Circulating GDF-15: a biomarker for metabolic dysregulation and aging in people living with HIV.

Despite effective control of HIV replication by antiretroviral therapy (ART), a significant number of people living with HIV (PLWH) fail to achieve complete immune reconstitution and thus are deemed immune non-responders (INRs). Compared with immune responders (IRs) who have restored their CD4 T cell numbers and functions, CD4 T cells from these INRs exhibit prominent mitochondrial dysfunction and premature aging, which play a major role in increasing the incidence of non-AIDS, non-communicable diseases (NCDs). To date, there are no reliable biomarkers that can be used to typify and manage PLWH, especially INRs with non-AIDS NCDs.

Potent human uric acid transporter 1 inhibitors: in vitro and in vivo metabolism and pharmacokinetic studies.

Human uric acid transporter 1 (hURAT1; SLC22A12) is a very important urate anion exchanger. Elevated urate levels are known to play a pivotal role in cardiovascular diseases, chronic renal disease, diabetes, and hypertension. Therefore, the development of potent uric acid transport inhibitors may lead to novel therapeutic agents to combat these human diseases.

A specific molecular beacon probe for the detection of human prostate cancer cells.

The small-molecule, water-soluble molecular beacon probe 1 is hydrolyzed by the lysate and living cells of human prostate cancer cell lines (LNCaP), resulting in strong green fluorescence. In contrast, probe 1 does not undergo significant hydrolysis in either the lysate or living cells of human nontumorigenic prostate cells (RWPE-1). These results, corroborated by UV-Vis spectroscopy and fluorescent microscopy, reveal that probe 1 is a sensitive and specific fluorogenic and chromogenic sensor for the detection of human prostate cancer cells among nontumorigenic prostate cells and that carboxylesterase activity is a specific biomarker for human prostate cancer cells.

Metabolism and pharmacokinetic studies of JPH203, an L-amino acid transporter 1 (LAT1) selective compound.

Many primary human tumors and tumor cell lines highly express human L-type amino acid transporter 1 (hLAT1); cancerous cells in vivo are strongly linked to LAT1 expression. Synthetic chemistry and in vitro screening efforts have afforded a variety of novel and highly hLAT1 selective compounds, such as JPH203 1. In a recent report, we demonstrated that 1 has potent in vitro and in vivo activity.

Investigating idebenone and idebenone linoleate metabolism: in vitro pig ear and mouse melanocyte studies.

Objective: The aim of this study was to investigate inherent in vitro permeability, metabolism, and cytotoxicity of idebenone - an active used to protect skin as an anti-aging agent - and compare it to idebenone linoleate.

Methods: Idebenone and idebenone linoleate were investigated in pig ear skin and melanoma (B16: F10 mouse) cells. Diffusion experiments were conducted at 37 degrees C (bath temperature) using Franz diffusion cells.

Inhibiting efflux with novel non-ionic surfactants: Rational design based on vitamin E TPGS.

Tocopheryl Polyethylene Glycol Succinate 1000 (TPGS 1000) can inhibit P-glycoprotein (P-gp); TPGS 1000 was not originally designed to inhibit an efflux pump. Recent work from our laboratories demonstrated that TPGS activity has a rational PEG chain length dependency. In other recent work, inhibition mechanism was investigated and appears to be specific to the ATPase providing P-gp energy.