Polymers
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2022
·Vol. 15
·期 1
·108
·
IF 4.967
Bin Chu,Xiaoli Li,Shiqiang Fan,Jinmei He,Xiaohong Ge,Hui Li,Changsheng Chen,Zhen Wang,Song Wang,Boning Li
Biodegradable materials are a next-generation invention for the treatment of congenital heart diseases. However, the corresponding technology used to develop ideal biomaterials still presents challenges. We previously reported the first biodegradable atrial septal defect (ASD) occluder made of poly-lactic acid (PLLA). Unfortunately, the PLLA occluder had a limited endothelialization effect. In this study, the surface of the occluder membrane was coated with sericin/CD34 antibodies to promote the growth of endothelial cells and the regeneration of defective tissue and enhance the repair of the atrial septal defect. The physicochemical properties of the coat on the surface of the fiber membrane were characterized. The sericin coat successfully covered the fiber surface of the membrane, and the thickness of the membrane increased with the sericin concentration. The swelling rate reached 230%. The microscopic observation of fluorescently labeled CD34 antibodies showed that the antibodies successfully attached to the fiber membrane; the fluorescence intensity of PLLA-SH5 was particularly high. The in vitro experiment showed that the PLLA-SH-CD34 fiber membrane was biocompatible and promoted the adhesion and proliferation of endothelial cells. According to our findings, the PLLA-SH-CD34 membrane provides a theoretical and technical basis for the research and development of novel biodegradable occluders.Keywords:biodegradable;CD34 antibody;endothelialization;fiber membrane
研究领域:
生物医学工程
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组织工程
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心血管疾病
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BEHAVIOURAL NEUROLOGY
·
2023
·
IF 2.8
Lijuan Chen,Jing Li,Xinglian Liu,Zhiwei Zhao,Yan Jin,Yikun Fu,Aiqin Zhou,Chengqun Wang,Yan Zhou
Vitamin B6 (VB6) exhibits therapeutic effects towards autism spectrum disorder (ASD), but its specific mechanism is poorly understood. Rat dams were treated with VB6 standard, VB6 deficiency, or VB6 supplementary diet, and the same treatment was provided to their offspring, with their body weights monitored. Three-chambered social test and open field test were employed to evaluate the effect of VB6 on autism-like behaviors. Gamma-aminobutyric acid (GABA) generation and synaptic inhibition of neurons in the hippocampus of rat were detected via immunofluorescence staining, followed by the measurement of GABA concentration through high-performance liquid chromatography (HPLC). The role of VB6 in the autophagy and apoptosis of cells was determined via Western blot and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). In order to conduct rescue experiments, the inhibition of mammalian target of rapamycin (mTOR) or the activation of GABA was achieved by drug administration to the offspring rats with VB6 deficiency. As a result, no evident difference in weight was observed in the offspring with varied VB6 treatments. VB6 deficiency impaired social interaction; aggravated self-grooming and bowel frequency; decreased GABA concentration, VIAAT, GAD67, vGAT expressions, and LC3 II/LC3 I ratio; increased p62 level and p-mTOR/mTOR ratio; and promoted cell apoptosis. Inhibition of mTOR reversed the effect of VB6 deficiency on cell autophagy. GABA activation or mTOR inhibition offset the role of VB6 deficiency in autism-like behaviors and hippocampal GABA expression. Collectively, VB6 deficiency induces autism-like behaviors in rats by regulating mTOR-mediated autophagy in the hippocampus.
