Multibarrier-penetrating drug delivery systems for deep tumor therapy based on synergistic penetration strategy.

Nanotherapies, valued for their high efficacy and low toxicity, frequently serve as antitumor treatments, but do not readily penetrate deep into tumor tissues and cells. Here we developed an improved tumor-penetrating peptide (TPP)-based drug delivery system. Briefly, the established TPP iNGR was modified to generate a linear NGR peptide capable of transporting nanotherapeutic drugs into tumors through a CendR pathway-dependent, neuropilin-1 receptor-mediated process. Although TPPs have been reported to reach intended tumor targets, they often fail to penetrate cell membranes to deliver tumoricidal drugs to intracellular targets. We addressed this issue by harnessing cell penetrating peptide technology to develop a liposome-based multibarrier-penetrating delivery system (mbPDS) with improved synergistic drug penetration into deep tumor tissues and cells. The system incorporated doxorubicin-loaded liposomes coated with nona-arginine (R9) CPP and cyclic iNGR (CRNGRGPDC) molecules, yielding Lip-mbPDS. Lip-mbPDS tumor-targeting, tumor cell/tissue-penetrating and antitumor capabilities were assessed using CD13-positive human fibrosarcoma-derived cell (HT1080)-based in vitro and in vivo tumor models. Lip-mbPDS evaluation included three-dimensional layer-by-layer confocal laser scanning microscopy, cell internalization/toxicity assays, three-dimensional tumor spheroid-based penetration assays and antitumor efficacy assays conducted in an animal model. Lip-mbPDS provided enhanced synergistic drug penetration of multiple biointerfaces for potentially deep tumor therapeutic outcomes.

Versatile dopamine-functionalized hyaluronic acid-recombinant human collagen hydrogel promoting diabetic wound healing via inflammation control and vascularization tissue regeneration.

The management of chronic wounds in diabetes remains challenging due to the complexity of impaired wound healing, delayed healing, susceptibility to infection, and elevated risk of reopening, highlighting the need for effective chronic wound management with innovative approaches such as multifunctional hydrogels. Here, we have produced HA-DA@rhCol hydrogels consisting of dopamine-modified hyaluronic acid and recombinant human collagen type-III (rhCol) by oxidative coupling of the catechol group using the H2O2/HRP catalytic system. The post-reactive hydrogel has a good porous structure, swelling rate, reasonable degradation, rheological and mechanical properties, and the catechol group and dopamine impart to the hydrogel tissue adhesiveness, antioxidant capacity, and excellent photothermal effects leading to superior in vitro antimicrobial activity. In addition, the ability of rhCol to confer hydrogels to promote angiogenesis and wound repair has also been investigated. Cytotoxicity and hemolysis tests demonstrated the good biocompatibility of the hydrogel. Wound closure, collagen deposition and immunohistochemical examination confirmed the ability of the hydrogel to promote diabetic wound healing. In summary, the adhesive hemostatic antioxidative hydrogel with rhCol to promote wound healing in diabetic rat is an excellent chronic wound dressing.

Corrigendum: Editorial: Recent innovations to inhibit scar formation for better skin regeneration.

[This corrects the article DOI: 10.3389/fsurg.2023.1325832.].

Recent Development and Applications of Polydopamine in Tissue Repair and Regeneration Biomaterials.

The various tissue damages are a severe problem to human health. The limited human tissue regenerate ability requires suitable biomaterials to help damage tissue repair and regeneration. Therefore, many researchers devoted themselves to exploring biomaterials suitable for tissue repair and regeneration. Polydopamine (PDA) as a natural and multifunctional material which is inspired by mussel has been widely applied in different biomaterials. The excellent properties of PDA, such as strong adhesion, photothermal and high drug-loaded capacity, seem to be born for tissue repair and regeneration. Furthermore, PDA combined with different materials can exert unexpected effects. Thus, to inspire researchers, this review summarizes the recent and representative development of PDA biomaterials in tissue repair and regeneration. This article focuses on why apply PDA in these biomaterials and what PDA can do in different tissue injuries.

Targeting Diverse Wounds and Scars: Recent Innovative Bio-design of Microneedle Patch for Comprehensive Management.

