Construction of a Decellularized Multicomponent Extracellular Matrix Interpenetrating Network Scaffold by Gelatin Microporous Hydrogel 3D Cell Culture System.

Interface tissue repair requires the construction of biomaterials with integrated structures of multiple protein types. Hydrogels that modulate internal porous structures provide a 3D microenvironment for encapsulated cells, making them promise for interface tissue repair. Currently, reduction of intrinsic immunogenicity and increase of bioactive extracellular matrix (ECM) secretion are issues to be considered in these materials. In this study, gelatin methacrylate (GelMA) hydrogel is used to encapsulate chondrocytes and construct a phase transition 3D cell culture system (PTCC) by utilizing the thermosensitivity of gelatin microspheres to create micropores within the hydrogel. The types of bioactive extracellular matrix protein formation by chondrocytes encapsulated in hydrogels are investigated in vitro. After 28 days of culture, GelMA PTCC forms an extracellular matrix predominantly composed of collagen type II, collagen type I, and fibronectin. After decellularization, the protein types and mechanical properties are well preserved, fabricating a decellularized tissue-engineered extracellular matrix and GelMA hydrogel interpenetrating network hydrogel (dECM-GelMA IPN) consisting of GelMA hydrogel as the first-level network and the ECM secreted by chondrocytes as the second-level network. This material has the potential to mediate the repair and regeneration of tendon-bone interface tissues with multiple protein types.

Ca2+ -dependent activator protein for secretion 1 promotes spontaneous recovery in ischemic stroke by regulating BDNF secretion.

Ischemic stroke triggers a cascade of events that facilitates neural protection and spontaneous recovery, which accounts for a major part of functional recovery. Despite the cellular and molecular facilitations on neural protection, the molecular mechanisms of spontaneous recovery have not been fully understood. Ca2+ -dependent activator protein for secretion 1 (CAPS1), a member of CAPS family, plays a major role in synaptic transmission and synaptic effectiveness by regulating vesicle exocytosis. Here, the molecular mechanism of CAPS1 in spontaneous recovery after ischemic stroke was studied. In this study, transient left middle cerebral artery occlusion (MCAO) was used as the ischemic stroke model. The whole brain magnetic resonance imaging (MRI) and neurological score analysis showed decreased infarct volume and neurological scores at 7 days as compared with 1 day after MCAO, suggesting the spontaneous recovery. Elisa and Western blot analysis showed elevated BDNF and CAPS1 expression levels in bilateral hippocampus at both 1 day and 3 days after MCAO. Then, inhibition of CAPS1 by adeno-associated virus (AAV) microinjection in the hippocampus attenuated the spontaneous recovery of both motor and memory impairment induced by MCAO. In addition, elevated p-TrkB levels were detected after MCAO, which were reduced by CAPS1-AAV microinjection, indicating that CAPS1 could induce BDNF secretion after ischemic stroke. Moreover, we found elevated combination of CAPS1 with dense core vesicles (DCV) in the hippocampus at both 1 day and 3 days after MCAO, which could also be inhibited by CAPS1-AAV microinjection, indicating the potential mechanism of CAPS1 in regulating BDNF release after MCAO. Finally, we found that CAPS1/BDNF signaling could influence the neurogenesis in the hippocampus after MCAO. In conclusion, CAPS1 regulates neurogenesis by up-regulating BDNF release in the hippocampus, which finally facilitate spontaneous recovery after ischemic stroke.

A Clinical Observation Study for Transnasal Endoscopic Marsupialization in the Treatment of Maxillary Cyst.

