Olfactory ensheathing cells promote nerve regeneration and functional recovery after facial nerve defects.

Olfactory ensheathing cells from the olfactory bulb and olfactory mucosa have been found to increase axonal sprouting and pathfinding and promote the recovery of vibrissae motor performance in facial nerve transection injured rats. However, it is not yet clear whether olfactory ensheathing cells promote the reparation of facial nerve defects in rats. In this study, a collagen sponge and silicone tube neural conduit was implanted into the 6-mm defect of the buccal branch of the facial nerve in adult rats. Olfactory ensheathing cells isolated from the olfactory bulb of newborn Sprague-Dawley rats were injected into the neural conduits connecting the ends of the broken nerves, the morphology and function of the regenerated nerves were compared between the rats implanted with olfactory ensheathing cells with the rats injected with saline. Facial paralysis was assessed. Nerve electrography was used to measure facial nerve-induced action potentials. Visual inspection, anatomical microscopy and hematoxylin-eosin staining were used to assess the histomorphology around the transplanted neural conduit and the morphology of the regenerated nerve. Using fluorogold retrograde tracing, toluidine blue staining and lead uranyl acetate staining, we also measured the number of neurons in the anterior exterior lateral facial nerve motor nucleus, the number of myelinated nerve fibers, and nerve fiber diameter and myelin sheath thickness, respectively. After surgery, olfactory ensheathing cells decreased facial paralysis and the latency of the facial nerve-induced action potentials. There were no differences in the general morphology of the regenerating nerves between the rats implanted with olfactory ensheathing cells and the rats injected with saline. Between-group results showed that olfactory ensheathing cell treatment increased the number of regenerated neurons, improved nerve fiber morphology, and increased the number of myelinated nerve fibers, nerve fiber diameter, and myelin sheath thickness. In conclusion, implantation of olfactory ensheathing cells can promote regeneration and functional recovery after facial nerve damage in rats.

Therapeutic ultrasound potentiates the anti-nociceptive and anti-inflammatory effects of curcumin to postoperative pain via Sirt1/NF-κB signaling pathway.

Background: Postoperative pain has well defined and is perceived by patients as one of the most obnoxious aspects of surgical pain. The aim of this study was to determine whether the combination of Therapeutic ultrasound (TUS) and Curcumin (CUR) resulted in an enhancement of their pain relieving activities in a rat model of postoperative pain. Methods: We explored the effect of these treatment and their interaction with signal transduction pathways involved in inflammatory. In this study, TUS and CUR alone or in combination were administered prior to or simultaneously with or after the incisional surgery. Results: At the start time of administration, we observed that the TUS plus CUR treatment reduced the mean paw withdrawal threshold more efficiently than CUR alone. Then we demonstrated that TUS potentiates the antinociceptive effect of CUR in a rat model of chronic postoperative pain and that the combination could facilitate the recovery of surgical pain. However, preventive value was not statistically significant when the treatments were given prior to the incisional surgery. We provide evidence that TUS plus CUR administrations were safe and significantly reduced the ED50 compared to treatment with the single CUR treatment in rats. TUS plus CUR administrations decreases incisional surgery induced activation of inflammatory cells and down-regulation of chemokines and proinflammatory cytokines, MCP-1, MIP-1α, IL-1ß, and TNF-α through regulating Sirt1/NF-κB signaling pathway. Conclusions: Taken together, our results indicate that the combinations of TUS and CUR can be more effective in the anti-nociceptive effects than the treatment with CUR alone.

Curcumin induces G2/M cell cycle arrest and apoptosis of head and neck squamous cell carcinoma in vitro and in vivo through ATM/Chk2/p53-dependent pathway.

Studies have demonstrated that curcumin (CUR) exerts its tumor suppressor function in a variety of human cancers including head and neck squamous cell carcinoma (HNSCC). However, the exact underlying molecular mechanisms remain obscure. Here, we aim to test whether CUR affects ATM/Chk2/p53 signaling pathway, leading to the induction of cell cycle arrest, inhibition of angiogenesis of HNSCC in vitro and in vivo. To this end, we conducted multiple methods such as MTT assay, Invasion assay, Flow cytometry, Western blotting, RT-PCR, and transfection to explore the functions and molecular insights of CUR in HNSCC. We observed that CUR significantly induced apoptosis and cell cycle arrest, inhibited angiogenesis in HNSCC. Mechanistically, we demonstrated that CUR markedly up-regulated ATM expression and subsequently down-regulated HIF-1α expression. Blockage of ATM production totally reversed CUR induced cell cycle arrest as well as anti-angiogenesis in HNSCC. Moreover, our results demonstrated that CUR exerts its antitumor activity through targeting ATM/Chk2/p53 signal pathway. In addition, the results of xenograft experiments in mice were highly consistent with in vitro studies. Collectively, our findings suggest that targeting ATM/Chk2/p53 signal pathway by CUR could be a promising therapeutic approach for HNSCC prevention and therapy.

Olfactory epithelium neural stem cell implantation restores noise-induced hearing loss in rats.