Wounds and the subsequent formation of scars constitute a unified and complex phased process. Effective treatment is crucial; however, the diverse therapeutic approaches for different wounds and scars, as well as varying treatment needs at different stages, present significant challenges in selecting appropriate interventions. Microneedle patch (MNP), as a novel minimally invasive transdermal drug delivery system, has the potential for integrated and programmed treatment of various diseases and has shown promising applications in different types of wounds and scars. In this comprehensive review, the latest applications and biotechnological innovations of MNPs in these fields are thoroughly explored, summarizing their powerful abilities to accelerate healing, inhibit scar formation, and manage related symptoms. Moreover, potential applications in various scenarios are discussed. Additionally, the side effects, manufacturing processes, and material selection to explore the clinical translational potential are investigated. This groundwork can provide a theoretical basis and serve as a catalyst for future innovations in the pursuit of favorable therapeutic options for skin tissue regeneration.

PD-1 blockade and radiotherapy combination for advanced Epstein-Barr virus-associated intrahepatic cholangiocarcinoma: a case report and literature review.

Advanced intrahepatic cholangiocarcinoma (ICC) is a rare malignant tumor of biliary epithelial cells, known for its extremely unfavorable prognosis. In the absence of intervention, patients typically survive for less than 5 months. Current guidelines from the Chinese Society of Clinical Oncology (CSCO), National Comprehensive Cancer Network (NCCN), and European Society for Medical Oncology (ESMO) recommend chemotherapy-based systemic therapy as the standard treatment for advanced ICC. However, the first-line regimen, consisting of gemcitabine in combination with cisplatin, generally results in a median survival of approximately one year, which is considered suboptimal. Significant progress has been made in radiotherapy techniques, molecular diagnostics, and tumor immune microenvironments. The integration of immune and radiation therapies has revolutionized treatment strategies for cholangiocarcinoma. Moreover, combined therapeutic regimens have shown promising results in improving survival rates among patients with advanced ICC. In this study, we present a case report of a 70-year-old male patient diagnosed with stage IV ICC, featuring metastases to the retroperitoneal, left adrenal, and left supraclavicular lymph nodes. The patient exhibited a high tumor mutational load, significant microsatellite instability, and hyper-expression of PD-L1 (90%), along with positive Epstein-Barr virus-encoded RNA (EBER). Pembrolizumab, a programmed cell death 1 (PD-1) inhibitor, was administered in conjunction with radiotherapy. As a result, considerable shrinkage and inactivation of the primary foci were observed, accompanied by the disappearance of metastases. Ultimately, the patient achieved complete remission and maintained progression-free survival for 41 months following the initial treatment. To the best of our knowledge, this represents the longest case of complete remission using a combination of immunotherapy and radiotherapy as a first-line regimen for the high tumor mutational load, microsatellite instability, and PD-L1 expression (90%) subtype of Epstein-Barr virus-associated ICC (EBVaICC). These findings suggest that the combination of PD-1 inhibitors with radiotherapy may serve as a promising therapeutic strategy for treating this particular cancer subtype.

Gene liposome nanocomplex-loaded dermal substitute promotes diabetic chronic wound healing and angiogenesis in rat.

The incidence of chronic diabetic wounds is increasing with the growing number of diabetic patients, and conventional wound dressings have proven to be ineffective in treating them. To address this challenge, researchers have developed artificial dermal substitutes using collagen and hyaluronic acid, which are crucial extracellular matrices. However, these subsitiues lack precision and targeted treatment. To overcome this limitation, a gene liposome nanocomplex-loaded dermal substitute (GDS) has been developed as a potential solution. This innovative biomaterial combines the benefits of liposome nanocomplexes with dermal substitutes to offer a more accurate and effective treatment option for chronic diabetic wounds. The GDS has the ability to deliver genes and therapeutic agents specifically to the wound site, promoting angiogenesis and accelerating the wound healing process. Overall, the GDS presents a promising new approach for the clinical treatment of chronic diabetic wounds, offering a targeted and effective solution for this growing problem.

A Rare Case of Acute Infectious Purpura Fulminans Caused by Klebsiella Pneumoniae and Human Herpesvirus Type 5.