The aim of this study was to investigate the feasibility and evaluate the clinical effects of transnasal marsupialization of maxillary cyst under nasal endoscope. Twenty patients with maxillary bone cysts were treated with endoscopic marsupialization. According to the location of the maxillary bone cyst, the opening window was selected in the nasal base or the inferior or middle nasal meatus. The cyst wall of the window was removed, and the fluid was drained out. The diameter of the opening window was more than 1 cm, so that the cyst and the maxillary sinus can be fused into a cavity. This ensured nasal drainage through the cyst cavity and nasal cavity or maxillary sinus. The patients were followed up for 6 to 18 months. No serious complications occurred. The cyst wall epithelialized 2 or 3 months after the operation, and the cyst cavity drained well with no recurrence. Intranasal marsupialization under a nasal endoscope is a feasible alternative for the treatment of maxillary cysts. It makes the procedure simple, safe, less traumatic, has definite clinical effects, and low recurrence rate. Especially suitable for maxillary cysts protruding into the nasal floor or maxillary sinus.

Nonmineralized and Mineralized Silk Fibroin/Gelatin Hybrid Scaffolds: Chacterization and Cytocompatibility In Vitro for Bone-Tissue Engineering.

In this study, nonmineralized silk fibroin/gelatin (SF/G) hybrid scaffolds and the mineralized SF/G/hydroxyapatite (SF/G/HA) hybrid scaffolds were fabricated using vacuum freeze-drying method and biomineralization technique. The morphology and mechanical properties of the 2 hybrid scaffolds were characterized. Furthermore, the cytotoxic profiles of the hybrid scaffolds were investigated in vitro by seeding the human osteoblast cells (hFOB1.19). The 2 hybrid scaffolds were both highly porous and the pore sizes of the SF/G as well as SF/G/HA hybrid scaffolds were 260 ±â€Š58 µm and 210 ±â€Š35 µm, respectively. Compared with the SF/G hybrid scaffold, the SF/G/HA hybrid scaffolds exhibited significantly enhanced compressive strength and modulus. Significant early cell adhesion and proliferation on the SF/G hybrid scaffolds were observed, while SF/G/HA hybrid scaffolds effectively improved osteogenic differentiation of hFOB1.19 after 10 days of coculture. The results confirmed that the 2 hybrid scaffolds were both cytocompatible and had almost no negative effects on the hFOB1.19 in vitro. However, the SF/G/HA hybrid scaffolds tended to be more promising for application in bone-tissue engineering with good mechanical property and osteogenic differentiation.

A Study on Environmental Factors for Nonsyndromic Cleft Lip and/or Palate.

The aim of the study was to investigate the association between environmental factors and nonsyndromic cleft of the lip and/or palate (NSCL/P) in Yantai District, China. A retrospective case-control study was carried out. A total of 236 NSCL/P children were selected from Department of Oral and Maxillofacial Surgery of Yantai Stomatological Hospital between September 2013 and December 2016 as cases; 209 controls were chosen from other diagnosis in the same department during the same period. The 2 groups matched age and sex. The parents of participants were inquired regarding the risk factors, and the answers were filled in a questionnaire by physicians. Chi-square and multivariate logistic regression analysis were used to analysis the data. There was significantly increased NSCL/P risk with high maternal age (P =0.002), family history (P = 0.001), abortion history (P = 0.033), poor parental education level (P = 0.008), maternal smoking (P = 0.044), maternal alcohol (P = 0.039), common cold or fever (P = 0.035), drug use (P = 0.006), and maternal stress (P = 0.049). Reduced NSCL/P risk was found with folic acid supplementation (P = 0.005), adequate maternal age (P = 0.002), and high parental education (P = 0.001). The proper amount of folic acid, the appropriate age of childbearing, and the high education were the protective factors of NSCL/P, whereas family history, abortion history, drug use during pregnancy, maternal tobacco and alcohol, and maternal stress were the risk factors for NSCL/P in Yantai District, China.

The potential roles of PKM2 in cerebrovascular diseases.

