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In the original publication [...].
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To date, the effect of resveratrol on tinnitus has not been reported. The attenuative effects of resveratrol (RSV) on a salicylate-induced tinnitus model were evaluated by in vitro and in vivo experiments. The gene expression of the activity-regulated cytoskeleton-associated protein (ARC), tumor necrosis factor-alpha (TNFα), and NMDA receptor subunit 2B (NR2B) in SH-SY5Y cells was examined using qPCR. Phosphorylated cAMP response element-binding protein (p-CREB), apoptosis markers, and reactive oxygen species (ROS) were evaluated by in vitro experiments. The in vivo experiment evaluated the gap-prepulse inhibition of the acoustic startle reflex (GPIAS) and auditory brainstem response (ABR) level. The NR2B expression in the auditory cortex (AC) was determined by immunohistochemistry. RSV significantly reduced the salicylate-induced expression of NR2B, ARC, and TNFα in neuronal cells; the GPIAS and ABR thresholds altered by salicylate in rats were recovered close to their normal range. RSV also reduced the salicylate-induced NR2B overexpression of the AC. These results confirmed that resveratrol exerted an attenuative effect on salicylate-induced tinnitus and may have a therapeutic potential.
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Neuroblastoma , Resveratrol , Acúfeno , Animales , Humanos , Ratas , Ratas Sprague-Dawley , Resveratrol/farmacología , Resveratrol/uso terapéutico , Salicilatos/farmacología , Acúfeno/inducido químicamente , Acúfeno/tratamiento farmacológico , Acúfeno/patología , Factor de Necrosis Tumoral alfa/uso terapéutico , Modelos Animales de EnfermedadRESUMEN
(1) Objective: In order to evaluate the effect of a pre-induced mesenchymal stem cell (MSC)-coated cellulose/collagen nanofibrous nerve conduit on facial nerve regeneration in a rat model both in vitro and in vivo. (2) Methods: After fabrication of the cellulose/collagen nanofibrous conduit, its lumen was coated with either MSCs or pre-induced MSCs. The nerve conduit was then applied to the defective main trunk of the facial nerve. Rats were randomly divided into three treatment groups (n = 10 in each): cellulose/collagen nanofiber (control group), cellulose/collagen nanofiber/MSCs (group I), and cellulose/collagen nanofiber/pre-induced MSCs (group II). (3) Results Fibrillation of the vibrissae of each group was observed, and action potential threshold was compared 8 weeks post-surgery. Histopathological changes were also observed. Groups I and II showed better recovery of vibrissa fibrillation than the control group. (4) Conclusions: Group II, treated with the pre-induced MSC-coated cellulose/collagen nanofibrous nerve conduit, showed the highest degree of recovery based on functional and histological evaluations.
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Celulosa , Colágeno , Nervio Facial , Células Madre Mesenquimatosas , Nanofibras , Regeneración Nerviosa , Animales , Celulosa/farmacología , Materiales Biocompatibles Revestidos , Colágeno/farmacología , Modelos Animales de Enfermedad , Nervio Facial/efectos de los fármacos , Nervio Facial/fisiología , Regeneración Tisular Dirigida , Células Madre Mesenquimatosas/fisiología , Nanofibras/administración & dosificación , Regeneración Nerviosa/efectos de los fármacos , Regeneración Nerviosa/fisiología , Ratas , Nervio Ciático/patología , Andamios del TejidoRESUMEN
BACKGROUND: Hypocapnia has been traditionally advocated during general anesthesia, even though it may induce deleterious physiological effects that result in unfavorable outcomes in patients. This study investigated the association between intraoperative end-tidal carbon dioxide (EtCO2) and length of hospital stay (LOS) in patients who underwent pylorus-preserving pancreaticoduodenectomy (PPPD). METHODS: The medical records of 759 patients from 2006 to 2015 were reviewed. The patients were divided into two groups based on the mean EtCO2 value during general anesthesia: the hypocapnia group (< 35 mmHg) and the normocapnia group (≥ 35 mmHg). The primary outcome was LOS between the groups. Secondary outcomes included the length of intensive care unit (ICU) stay, postoperative 30-day, 1-year, and 2-year mortality, and perioperative factors associated with LOS. RESULTS: A total of 727 patients were finally analyzed. The median LOS of the hypocapnia group was significantly longer than that of the normocapnia group (22 days vs. 18 days, respectively; p < 0.001). Postoperative mortality did not differ between the groups. Cox regression analysis revealed that hypocapnia was an independent risk factor for longer LOS (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.37-1.89; p < 0.001). Age and postoperative pancreatic fistula were also risk factors for a longer LOS. CONCLUSIONS: It was concluded that low levels of intraoperative EtCO2 during general anesthesia were associated with an increased LOS for patients undergoing PPPD.