研究领域:
神经科学
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药理学
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行为科学
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分子生物学
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Neuroscience Bulletin
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2026
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IF 6.8
Xu Daxiang,Zhang Baoshen,Jiang Pengfei,Zhu Pei,Mi Da,Huang Wei,Ba Ru,Zhao Chunjie
Striatal dysfunction is a feature of autism spectrum disorder (ASD); however, the molecular mechanisms underlying its development remain unclear. Mutations in the transcription factor FOXG1 lead to FOXG1 syndrome, which shares core clinical features with ASD. In the present study, we conditionally deleted Foxg1 in the striatal direct pathway spiny projection neurons (dSPNs) to create Foxg1 conditional knockout (cKO) mice, which we found recapitulated classic ASD-like symptoms, including social deficits, communication impairments, and restricted repetitive behaviors. Loss of FOXG1 further resulted in simplified dendritic arborization and reduced dendritic spine density. We found that FOXG1 drives a set of ASD risk genes, including synaptic receptors and scaffolding proteins, to coordinate the development and function of dSPNs. Further, FOXG1 directly regulated the transcription of GABA B receptor subunit 2 to control the activity of dSPNs. Pharmacological enhancement of the GABA B receptor activity effectively restored the excitation/inhibition balance and ameliorated behavioral abnormalities in Foxg1 cKO mice. Our findings reveal a novel role for FOXG1 in dSPNs, provide new insights into the pathogenesis of ASD and FOXG1 syndrome, and indicate that targeting GABA B receptor activation may serve as a potential therapeutic strategy for ASD.
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Metabolites
·
2025
·Vol. 15
·期 2
·134
·
IF 3.7
Yunchen Meng,Yiling Hu,Yaqi Xue,Zhiping Zhen
Objectives:This study aimed to investigate the regulatory impact of early swimming intervention on striatal metabolism inShank3gene knockout ASD model rats.Methods:Shank3gene knockout exon 11–21 male 8-day-old SD rats were used as experimental subjects and randomly divided into the following three groups: aShank3knockout control group (KC), a wild-type control group (WC) from the same litter, and aShank3knockout swimming group (KS). The rats in the exercise group received early swimming intervention for 8 weeks starting at 8 days old. LC-MS metabolism was employed to detect the changes in metabolites in the striatum.Results:There were 17 differential metabolites (14 down-regulated) between the KC and WC groups, 19 differential metabolites (18 up-regulated) between the KS and KC groups, and 22 differential metabolites (18 up-regulated) between the KS and WC groups.Conclusions:The metabolism of striatum inShank3knockout ASD model rats is disrupted, involving metabolites related to synaptic morphology, and the Glu and GABAergic synapses are abnormal. Early swimming intervention regulated the striatal metabolome group of the ASD model rats, with differential metabolites primarily related to nerve development, synaptic membrane structure, and synaptic signal transduction.
研究领域:
神经科学
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代谢组学
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行为学
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2025
·
IF 5.2
Honglin Li,Ya Chen,Yue Qiu
Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social interaction and repetitive, stereotyped behaviors. There is no universally effective pharmacological treatment targeting its core symptoms. Oxytocin, an endogenous polypeptide known as the “social hormone”, has shown potential in improving emotional recognition and social interactions in individuals with ASD. However, its clinical application has been limited due to its short half-life and poor blood–brain barrier penetration. To address these challenges, we utilized peptide lipidation technology to enhance the pharmacokinetic properties and brain bioavailability of oxytocin. A series of lipidated oxytocin analogs was designed and synthesized, exhibiting superior brain distribution and pharmacokinetic profiles in valproic acid-induced autistic rat models compared to unmodified oxytocin. Among these analogs, C16-modified oxytocin (C16-OT), administered intrathecally, achieved the most extensive brain distribution with limited presence in the blood, resulting in long-lasting improvements in autistic behaviors. These improvements, including enhanced social behaviors and reduced stereotypical actions, were sustained for up to 42 days, contrasting with the brief effects typically reported in previous studies. Furthermore, a comparison of administration routes revealed that intrathecal injection achieved higher brain concentrations and more prolonged social behavioral improvements than intranasal delivery. These findings provide robust preclinical evidence that C16-OT, through optimized lipidation and intrathecal delivery, offers sustained central nervous system activity and significant, long-term reversal of social behavioral deficits in rats with autism.