Pyruvate kinase M2 (PKM2), a key enzyme involved in glycolysis,plays an important role in regulating cell metabolism and growth under different physiological conditions. PKM2 has been intensively investigated in multiple cancer diseases. Recent years, many studies have found its pivotal role in cerebrovascular diseases (CeVDs), the disturbances in intracranial blood circulation. CeVDs has been confirmed to be closely associated with oxidative stress (OS), mitochondrial dynamics, systemic inflammation, and local neuroinflammation in the brain. It has further been revealed that PKM2 exerts various biological functions in the regulation of energy supply, OS, inflammatory responses, and mitochondrial dysfunction. The roles of PKM2 are closely related to its different isoforms, expression levels in subcellular localization, and post-translational modifications. Therefore, summarizing the roles of PKM2 in CeVDs will help further understanding the molecular mechanisms of CeVDs. In this review, we illustrate the characteristics of PKM2, the regulated PKM2 expression, and the biological roles of PKM2 in CeVDs.

Human umbilical cord mesenchymal stem cells overexpressing RUNX1 promote tendon-bone healing by inhibiting osteolysis, enhancing osteogenesis and promoting angiogenesis.

BACKGROUND: Rotator cuff injury (RCI) is a common shoulder injury, which is difficult to be completely repaired by surgery. Hence, new strategies are needed to promote the healing of tendon-bone. OBJECTIVE: We aimed to investigate the effect of human umbilical cord mesenchymal stem cells (hUC-MSCs) overexpressing RUNX1 on the tendon-bone healing after RCI, and to further explore its mechanism. METHODS: Lentiviral vector was used to mediate the overexpression of RUNX1. RUNX1-overexpressed UCB-MSCs (referred to as MSC-RUNX1) were co-cultured with osteoclasts, and TRAP staining was performed to observe the formation of osteoclasts. Then MSC-RUNX1 was cultured in osteogenic differentiation medium, Alizarin red staining was conducted to detect osteogenic differentiation. The expression of markers of osteogenesis and osteoclast was detected by RT-qPCR. EA. hy926 cells were co-cultured with MSC-RUNX1. Transwell assay was used to detect the migration, and the expression of angiogenesis related-genes VEGF and TGF-ß was detected by RT-qPCR. The rat rotator cuff reconstruction model was established and MSCs were injected at the tendon-bone junction. Biomechanical test and micro-CT scanning were performed, and HE, Masson and Alcian Blue staining were used for histological evaluation of tendon-bone healing. TUNEL and PCNA immunofluorescence (IF) staining were performed to evaluate apoptosis and proliferation at the tendon-bone healing site. The levels of TNF-α, IL-6 and IL-8 in serum were detected by ELISA. The expression of CD31 and Endomucin that related to angiogenesis was detected by IF. Safranin O-fast and TRAP/CD40L immunohistochemical staining were used to assess the levels of osteoclasts and osteoblasts at the tendon-bone healing site. RESULTS: hUC-MSCs overexpressing RUNX1 inhibited osteoclast formation and promoted osteogenic differentiation. MSC-RUNX1 could promote the migration and tube formation of EA. hy926 cells, and up-regulate the levels of VEGF and TGF-ß. Model mice treated with MSC-RUNX1 partially restored the biomechanical indexes. Treatment of MSC-RUNX1 obviously increased the bone density, accompanied by the formation of new bone. In vivo experiments showed that MSC-RUNX1 treatment could promote tendon-bone healing and inhibit inflammatory response in rats. MSC-RUNX1 treatment also promoted angiogenesis at the tendon-bone healing site, while inhibiting osteoclast formation and promoting osteogenic differentiation. CONCLUSION: hUC-MSCs overexpressing RUNX1 can inhibit the formation of osteoclasts and differentiation of osteoblasts, promote angiogenesis and inhibit inflammation, thereby promoting tendon-bone healing after RCI.

Tissue-engineered collagen matrix loaded with rat adipose-derived stem cells/human amniotic mesenchymal stem cells for rotator cuff tendon-bone repair.

