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Stiffness-tunable biomaterials provide a good extracellular matrix environment for axon growth and regeneration

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Neural Regeneration Research 2025年第5期20卷 1364-1376页

作者： Ronglin Han Lanxin Luo Caiyan Wei Yaru Qiao Jiming Xie Xianchao Pan Juan Xing department of Pathophysiology School of Basic Medical SciencesSouthwest Medical UniversityLuzhouSichuan ProvinceChina department of Medicinal Chemistry School of PharmacySouthwest Medical UniversityLuzhouSichuan ProvinceChina

Neuronal growth, extension, branching, and formation of neural networks are markedly influenced by the extracellular matrix—a complex network composed of proteins and carbohydrates secreted by cells. In addition to providing physical support for cells, the extracellular matrix also conveys critical mechanical stiffness cues. During the development of the nervous system, extracellular matrix stiffness plays a central role in guiding neuronal growth, particularly in the context of axonal extension, which is crucial for the formation of neural networks. In neural tissue engineering, manipulation of biomaterial stiffness is a promising strategy to provide a permissive environment for the repair and regeneration of injured nervous tissue. Recent research has fine-tuned synthetic biomaterials to fabricate scaffolds that closely replicate the stiffness profiles observed in the nervous system. In this review, we highlight the molecular mechanisms by which extracellular matrix stiffness regulates axonal growth and regeneration. We highlight the progress made in the development of stiffness-tunable biomaterials to emulate in vivo extracellular matrix environments, with an emphasis on their application in neural repair and regeneration, along with a discussion of the current limitations and future prospects. The exploration and optimization of the stiffness-tunable biomaterials has the potential to markedly advance the development of neural tissue engineering.

关键词： alginate axon growth biomaterials extracellular matrix neural repair neurons neuroregeneration polyacrylamide polydimethylsiloxane stiffness

Emerging role of A-kinase anchoring protein 5 signaling in reward circuit function

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Neural Regeneration Research 2025年第10期20卷 2913-2914页

作者： William J.Flerlage Mark L.Dell’Acqua Brian M.Cox Fereshteh S.Nugent Uniformed Services University of the Health Sciences Department of Pharmacology and Molecular TherapeuticsBethesdaMDUSA department of pharmacology University of Colorado School of MedicineAnschutz Medical CampusAuroraCOUSA

There is a strong evidence supporting the hypothesis of synaptic dysfunction as a major contributor to neural circuit and network disruption underlying emotional and mood dysregulation in psychiatric disorders(Simmons et al.,2024).Diverse sets of distinct molecular signaling pathways converge on the synapse to regulate synaptogenesis,synaptic function,and synaptic plasticity in brain regions and circuits through complex interactions organized by numerous multivalent protein scaffolds,including the family of proteins known as A-kinase anchoring proteins(AKAPs).

关键词： function supporting

Hydrogen sulfide reduces oxidative stress in Huntington's disease via Nrf2

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Neural Regeneration Research 2025年第6期20卷 1776-1788页

作者： Zige Jiang Dexiang Liu Tingting Li Chengcheng Gai Danqing Xin Yijing Zhao Yan Song Yahong Cheng Tong Li Zhen Wang department of Physiology School of Basic Medical SciencesCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina department of medical Psychology and Ethics School of Basic Medicine SciencesCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina department of Neurosurgery Surgery Qingdao Municipal HospitalQingdaoShandong ProvinceChina

The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.

关键词： apoptosis cystathionine-β-synthase nuclear factor erythroid 2-related factor 2 Huntington's disease hydrogen sulfide mitochondrion neuroplasticity oxidative stress quinolinic acid reactive oxygen species

Taurine: A Comprehensive Review of Its Origin， Pharmacological Properties， Potential Health Benefits， Therapeutic Applications， and Safety Profile

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Food Science and Human Wellness 2025年

作者： Pengfei Zhao Ying Qi department of pharmacology， school of Pharmacy， China medical University (Shenyang) department of Radiology， Shengjing Hospital of China medical University