研究领域:
神经科学
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药理学
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行为科学
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分子生物学
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Neuroscience Bulletin
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2026
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IF 6.8
Yang Dingding,Liu Qian,Ran Hangjun,Xue Teng,Lu Yifan,Yang Xiao,Wang Jiaming,Liu Ling,Wang Wenting,Nie Binbin,Cai Guohong,Wu Shengxi
Olfaction is crucial for rodent social behavior, and olfactory dysfunction has been observed in multiple autism spectrum disorder (ASD) models, but its phenotype in Shank3 ⁻/⁻ mice (a classic ASD model) remains unclear. We systematically assessed olfactory function in Shank3 ⁻/⁻ mice by using a modified olfactory three-chamber test and optimized ultrasonic vocalization (USV) detection in combination with resting-state functional magnetic resonance imaging (rs-fMRI), whole-brain c-Fos mapping, and three-dimensional (3D) behavioral analysis. Our results showed abnormal odor preference and hyperconnectivity in olfaction-associated brain networks. Upon exposure to neutral, appetitive, and social pheromone odors, Shank3 ⁻/⁻ mice displayed atypical whole-brain c-Fos activation patterns, which were coupled with synchronized locomotor suppression and stereotyped behaviors. This study maps the neural-behavioral responses to odors in Shank3 -/- mice, linking olfactory deficits to autism-like behaviors, and highlights the olfactory system as a targetable pathway for sensory-based autism therapies.
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MOLECULAR PSYCHIATRY
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2026
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IF 10.4
Huang Miaoqi,Ye Han,Xu Yong,Xie Jiaoyan,Wang Xinyu,Luo Yan,Liu Peng,Ma Xuanyue,Zhang Shiqing,Jiang Bin,Ye Wen-Cai,Peng Yinghui,Shi Lei
Perturbed protein synthesis plays a crucial role in the pathogenesis of autism spectrum disorder (ASD), but the altered translational pattern and underlying mechanism remain poorly understood. Here, we identified an exaggeration of global protein synthesis in the cerebral cortex of offspring mice following prenatal exposure of valproic acid (VPA), a well-established ASD model. Integrative analysis of polyribosome-based translatome and proteome data revealed remarkable upregulation of ribosomal and mitochondrial genes in VPA-exposed cortex at both translational and protein levels, but not transcriptional levels. Further analysis pinpoints that overactivation of the translation initiation factor eIF4E causes the aberrant translatome and mitochondrial impairments in VPA-exposed cortex. Pharmacological inhibition of eIF4E phosphorylation during juvenile displayed persistent effectiveness in mitigating ASD-like social deficits and stereotyped behavior in VPA mice until adulthood. Collectively, these findings demonstrate that eIF4E overactivation leads to imbalanced protein synthesis that favors translation of ribosomal and mitochondrial genes, causing core ASD-like behaviors.
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Food & Function
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2026
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IF 6.3
Meng Sun,Xin Wang,Qian Zhang,Ziyi Wang,Jianhong Luo,Junyu Xu,Xiaoqiong Li
Autism spectrum disorder (ASD), a neurodevelopmental condition with complex etiology involving gut–brain axis interactions. It remains elusive how prebiotics modulate this axis to alleviate ASD symptoms. This study aimed to investigate whether xylitol, a potential prebiotic, improves behavioral and neural deficits in Chd8+/− mice, a genetic model of ASD, and to explore the associated roles of gut microbiome, neurotransmitters and synaptic morphology in these effects. We found that Chd8+/− mice exhibited disrupted gut microbiota, imbalanced levels of key neuromodulators including indole-3-lactic acid (ILA), asparagine (Asn) and glycine (Gly), as well as reduced density of dendritic spine and maturity in the mPFC and hippocampal CA1 regions, and diminished c-Fos activation in response to social stimuli. Xylitol supplementation significantly ameliorated social deficits, restored microbial composition and neurotransmitter metabolite profiles, and rescued synaptic maturation and neuronal activity in these mice. These findings suggest that xylitol may act via the gut–brain axis to reverse ASD like phenotypes, although direct causal evidence remains to be established. Nonetheless, this work supports the potential of xylitol as a dietary intervention for ASD.