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Dióxido de Carbono , Pancreaticoduodenectomía , Humanos , Tiempo de Internación , Pancreaticoduodenectomía/efectos adversos , Complicaciones Posoperatorias/epidemiología , Píloro/cirugíaRESUMEN
Increased oxidative stress is a crucial factor for the progression of cellular senescence and aging. The present study aimed to investigate the effects of licochalcone D (Lico D) on oxidative stress-induced senescence, both in vitro and in vivo, and explore its potential mechanisms. Hydrogen peroxide (200 µM for double time) and D-galactose (D-Gal) (150 mg/kg) were used to induce oxidative stress in human bone marrow-mesenchymal stem cells (hBM-MSCs) and mice, respectively. We performed the SA-ß-gal assay and evaluated the senescence markers, activation of AMPK, and autophagy. Lico D potentially reduced oxidative stress-induced senescence by upregulating AMPK-mediated activation of autophagy in hBM-MSCs. D-Gal treatment significantly increased the expression levels of senescence markers, such as p53 and p21, in the heart and hippocampal tissues, while this effect was reversed in the Lico D-treated animals. Furthermore, a significant increase in AMPK activation was observed in both tissues, while the activation of autophagy was only observed in the heart tissue. Interestingly, we found that Lico D significantly reduced the expression levels of the receptors for advanced glycation end products (RAGE) in the hippocampal tissue. Taken together, our findings highlight the antioxidant, anti-senescent, and cardioprotective effects of Lico D and suggest that the activation of AMPK and autophagy ameliorates the oxidative stress-induced senescence.
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Proteínas Quinasas Activadas por AMP/metabolismo , Senescencia Celular/efectos de los fármacos , Chalconas/farmacología , Estrés Oxidativo/efectos de los fármacos , Envejecimiento/efectos de los fármacos , Envejecimiento/metabolismo , Animales , Antioxidantes/farmacología , Autofagia/efectos de los fármacos , Cardiotónicos/farmacología , Células Cultivadas , Galactosa/metabolismo , Corazón/efectos de los fármacos , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Humanos , Peróxido de Hidrógeno/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Regulación hacia Arriba/efectos de los fármacosRESUMEN
High-dose salicylate induces temporary moderate hearing loss and the perception of a high-pitched tinnitus in humans and animals. Previous studies demonstrated that high doses of salicylate increase N-methyl-d-aspartate (NMDA) receptor levels, resulting in a rise in Ca2+ influx and induction of excitotoxicity. Glutamate excitotoxicity is associated with failure in the maintenance of calcium homeostasis, mitochondrial dysfunction, and production of reactive oxygen species (ROS). Valproic acid (VPA) is widely used for the management of bipolar disorder, epilepsy, and migraine headaches, and is known to regulate NMDA receptor activity. In this study, we examined the beneficial effects of VPA in a salicylate-induced tinnitus model in vitro and in vivo. Cells were pretreated with VPA followed by salicylate treatment. The expression levels of NMDA receptor subunit NR2B, phosphorylated cAMP response element-binding protein-an apoptosis marker, and intracellular levels of ROS were measured using several biochemical techniques. We observed increased expression of NR2B and its related genes TNFα and ARC, increased intracellular ROS levels, and induced expression of cleaved caspase-3. These salicylate-induced changes were attenuated in the neuronal cell line SH-SY5Y and rat cortical neurons after VPA pretreatment. Together, these results provide evidence of the beneficial effects of VPA in a salicylate-induced temporary hearing loss and tinnitus model.