Taurine， a multifunctional sulfur-containing amino acid and conditionally essential nutrient for humans， plays a key role in various biological processes and has attracted significant attention for its therapeutic potential. Originally isolated from ox bile， taurine has broad applications， but a comprehensive understanding of its pharmacological properties， health benefits， and safety profile remains incomplete. In this review， we critically evaluate the existing evidence on taurine’s effects based on an extensive literature search of multiple databases， including PubMed， Web of Science， Scopus， ScienceDirect， Google Scholar， CNKI， and Baidu Scholar， up to May 2024. Taurine demonstrates a range of beneficial effects， including antioxidant and anti-inflammatory activities， modulation of lipid metabolism， neuroprotection， and cardiovascular protection. It has shown substantial impacts on anti-tumor activity， immune system modulation， blood pressure and lipid regulation， glycemic control， hepatobiliary protection， and potential anti-aging effects. However， the precise regulatory pathways underlying these benefits are not yet fully understood. Epidemiological studies indicate a correlation between high taurine dosage and a reduced risk of diseases. However， direct evidence from interventional studies remains insufficient， and existing clinical trials require further in-depth investigation. Concerns about improper use and potential health risks also highlight the need for thorough safety assessments. To address these gaps， we recommend conducting well-designed， long-term randomized controlled trials to establish effective doses for disease prevention and assess taurine’s potential as a primary or adjunct therapy. This review aims to guide future research and support public health efforts， ultimately improving health outcomes.

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Compartmentalized regulation of organelle integrity in neurodegenerative diseases:lessons from the Drosophila motor neuron

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Neural Regeneration Research 2025年第1期20卷 195-196页

作者： Hyun Sung department of Neurology Johns Hopkins University School of MedicineBaltimoreMDUSA medical Research Institute and Department of PharmacologyPusan National University School of MedicineYangsanRepublic of Korea

Neurons are highly polarized,morphologically asymmetric,and functionally compartmentalized cells that contain long axons extending from the cell *** this reason,their maintenance relies on spatiotemporal regulation of organelle distribution between the somatodendritic and axonal *** some organelles,such as mitochondria and smooth endoplasmic reticulum,are widely distributed throughout the neuron,others are segregated to either the somatodendritic or axonal *** example,Golgi outposts and acidified lysosomes are predominantly present in the somatodendritic domain and rarely distributed along the axon,whereas newly formed autophagosomes and synaptic vesicles are mainly distributed in the distal axon(Britt et al.,2016).

关键词： organelle regulation distribution

A new Synbiotic supplementation ameliorates ulcerative colitis via modulating microbial homeostasis， protecting intestinal barrier integrity， and maintaining immunity homeostasis in mice

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Food Science and Human Wellness 2025年

作者： Yongbo Kang Liping Li Jing Guo Yue Cai Ying Yang department of microbiology and immunology， school of basic medical Sciences， Shanxi medical University department of Endocrinology Affiliated Hospital of Yunnan University

Ulcerative colitis [UC] is established by a chronic， diffuse inflammation of colonic mucosa with poorly defined etiology， and without sufficient treatment or cure available for remission. In this context， there is a growing recognition and consensus that synbiotic supplement may be promising and impactful strategies towards ameliorating UC and related inflammatory disorders， garnering significant attention from researchers as an alternative therapy. Herein， we innovatively prepared a novel synbiotic combination including Lactobacillus acidophilus， Bifidobacterium infants and prebiotics konjac glucomannan oligosaccharides [KGMO] to explore the potential therapeutic effects in dextran sodium sulfate [DSS] induced UC mouse model. The results demonstrated that the synbiotic effectively improved colitis symptoms in mice by mitigating weight loss， disease activity index [DAI]， colonic pathological damage， and colonic oxidative stress. it also observed that the synbiotic preserve intestinal barrier function integrity， reduces metabolic endotoxemia as well as inhibits the TLR4/NF-κB， NLRP3/Caspase-1， and Nrf2/Keap1 signaling pathway. Furthermore， the synbiotic modulated microbial homeostasis directly by enhancing beneficial microbes and reducing potentially harmful bacteria. In addition， microbiome phenotype prediction and bacterial functional potential prediction analysis demonstrated that the synbiotic supplementation regulated gut microbiota function involving inflammatory injury， metabolism， immune response， and pathopoiesia. Especially， the synbiotic not only restored the balance of Th1/Th2 cells as well as Th17/Treg cells along with specific inflammatory factors expression， but also maintained bile acid homeostasis by regulating FXR/FGF15 signaling pathway. Especially important is that the synbiotic was as effective as mesalazine against UC. According to above data， it is seen that this novel synbiotic could be a good candidate drug for ameliorating UC through its ant

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Targeting Epac2 and GluA3-containing AMPARs:a novel therapeutic strategy for Alzheimer's disease

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Neural Regeneration Research 2025年第11期20卷 3223-3224页

作者： Tong Zhang Martina Schmidt department of Molecular pharmacology Groningen Research Institute of PharmacyUniversity of GroningenGroningenThe Netherlands school of Pharmacy Tianjin Medical UniversityTianjinChina

Alzheimer's disease(AD)is a neurodegenerative disease that manifests progressive decline in memory and *** the early stage of AD,memory retrieval is impaired preceding memory acquisition and consolidation(Roy et al.,2016).Prior to the onset of symptoms,pathological amyloid-β(Aβ)plagues and tau protein tangles accumulate in extracellular and intracellular spaces,respectively,leading to *** these hallmark pathologies,Aβ is proposed to be the primary etiology by triggering a cascade of pathogenic events,including neuroinflammation,oxidative stress,tau hyperphosphorylation,synaptic/neuronal dysfunction,and neuronal death(Zhang et al.,2023b).