The rotator cuff tendon-bone interface tissue exhibits high heterogeneity in its composition and structure, with collagen being its primary component. Here, we prepared tissue-engineered decellularized live hyaline cartilage grafts (dLHCG), this dLHCG scaffold's bioactive ECM mainly consists of collagen II, proteoglycans, and fibronectin, presenting a cartilage-like lacuna microstructure. The dLHCG scaffold loaded human amniotic mesenchymal stem cells (hAMSCs) and adipose stem cells (ADSCs) were implanted into the interface. The dLHCG scaffold could maintain the pluripotency of stem cells, supporting the proliferation, osteogenic differentiation, and tenogenic differentiation of the MSCs. The collagen II, through the integrin α2ß1-FAK-JNK signaling axis, promotes Runx-2 activation, playing a better regulatory role in the early osteogenic differentiation of MSCs, enhancing bone defect repair through an endochondral ossification process. The in vivo rat model demonstrated that 12 weeks post-operation, the MSC-loaded dLHCG scaffold group exhibited continuous aligned collagen fibers at the tendon-bone interface, with significantly enhanced biomechanical function compared to the control group. The dLHCG scaffold create an efficient interface, which promoting the restoration of the soft-hard gradient structure tissue at the junction between the scaffold and the host tissue, thereby providing a rational and promising strategy for the rapid healing of the rotator cuff injury.

3D-printed biomimetic scaffolds loaded with ADSCs and BMP-2 for enhanced rotator cuff repair.

Rotator cuff tear repair poses significant challenges due to the complex gradient interface structure. In the face of disease-related disruptions in the tendon-bone interface (TBI), the strategy of constructing a biomimetic scaffold is a promising avenue. A novel 3D-printed rotator cuff scaffold loaded adipose stem cells (ADSCs), bone morphogenetic protein-2 (BMP-2), and collagen type I (COL I). The efficiency of the slow-release BMP-2 design depended on the dopamine-hyaluronic acid (HAD) and BMP-2 reaction. The cumulative release of BMP-2 was 44.97 ± 5.45% at 4 weeks. The 3D-printed bilayer scaffold, incorporating COL I and BMP-2, effectively promoted the differentiation of ADSCs into osteogenic, tenogenic, and chondrogenic lineages in vitro. The combination of 3D-printed bioactive scaffolds and ADSCs demonstrated a superior repair effect on rotator cuff injuries in vivo. Therefore, these findings indicates that the 3D-printed biomimetic scaffold loaded with ADSCs and BMP-2 holds potential as a promising graft for TBI healing.

Dual cross-linked COL1/HAp bionic gradient scaffolds containing human amniotic mesenchymal stem cells promote rotator cuff tendon-bone interface healing.

The tendon-bone interface heals through scar tissue, while the lack of a natural interface gradient structure and collagen fibre alignment leads to the occurrence of retearing. Therefore, the promotion of tendon healing has become the focus of regenerative medicine. The purpose of this study was to develop a gradient COL1/ hydroxyapatite (HAp) biomaterial loaded with human amniotic mesenchymal stem cells (hAMSCs). The performance of common cross-linking agents, Genipin, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS), and dual cross-linked materials were compared to select the best cross-linking mechanism to optimize the biological and mechanical properties of the scaffold. The optimal COL1/HAp-loaded with hAMSCs were implanted into the tendon-bone rotator cuff interfaces in rats and the effect on the tendon-bone healing was assessed by micro-CT, histological analysis, and biomechanical properties. The results showed that Genipin and EDC/NHS dual cross-linked COL1/HAp had good biological activity and mechanical properties and promoted the proliferation and differentiation of hAMSCs. Animal experiments showed that the group using a scaffold loaded with hAMSCs had excellent continuity and orientation of collagen fibers, increased fibrocartilage and bone formation, and significantly higher biomechanical functions than the control group at the interface at 12 weeks post operation. This study demonstrated that dual cross-linked gradient COL1/HAp-loaded hAMSCs could promote interface healing, thereby providing a feasible strategy for tendon-bone interface regeneration.

