Exploring compounds to be used as cosmetic agents that activate peroxisome proliferator-activated receptor alpha.

Objective: The human epidermis is formed by the proliferation and differentiation of keratinocytes adjacent to the basement membrane. The outermost layer, the stratum corneum, is equipped with a barrier function that prevents water evaporation, and intercellular lipids play an important role in this barrier function. When the barrier is functioning normally, evaporation is prevented; however, when barrier function is impaired, moisture evaporates, resulting in dry and rough skin.

Structural Basis for PPARα Activation by 1H-pyrazolo-[3,4-b]pyridine Derivatives.

Small-molecule agonism of peroxisome proliferator-activated receptor α (PPARα), a ligand-activated transcriptional factor involved in regulating fatty acid metabolism, is an important approach for treating dyslipidemia. Here, we determined the structures of the ligand-binding domain (LBD) of PPARα in complex with 1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid derivatives, which were recently identified as PPARα-selective activators with markedly different structures from those of the well-known PPARα agonists fibrates. The crystal structures of the complexes showed that they form a canonical hydrogen-bond network involving helix 12 in the LBD, which is thought to be essential for PPARα activation, as also observed for fibrates.

Structural development of 1H-pyrazolo-[3,4-b]pyridine-4-carboxylic acid derivatives as human peroxisome proliferator-activated receptor alpha (PPARα)-selective agonists.

We previously reported that 1H-pyrazolo-[3,4-b]pyridine-4-carboxylic acid derivative 6 is an agonist of human peroxisome proliferator-activated receptor alpha (hPPARα). Here, we prepared a series of 1H-pyrazolo-[3,4-b]pyridine-4-carboxylic acid derivatives in order to examine the structure-activity relationships (SAR). SAR studies clearly indicated that the steric bulkiness of the substituent on 1H-pyrazolo-[3,4-b]pyridine ring, the position of the distal hydrophobic tail part, and the distance between the distal hydrophobic tail part and the acidic head part are critical for hPPARα agonistic activity.

Discovery of peroxisome proliferator-activated receptor α (PPARα) activators with a ligand-screening system using a human PPARα-expressing cell line.

Peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor that belongs to the superfamily of nuclear hormone receptors. PPARα is mainly expressed in the liver, where it activates fatty acid oxidation and lipoprotein metabolism and improves plasma lipid profiles. Therefore, PPARα activators are often used to treat patients with dyslipidemia.

Favorable outcome of intraoperative radiotherapy to the primary site in patients with metastatic prostate cancer.

Background: The aim of this study was to determine whether local radiotherapy to the prostate by intraoperative radiotherapy (IORT) increases the overall and cancer-specific survival rates of patients with metastatic prostate cancer.

Methods: Between 1993 and 2000, 102 patients with prostate cancer were treated with a combination of (a) IORT of the prostate (25 or 30 Gy per fraction); (b) external beam radiotherapy of the prostate (30 Gy in 10 fractions), starting approximately 1 week post-operatively; and (c) endocrine treatment. Of these, 16 patients had stage D1 disease (D1 IORT group), 32 had stage D2 disease without visceral metastasis (D2 IORT group), and 38 had stage D2 disease without visceral metastasis and did not receive local therapy (D2 control group).

The processus vaginalis transection method is superior to the simple prophylactic procedure for prevention of inguinal hernia after radical prostatectomy.

Background: We compared retrospectively the efficacy of two methods for prevention of post-radical prostatectomy inguinal hernia: blunt dissection of the peritoneum at the internal inguinal ring, and isolation of the spermatic cord from the peritoneum (simple prophylactic procedure) and transection of the processus vaginalis.

Methods: Of the 367 patients who underwent open radical retropubic prostatectomy for clinically localized prostate cancer between February 2005 and March 2012 at Saitama Cancer Center Hospital, 344 patients whose follow-up period was more than 2 years were enrolled in this study. Of these patients, 178 patients received the simple prophylactic procedure and 57 underwent processus vaginalis transection.