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SENSORS AND ACTUATORS B-CHEMICAL
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2020
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IF 7.1
Xianfeng Wang,Xiaolong Chen,Chengxiang Chu,Yuanyi Deng,Mei Yang,Zhong Ji,Faliang Xu,Danqun Huo,Yang Luo,Changjun Hou
High-performance detection of adenosine triphosphate (ATP) is of great importance due to its irreplaceable roles in various physiological processes. In this work, a four-stage signal amplification was established for ATP detection based on an allosteric probe-conjugated strand displacement amplification (SDA) integrated with CRISPR/Cpf1 system (ASD-Cpf1). An allosteric probe (AH) with a hairpin structure was designed to reduce background interference from self-extension and non-specific amplification during the SDA reaction. ATP bound with the aptamer segment at 5′-terminal of AH probe and subsequently opened the AH probe to activate the SDA reaction. The amplification products were recognized by CRISPR/Cpf1 system and triggered the ssDNase activity of Cpf1, resulting in robust cleavage of surrounding DNA FQ-reporter (fluorophore-quencher labeled short single-stranded DNA sequence). With the four-step amplification, ATP was measured with high sensitivity and low background interference. Under the optimal conditions, a linear relationship was obtained between the fluorescence response and ATP concentrations ranging from 2 pM to 10 μM with a limit of detection (LOD) as low as 1.8 pM. Successful detection of ATP in diluted human serum samples further indicated that ASD-Cpf1 system provided a potential platform for detection of small molecules.
研究领域:
分析化学
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分子生物学
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生物技术
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Microbiome
·
2023
·Vol. 11
·期 1
·1-23
·
IF 15.5
Wang Tingting,Chen Beidi,Luo Mingcui,Xie Lulu,Lu Mengxi,Lu Xiaoqian,Zhang Shuai,Wei Liyi,Zhou Xinli,Yao Baozhen,Wang Hui,Xu Dan
Background Autism spectrum disorder (ASD) has been associated with intrauterine growth restriction (IUGR), but the underlying mechanisms are unclear. Results We found that the IUGR rat model induced by prenatal caffeine exposure (PCE) showed ASD-like symptoms, accompanied by altered gut microbiota and reduced production of indole 3-propionic acid (IPA), a microbiota-specific metabolite and a ligand of aryl hydrocarbon receptor (AHR). IUGR children also had a reduced serum IPA level consistent with the animal model. We demonstrated that the dysregulated IPA/AHR/NF-κB signaling caused by disturbed gut microbiota mediated the hippocampal microglia hyperactivation and neuronal synapse over-pruning in the PCE-induced IUGR rats. Moreover, postnatal IPA supplementation restored the ASD-like symptoms and the underlying hippocampal lesions in the IUGR rats. Conclusions This study suggests that the microbiota-IPA-brain axis regulates ASD susceptibility in PCE-induced IUGR offspring, and supplementation of microbiota-derived IPA might be a promising interventional strategy for ASD with a fetal origin.
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Food & Function
·
2023
·Vol. 15
·期 1
·387-400
·
IF 6.1
Chuanchuan Wang,Weixuan Chen,Yishan Jiang,Xiao Xiao,Qianhui Zou,Jiarui Liang,Yu Zhao,Qianxu Wang,Tian Yuan,Rui Guo,Xuebo Liu,Zhigang Liu
Autism Spectrum Disorder (ASD), a complex neurodevelopmental disorder marked by social communication deficits and repetitive behaviors, may see symptom amelioration through gut microbiota modulation. This study investigates the effects of a synbiotic – specifically a probiotic amplified by prebiotic supplementation – on ASD-like mouse model's social deficiencies. This model was established via valproic acid injection into pregnant females. Post-weaning, male progeny received daily synbiotic treatment, a combination of Lactobacillus reuteri (L. reuteri) and inulin, for four weeks. Results indicated that the synbiotic rectified social impairments and attenuated inflammatory cytokine expressions in the brain. Moreover, synbiotic intervention protected gut barrier integrity and altered the gut microbiota composition, enhancing the butyrate-producing Bifidobacterium abundance. The synbiotic elevated metabolites such as butyrate and 3-hydroxybutyric acid (3-HB), alongside upregulated genes associated with 3-HB synthesis in the colon and liver, and brain receptors. Conclusively, the synbiotic combination of L. reuteri and inulin mitigated ASD-related social impairments, partially via their regulatory effect on the gut–brain axis.
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