Development and Validation of a Predictive Model for Chronic Postsurgical Pain After Arthroscopic Rotator Cuff Repair: A Prospective Cohort Study.

Purpose: Chronic pain management continues to present a significant challenge following arthroscopic shoulder surgery. Our purpose was to detect chronic postsurgical pain (CPSP) in patients who had undergone arthroscopic rotator cuff repair (ARCR) and develop a nomogram capable of predicting the associated risk. Patients and Methods: We collected the demographic and clinical data of 240 patients undergoing ARCR in our hospital from January 2021 to May 2022. The pain level was monitored and evaluated three months after ARCR. LASSO regression was used to screen out pain-predicting factors, which were subsequently used to construct a nomogram. Internal validation was carried out using Bootstrap resampling. The data of 78 patients who underwent ARCR in our hospital from August 2022 to December 2022 were also collected for external verification of the nomogram. The predictive model was evaluated using the receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA). Results: Age, duration of preoperative shoulder pain (DPSP), C-reactive protein (CRP), number of tear tendons, and American Shoulder and Elbow Surgical Score (ASES) were screened by LASSO regression as predictive factors for CPSP. These factors were then used to construct a chronic pain risk nomogram. The area under the curve (AUC) of the predictive and validation models were 0.756 (95% CI: 0.6386-0.8731) and 0.806 (95% CI: 0.6825-0.9291), respectively. Furthermore, the calibration curves and decision curve analysis (DCA) for both models indicated strong performance, affirming the reliability of this predictive model. Conclusion: The CPSP risk model that has been developed exhibits strong predictive capabilities and practical utility. It offers valuable support to clinical healthcare professionals in making informed treatment decisions, reducing the unnecessary use of analgesic drugs, and optimizing the allocation of medical resources.

Retrieval of total suspended matter (TSM) and chlorophyll-a (Chl-a) concentration from remote-sensing data for drinking water resources.

The concentrations of chlorophyll-a (Chl-a) and total suspended matter (TSM) are major water quality parameters that can be retrieved using remotely sensed data. Water sampling works were conducted on 15 July 2007 and 13 September 2008 concurrent with the Indian Remote-Sensing Satellite (IRS-P6) overpass of the Shitoukoumen Reservoir. Both empirical regression and back-propagation artificial neural network (ANN) models were established to estimate Chl-a and TSM concentration with both in situ and satellite-received radiances signals. It was found that empirical models performed well on the TSM concentration estimation with better accuracy (R (2) = 0.94, 0.91) than their performance on Chl-a concentration (R (2) = 0.62, 0.75) with IRS-P6 imagery data, and the models accuracy marginally improved with in situ spectra data. Our results indicated that the ANN model performed better for both Chl-a (R (2) = 0.91, 0.82) and TSM (R (2) = 0.98, 0.94) concentration estimation through in situ collected spectra; the same trend followed for IRS-P6 imagery data (R (2) = 0.75 and 0.90 for Chl-a; R (2) = 0.97 and 0.95 for TSM). The relative root mean square errors (RMSEs) from the empirical model for TSM (Chl-a) were less than 15% (respectively 27.2%) with both in situ and IRS-P6 imagery data, while the RMSEs were less than 7.5% (respectively 18.4%) from the ANN model. Future work still needs to be undertaken to derive the dynamic characteristic of Shitoukoumen Reservoir water quality with remotely sensed IRS-P6 or Landsat-TM data. The algorithms developed in this study will also need to be tested and refined with more imagery data acquisitions combined with in situ spectra data.

[Research on hyperspectral remote sensing in monitoring snow contamination concentration].

Contaminants in the snow can be used to reflect regional and global environmental pollution caused by human activities. However, so far, the research on space-time monitoring of snow contamination concentration for a wide range or areas difficult for human to reach is very scarce. In the present paper, based on the simulated atmospheric deposition experiments, the spectroscopy technique method was applied to analyze the effect of different contamination concentration on the snow reflectance spectra. Then an evaluation of snow contamination concentration (SCC) retrieval methods was conducted using characteristic index method (SDI), principal component analysis (PCA), BP neural network and RBF neural network method, and the estimate effects of four methods were compared. The results showed that the neural network model combined with hyperspectral remote sensing data could estimate the SCC well.

