Cichoric Acid May Play a Role in Protecting Hair Cells from Ototoxic Drugs.

Ototoxic hearing loss due to antibiotic medication including aminoglycosides and excess free radical production causes irreversible hair cell injury. Cichoric acid, a naturally occurring phenolic acid, has recently been found to exert anti-oxidative and anti-inflammatory properties through its free radical scavenging capacity. The present study aimed to investigate the protective effects of cichoric acid against neomycin-induced ototoxicity using transgenic zebrafish (pvalb3b: TagGFP). Our results indicated that cichoric acid in concentrations up to 5 µM did not affect zebrafish viability during the 2 h treatment period. Therefore, the otoprotective concentration of cichoric acid was identified as 5 µM under 2 h treatment by counting viable hair cells within the neuromasts of the anterior- and posterior-lateral lines in the study. Pretreatment of transgenic zebrafish with 5 µM of cichoric acid for 2 h significantly protected against neomycin-induced hair cell death. Protection mediated by cichoric acid was, however, lost over time. A terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and FM4-64 staining, respectively, provided in situ evidence that cichoric acid ameliorated apoptotic signals and mechanotransduction machinery impairment caused by neomycin. A fish locomotor test (distance move, velocity, and rotation frequency) assessing behavioral alteration after ototoxic damage revealed rescue due to cichoric acid pretreatment before neomycin exposure. These findings suggest that cichoric acid in 5 µM under 2 h treatment has antioxidant effects and can attenuate neomycin-induced hair cell death in neuromasts. Although cichoric acid offered otoprotection, there is only a small difference between pharmacological and toxic concentrations, and hence cichoric acid can be considered a rather prototypical compound for the development of safer otoprotective compounds.

Effect of multidisciplinary team care on the risk of recurrence in breast cancer patients: A national matched cohort study.

BACKGROUND: Cancer has been the leading cause of death in the past decade in Taiwan, with breast cancer being the most common type of cancer in females. Very few studies looked at the risk of recurrence in patients who received multidisciplinary team (MDT) care. We analyzed the influence of MDT on the risk of recurrence and death in breast cancer patients. METHOD: In this retrospective study, we included newly diagnosed patients from 2004 to 2010. The study included 9,266 breast cancer patients who were enrolled in MDT care and 9,266 patients who were not. The study used log-rank test to analyze patients' characteristics, hospital characteristics, cancer staging, and treatment methods to compare the recurrence rates in MDT care and non-MDT care participants. We used Cox proportional hazards model to examine the effect of MDT and associated factors on the risk of recurrence and mortality of breast cancer patients. RESULTS: Relative risk of recurrence was lower for patients who received MDT care than for patients who did not (HR, 0.84; 95%CI: 0.70-0.99) after matching. The mortality risk for breast cancer patients with relapse was 8.48 times (95%CI: 7.53-9.54) than that for patients without relapse. CONCLUSIONS: The relative risk of recurrence and death was significantly lower for breast cancer patients who received MDT care than for those who did not. We suggest that MDT care be implanted in the National Health Policy settings of breast cancer patients.

The Functional Role of CONNEXIN 26 Mutation in Nonsyndromic Hearing Loss, Demonstrated by Zebrafish Connexin 30.3 Homologue Model.

Nonsyndromic hearing loss (NSHL) is of great clinical importance, and mutations in the GJB2 gene and the encoded human CONNEXIN 26 (CX26) protein play important roles in the genetic pathogenesis. The CX26 p.R184Q mutation was shown to be a dominant-negative effect in our previous study. Previously, we also demonstrated that zebrafish Cx30.3 is orthologous to human CX26. In the present study, we established transgenic zebrafish models with mutated Cx30.3 specifically expressed in the supporting cells of zebrafish inner ears driven by the agr2 promoter, to demonstrate and understand the mechanism by which the human CX26 R.184 mutation causes NSHL. Our results indicated that significant structural changes in the inner ears of transgenic lines with mutations were measured and compared to wild-type zebrafish. Simultaneously, significant alterations of transgenic lines with mutations in swimming behavior were analyzed with the zebrafish behavioral assay. This is the first study to investigate the functional results of the CX26 p.R184Q mutation with in vivo disease models. Our work supports and confirms the pathogenic role of the CX26 p.R184Q mutation in NSHL, with a hypothesized mechanism of altered interaction among amino acids in the connexins.