Polyphenols in Inner Ear Neurobiology, Health and Disease: From Bench to Clinics.

There is substantial experimental and clinical interest in providing effective ways to both prevent and slow the onset of hearing loss. Auditory hair cells, which occur along the basilar membrane of the cochlea, often lose functionality due to age-related biological alterations, as well as from exposure to high decibel sounds affecting a diminished/damaged auditory sensitivity. Hearing loss is also seen to take place due to neuronal degeneration before or following hair cell destruction/loss. A strategy is necessary to protect hair cells and XIII cranial/auditory nerve cells prior to injury and throughout aging. Within this context, it was proposed that cochlea neural stem cells may be protected from such aging and environmental/noise insults via the ingestion of protective dietary supplements. Of particular importance is that these studies typically display a hormetic-like biphasic dose-response pattern that prevents the occurrence of auditory cell damage induced by various model chemical toxins, such as cisplatin. Likewise, the hormetic dose-response also enhances the occurrence of cochlear neural cell viability, proliferation, and differentiation. These findings are particularly important since they confirmed a strong dose dependency of the significant beneficial effects (which is biphasic), whilst having a low-dose beneficial response, whereas extensive exposures may become ineffective and/or potentially harmful. According to hormesis, phytochemicals including polyphenols exhibit biphasic dose-response effects activating low-dose antioxidant signaling pathways, resulting in the upregulation of vitagenes, a group of genes involved in preserving cellular homeostasis during stressful conditions. Modulation of the vitagene network through polyphenols increases cellular resilience mechanisms, thus impacting neurological disorder pathophysiology. Here, we aimed to explore polyphenols targeting the NF-E2-related factor 2 (Nrf2) pathway to neuroprotective and therapeutic strategies that can potentially reduce oxidative stress and inflammation, thus preventing auditory hair cell and XIII cranial/auditory nerve cell degeneration. Furthermore, we explored techniques to enhance their bioavailability and efficacy.

Impact of the -174 G > C IL-6 polymorphism on bioelectrical parameters in obese subjects after laparoscopic adjustable gastric banding.

BACKGROUND: Recent data demonstrated that the -174 G > C IL-6 polymorphism may account for differences in the therapeutic response to laparoscopic adjustable gastric banding (LAGB) surgery. OBJECTIVE: We investigated the impact of -174 G > C IL-6 polymorphism on weight loss, body composition, and fluid distribution changes in obese subjects after LAGB. DESIGN AND OUTCOME MEASURES: Twenty obese subjects were selected and studied at baseline and 3 months after LAGB. Genetic assessment of -174 G > C IL-6 polymorphism and anthropometric and bioelectrical impedance analysis were performed. RESULTS: At baseline, C(+) carriers had a lower extracellular water (ECW) and higher intra-CW, phase angle (PA), reactance X(c), and X(c)/height. LAGB surgery determined significant reductions in weight and BMI. After LAGB, in C(-) carriers, significant decreases in weight, BMI, and ECW and increases in BCM, BCMI, ICW, PA, and X(c)/H were highlighted. In C(+) carriers, significant reductions in weight, BMI, ICW, and PA and increases in ECW, Na/K, resistance (R), and R/height were obtained. Significant higher reductions in BMI and X(c)/H were observed in C(+) with respect to C(-) carriers. CONCLUSIONS: Genotyping of genetic variants, for example, the -174 G > C polymorphism of IL-6, gives the opportunity to predict therapeutic response, in terms of body composition outcomes after LAGB.

Limited fatty infiltration due to apoptosis in human degenerated temporomandibular joint disks: an immunohistochemical study.

In this study, we hypothesized that caspase 3, which plays a central role in the execution phase of cell apoptosis, could be involved in limiting fatty degeneration of the temporomandibular joint (TMJ) disks and therefore inhibit the TMJ disk tissue from completely degenerating into fatty tissue. Therefore, caspase 3 immunohistochemical expression in human TMJ degenerated disks was studied. Fifty-nine degenerated TMJ disks were stained with Harry's hematoxylin, and they were then examined with light microscopy to detect any pathologic changes typical of fatty degeneration. Sections from the same TMJ disk were immunostained also by a polyclonal anti-caspase 3 antibody. On morphologic observations, 11 disks of 59 degenerated ones also presented a fatty infiltration. Immunostaining with caspase 3 antibody was detected on adipocytes in the cytoplasm as well as the nuclei. Our results sustain the hypothesis that fatty degeneration is limited by apoptosis, being adipocytes immunolabeled by caspase 3 antibody. Hence, apart from the several factors that can trigger degeneration changes in TMJ disk, their appearance, spread, and permanence, at least for fatty degeneration, seem to be influenced by apoptosis.