[Light absorption by suspended particulate matter in Chagan Lake, Jilin].

Spectral characteristics and the magnitudes of light absorption by suspended particulate matter were determined by spectrophotometry in this optically complex Lake Chagan waters for the purpose of surveying the natural variability of the absorption coefficients to parameterize the bio-optical models for converting satellite or in-situ water reflectance signatures into water quality information. Experiments were carried out on seasonal frozen Lake Chagan, one representative inland case-2 water body in Northeast of China. Particulate absorption properties analyzed using the field data on July 15th and October 12th 2009 were measured using the quantitative filter technique to produce absorption spectra containing several fractions that could be attributed to two main optical active constituents (OACs) phytoplankton pigments and non-algal particulates (mineral sediments, and organic detritus). Results suggested that the suspended particulate matter (SPM) concentration was higher while phytoplankton biomass (chlorophyll-a concentration) was lower in July and that in October. The spectral shape of total suspended particulate matter resembled that of non-algal particulates which contributed greater than phytoplankton in total particulate absorption during both periods. An obvious absorption peak occurring at around 440 nm exhibited an increase in phytoplankton contribution in October. Non-algal particulate absorption at 440 nm (a(NAP) (440)) had better correlation with total suspended particulate matter concentration than that with chlorophyll-a over the two periods. Light absorption by phytoplankton pigments in the Chagan lake region was generally lower than that of non-algal components. Chl. a dominating phytoplankton pigment composition functioned exponentially with its absorption coefficients at 440 and 675 nm specifically, the average values of which in July were 0.146 8 m2 x mg(-1) and 0.050 3 respectively while in October they were 0.153 3 and 0.013 2 m2 x mg(-1) varying regionally and seasonally due to the changes in specific composition, light and nutrient conditions.

[Comparison of methods for estimating soybean chlorophyll content based on visual/near infrared reflection spectra].

The estimation of crop chlorophyll content could provide technical support for precision agriculture. Canopy spectral reflectance was simulated for different chlorophyll levels using radiative transfer models. Then with multiperiod measured hyperspectral data and corresponding chlorophyll content, after extracting six wavelet energy coefficients from the responded bands, an evaluation of soybean chlorophyll content retrieval methods was conducted using multiple linear regression, BP neural network, RBF neural network and PLS method. The estimate effects of the three methods were compared afterwards. The result showed that the three methods based on wavelet analysis have an ideal effect on the chlorophyll content estimation. R2 of validated model of multiple linear regression, BP neural network, RBF neural network and PLS method were 0. 634, 0. 715, 0. 873 and 0.776, respectively. PLS based on Gaussian kernel function and RBF NN methods were better with higher precision, which could estimate chlorophyll content stably.

Selecting sites for converting farmlands to wetlands in the Sanjiang Plain, Northeast China, based on remote sensing and GIS.

Wetlands in the Sanjiang Plain are rich in biodiversity and natural resources in the northeast of China. However, this wetland area has decreased in size and deteriorated in quality owing to expanded agricultural activities since the 1950s. Converting farmlands to wetlands is necessary to improve these conditions. Using Remote Sensing (RS) and Geographic Information Systems (GIS) technologies, we derived farmland productivity data and hydrology data for the Sanjiang Plain. The farmland productivity data were derived from land use and net primary productivity (NPP) data of the MODIS products. We obtained three productivity farmland classes (low, medium, and high) through the NPP anomaly percentage method. We were only concerned with the low-productivity farmland. Hydrology data were modeled with a wetness index, which was derived from Digital Elevation Model (DEM) data. Based on these two data layers, we identified and prioritized sites for the conversion of farmlands to wetlands. The areas with low farmland productivity and medium or high wetness values have potential to support the conversion of farmlands to wetlands. Potential sites were prioritized in terms of patch size and proximity to natural wetlands and water bodies. We obtained three priority classes, among which the high-priority class would be used as the areas for the recent conversion of farmlands to wetlands. The area of this class was 75,888 ha and accounted for 1.3% of the total farmland area.

