Human CDKN1B blocking peptide

Flavonoids are phenolic substances with chemo-preventive and chemotherapeutic properties. They are widely found in fruits and vegetables. The polyphenols quercetin and curcumin have antioxidant, anti-inflammatory, anti-carcinogenic, and pro-apoptotic properties. They were successfully used against different human cancers, especially chronic myeloid leukemia cancer cells. We have previously investigated anti-proliferative and apoptotic effects of quercetin and curcumin combination in K562 cells. Our data showed that they had beneficial synergistic effects. Based on these findings, we aimed to clarify signaling pathways involved in synergistic combination treatment with quercetin and curcumin in these cells. Proteins were investigated by Western blotting and by confocal microscopy. Changes in several genes in 10 different pathways related to cell proliferation, apoptosis, cell cycle, inflammation, hypoxia and oxidative stress were observed. Combination of quercetin and curcumin was effective on genes that were particularly related to p53, NF-kappa B and TGF-alpha pathways. Down-regulatory (CDKN1B, AKT1, IFN-gamma) and up-regulatory (BTG2, CDKN1A, FAS) effects on genes and related protein expressions may provide a multi-targeted therapy potential for chronic myeloid leukemia cancer cells without affecting healthy cells.

Insulin-like peptide 3 (INSL3) is an important hormone for testicular descent during embryonic development and a factor for assessing functional status of Leydig cells of testes, but there is limited number of equine studies. Anti-Mullerian hormone (AMH) is a useful diagnostic marker for cryptorchidism in horses. This study aimed to compare serum concentrations and testicular expression intensity of INSL3 and AMH in intact and cryptorchid male horses. Serum INSL3 concentrations in intact (n = 9; mean +/- SEM, 19.9 +/- 5.9 ng/mL) and noncastrated unilateral cryptorchid (UC) male horses (n = 16; mean +/- SEM, 16.8 +/- 4.1 ng/mL) were higher compared with hemicastrated unilateral cryptorchid (HCUC) male horses (n = 9; mean +/- SEM, 3.8 +/- 0.7 ng/mL) (P < 0.05). And serum INSL3 in bilateral cryptorchid (BC) male horses (n = 4; 1.9 +/- 0.4; mean +/- SEM, ng/mL) were lower compared with intact male horses (P < 0.05). Serum AMH concentrations in BC male horses (n = 3; mean +/- SEM, 30.6 +/- 4.8 ng/mL) were higher compared with intact male horses (n = 5; mean +/- SEM, 12.2 +/- 3.9 ng/mL) (P < 0.05). Immunostaining of scrotal and cryptorchid testis showed that Sertoli cells were positive for AMH, and Leydig cells were positive for INSL3. Staining intensity of AMH was higher in cryptorchid testis than in scrotal testis (P < 0.05). Furthermore, AMH expression intensity was higher in abdominal testis than in inguinal testis (P < 0.05). Immunostaining intensity of INSL3 in the testis was positively correlated with serum INSL3 (r, 0.7; P < 0.01), seminiferous tubule area (r, 0.727; P < 0.01), and Johnsen score for spermatogenesis (r, 0.604; P < 0.05), whereas immunostaining intensity of AMH in the testis was negatively correlated with seminiferous tubule area (r,-0.814; P < 0.01) and Johnsen score for spermatogenesis (r,-0.807; P < 0.01). Our findings suggested that AMH is a good biomarker for diagnosing cryptorchidism in male horses, in addition to INSL3 values to assess the testis of intact and cryptorchid male horses. (C) 2020 Elsevier Inc. All rights reserved.