miR-195 inhibits the proliferation and migration of chondrocytes by targeting GIT1.

Previous studies have demonstrated that G-protein coupled receptor kinase interacting protein-1 (GIT1) and microRNAs (miRNAs) serve an important role in chondrocyte proliferation and migration. However, a limited number of studies conducted thus far have investigated the association between GIT1 and miRNAs. In the present study, putative miR­195 binding sites in the GIT1 3'­untranslated region were identified using common bioinformatic algorithms (miRanda, TargetScan, miRBase and miRWalk), and it was demonstrated that they may be involved in regulating GIT1 expression. Following transfection of miR­195 mimics in chondrocytes, the expression of GIT1 was significantly reduced, whereas the expression was significantly increased following transfection with miR­195 inhibitors. In addition, the results of the current study demonstrated that increased miR­195 expression may downregulate chondrocyte proliferation and reduce cell migration. However, chondrocyte proliferation and migration was enhanced following suppression of miR­195 expression. Furthermore, upon co­transfection of miR­195 and GIT1 expression vectors, the inhibitory effect of miR­195 on chondrocyte proliferation and migration was attenuated. Therefore, miR­195 may affect chondrocyte proliferation and migration via targeted regulation of GIT1 expression. The results of the current study provide novel evidence for the regulatory mechanisms of miRNAs in bone and cartilage tissues, which may facilitate further research and provide a greater understanding of different osteoarticular diseases.

Association between histone deacetylases and the loss of cochlear hair cells: Role of the former in noise-induced hearing loss.

Noise-induced hearing loss (NIHL) is one of the most frequent disabilities in industrialized countries. It has been demonstrated that hair cell loss in the auditory end organ may account for the majority of ear pathological conditions. Previous studies have indicated that histone deacetylases (HDACs) play an important role in neurodegenerative diseases, including hearing impairment, in older persons. Thus, we hypothesized that the inhibition of HDACs would prevent hair cell loss and, consequently, NIHL. In the present study, a CBA/J mouse model of NIHL was established. Following an injection with the HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA), the expression levels of HDAC1, HDAC4 and acetyl-histone H3 (Lys9) (H3-AcK9) were measured. The number of hair cells was quantified and their morphology was observed. The results revealed that 1 h following exposure to 110 dB SPL broadband noise, there was a significant increase in HDAC1 and HDAC4 expression, and a marked decrease in the H3-AcK9 protein levels, as shown by western blot analysis. Pre-treatment with SAHA significantly inhibited these effects. Two weeks following exposure to noise, the mice exhibited significant hearing impairment and an obvious loss in the number of outer hair cells. An abnormal cell morphology with cilia damage was also observed. Pre-treatment with SAHA markedly attenuated these noise-induced effects. Taken together, the findings of our study suggest that HDAC expression is associated with outer hair cell function and plays a significant role in NIHL. Our data indicate that SAHA may be a potential therapeutic agent for the prevention of NIHL.

Histone deacetylase inhibitor sodium butyrate attenuates gentamicin-induced hearing loss in vivo.

OBJECTIVE: Although histone deacetylase (HDAC) inhibition has been shown to protect against gentamicin (GM)-induced hearing loss in vitro, its protective effect has not been proven in vivo. In the present study, the aim was to investigate the protective effect of sodium butyrate (NaB), a specific HDAC inhibitor, on GM-induced ototoxicity in vivo. METHODS: Forty 8-week-old albino guinea pigs were divided into two experimental groups. Group 1 (n=10) underwent bilateral ear surgery to place sponges (0.3mm(3)) permeated with NaB (10µl, 100mg/ml) and physiological saline (10µl; control) in the right and left round window niches, respectively. The sponges were left in place for 15days to evaluate the effects of NaB at the applied concentration. Group 2 (n=30) underwent the same bilateral ear surgery described for Group 1, except three days after surgery, the animals received intramuscular GM injections (200mg/kg/day) for 5 consecutive days. Seven days after the final GM injection, the protective effects of NaB were examined. RESULTS: After 15days of NaB treatment (10µl, 100mg/ml), an increase in histone acetylation was detected in Corti organ samples. Auditory brainstem response (ABR) threshold shifts and hair cell loss were also reduced in NaB-treated ears after GM administration. Furthermore, GM treatment increased HDAC1 expression in outer hair cells (OHCs) in vivo, and NaB blocked this action. CONCLUSION: GM increases HDAC1 expression in OHCs, and NaB is able to block this action. Thus, it appears that the HDAC inhibitor, NaB, attenuates GM-induced hearing loss in guinea pigs.

[Multi-center study on the treatment of sudden total deafness].

