvement of non-conserved residues important for PGE2 binding to the constrained EP3 eLP2 using NMR and site-directed mutagenesis.

A peptide constrained to a conformation of second extracellular loop of human prostaglandin-E(2) (PGE(2)) receptor subtype3 (hEP3) was synthesized. The contacts between the peptide residues at S211 and R214, and PGE(2) were first identified by NMR spectroscopy. The results were used as a guide for site-directed mutagenesis of the hEP3 protein. The S211L and R214L mutants expressed in HEK293 cells lost binding to [(3)H]PGE(2). This study found that the non-conserved S211 and R214 of the hEP3 are involved in PGE(2) recognition, and implied that the corresponding residues in other subtype receptors could be important to distinguish the different configurations of PGE(2) ligand recognition sites.