关键词： Alzheimer impaired Aβ

Strengths,weaknesses,opportunities,and threats analysis of combination therapy for inflammatory bowel disease

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World Journal of Gastroenterology 2025年第9期31卷 176-182页

作者： Jia-Wang Yan Mei Nie Hang Zhang Yan-Miao Liu Fu-Shan Tang department of Clinical Pharmacy Zunyi Medical UniversityZunyi 563006Guizhou ProvinceChina Key Laboratory of basic pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education Zunyi Medical UniversityZunyi 563006Guizhou ProvinceChina Key Laboratory of basic pharmacology of Guizhou Province and school of Pharmacy Zunyi Medical UniversityZunyi 563006Guizhou ProvinceChina The First Clinical Institute Zunyi Medical UniversityZunyi 563006Guizhou ProvinceChina

Inflammatory bowel disease(IBD),encompassing Crohn’s disease and ulcerative colitis,manifests as a chronic,recurrent,and refractory intestinal inflammatory condition significantly impacting patients’quality of *** ongoing research,its etiology and pathogenesis remain incompletely *** advancements in medical research highlight the critical role of drug combination therapies in managing *** paper employs the strengths,weaknesses,opportunities,and threats framework to evaluate the four strategic elements(strengths,weaknesses,opportunities,and threats)pertaining to combination therapies for *** the strengths,the paper underscores the efficacy of multi-targeted strategies,the advancement of personalized medicine,and the mitigation of drug ***,the analysis identifies significant weaknesses,including the prohibitive cost of treatment,issues with patient compliance,and the necessity for comprehensive long-term safety *** paper also delineates opportunities to augment therapeutic success through the incorporation of biomarkers,the application of artificial intelligence,and extensive international collaborative *** contrast,the paper does not shy away from addressing the threats,which include the potential for therapeutic resistance and the logistical challenges inherent in global therapy *** initiatives aim to refine future therapeutic practices,fostering safer,more effective,and personalized treatment paradigms for IBD patients.

关键词： Inflammatory bowel disease Ulcerative colitis Crohn’s disease Combination therapy Strengths,weaknesses,opportunities,threats analysis

Müller cells are activated in response to retinal outer nuclear layer degeneration in rats subjected to simulated weightlessness conditions

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Neural Regeneration Research 2025年第7期20卷 2116-2128页

作者： Yuxue Mu Ning Zhang Dongyu Wei Guoqing Yang Lilingxuan Yao Xinyue Xu Yang Li Junhui Xue Zuoming Zhang Tao Chen Aerospace Clinical medical Center School of Aerospace MedicineAir Force Medical UniversityXi’anShaanxi ProvinceChina department of Aviation Medicine Xijing HospitalAir Force Medical UniversityXi’anShaanxi ProvinceChina department of Emergency Medicine Wuhan No.1 HospitalWuhanHubei ProvinceChina Third Regiment School of Basic MedicineAir Force Medical UniversityXi’anShaanxi ProvinceChina Fourth Regiment School of Basic MedicineAir Force Medical UniversityXi’anShaanxi ProvinceChina

A microgravity environment has been shown to cause ocular damage and affect visual acuity,but the underlying mechanisms remain ***,we established an animal model of weightlessness via tail suspension to examine the pathological changes and molecular mechanisms of retinal damage under *** 4 weeks of tail suspension,there were no notable alterations in retinal function and morphology,while after 8 weeks of tail suspension,significant reductions in retinal function were observed,and the outer nuclear layer was thinner,with abundant apoptotic *** investigate the mechanism underlying the degenerative changes that occurred in the outer nuclear layer of the retina,proteomics was used to analyze differentially expressed proteins in rat retinas after 8 weeks of tail *** results showed that the expression levels of fibroblast growth factor 2(also known as basic fibroblast growth factor)and glial fibrillary acidic protein,which are closely related to Müller cell activation,were significantly *** addition,Müller cell regeneration and Müller cell gliosis were observed after 4 and 8 weeks,respectively,of simulated *** findings indicate that Müller cells play an important regulatory role in retinal outer nuclear layer degeneration during weightlessness.

关键词： glial fibrous acidic protein gliosis Müller cells nerve growth factor neural differentiation neurodegeneration proteomic retinal degeneration retinal outer nuclear layer simulated weightlessness