Background: Purpura fulminans (PF), a rare, life-threatening disorder, is a hematological emergency in which there is skin necrosis, disseminated intravascular coagulation (DIC), and protein C deficiency. In PF, the skin necrosis and DIC are secondary to protein C deficiency. This may progress rapidly to multiorgan failure caused by the thrombotic occlusion of small- and medium-sized blood vessels. Case Report: This article presents the case of a 22-year-old male with fever as well as necrotic and purpuric skin lesions. The ultrasound and computed tomography scans revealed infections in the skin wounds as well as venous microthrombosis and thrombosis in multiple intracranial and pulmonary vessels. The laboratory tests showed signs of sepsis, thrombocytopenia, an abnormal decrease in protein C and antithrombin III, DIC, multiple organ and system failures, gastric varices, and gastrointestinal hemorrhage. The blood, sputum, and secretions under the skin lesions were cultured and were positive for Klebsiella pneumoniae. The results of the high-throughput genetic testing of the pathogenic microorganism DNA were consistent. In addition, human herpesvirus type 5 was detected. The histopathological examination of the skin lesions revealed pathological features consistent with PF. After successful treatment by the departments of Dermatology, Emergency Critical Care Medicine, and the Intensive Care Unit, the patient was discharged after 67 days of hospitalization. Conclusion: Adults with acquired protein C and/or S deficiency states, including certain bacterial and viral infections, who drink alcohol and take varieties of non-steroidal anti-inflammatory analgesics at the same time, may develop acute infectious PF. Clinicians should be aware of this for early diagnosis and treatment.

Comprehensive Analysis of Potential Biomarkers of Acute Lymphoblastic Leukemia in Children by Using a Competing Endogenous RNA Network.

Acute lymphoblastic leukemia (ALL) is the most serious hematological carcinoma in adolescents. The significance of long noncoding RNAs (lncRNAs) and their regulative role in the proliferation and differentiation of myeloid cells in cancer has been recently reported. Nevertheless, key RNAs and the regulatory mechanism of competitive endogenous RNA (ceRNA) network affected by pediatric ALL are not fully illustrated. In this study, phase 2 and 3 pediatric ALL RNA profiles were extracted from the TARGET database and used to identify lncRNAs, microRNAs, and messenger RNAs in high-risk ALL and reconstruct the sponge ceRNA regulatory network. Results indicated that 44 lncRNAs, 25 miRNAs, and 115 mRNA were up/downregulated. Functional analysis with differentially expressed RNAs (DERNAs) showed enriched significant signaling pathways, including PI3K-Akt and p53 signaling cascades and other pathways associated with the tumor. Seventeen differential hub RNAs, including LINC00909, BZRAP1-AS1, C17orf76-AS1, HCG11, MIAT, SNHG5, SNHG15, and TP73-AS1, were identified. The Cox model of correlation indicated that 14 of these RNAs were associated with the progression of pediatric ALL. These findings would help clarify the regulatory role of several lncRNAs as well as provide insights into the leukemogenesis of pediatric ALL to further explore novel prognostic markers/therapeutic targets for ALL.

Optimal time-points for detecting expression levels of BAALC, EVI1, and WT1 genes in patients with acute myeloid leukemia: a meta-analysis.

OBJECTIVES: This meta-analysis examined the prognostic role of brain and acute leukemia, cytoplasmic (BAALC), Ecotropic virus integration site-1 (EVI1) and Wilms' tumor 1 (WT1) genes at different time-points during conventional chemotherapy. METHODS: A systematic search of publications indexed in the electronic databases from January 1988 to October 2020 was performed. Over 7525 cases of AML from 25 studies were involved. RESULTS: At diagnosis, overexpression of either BAALC or EVI1 had a negative impact on complete remission achievement (Summary Odds ratios [SORs] for BAALC = 0.32; SORs for EVI1 = 0.49) and survival outcome. The summary hazard ratios of overall survival (OS) and disease-free survival (DFS) were 1.97 and 2.04 for BAALC and 1.33 and 1.86 for EVI1, respectively. The prognostic value of pretreatment WT1 levels was heterogeneous while subgroup analyses unveiled that overexpressed WT1 may correlate with a favorable outcome (summary hazard ratio [SHR] for OS = 0.42). Both WT1 and BAALC played a role in prognosis assessment at post-induction and the diagnostic performance of WT1 transcript reduction was superior to the absolute WT1 level. Post-consolidation WT1 overexpression consistently indicated an increased risk of relapse, while the combined HR for RFS was statistically insignificant (SHR = 4.22). CONCLUSION: These findings confirm the application of BAALC and EVI1 at diagnosis, WT1 after induction chemotherapy in AML patients throughout conventional chemotherapy.

Sildenafil improves right ventricular remodelling in monocrotaline-induced rats by decreasing myocardial apoptosis and activating peroxisome proliferator-activated receptors.