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Fármacos Neuroprotectores/farmacología , Salicilatos/farmacología , Acúfeno/inducido químicamente , Acúfeno/tratamiento farmacológico , Ácido Valproico/farmacología , Animales , Línea Celular Tumoral , Ácido Glutámico/metabolismo , Humanos , Masculino , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Acúfeno/metabolismoRESUMEN
Oxidative stress-induced neurodegeneration is one of several etiologies underlying neurodegenerative disease. In the present study, we investigated the functional role of histone methyltransferase G9a in oxidative stress-induced degeneration in human SH-SY5Y neuroblastoma cells. Cell viability significantly decreased on H2O2 treatment; however, treatment with the G9a inhibitor BIX01294 partially attenuated this effect. The expression of neuron-specific genes also decreased in H2O2- treated cells; however, it recovered on G9a inhibition. H2O2-treated cells showed high levels of H3K9me2 (histone H3 demethylated at the lysine 9 residue), which is produced by G9a activation; BIX01294 treatment reduced aberrant activation of G9a. H3K9me2 occupancy of the RE-1 site in neuron-specific genes was significantly increased in H2O2-treated cells, whereas it was decreased in BIX01294-treated cells. The differentiation of H2O2-treated cells also recovered on G9a inhibition by BIX01294. Consistent results were observed when used another G9a inhibitor UCN0321. These results demonstrate that oxidative stress induces aberrant activation of G9a, which disturbs the expression of neuron-specific genes and progressively mediates neuronal cell death. Moreover, a G9a inhibitor can lessen aberrant G9a activity and prevent neuronal damage. G9a inhibition may therefore contribute to the prevention of oxidative stress-induced neurodegeneration.
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Contact guidance can promote cell alignment and is thus widely employed in tissue regeneration. In particular, skeletal muscle consists of long fibrous bundles of multinucleated myotubes formed by the fusion and differentiation of the satellite cells of myoblasts. Herein, a functional bioink and cell-printing process supplemented with an electric field are proposed for obtaining highly aligned myoblasts in a collagen-based bioink. To achieve the goal, we mixed Au nanowires (GNWs) with the collagen-based bioink to provide aligned topographical cues to the laden cells. Because the aligned GNWs could clearly provide topographical cues to the cells, we adjusted various processing parameters (flow rate, nozzle speed, and processing temperature) and applied an external electric field to optimally align the GNWs. By selecting an appropriate condition, the GNWs in the printed C2C12-laden structure were well aligned in the printing direction, and they eventually induced a high degree of myoblast alignment and efficient myotube formation. Through the several in vitro cellular activities and in vivo works revealing the myogenesis of the cell-laden structure, we conclude that the collagen/GNW-based cell-laden structure fabricated using the proposed method is a new prospective platform for the effective formation of muscle tissues.
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Colágeno , Oro , Tinta , Nanopartículas del Metal/química , Músculo Esquelético/fisiología , Mioblastos Esqueléticos/metabolismo , Nanocables/química , Regeneración/efectos de los fármacos , Animales , Línea Celular , Colágeno/química , Colágeno/farmacología , Oro/química , Oro/farmacología , RatonesRESUMEN
The four methods for assigning bacterial species are the Clinical and Laboratory Standards Institute (CLSI), modified CLSI (mCLSI), phylogenetic analysis (PA) and closest match (CM) methods, these are used to identify the genus and species using 16S rRNA gene sequence results. In this study, the results of identification by these four methods of 37 aerobic reference strains, 30 anaerobic reference strains, 15 Acinetobacter reference strains and 167 Acinetobacter clinical strains were compared. The rates of accurate identification to the species level using the CLSI, mCLSI, PA and CM methods were as follows: 24.3, 86.5, 86.5 and 89.2%, respectively, for the 37 aerobic reference strains; 73.3%, 96.7%, 90.0% and 93.3%, respectively, for the 30 anaerobic reference strains; 40.0%, 93.3%, 100% and 93.3%, respectively, for the 15 Acinetobacter reference strains; and 53.9%, 90.4%, 95.8% and 90.4%, respectively, for the 167 Acinetobacter clinical strains. The rates of accurate identification to the genus level using the CLSI, mCLSI, PA, and CM methods were as follows: 91.9%, 91.9%, 94.6% and 91.9%, respectively, for the 37 aerobic reference strains; 100%, 100%, 100% and 100%, respectively, for all of the 30 anaerobic reference strains, 15 Acinetobacter reference strains and the 167 Acinetobacter clinical strains. The mCLSI is the most practical and pragmatic method for identification of species based on 16S rRNA sequences for hospital, research or industry laboratories because it performs well and involves a simple procedure.