OBJECTIVE: To assess the results of drug therapy in patients with severe idiopathic sudden sensorineural hearing loss (ISSHL) with total frequency hearing loss. METHODS: A prospective randomized, single blind, multi-center clinical trial was designed. The untreated patients with ISSHL were included, who had severe hearing loss (pure tone audiometry showed patients had total frequency hearing loss, and their mean auditory threshold of 500, 1000, 2000, 4000 Hz was beyond 81 dB HL), age between 18 to 65 years old, and within 14 days of the onset . The patients were divided into one of the four drug groups [batroxobin, batroxobin + ginkgo biloba leaves extract (EGb), batroxobin + EGb + glucocorticoids, EGb + glucocorticoids] according to the random table, and receive treatment. RESULTS: Totally 276 patients with unilateral severe ISSHL were included from 33 hospitals, from August 2007 to October 2011. Among them, male patients accounted for 135 (48.91%), female 141 (51.09%); the average age was (41.7 ± 13.3)years. Forty cases were recovered (14.49%), 78 cases had marked effective (28.26%), 76 cases were effective (27.54%), 82 cases were in-effective (29.71%), and the total effective rate was 70.29%. Among four drug groups, the separate effective rate were 73.33%, 61.43%, 78.31% and 67.95% respectively, no significant difference was found between groups (χ(2) = 9.97,P = 0.62). Among the four groups, the separate cure rate for hearing loss were 11.11%, 12.86%, 16.87% and 15.38%, the glucocorticoid groups were significantly better than those not used. Among severe sudden deafness patients, 92.39% cases accompanied with tinnitus, 44.93% with dizziness (or vertigo), 50.36% with ear stuffy. There had no significant difference between the four groups with accompanied symptoms (all P > 0.05). CONCLUSIONS: It is value to give active treatment to sever sudden deafness patients because of an effective rate of 70%. However, the doctors and patients should be mind of a cure rate of only 14%. Steroids are recommended bacause it may play a role in the improvement rate.

Protective role of hydrogen sulfide against noise-induced cochlear damage: a chronic intracochlear infusion model.

BACKGROUND: A reduction in cochlear blood flow plays an essential role in noise-induced hearing loss (NIHL). The timely regulation of cochlear perfusion determines the progression and prognosis of NIHL. Hydrogen sulfide (H(2)S) has attracted increasing interest as a vasodilator in cardiovascular systems. This study identified the role of H(2)S in cochlear blood flow regulation and noise protection. METHODOLOGY/PRINCIPAL FINDINGS: The gene and protein expression of the H(2)S synthetase cystathionine-γ-lyase (CSE) in the rat cochlea was examined using immunofluorescence and real-time PCR. Cochlear CSE mRNA levels varied according to the duration of noise exposure. A chronic intracochlear infusion model was built and artificial perilymph (AP), NaHS or DL-propargylglycine (PPG) were locally administered. Local sodium hydrosulfide (NaHS) significantly increased cochlear perfusion post-noise exposure. Cochlear morphological damage and hearing loss were alleviated in the NaHS group as measured by conventional auditory brainstem response (ABR), cochlear scanning electron microscope (SEM) and outer hair cell (OHC) count. The highest percentage of OHC loss occurred in the PPG group. CONCLUSIONS/SIGNIFICANCE: Our results suggest that H(2)S plays an important role in the regulation of cochlear blood flow and the protection against noise. Further studies may identify a new preventive and therapeutic perspective on NIHL and other blood supply-related inner ear diseases.

Determining leak locations during transnasal endoscopic repair of cerebrospinal fluid rhinorrhea.

OBJECTIVE: For transnasal endoscopic repair procedures to be successful, it is critical to identify leak locations during surgery. We aim to evaluate different methods to more accurately detect leak locations during the endoscopic repair of cerebrospinal fluid rhinorrhea. MATERIALS AND METHODS: We performed a retrospective chart review of 39 cases undergoing endoscopic repair of cerebrospinal fluid rhinorrhea. The leak locations were determined using preoperative nasal endoscopy, radioisotope scanning, the intraoperative image-guided system, and intraspinal normal saline injection. RESULTS: The cerebrospinal fluid leak location was in the sphenoidal sinus in 9 cases, the ethmoid sinus in 17 cases, and in the frontal sinus in 1 case. The leak locations could not be determined in the remaining 12 cases using this method alone. For these 12 cases, after the ethmoid sinus was opened and the lateral wall of sphenoidal sinus was exposed with the aid of the intraoperative image-guided system, outflow of cerebrospinal fluid was present on the lateral wall of sphenoidal sinus (in 1 case) and on the ethmoid roof (in 3 cases). Furthermore, using intraspinal saline injection (20-30 ml), leak locations were detected in the sphenoidal sinus (2 cases) and in ethmoid sinus (6 cases) of the remaining cases. CONCLUSION: For cerebrospinal fluid rhinorrhea patients whose leak locations are difficult to determine, surgeons can increase their operative success rates by performing radioisotope scanning and intraspinal saline injections and by using image-guided surgical systems. These safe and effective methods can be used to successfully detect leak locations during transnasal endoscopic repair of cerebrospinal fluid leaks.