OBJECTIVE: In this study, we aimed to elucidate the restorative effects of olfactory epithelium neural stem cells (oe-NSCs) implantation on noise-induced hearing loss and establish their mechanism of action. METHODS: To model hearing loss, rats were subjected to consecutive seven-day noise exposure. Then, oe-NSCs were implanted into cochlear tissue by retroauricular approach. Auditory brainstem response (ABR) method was used to evaluate the hearing function. Immunohistochemical staining was utilized to determine cell survival and migration of oe-NSCs. After IL-1ß stimulation, nerve growth factor (NGF), neurotrophin-3 (NT-3), and NT-4 levels were evaluated in oe-NSCs. The protective action of oe-NSCs against hydrogen peroxide-induced cell injury was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). RESULTS: oe-NSCs implantation into cochlear tissues ameliorated the noise-induced hearing impairment (p<0.05). After implantation, green fluorescent cells were observed in an even suspension in the lymph fluid of the cochlea, and 65% of the GFP(+) cells reached the cochlear duct wall three days after implantation, but did not expand to the Corti-organ. After IL-1ß stimulation, olfactory epithelial stem cell increased their secretion of NGF and NT-3 (p<0.05), but not that of NT-4. TUNEL assay results revealed that oe-NSCs co-culturing with injured neurons reduced the apoptotic cell death induced by hydrogen peroxide. CONCLUSION: After transplantation into the inner ear, oe-NSCs not only survived, but also migrated around the spiral ganglion neurons (SGNs) in Rosenthal's canal (RC). Hearing loss induced by noise exposure was restored after oe-NSCs implantation. Mechanically, oe-NSCs secreted NGF and NT-3, which likely contributed to the prevention of neuronal injury. This study provides novel data in support of the effective action of implanted oe-NSCs in the restoration of noise-induced hearing loss in a rat model.

Curcumin as therapeutics for the treatment of head and neck squamous cell carcinoma by activating SIRT1.

SIRT1 is one of seven mammalian homologs of Sir2 that catalyzes NAD(+)-dependent protein deacetylation. The aim of the present study is to explore the effect of SIRT1 small molecule activator on the anticancer activity and the underlying mechanism. We examined the anticancer activity of a novel oral agent, curcumin, which is the principal active ingredient of the traditional Chinese herb Curcuma Longa. Treatment of FaDu and Cal27 cells with curcumin inhibited growth and induced apoptosis. Mechanistic studies showed that anticancer activity of curcumin is associated with decrease in migration of HNSCC and associated angiogenesis through activating of intrinsic apoptotic pathway (caspase-9) and extrinsic apoptotic pathway (caspase-8). Our data demonstrating that anticancer activity of curcumin is linked to the activation of the ATM/CHK2 pathway and the inhibition of nuclear factor-κB. Finally, increasing SIRT1 through small molecule activator curcumin has shown beneficial effects in xenograft mouse model, indicating that SIRT1 may represent an attractive therapeutic target. Our studies provide the preclinical rationale for novel therapeutics targeting SIRT1 in HNSCC.

Botox transient treatment of tinnitus due to stapedius myoclonus: case report.

OBJECT: To explore the feasibility of using botulinum toxin type A (BTXA) to treat tinnitus due to stapedius myoclonus. METHOD: A piece of gelfoam containing BTXA (25 U/ml) was placed, through a perforation in tympanic membrane, into the middle ear cavity of a patient suffering from tinnitus due to stapedius myoclonus. RESULTS: The tinnitus disappeared on the second day after the BTXA treatment. The patient was free of symptoms during a 3-month follow-up period. Tinnitus reappeared at 4 months, and disappeared after second BTXA local treatment. CONCLUSION: Local BTXA treatment may be considered as a treatment for tinnitus caused by stapedius myoclonus.

[MRNA expression of complement C3 and C4 in rat nasal mucosa with allergic rhinitis].

OBJECTIVE: To investigate the level of mRNA expression of complement C3 and C4 in rat nasal mucosa and to reveal the relationship with the pathogenesis of allergic rhinitis (AR) . METHODS: Twenty healthy SD rats were randomly divided into AR group and control group, 10 rats for each group. Ten rats was sensitized and intranasally challenged by ovalbumin and Al (OH)3 (as supplement) as allergic rhinitis models, and the control group was treated by saline. RT-PCR was performed to investigate the level of mRNA expression of complement C3 and C4 in nasal mucosa of both groups. RESULTS: C3 and C4 mRNA were detected in both groups. The relative intensity of gene expression was measured. The relative intensity of C3 mRNA expression was 6183+/-1376 in AR group, 4444+/-989 in control group, C4 mRNA was 4398 +/-948 in AR group, and 2771+/-407 in control group. Expression of C3 and C4 in AR group was higher than that of the controls ( P < 0. 05) . CONCLUSION: The high level of C3 and C4 mRNA expression in nasal mucosa of rats with allergic rhinitis suggests that C3 and C4 are involved in the immunopathology of allergic rhinitis. The result implies that complement system involved in the rat's allergic rhinitis is possibly activated through the classical pathway.