OBJECTIVES: To assess the effect of sildenafil on monocrotaline-induced right ventricular (RV) remodeling and investigate the possible mechanism. METHODS: Rats were subcutaneously injected with monocrotaline to establish an RV remodeling model and then administered sildenafil (25 mg/kg) from days 1 to 28. After 28 days of administration, the RV systolic pressure and the RV hypertrophy index (RVHI) were measured. The morphology of the right ventricle was observed by H&E staining. The ultrastructure of the right ventricle was observed using a transmission electron microscope. The myocardial apoptosis of the right ventricle was evaluated by TUNEL staining. The protein expression of apoptosis-related proteins and PPARs were examined by western blotting. KEY FINDINGS: The results indicated that sildenafil decreased the RV systolic pressure and RVHI, and improved the microstructure and ultrastructure of the right ventricle in monocrotaline-induced rats. In addition, sildenafil suppressed myocardial apoptosis and promoted the protein expression of PPARs of the right ventricle in monocrotaline-induced rats. CONCLUSION: Sildenafil inhibits RV remodeling in monocrotaline-induced rats, which might be partially mediated by reducing myocardial apoptosis and activating PPARs.

Efficacy and safety of retention enema with traditional Chinese medicine for ulcerative colitis: A meta-analysis of randomized controlled trials.

OBJECTIVE: To assess the efficacy and safety of retention enema with traditional Chinese medicine (TCM) for ulcerative colitis (UC) through a meta-analysis of published studies. METHODS: Literatures were retrieved from five electronic databases. Quality evaluation and meta-analysis were respectively conducted using the Cochrane collaboration and RevMan5.3. Overall quality of evidence was evaluated using GRADE system. Effect sizes were pooled using random effect models. RESULTS: Seventeen RCTs were included. Compared with routine pharmacotherapies (RPs), TCM enema exhibited a statistically significant difference in clinical efficacy and reduction of the recurrence rate. The results of qualitative description for other endpoints, such as improvements in anabrosis, ulcer, diarrhea, and hematochezia, suggested that TCM enema had better efficacy than RPs. Furthermore, the incidence of side effects in TCM was lower than that in RPs. CONCLUSION: This meta-analysis confirmed the efficacy and safety of TCM enema for improving UC symptoms. However, further well-designed researches are needed.

[Values of MCV,MCH,ROFT and HbA2 for Screening α-Thalassemia in Guangdong Area].

OBJECTIVE: To investigate the values of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), red cell osmotic fragility test(ROFT) and hemoglobin A2(HbA2) in screening of α-thalassemia in Guangdong area. METHODS: A total of 285 peripheral blood samples in patients treated in our hospital from January 2017 to December 2017 were collected. The detection of thalassemia gene was used as the gold standard, while blood routine examination, hemoglobin electrophoresis, and red cell osmotic fragility test were simultaneously performed. The optimal cut-off values in MCV, MCH, ROFT and HbA2 in α-thalassemia were determined by receiver operator characteristic curve (ROC curve). RESULTS: The most common types of α-thalassemia gene was --SEA/αα (54.59%). Compared with the control group, the differences in MCV, MCH, ROFT and HbA2 showed statistically significantce between different types of α-thalassemia (P<0.05). The best cut-off values of MCV, MCH, ROFT, and HbA2 in the diagnosis of α-thalassemia were 81.45 fl, 27.35 pg, 79.95%, and 2.55% respectively. CONCLUSION: For different laboratories, the cut-off values need to be established for screening α-thalassemia suitable in their own local region．The values of MCV, MCH, ROFT and HbA2 shows higher accuracy and sensitivity in the diagnosis of α-thalassemia. It is recommended to use MCV<81.45fl, MCH<27.35 pg, ROFT<79.95% and HbA2<2.55% as the standards for screening α-thalassemia in Guangdong area.

Chronic exercise buffers the cognitive dysfunction and decreases the susceptibility to seizures in PTZ-treated rats.