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Bacterias/aislamiento & purificación , Infecciones Bacterianas/diagnóstico , Técnicas Bacteriológicas/métodos , ADN Ribosómico/genética , Técnicas de Diagnóstico Molecular/métodos , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Bacterias/clasificación , Bacterias/genética , ADN Bacteriano/química , ADN Bacteriano/genética , ADN Ribosómico/química , Genes de ARNr , HumanosRESUMEN
The cause and pathogenesis of sudden sensorineural hearing loss (SSNHL) remain unknown. IL-1ß is one of the most powerful inflammatory cytokines. The aim of this study was to evaluate the relationships between interleukin-1 ß (IL-1ß) gene polymorphisms (-511 C/T and +3953 C/T) in patients with SSNHL. One hundred two patients affected by SSNHL and 595 controls were genotyped for IL-1ß gene polymorphisms. The polymorphisms were analyzed by polymerase chain reaction amplification and DNA fragment separation via electrophoresis. Compared to controls, the IL-1ß (+3953) T allele increased the relative risk of SSNHL in subjects with IL-1ß (-511) TT genotype (p = 0.022, OR = 9.111, 95% CI = 1.441-57.618). In this study, polymorphisms in the IL-1ß -511 and IL-1ß +3953 loci were assessed for evidence of association with SSNHL. From this assessment, a significant difference in carriage of both the IL-1ß -511 T allele and the IL-1ß +3953 T allele was observed between SSNHL and controls. This suggests that the IL-1ß -511 and +3953 loci may play an important role in the etiopathogenesis of SSNHL.
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Pérdida Auditiva Sensorineural/genética , Pérdida Auditiva Súbita/genética , Interleucina-1beta/genética , Alelos , Femenino , Genotipo , Pérdida Auditiva Sensorineural/inmunología , Pérdida Auditiva Súbita/inmunología , Humanos , Interleucina-1beta/inmunología , Masculino , Persona de Mediana Edad , Polimorfismo GenéticoRESUMEN
The impact of metformin on the rat facial nerve following crush injury has only occasionally been documented to date. The purpose of the current investigation was to use functional and electrophysiological evaluations to investigate the effects of metformin administration on recovery following crush injury to the rat facial nerve. The rats were randomly divided into four groups: the nonDM/PBS group (n = 4), the nonDM/metformin group (n = 4), the DM/PBS group (n = 4), and the DM/metformin group (n = 4). Diabetes was generated by an intraperitoneal injection of streptozotocin. Facial nerve paralysis was induced by a crush injury 7 days after diabetes induction. The blood glucose levels of the DM/PBS and DM/metformin groups were maintained at over 300 mg/dL, whereas the blood glucose levels of the nonDM/PBS and nonDM/metformin groups were maintained at less than 150 mg/dL. There was no significant difference between the two nonDM groups. In comparison to the PBS group, the metformin group's recurrence of vibrissa fibrillation occurred noticeably sooner over time. The nonDM/metformin group showed the highest recovery rate in the second, third, and fourth weeks post-crush, respectively. The threshold of action potential 4 weeks after crush injury showed that the nonDM/metformin group had a significantly lower mean threshold of MAP compared to other groups. The short-term effect of metformin on the recovery of facial nerve blood flow (FNBF) was significantly increased compared to the DM/PBS group. However, there was no significant difference in FNBF between the nonDM/metformin and nonDM/PBS groups. A diabetic condition promoted a delay in FN regeneration. Metformin is able to accelerate functional recovery in diabetic or nondiabetic FN-injured rats. Further studies using a morphometric or molecular approach are planned to understand the pharmacologic mechanism of metformin.
