Antitumor effect of BPR-DC-2, a novel synthetic cyclic cyanoguanidine derivative,involving the inhibition of MDR-1 expression and down-regulation of p-AKT and PARP-1 in lung cancer

In our previous study, a series of novel cyclic cyanoguanidine compounds, eg. 5-substituted 2-cyanoimino-4-imidazodinone and 2-cyanoimino-4- pyrimidinone derivatives have been successfully synthesized and showed remarkable cytotoxicity in several cancer cell lines. In this present study, it is our aim to screen more potential candidates among the cyclic pyridyl cyanoguanidine compounds (BPR-DC-1, 2, 3) by in vitro and in vivo studies for the therapy of lung cancer, alternatively. Our results showed that BPR-DC-2 significantly inhibited proliferation of tumor cells with an IC50 of 3.60 ± 1.27 and 14.81 ± 4.23 μM in human lung carcinoma cells, H69 and A549, respectively by the MTT assay at 48 hr; BPR-DC-2 also obviously suppressed the tumor proliferation and MDR-1 gene expression, even induced cell apoptosis in the ex vivo histocultured lung tumor. We further demonstrated that, in the nude mouse model of metastatic lung cancer, BPR-DC-2 could diminish the tumor mass, retard the progression of metastasis, and prolong the survival time. In addition, it was found that BPR-DC-2 exerted its anti-tumor effects through the inhibition of MDR-1 gene expression and down-regulation of tumor anti-apoptosis signals (activated p-AKT and over-expression of PARP-1) by western blotting analysis. In conclusion, in this present study we have demonstrated that BPR-DC-2, derived from a series of novel synthetic cyclic cyanoguanidine compounds, has proved its potential as an anti-tumor drug candidate in treating lung cancer.     

Activation of peroxisome proliferator-activated receptor-gamma by rosiglitazone protects human islet cells against human islet amyloid polypeptide toxicity by a phosphatidylinositol 3'-kinase-dependent pathway

BACKGROUND: Type 2 diabetes mellitus (T2DM) is characterized by a deficit in beta-cell mass, increased beta-cell apoptosis, and islet amyloid derived from islet amyloid polypeptide (IAPP). Human IAPP (h-IAPP) applied to beta-cells forms toxic oligomers that induce apoptosis. Thiazolidinediones, ligands of peroxisome proliferator-activated receptor-gamma (PPAR-gamma), can delay the onset of T2DM. OBJECTIVE: We questioned whether activation of endogenous PPAR-gamma in human islets by rosiglitazone (RSG) inhibits h-IAPP-induced islet cell death and, if so, by which mechanism. METHODS AND RESULTS: Vehicle or h-IAPP was applied to human islets with or without RSG (10 and 50 microM) for 48 h. A 2-fold increase in the number of terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick end labeling-positive nuclei was detected in h-IAPP-treated human islets (P < 0.001). RSG (10 and 50 microM) prevented h-IAPP-induced apoptosis in human islets (P < 0.001). Thioflavin T binding assays confirmed that this effect was not mediated by interference with h-IAPP oligomerization. Expression of dominant negative PPAR-gamma in human islets prevented the protective effect of RSG. RSG activation of PPAR-gamma resulted in downstream activation of the serine/threonine protein kinase Akt, an outcome that was inhibited by a specific phosphatidylinositol 3-kinase inhibitor, which ablated RSG protection against h-IAPP-induced islet cell apoptosis. CONCLUSION: We conclude that in human islets, activation of PPAR-gamma inhibits h-IAPP-induced islet cell apoptosis, and this action is at least in part mediated through activation of the phosphatidylinositol 3'-kinase-Akt cascade. If this action is present in vivo, then thiazolidinediones have the potential to decrease beta-cell apoptosis in T2DM and reduce loss of beta-cell mass.     

Identification of fungal pathogens from clinical specimens using multi-locus PCR coupled with electrospray ionization mass spectrometry

Polymerase chain reaction coupled with electrospray ionization mass spectrometry (PCR/ESI-MS) was successfully used to identify a variety of fungi, including mixed fungal species, from 10 of 12 clinical specimens (10 culture-negative) of biopsy tissues or body fluids from patients with fungal infections. The application of PCR/ESI-MS for identifying fungal pathogens is discussed.     

Childhood subacute inflammatory demyelinating polyneuropathy

Subacute inflammatory demyelinating polyneuropathy (SIDP) is an acquired immune-mediated peripheral polyneuropathy with clinical course between 4 weeks and 8 weeks. Rare childhood cases with SIDP had been described in the current literature. We report the first case of childhood SIDP in Taiwan with thorough clinical studies. All of the clinical presentations, laboratory data, electrophysiological studies, and image tools were compatible with childhood SIDP. Benign neurological recovery without relapse was correlated with electrophysiological evidence of demyelination predominantly.     

Remote real-time monitoring of free flaps via smartphone photography and 3G wireless Internet: a prospective study evidencing diagnostic accuracy

This prospective study was designed to compare the accuracy rate between remote smartphone photographic assessments and in-person examinations for free flap monitoring. One hundred and three consecutive free flaps were monitored with in-person examinations and assessed remotely by three surgeons (Team A) via photographs transmitted over smartphone. Four other surgeons used the traditional in-person examinations as Team B. The response time to re-exploration was defined as the interval between when a flap was evaluated as compromised by the nurse/house officer and when the decision was made for re-exploration. The accuracy rate was 98.7% and 94.2% for in-person and smartphone photographic assessments, respectively. The response time of 8 ± 3 min in Team A was statistically shorter than the 180 ± 104 min in Team B (P = 0.01 by the Mann-Whitney test). The remote smartphone photography assessment has a comparable accuracy rate and shorter response time compared with in-person examination for free flap monitoring.