Epilepsy is a serious neurological disorder posing a severe burden to our society. Cognitive deficits are very common comorbidities of epilepsy. It is known that enhanced cognition has been demonstrated as an indicator for successful treatment of epilepsy. Physical exercise shows a positive consequence on cognition in healthy individuals and improves health and life conditions in people with epilepsy. However, there is no direct evidence to determine the role and the potential mechanism of physical exercise on the cognitive impairment and the relationship of susceptibility to seizures. The goal of the current investigation was to explore whether sustained physical exercise improves the cognitive dysfunction and simultaneously decreases the susceptibility to seizures in rats with epilepsy. Rats were treated with pentylenetetrazole (PTZ) (35 mg/kg, i.p. [intraperitoneally]) for 36 days to induce chronic epilepsy. During the induction period, rats were exposed to voluntary wheel running or forced swimming 30 min prior to each PTZ injection from the 16th day. The cognition of rats was evaluated by object recognition test and passive avoidance test. The susceptibility to seizures was evaluated by seizure frequency and duration. The levels of synaptic-related proteins including PSD95 (postsynaptic density 95), Synapsin, GluA1, and BDNF (brain-derived neurotrophic factor) were measured to evaluate the hippocampal synaptic plasticity. Furthermore, the GAD67 (glutamic acid decarboxylase) levels and GABA (γ-aminobutyric acid)ergic function in PTZ-treated rats were also determined. Finally, antagonist of GABAAR (GABAA receptors) bicuculline was used to explore the reversal effects of physical activity on seizures and cognition. The results showed that rats subjected to voluntary wheel running or forced swimming showed a significant reduction of seizure frequency and duration in PTZ-treated group relative to rats without running or swimming. In addition, both running and swimming improved cognitive function as measured by enhanced performance in object recognition test and passive avoidance test. Furthermore, the reduced levels of synaptic-related proteins and GABAergic function were reversed by exercise compared with rats without exercise. Moreover, antagonism of hippocampal CA3 (cornu ammonis 3) GABAergic neurons blocks the reversal effects of physical activity on seizures and cognition in PTZ-treated rats. These data showed that chronic physical exercise reduced the frequency of seizures and improved the cognitive function in a rat model of chronic epilepsy through normalization of CA3 synaptic plasticity and GABAergic function. Our findings suggest that chronic physical exercise has beneficial effects on controlling seizure through enhancement of cognition and highlights the possibility to translate into reduced seizure recurrence in people with epilepsy.

Efficacy of traditional Chinese medicine for chronic gastritis: A meta-analysis of randomized controlled trials.

BACKGROUND: To systematically evaluate efficacy of traditional Chinese medicine (TCM) in treating chronic gastritis (CG). METHODS: Data sources from PubMed, Embase, Springer Link, China National Knowledge Infrastructure, Chinese Scientific Journals Database, Chinese Biomedicine Database, and Wan-fang database were searched up to July 5, 2018. Review Manager software version 5.3, the Cochrane Collaboration's risk of bias tool, and the Grading of Recommendations Assessment, Development, and Evaluation profiler software were conducted for this meta-analysis. RESULTS: Sixteen studies involving 1673 participants (906 vs 767) were included in this study. Pooled data showed significant statistical differences between TCM groups and current routine pharmacotherapy (RP) groups in overall clinical efficacy (odds ratio [OR] 4.65; 95% confidence interval [CI] 3.29, 6.56; P < .00001), efficacy under endoscopy (OR 2.46; 95% CI 1.12, 5.43; P = .03), stomach distension (mean difference [MD] -0.37; 95% CI -0.56, -0.19; P < .0001), stomachache (standardized MD [SMD] -0.80; 95% CI -1.45, -0.14; P = .02), and belching (SMD -2.00; 95% CI -3.80, -0.20; P = .03). However, acid regurgitation (SMD -0.71; 95% CI -1.69, 0.28; P = .16) and anorexia (SMD -0.75; 95% CI -2.30, 0.80; P = .35) showed no significant statistical differences between 2 groups. In addition, incidence of adverse reactions of TCM groups was lower than that of RP groups. CONCLUSION: Evidence from this meta-analysis suggests that TCM could be more efficacious than current RP in treating CG. But further standardized research of rigorous design should be needed to further validate its efficacy.

Anisotropic nanocomposite films of hydroxypropylcellulose and graphene oxide with multi-responsiveness.

Anisotropic nanocomposite films of hydroxypropylcellulose (HPC) and graphene oxide (GO) were fabricated by blade-coating of the aqueous mixture to align the substance and subsequent solvent evaporation to freeze the oriented structure. Owing to the anisotropic structure, the composite films showed anisotropic mechanical properties and response to external stimuli. The influences of GO content, stretch rate, and relative humidity on the anisotropic structure and mechanical properties of the films were investigated. The incorporation of GO did not destroy the anisotropic structure of the HPC film, but improved the mechanical properties to some extent and favoured the bending deformation and locomotion of the composite film under the humidity gradient. These behaviours were associated with the large aspect ratio and excellent gas barrier property of GO nanosheets that favoured suppressing the slippage of HPC chains and enhanced the differential volume change at the top and bottom surfaces of the film. The composite HPC film with GO or reduced GO also responded to near-infrared light due to the photothermal effect and the variation of HPC matrix at a high temperature. This facile strategy should be applicable to other natural or synthetic polymers to fabricate anisotropic composite films with potential applications as optical devices, sensors, and actuators.

