Isabel Rodriguez

Sensorineural hearing loss (SNHL), characterized by damage to the inner ear or auditory nerve, is a prevalent auditory disorder. This study explores the potential of Castanopsis echinocarpa (CAE) as a therapeutic agent for SNHL. In vivo experiments were conducted using zebrafish and mouse models. Zebrafish with neomycin-induced ototoxicity were treated with CAE, resulting in otic hair cell protection with an EC₅₀ of 0.49 µg/mL and a therapeutic index of 1020. CAE treatment improved auditory function and protected cochlear sensory cells in a mouse model after noise-induced hearing loss (NIHL). RNA sequencing of NIHL mouse cochleae revealed that CAE up-regulates genes involved in neurotransmitter synthesis, secretion, transport, and neuronal survival. Real-time qPCR validation showed that NIHL decreased the mRNA expression of genes related to neuronal function, such as Gabra1, Gad1, Slc32a1, CaMK2b, CaMKIV, and Slc17a7, while the CAE treatment significantly elevated these levels. In conclusion, our findings provide strong evidence that CAE protects against hearing loss by promoting sensory cell protection and enhancing the expression of genes critical for neuronal function and survival.

Insulin resistance, which occurs when insulin levels are sufficiently high over a prolonged period, causing the cells to fail to respond normally to the hormone. As a system for insulin resistance and diabetes drug development, insulin-resistant rodent models have been clearly established, but there is a limitation to high-throughput drug screening. Recently, zebrafish have been identified as an excellent system for drug discovery and identification of therapeutic targets, but studies on insulin resistance models have not been extensively performed. Therefore, we aimed to make a rapid insulin-resistant zebrafish model that complements the existing rodent models. To establish this model, zebrafish were treated with 10 μM insulin for 48 h. This model showed characteristics of insulin-resistant disease such as damaged pancreatic islets. Then we confirmed the recovery of the pancreatic islets after pioglitazone treatment. In addition, it was found that insulin-resistant drugs have as significant an effect in zebrafish as in humans, and these results proved the value of the zebrafish insulin resistance model for drug selection. In addition, RNA sequencing was performed to elucidate the mechanism involved. KEGG pathway enrichment analysis of differentially expressed genes showed that insulin resistance altered gene expression due to the MAPK signaling and calcium signaling pathways. This model demonstrates the utility of the zebrafish model for drug testing and drug discovery in insulin resistance and diabetes.

Avocado oil is beneficial to human health and has been reported to have beneficial effects on sensorineural hearing loss (SNHL). However, the compounds in avocado oil that affect SNHL have not been identified. In this study, we identified 20 compounds from avocado oil, including two new and 18 known fatty acid derivatives, using extensive spectroscopic analysis. The efficacy of the isolated compounds for improving SNHL was investigated in an ototoxic zebrafish model. The two new compounds, namely (2R,4R,6Z)-1,2,4-trihydroxynonadec-6-ene and (2R,4R)-1,2,4-trihydroxyheptadecadi-14,16-ene (compounds 1 and 2), as well as compounds 7, 9, 14, 17 and 19 showed significant improvement in damaged hair cells in toxic zebrafish. These results led to the conclusion that compounds from avocado oil as well as oil itself have a regenerative effect on damaged otic hair cells in ototoxic zebrafish.

Ginger (Zingiber officinale Roscoe) and its active compounds (gingerols, shogaols and paradols) have been reported as having beneficial functions for several diseases, including diabetes. In this study, we revealed that the steaming process could enhance the anti-diabetic potential of ginger. To confirm the anti-diabetic effect of steamed ginger extract (GG03), we assessed pancreatic islets impaired by alloxan in zebrafish and demonstrated anti-hyperglycemic efficacy in a mouse model. The EC₅₀ values of ginger extract (GE) and GG03 showed that the efficacy of GG03 was greater than that of GE. In addition, LC₅₀ values demonstrated that GG03 had lower toxicity than GE, and the comparison of the Therapeutic Index (TI) proved that GG03 is a safer functional food. Furthermore, our data showed that GG03 significantly lowered hyperglycemia in a diabetic mouse model. HPLC was performed to confirm the change in the composition of steamed ginger. Interestingly, GG03 showed a 375% increase in 1-dehydro-6-gingerdione (GD) compared with GE. GD has not yet been studied much pharmacologically. Thus, we identified the protective effects of GD in the damaged pancreatic islets of diabetic zebrafish. We further assessed whether the anti-diabetic mechanism of action of GG03 and GD involves insulin secretion. Our results suggest that GG03 and GD might stimulate insulin secretion by the closure of K_ATP channels in pancreatic β-cells.

