FOXG1 promotes aging inner ear hair cell survival through activation of the autophagy pathway.

Presbycusis is the cumulative effect of aging on hearing. Recent studies have shown that common mitochondrial gene deletions are closely related to deafness caused by degenerative changes in the auditory system, and some of these nuclear factors are proposed to participate in the regulation of mitochondrial function. However, the detailed mechanisms involved in age-related degeneration of the auditory systems have not yet been fully elucidated.

The nuclear transcription factor FoxG1 affects the sensitivity of mimetic aging hair cells to inflammation by regulating autophagy pathways.

Inflammation is a self-defense response to protect individuals from infection and tissue damage, but excessive or persistent inflammation can have adverse effects on cell survival. Many individuals become especially susceptible to chronic-inflammation-induced sensorineural hearing loss as they age, but the intrinsic molecular mechanism behind aging individuals' increased risk of hearing loss remains unclear. FoxG1 (forkhead box transcription factor G1) is a key transcription factor that plays important roles in hair cell survival through the regulation of mitochondrial function, but how the function of FoxG1 changes during aging and under inflammatory conditions is unknown.

Treatment of autosomal dominant hearing loss by in vivo delivery of genome editing agents.

Although genetic factors contribute to almost half of all cases of deafness, treatment options for genetic deafness are limited. We developed a genome-editing approach to target a dominantly inherited form of genetic deafness. Here we show that cationic lipid-mediated in vivo delivery of Cas9-guide RNA complexes can ameliorate hearing loss in a mouse model of human genetic deafness.

Role of the Ubiquitin C-Terminal Hydrolase L1-Modulated Ubiquitin Proteasome System in Auditory Cortex Senescence.

Background/aims: According to recent studies, central auditory impairments are closely related to neurodegenerative diseases. However, the mechanism of central presbycusis remains unclear. Ubiquitin C-terminal hydrolase L1 (UCHL1) is important in maintaining proteasomal activity; however, the detailed mechanism has not yet been fully elucidated.

Sensitivity of spiral ganglion neurons to damage caused by mobile phone electromagnetic radiation will increase in lipopolysaccharide-induced inflammation in vitro model.

Background: With the increasing popularity of mobile phones, the potential hazards of radiofrequency electromagnetic radiation (RF-EMR) on the auditory system remain unclear. Apart from RF-EMR, humans are also exposed to various physical and chemical factors. We established a lipopolysaccharide (LPS)-induced inflammation in vitro model to investigate whether the possible sensitivity of spiral ganglion neurons to damage caused by mobile phone electromagnetic radiation (at specific absorption rates: 2, 4 W/kg) will increase.

Age-related changes in mitochondrial antioxidant enzyme Trx2 and TXNIP-Trx2-ASK1 signal pathways in the auditory cortex of a mimetic aging rat model: changes to Trx2 in the auditory cortex.

Age-associated degeneration in the central auditory system, which is defined as central presbycusis, can impair sound localization and speech perception. Research has shown that oxidative stress plays a central role in the pathological process of central presbycusis. Thioredoxin 2 (Trx2), one member of thioredoxin family, plays a key role in regulating the homeostasis of cellular reactive oxygen species and anti-apoptosis.

Increased p66Shc in the inner ear of D-galactose-induced aging mice with accumulation of mitochondrial DNA 3873-bp deletion: p66Shc and mtDNA damage in the inner ear during aging.

Aging has been associated with mitochondrial DNA damage. P66Shc is an age-related adaptor protein that has a substantial impact on mitochondrial metabolism through regulation of the cellular response to oxidative stress. Our study aimed to establish a D-galactose (D-gal)-induced inner ear aging mouse model and to investigate the potential role of p66Shc and its serine 36-phosphorylated form in the inner ear during aging by using this model.

The effect of overexpression of PGC-1α on the mtDNA4834 common deletion in a rat cochlear marginal cell senescence model.

Aging is a natural process usually defined as a progressive loss of function with an accumulation of senescent cells. The clinical manifestations of this process include age-related hearing loss (AHL)/presbycusis. Several investigations indicated the association between a mitochondrial common deletion (CD) (mtDNA 4977-bp deletion in humans, corresponding to 4834-bp deletion in rats) and presbycusis.

Mitochondrial transcription factor A overexpression and base excision repair deficiency in the inner ear of rats with D-galactose-induced aging.

Oxidative damage to mtDNA is associated with excessive reactive oxygen species production. The mitochondrial common deletion (mtDNA 4977-bp and 4834-bp deletion in humans and rats, respectively) is the most typical and frequent form of mtDNA damage associated with aging and degenerative diseases. The accumulation of the mitochondrial common deletion has been proposed to play a crucial role in age-related hearing loss (presbycusis).

Contribution of common deletion to total deletion burden in mitochondrial DNA from inner ear of d-galactose-induced aging rats.

Mitochondrial DNA (mtDNA) mutations, especially deletions, have been suggested to play an important role in aging and degenerative diseases. In particular, the common deletion in humans and rats (4977bp and 4834bp deletion, respectively) has been shown to accumulate with age in post-mitotic tissues with high energetic demands. Among numerous deletions, the common deletion has been proposed to serve as a molecular marker for aging and play a critical role in presbyacusis.

Increased mitochondrial DNA damage and decreased base excision repair in the auditory cortex of D-galactose-induced aging rats.

Aging has been associated with mitochondrial DNA (mtDNA) common deletion (CD). Age changes in the central auditory system are well known to affect speech perception. Base excision repair (BER) is the major type of DNA repair in mitochondria.

[Protection of cochlear function from aminoglycosides ototoxicity by manganese superoxide dismutase gene in aging rat].