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In bone tissue engineering, efficient formation of vascularized bone tissue is a challenging issue. Here, we introduce a new strategy for effectively using multiple cells laden in a hybrid structure, such as endothelial cell (EC) spheroids and homogeneously distributed human adipose stem cells (hASCs) for bone regeneration. Methods: To fabricate the EC spheroids, cell-mixed mineral oil was used, and microscale droplets of the cell mixture were interlayered between the bioprinted hASC-laden struts. In vitro cellular responses of spheroid-laden multiple-cell constructs have been evaluated by comparing with the cell constructs bioprinted with the mixture of hASCs and ECs. In addition, mastoid obliterated rat model has been used to observe in vivo bone formation of those cell constructs. Results: The spheroid-laden multiple-cell constructs induced outstanding angiogenesis and osteogenic activities compared to a conventionally bioprinted multiple-cell construct. The enhanced biological results were clearly due to the EC spheroids, which triggered highly cooperative crosstalk between ECs and stem cells. The co-culture of the hASC constructs with the EC spheroids exhibited enhanced osteogenic- and angiogenic-related gene expression in vitro. In addition, in a rat obliterated mastoid model, considerably greater new bone formation and more competent development of new blood vessels were observed compared to those achieved with the normally bioprinted multiple cell-loaded structure. Conclusion:In vitro and in vivo results demonstrated that the bioprinted spheroid-laden multiple-cell construct is a potential candidate for use in bone tissue engineering.
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Bioimpresión , Ingeniería de Tejidos , Animales , Bioimpresión/métodos , Huesos , Células Endoteliales , Humanos , Osteogénesis , Ratas , Esferoides Celulares , Ingeniería de Tejidos/métodos , Andamios del Tejido/químicaRESUMEN
With the recent development of bioprinting technology, various attempts have been made to replace bioprinting technologies and regenerative medicine are more directed towards transplantation/reconstructive surgeries only with the implantation of scaffolds. The purpose of this study is to determine whether the growth factors, human umbilical cord serum (hUCS) and bFGF (basic fibroblast growth factor), have a synergistic effect on eardrum regeneration, when used with a cell-printed scaffold in a chronic tympanic membrane perforation (TMP) model. In this study, in vitro cellular activities for bioprinted cell-laden collagen scaffolds using human adipose stem cells (hASCs) and supplemented with 10 [Formula: see text]/mL hUCS and 10 ng/mL bFGF were performed. The mixture of the growth factors in the cell-laden structures effectively affects various in vitro cellular responses including the proliferation of hASCs and the migration of keratinocytes due to the synergistic effect of the growth factors and hASCs. For the in vivo evaluation, a rat TMP model was used, and the TMP regeneration was assessed by otoscopic examination, hearing threshold measurement, and histologic examination. Although the cell-laden structure containing hUCS was more enhancing effect compared to the structure with bFGF, more synergistic effect in the structure using hUCS/bFGF was observed. Based on the results, we believe that the cell-laden structure incorporating hUCS and bFGF can induce significant regeneration of chronic tympanic membrane perforation.
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Andamios del Tejido , Perforación de la Membrana Timpánica , Membrana Timpánica , Animales , Colágeno/química , Ratas , Regeneración , Células Madre/metabolismo , Perforación de la Membrana Timpánica/metabolismo , Perforación de la Membrana Timpánica/terapiaRESUMEN
Hypertrophic pachymeningitis (HP) is defined by inflammation and thickening of the dura mater, and the etiologic factors are idiopathic or secondary to various conditions. To date, HP in the internal auditory canal (IAC) has rarely been reported. There have only been 3 reports of HP in the IAC. Magnetic resonance imaging showed enhancement of along the IAC and vestibule. After antibiotic treatment, enhancement was reduced with visible seventh and eighth nerves. The patient underwent tympanomastoidectomy. To our knowledge, this is the first case of HP associated with a labyrinth fistula complicated by cholesteatoma. We report MRI image with literatures.
