Additional file 2: of Auditing sex- and gender-based medicine (SGBM) content in medical school curriculum: a student scholar model

Comparative Analysis of MS-2 Student Scholar Audit of SGBM Content in Texas Tech Medical School Curriculum to Key SGBM Topics Outlined in the Principles of Gender Specific Medicine, 2nd Ed. (PDF 137 kb

Intracellular Trafficking Pathways for Nuclear Delivery of Plasmid DNA Complexed with Highly Efficient Endosome Escape Polymers

Understanding the pathways for nuclear entry could see vast improvements in polymer design for the delivery of genetic materials to cells. Here, we use a novel diblock copolymer complexed with plasmid DNA (pDNA) to determine both its cellular entry and nuclear pathways. The diblock copolymer (A-C3) is specifically designed to bind and protect pDNA, release it at a specific time, but more importantly, rapidly escape the endosome. The copolymer was taken up by HEK293 cells preferentially via the clathrin-mediated endocytosis (CME) pathway, and the pDNA entered the nucleus to produce high gene expression levels in all cells after 48 h, a similar observation to the commercially available polymer transfection agent, PEI Max. This demonstrates that the polymers must first escape the endosome and then mediate transport of pDNA to the nucleus for occurrence of gene expression. The amount of pDNA within the nucleus was found to be higher for our A-C3 polymer than PEI Max, with our polymer delivering 7 times more pDNA than PEI Max after 24 h. We further found that entry into the nucleus was primarily through the small nuclear pores and did not occur during mitosis when the nuclear envelope becomes compromised. The observation that the polymers are also found in the nucleus supports the hypothesis that the large pDNA/polymer complex (size ∼200 nm) must dissociate prior to nucleus entry and that cationic and hydrophobic monomer units on the polymer may facilitate active transport of the pDNA through the nuclear pore

Additional file 2: of Clinical efficacy and IL-17 targeting mechanism of Indigo naturalis as a topical agent in moderate psoriasis

Enrichment of ingenuity pathways by gene signature from a predominately White psoriasis population [27]. (DOCX 18 kb

Additional file 3: of Clinical efficacy and IL-17 targeting mechanism of Indigo naturalis as a topical agent in moderate psoriasis

Enrichment of ingenuity pathways by gene signature of Indigo naturalis treatment of moderate psoriasis from our study population. (DOCX 23 kb

Additional file 1: of Clinical efficacy and IL-17 targeting mechanism of Indigo naturalis as a topical agent in moderate psoriasis

Enrichment of ingenuity pathways by moderate psoriasis gene signature from our study population. (DOCX 22 kb

Discovery of Imigliptin, a Novel Selective DPP‑4 Inhibitor for the Treatment of Type 2 Diabetes

We report our discovery of a novel series of potent and selective dipeptidyl peptidase IV (DPP-4) inhibitors. Starting from a lead identified by scaffold-hopping approach, our discovery and development efforts were focused on exploring structure–activity relationships, optimizing pharmacokinetic profile, improving <i>in vitro</i> and <i>in vivo</i> efficacy, and evaluating safety profile. The selected candidate, Imigliptin, is now undergoing clinical trial

Multivalent Antiviral XTEN–Peptide Conjugates with Long in Vivo Half-Life and Enhanced Solubility

XTENs are unstructured, nonrepetitive protein polymers designed to prolong the in vivo half-life of pharmaceuticals by introducing a bulking effect similar to that of poly­(ethylene glycol). While XTEN can be expressed as a recombinant fusion protein with bioactive proteins and peptides, therapeutic molecules of interest can also be chemically conjugated to XTEN. Such an approach permits precise control over the positioning, spacing, and valency of bioactive moieties along the length of XTEN. We have demonstrated the attachment of T-20, an anti-retroviral peptide indicated for the treatment of HIV-1 patients with multidrug resistance, to XTEN. By reacting maleimide-functionalized T-20 with cysteine-containing XTENs and varying the number and positioning of cysteines in the XTENs, a library of different peptide–polymer combinations were produced. The T-20-XTEN conjugates were tested using an in vitro antiviral assay and were found to be effective in inhibiting HIV-1 entry and preventing cell death, with the copy number and spacing of the T-20 peptides influencing antiviral activity. The peptide–XTEN conjugates were also discovered to have enhanced solubilities in comparison with the native T-20 peptide. The pharmacokinetic profile of the most active T-20-XTEN conjugate was measured in rats, and it was found to exhibit an elimination half-life of 55.7 ± 17.7 h, almost 20 times longer than the reported half-life for T-20 dosed in rats. As the conjugation of T-20 to XTEN greatly improved the in vivo half-life and solubility of the peptide, the XTEN platform has been demonstrated to be a versatile tool for improving the properties of drugs and enabling the development of a class of next-generation therapeutics