Objective: determine the feasibility of manganese superoxide dismutase (MnSOD) gene therapy for protecting the cochlear function against aminoglycoside-induced oxidative stress in aging rats.

Methods: The aging model of SD rats were obtained with 8 weeks daily of D-gal (150 mg/kg per day) hypodermic injection. In the 9th week, amikacin (500 mg/kg per day) were injected intramuscularly into some aging SD rats.

[Comparison of gene transfer into the cochlea using adeno-associated virus versus adenovirus vectors].

Objective: To determine which of the two, recombinant adeno-associated viral vector 2 (rAAV2) and recombinant adenovirus vector 5 (rAd5), is more suitable for gene transfer in rodent cochlea.

Methods: The rAAV2-EGFP and rAd5-EGFP particles were injected into the perilymph through round window membrane. The target tissue accessibility, time course of expression, tissue toxicity of gene transfer and effects on hearing were evaluated.

[Oxidative stress experimental model of rat with stria vascularis marginal cells injury induced by hydrogen peroxide in vitro].

Objective: To set up the oxidative stress experimental model of rat cochlea with stria vascularis marginal cells injury induced by hydrogen peroxide in vitro.

Methods: Cultured marginal cells of rat were treated by 200, 300, 400, 600 and 800 micromol/L hydrogen peroxide (H(2)O(2)) for 0.5, 1, 2, 4, 16 and 24 hours, respectively.

[Sensitivity to the ototoxicity of kanamycin of the rat model for mimetic aging in the inner ear].

Objective: To research the animal model with mimetic aging effect in the inner ear predispose to the ototoxicity of kanamycin.

Methods: Fifty wistar rats were randomly divided into four groups: group A (D-galactose group, n = 14) were treated with hypodermic 5% D-galactose (150 mg x kg(-1) x d(-1)) for 8 weeks and then with intraperitoneal saline for 10 days; group B (D-galactose and kanamycin group, n = 14) were given the same dose of D-galactose but kanamycin (500 mg x kg(-1) x d(-1)) instead of saline; group C (kanamycin group, n = 12) were treated with saline for 8 weeks and then with intraperitoneal kanamycin for 10 days;group D (control group, n = 10) were given saline only. Auditory brainstem response (ABR) was used to detect the hearing threshold of rats and colorimetry was used to analyze the activity of the GSH-PX.

[Timed balance test and static posturography in the patients with unilateral vestibular hypofunction].

Objective: To investigate the balance function of the patients with unilateral vestibular hypofunction (UVH) by timed balance tests and static posturography (SPG).

Methods: Sixty-five subjects with UVH and 92 healthy subjects were taken the timed balance tests under differential stance including (1) standard Romberg test, (2) feet apart stance test, (3) tandem and (4) unilateral standing tests with eyes open and eyes closed. The average timing that subjects kept balance before falling in each standing conditions was recorded by stopwatch as the timed result.

[Clinical value of preoperative comprehensive evaluation of cataract surgery in age-related cataract].

Objective: To evaluate the clinical results, the selection of time and procedures of surgery and preoperative evaluation of the phacoemulsification or small incision cataract surgery with intraocular lens implantation (PSI) in senile cataract patients with cardiovascular disease.

Methods: The authors performed a retrospective study in 218 senior patients (255 eyes) with cardiovascular disease, which were treated by PSI in the past 5 years.

Results: Thirteen cases (14 eyes) did not have PSI due to surgical contraindication or impossible to tolerate the operation or impossible to obtain an improvement of visual acuity after operation.

Comparison of three methods for isolation of nucleic acids from membranate inner ear tissue of rats.

Background: Mitochondrial DNA mutations have been found in sensorineural deafness. The aim of this study was to compare three methods for extraction of nucleic acid from membranate inner ear tissue of rats.

Methods: Alkaline denaturation, a conventional phenol-chloroform method and Trizol reagent were respectively used to extract the slight nucleic acid from membranate inner ear tissue of rats.

The relation between D-galactose injection and mitochondrial DNA 4834 bp deletion mutation.

Since,D-galactose (D-gal) overload model has been used as a premature aging model, we hypothesized that it may also lead to accelerated aging in the inner ear. Furthermore, though the mitochondrial DNA (mtDNA) 4834 bp deletion mutation has been considered as the marker of aging, there is no information available in the literature concerning the mtDNA 4834 bp deletion mutation condition of the D-gal induced premature aging model. We investigate the changes in inner ear enzymatic activity, the occurring of mtDNA 4834 bp deletion in inner ear and other tissues and the relating hearing thresholds after the administration of high dosage (150 mg/kg per day) and low dosage (50 mg/kg per day) of D-gal to rats.

The effect of the mtDNA4834 deletion on hearing.

Mutations in mitochondrial DNA (mtDNA) are associated with diverse pathological states in humans, notably sensorineural deafness. In humans, mtDNA4977 deletion, known as common deletion, is thought to play a critical role in presbyacusis. A similar mtDNA deletion occurs in the naturally aging rats is mtDNA4834 deletion.

[Protective roles of vitamin E and coenzyme Q10 in the inner ear mitochondrial DNA 4834 bp deletion mutation of rats].

Objective: To explore the protective roles of vitamin E and coenzyme Q10 in the inner ear mitochondrial DNA 4834 bp deletion mutation of rats.

Methods: Forty-six Wistar rats were randomly divided into three groups. The rats of group A (18 rats) had admitted adriamycin 1 mg/kg by intraperitoneal injection twice a week and had taken vitamin E 50 mg/kg, coenzyme Q10 10 mg/kg orally everyday for three months.