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Colesteatoma , Fístula , Meningitis , Enfermedades Vestibulares , Colesteatoma/complicaciones , Colesteatoma/patología , Duramadre/patología , Fístula/complicaciones , Fístula/patología , Humanos , Hipertrofia/complicaciones , Imagen por Resonancia Magnética , Meningitis/complicaciones , Enfermedades Vestibulares/complicacionesRESUMEN
BACKGROUND/AIM: Recently, hyaluronic acid disc has been known to enhance the success rate of fat myringoplasty. However, hyaluronic acid disc (Epidisc) is not covered by south Korean medical insurance. To date, fat myringoplasty using middle ear packing has rarely been reported. In this study, we studied whether middle ear packing with dexamethasone soaked gelfoam and fibrin glue over the fat graft could promote the success rate of tympanic membrane perforation (TMP) closure without hyaluronic acid disc, regardless of perforation size. PATIENTS AND METHODS: Between January 2005 and July 2020, a total of 209 patients who underwent fat myringoplasty due to chronic TMP at a tertiary referral center were enrolled, and the success rate and audiologic outcomes were analyzed. RESULTS: The mean successful tympanic membrane (TM) closure rate was 88.0%. The success rate by different age groups showed no significant difference. Further, the size of perforation showed no significant difference, and the perforation site (anterior or posterior) was not significant. The preoperative mean thresholds of air conduction (AC), bone conduction (BC), and air-bone gap (ABG) were 55.71, 12.98, and 42.73 dB respectively. The postoperative mean thresholds of AC, BC, and ABG were 23.67, 12.98, and 10.69 dB, respectively. Change in preoperative and postoperative hearing showed was statistically significant. CONCLUSION: Middle ear packing by gelfoam combined with external ear canal packing using fibrin glue enabled stable adhesion between the remnant TM and the fat graft. Regardless of the size of the TMP, the success rate of the fat myringoplasty by our technique can be enhanced without use of hyaluronic acid disc.
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Miringoplastia , Perforación de la Membrana Timpánica , Oído Medio , Adhesivo de Tejido de Fibrina , Humanos , Ácido Hialurónico , Estudios Retrospectivos , Resultado del Tratamiento , Membrana Timpánica , Perforación de la Membrana Timpánica/cirugíaRESUMEN
Bioengineering scaffolds have been improved to achieve efficient regeneration of various damaged tissues. In this study, we attempted to fabricate mechanically and biologically activated 3D printed scaffold in which porous gelatin/hydroxyapatite (G/H) as a matrix material provided outstanding mechanical properties with recoverable behavior, and human placental extracts (hPE) embedded in the scaffold were used as bioactive components. Methods: Various cell types (human adipose-derived stem cells; hASCs, pre-osteoblast; MC3T3-E1, human endothelial cell line; EA.hy926, and human dermal fibroblast; hDFs) were used to assess the effect of the hPE on cellular responses. High weight fraction (~ 70 wt%) of hydroxyapatite (HA) in a gelatin solution supplemented with glycerol was used for the G/H scaffold fabrication, and the scaffolds were immersed in hPE for the embedding (G/H/hPE scaffold). The osteogenic abilities of the scaffolds were investigated in cultured cells (hASCs) assaying for ALP activity and expression of osteogenic genes. For the in vivo test, the G/H and G/H/hPE scaffolds were implanted in the rat mastoid obliteration model. Results: The G/H/hPE scaffold presented unique elastic recoverable properties, which are important for efficient usage of implantable scaffolds. The effects of G/H and G/H/hPE scaffold on various in vitro cell-activities including non-toxicity, biocompatibility, and cell proliferation were investigated. The in vitro results indicated that proliferation (G/H = 351.1 ± 13.3%, G/H/hPE = 430.9 ± 8.7% at day 14) and expression of osteogenic markers (ALP: 3.4-fold, Runx2: 3.9-fold, BMP2: 1.7-fold, OPN: 2.4-fold, and OCN: 4.8-fold at day 21) of hASCs grown in the G/H/hPE scaffold were significantly enhanced compared with that in cells grown in the G/H scaffold. In addition, bone formation was also observed in an in vivo model using rat mastoid obliteration. Conclusion:In vitro and in vivo results suggested that the G/H/hPE scaffold is a potential candidate for use in bone tissue engineering.
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Gelatina , Extractos Placentarios , Animales , Diferenciación Celular , Proliferación Celular , Durapatita , Femenino , Osteogénesis , Placenta , Extractos Placentarios/farmacología , Extractos Vegetales/farmacología , Embarazo , Impresión Tridimensional , Ratas , Ingeniería de Tejidos/métodos , Andamios del TejidoRESUMEN
Tinnitus is the perception of phantom noise without any external auditory sources. The degeneration of the function or activity of the peripheral or central auditory nervous systems is one of the causes of tinnitus. This damage has numerous causes, such as loud noise, aging, and ototoxicity. All these sources excite the cells of the auditory pathway, producing reactive oxygen species that leads to the death of sensory neural hair cells. This causes involuntary movement of the tectorial membrane, resulting in the buzzing noise characteristic of tinnitus. Autophagy is an evolutionarily conserved catabolic scavenging activity inside a cell that has evolved as a cell survival mechanism. Numerous studies have demonstrated the effect of autophagy against oxidative stress, which is one of the reasons for cell excitation. This review compiles several studies that highlight the role of autophagy in protecting sensory neural hair cells against oxidative stress-induced damage. This could facilitate the development of strategies to treat tinnitus by activating autophagy.