Estimation of chlorophyll-a concentration using field spectral data: a case study in inland Case-II waters, North China.

In the remote sensing of chlorophyll-a (Chla) in inland Case-II waters, the assumption that the optical parameter of Chla specific absorption coefficient a*ph remains constant usually restrains application of many models. In this paper, we presented a newly developed model [Rrs(-1)(lambda1) - Rrs(-1)(lambda2)] x Rrs(lambda3) x a*ph(-1)(lambda1) which was improved on a previous three-band model to isolate interferences from a*ph. In terms of the importance of water optical properties in the model development, spectral and absorption characteristics were analyzed for Shitoukoumen Reservoir and Songhua Lake in Northeast China, as typical examples of inland Case-II waters. Both waters showed overwhelming absorption sum of tripton and chromophoric dissolved organic matter (CDOM) owing to their relatively low Chla contents (1.53 to 19.35 microgl(-1)). According to the optical characteristics of waters studied, optimal positions for lambda (1), lambda (2) and lambda (3) were spectrally tuned to be at 664, 684 and 705 nm, respectively. The model allowed accurate Chla estimation with a determination coefficient (R (2)) close to 0.98 and a root mean square error (RMSE) of 0.87 microgl(-1). Comparison of different models further showed the stability of the improved model, implying its potential use in water color remote sensing. Although the findings underline the rationale behind the improved model, an extensive database containing data in different water conditions and water types is required to generalize its application.

Conditioned taste aversion memory extinction temporally induces insular cortical BDNF release and inhibits neuronal apoptosis.

BACKGROUND: Memory extinction has been reported to be related to psychiatric disorders, such as post-traumatic stress disorder (PTSD). Secretion and synthesis of brain-derived neurotrophic factor (BDNF) have been shown to temporally regulate various memory processes via activation of tropomyosin-related kinase B (TrkB) receptors. However, whether memory extinction induces the synthesis and secretion of BDNF on the basis of its localization is not understood. In this study, we aim to investigate activity-dependent BDNF secretion and synthesis in the insular cortex (IC) in the setting of conditioned taste aversion (CTA) memory extinction. MATERIALS AND METHODS: Rats were subjected to CTA memory extinction and BDNF antibody (or the equal volume of vehicle) was microinjected into the IC immediately after the extinction testing. Real-time polymerase chain reaction and in situ hybridization were used to detect the gene expression of BDNF, NGF and NT4. The protein levels of BDNF were determined through the enzyme-linked immunosorbent assay. In addition, the levels of phosphorylated TrkB normalized to total TrkB were evaluated using immunoprecipitation and immunoblotting. c-Fos, total extracellular signal-regulated kinase (Erk), phosphorylated Erk, and apoptosis-related protein (caspase-3), were detected by Western blotting. RESULTS: We found that blocking BDNF signaling within the IC disrupts CTA extinction, suggesting that BDNF signaling in the IC is necessary for CTA extinction. Increased expression levels of c-Fos indicate the induced neuronal activity in the IC during CTA extinction. In addition, temporal changes in the gene expression and protein levels of BDNF in the IC were noted during extinction. Moreover, we found that phosphorylation of TrkB increased prior to the enhanced BDNF expression, suggesting that CTA extinction induces rapid activity-dependent BDNF secretion in the IC. Finally, we found decreased expression of caspase-3 in the IC after CTA extinction. CONCLUSION: These results demonstrate that CTA memory extinction temporally induces the release and synthesis of BDNF in the IC and inhibits neuronal apoptosis.