Manganese(II), lead(II) and cadmium(II) coordination complexes containing a tetrazole-based acylamide ligand: synthesis and the influence of the metal ions on the structures.

Three new manganese(II), lead(II) and cadmium(II) coordination complexes have been prepared by reaction of N-(1H-tetrazol-5-yl)cinnamamide (HNTCA) with divalent metal salts (MnCl2, PbCl2 and CdCl2) in a mixed-solvent system, affording mononuclear to trinuclear structures namely, bis(methanol-κO)bis[5-(3-phenylprop-2-enamido)-1H-1,2,3,4-tetrazol-1-ido-κ2N1,O]manganese(II), [Mn(C10H8N5O)2(CH3OH)2], (1), bis[µ-5-(3-phenylprop-2-enamido)-1H-1,2,3,4-tetrazol-1-ido]-κ3N1,O:N2;κ3N2:N1,O-bis{aqua[5-(3-phenylprop-2-enamido)-1H-1,2,3,4-tetrazol-1-ido-κ2N1,O]lead(II)}, [Pb2(C10H8N5O)4(H2O)2], (2), and hexakis[µ2-5-(3-phenylprop-2-enamido)-1H-1,2,3,4-tetrazol-1-ido-κ3N1,O:N2]tricadmium(II), [Cd3(C10H8N5O)6], (3). The structures of these three compounds reveal that the nature of the metal ions and the side groups of the organic building blocks have a significant effect on the structures of the coordination compounds formed. Intermolecular hydrogen bonds link the molecules into two-dimensional [complex (1)] and three-dimensional hydrogen-bonded networks. Complexes (2) and (3) show significant fluorescence, while complex (1) displays no fluorescence.

[Role of Hepatocyte Growth Factor in Wound Repair].

Hepatocyte growth factor (HGF) is a multifunctional cytokine that is related to many diseases. HGF mainly contributes to cell migration,proliferation,and survival and regulates vascular angiogenesis,matrix deposition,and degradation of wound healing. HGF also promotes wound reepithelialization and reduces scar formation. This review article summarizes the role of HGF in wound repair and the relationship between HGF and other growth factors,especially when applied for the clinical treatment of chronic skin ulcers.

AMPA Receptor Antagonist NBQX Decreased Seizures by Normalization of Perineuronal Nets.

Epilepsy is a serious brain disorder with diverse seizure types and epileptic syndromes. AMPA receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzoquinoxaline-2,3-dione (NBQX) attenuates spontaneous recurrent seizures in rats. However, the anti-epileptic effect of NBQX in chronic epilepsy model is poorly understood. Perineuronal nets (PNNs), specialized extracellular matrix structures, surround parvalbumin-positive inhibitory interneurons, and play a critical role in neuronal cell development and synaptic plasticity. Here, we focused on the potential involvement of PNNs in the treatment of epilepsy by NBQX. Rats were intraperitoneally (i.p.) injected with pentylenetetrazole (PTZ, 50 mg/kg) for 28 consecutive days to establish chronic epilepsy models. Subsequently, NBQX (20 mg/kg, i.p.) was injected for 3 days for the observation of behavioral measurements of epilepsy. The Wisteria floribundi agglutinin (WFA)-labeled PNNs were measured by immunohistochemical staining to evaluate the PNNs. The levels of three components of PNNs such as tenascin-R, aggrecan and neurocan were assayed by Western blot assay. The results showed that there are reduction of PNNs and decrease of tenascin-R, aggrecan and neurocan in the medial prefrontal cortex (mPFC) in the rats injected with PTZ. However, NBQX treatment normalized PNNs, tenascin-R, aggrecan and neurocan levels. NBQX was sufficient to decrease seizures through increasing the latency to seizures, decrease the duration of seizure onset, and reduce the scores for the severity of seizures. Furthermore, the degradation of mPFC PNNs by chondroitinase ABC (ChABC) exacerbated seizures in PTZ-treated rats. Finally, the anti-epileptic effect of NBQX was reversed by pretreatment with ChABC into mPFC. These findings revealed that PNNs degradation in mPFC is involved in the pathophysiology of epilepsy and enhancement of PNNs may be effective for the treatment of epilepsy.