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There is a scarcity of experimental studies on peripheral nerve regeneration using placental extract (PE). This study aimed to investigate the effects of topical PE application on recovery after crush injury to the rat facial nerve using functional, electrophysiological, and morphological evaluations. The viability of the RSC96 Schwann cells treated with PE (0.5~4 mg/ml) increased significantly. Immunoblot test revealed that PE application enhanced the migration of RSC96 cells. Quantitative polymerase chain reaction demonstrated that PE increased the expression of neurotropic genes. The recovery from vibrissa fibrillation in the PE-treated group was superior to that in the control group. The threshold of action potential was also significantly lower in the PE group. Histopathological examination showed that crushed facial nerves treated with PE exhibited larger axons. The surrounding myelin sheaths were more distinct and thicker in the PE-treated group. Hence, PE may be considered a topical therapeutic agent for treating traumatic facial nerve paralysis.
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Collagen- and bioceramic-based composites have been widely used in hard tissue engineering because they are analogous to the organic/inorganic constituents of native bones. However, biocomposites based on collagen and bioceramics show low mechanical stiffness and limited osteogenic activities. To elevate the low biophysical and biological activities, we have introduced a new biocomposite structure. Herein, we propose a biocomposite mimicking not only the physical structure of the extracellular matrix (ECM) structure but also the biochemical components of native bone tissues. Several components including fibrillated collagen, calcium-deficient hydroxyapatite (CDHA) obtained from α-tricalcium phosphate hydrolysis, and human umbilical cord serum (hUCS) were used to generate a unique structure of the biocomposite. The 3D-printed composites were topographically similar to the nanofibrous ECM and exhibited a mechanically stable structure. We also evaluated the in vitro biocompatibilities of the biocomposite using human adipose stem cells and found that the collagen/hUCS/CDHA scaffold accelerated the in vitro osteogenic differentiation of human adipose-derived stem cells and in vivo osteogenesis in a mastoid obliterated rat model.
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Tejido Adiposo/metabolismo , Apatitas/química , Regeneración Ósea , Huesos/metabolismo , Colágeno/química , Sangre Fetal/química , Células Madre Mesenquimatosas/metabolismo , Suero/química , Tejido Adiposo/patología , Animales , Huesos/patología , Combinación de Medicamentos , Humanos , Células Madre Mesenquimatosas/patología , Ratas , Ratas Sprague-Dawley , Ingeniería de Tejidos , Andamios del TejidoRESUMEN
Hearing loss is one of the major worldwide health problems that seriously affects human social and cognitive development. In the auditory system, three components outer ear, middle ear and inner ear are essential for the hearing mechanism. In the inner ear, sensory hair cells and ganglion neuronal cells are the essential supporters for hearing mechanism. Damage to these cells can be caused by long-term exposure of excessive noise, ototoxic drugs (aminoglycosides), ear tumors, infections, heredity and aging. Since mammalian cochlear hair cells do not regenerate naturally, some therapeutic interventions may be required to replace the damaged or lost cells. Cochlear implants and hearing aids are the temporary solutions for people suffering from severe hearing loss. The current discoveries in gene therapy may provide a deeper understanding in essential genes for the inner ear regeneration. Stem cell migration, survival and differentiation to supporting cells, cochlear hair cells and spiral ganglion neurons are the important foundation in understanding stem cell therapy. Moreover, mesenchymal stem cells (MSCs) from different sources (bone marrow, umbilical cord, adipose tissue and placenta) could be used in inner ear therapy. Transplanted MSCs in the inner ear can recruit homing factors at the damaged sites to induce transdifferentiation into inner hair cells and ganglion neurons or regeneration of sensory hair cells, thus enhancing the cochlear function. This review summarizes the potential application of mesenchymal stem cells in hearing restoration and combining stem cell and molecular therapeutic strategies can also be used in the recovery of cochlear function.