Sensorineural hearing loss (SNHL) is one of the most common causes of disability, affecting over 466 million people worldwide. However, prevention or therapy of SNHL has not been widely studied. Avocado oil has shown many health benefits but it has not yet been studied in regards to SNHL. Therefore, we aimed to investigate the efficacy of avocado oil on SNHL in vitro and in vivo and elucidate its mode of action. For the present study, we used enhanced functional avocado oil extract (DKB122). DKB122 led to recovery of otic hair cells in zebrafish after neomycin-induced otic cell damage. Also, DKB122 improved auditory sensory transmission function in a mouse model of noise induced-hearing loss and protected sensory hair cells in the cochlea. In addition, RNA sequencing was performed to elucidate the mechanism involved. KEGG pathway enrichment analysis of differentially expressed genes showed that DKB122 protected House Ear Institute-Organ of Corti 1 (HEI-OC1) cells against neomycin-related alterations in gene expression due to oxidative stress, cytokine production and protein synthesis.

Proper hydration is one of the major aims in haemodialysis (HD) and peritoneal dialysis (PD). Bioimpedance spectroscopy appears to be a promising method for the evaluation and follow up of the hydration status in dialysis patients (P). We compared body composition between stable patients on HD and PD after six months. An observational study with 62 P on HD and 19 P on PD was performed. Clinical, biochemical and bioimpedance parameters were analysed. In the comparative study, PD P were younger (50 ± 10 vs 57 ± 14 years, P=.031). The Charlson Comorbidity Index (4.8 ± 3 vs 7.5 ± 3, P<.001), time on dialysis (16.9 ± 18.01 vs 51.88 ± 68.79 months, P=.020) and C-Reactive Protein [3 (3-9.3) vs 5.25 (1-76.4)] were lower. Total protein levels (7.46 ± 0.44 vs 7.04 ± 0.55 g/dl, P=.005) and transferrin levels (205 ± 41 vs 185 ± 29 mg/dl, P=.024) were higher. BIS: Intracellular water (19.67 ± 3.61 vs 16.51 ± 3.36 litres, P=.010), lean tissue mass (LTM) (37.20 ± 8.65 vs 32.57 ± 8.72 kg, P=.029), total cellular mass (TCM) (20.53 ± 5.65 vs 17.56 ± 5.91 kg, P=.033), and bioelectrical impedance phase angle (Phi 50) (5.81 ± 0.86 vs 4.74 ± 0.98, P=.000) were higher than in HD P. Overhydration: 22% in HD y 10% in PD, in conditions referred to in methods. Six months later, PD P increased in weight (73.75 ± 12.27 vs 75.22 ± 11.87 kg, P=.027), total fat (FAT) (26.88 ± 10 vs 30.02 ± 10 kg, P=.011) and relative fat (Rel FAT) (35.75 ± 9.87 vs 39.34 ± 9.12, P=.010); and decreased in ICW (18.56 ± 3.45 vs 17.65 ± 3.69 l, P=.009), LTM (36.95 ± 8.88 vs 34 ± 9.70 kg, P=.008) and relative LTM (Rel LTM) (50.85 ± 12.33 vs 45.40 ± 11.95%, P=.012). In the multivariate analysis, weight variation (∆) was related to ∆ FAT (P < .001). We found a correlation between fat increase and lean tissue mass decrease. Six months later, in HD P, we observed a reduction in ECW (15.11 ± 2.45 vs 14.00 ± 2.45, P.001), without changes in other parameters. Bioelectrical impedance analysis facilitates the assessment of changes in body composition so as to correct dry weight and to introduce changes in treatment schedule..