Parkinson's disease（PD） is the second most common neurodegenerative disease in the world， which seriously affects the lives of patients. With the acceleration of aging process， the number of patients continues to rise. Its main pathological features are aggregation of α-synuclein and degenerative death of dopaminergic neurons in the substantia nigra. However， the pathogenesis of PD is still unclear. According to reports， the brain-derived neurotrophic factor（BDNF）/tyrosine kinase receptor B（TrkB） signaling pathway is highly expressed and activated in dopaminergic neurons in the substantia nigra， which is closely related to neurophysiological processes such as neurogenesis， synaptic plasticity， neuroinflammation， and oxidative stress. It plays an important role in the occurrence and development of PD. At present， the treatment methods of Western medicine for PD are mainly based on drugs such as levodopa and dopamine agonists to alleviate motor symptoms， but with the increase of dose， the adverse reactions are significantly enhanced. Traditional Chinese medicine（TCM） has attracted people to explore its therapeutic effects on PD due to its characteristics of homology of medicine and food， economy， minor adverse reactions and multi-target action. Therefore， this paper systematically reviews the role of BNDF/TrkB pathway in the pathogenesis of PD and the mechanism of TCM formulas， extracts and monomers in the treatment of PD by regulating the BNDF/TrkB pathway according to retrieving the latest research reports at home and abroad， so as to provide a reference for the clinical application of related TCM and the development of new drugs for PD.

BACKGROUND: Tissue engineering holds promise for vascular repair and regeneration by mimicking the extracellular matrix of blood vessels. However, achieving a functional and thick vascular wall with aligned fiber architecture by electrospinning remains a significant challenge. METHODS: A novel electrospinning setup was developed that utilizes an auxiliary electrode and a spring. The impact of process parameters on fiber size and morphology was investigated. The structure and functions of the scaffolds were evaluated through material characterization and assessments of cellular biocompatibility. RESULTS: The new setup enabled controlled deposition of fibers in different designed orientations. The fabricated small-diameter vascular scaffolds consisted of an inner layer of longitudinally oriented fibers and an outer layer of circumferentially oriented fibers (L + C vascular scaffold). Key parameters, including rotational speed, the utilization of the auxiliary electrode, and top-to-collector distance (TCD) significantly influenced fiber orientation. Additionally, voltage, TCD, feed rate, needle size, auxiliary electrode and collector-auxiliary electrode distance affected fiber diameter and distribution. Mechanical advantages and improved surface wettability of L + C vascular scaffold were confirmed through tensile testing and water contact angle. Cellular experiments indicated that L + C vascular scaffold facilitated cell adhesion and proliferation, with human umbilical vein endothelial cells and smooth muscle cells attaching and elongating along the fiber direction of the inner and outer layer, respectively. CONCLUSION This study demonstrated the feasibility of fabricating fiber-aligned, thick-walled vascular scaffolds using a modified electrospinning setup. The findings provided insights into how the auxiliary electrode, specific collector influenced fiber deposition, potentially advancing biomimetic vascular scaffold engineering.

BACKGROUND:In previous studies,the equivalent structure of three-dimensional cell reconstruction of tissue engineering oral mucosa is similar to normal oral mucosa,including epithelial-like structure,lamina propria-like structure,and vascular lumen-like structure,and has initially achieved the establishment of vascular equivalent,but its vascularization characteristics are not very clear.OBJECTIVE:Vascular-like structures of vascularized oral mucosa equivalent were obtained by targeting vascular endothelial cells specific marker expression profiles correlated with laser capture microdissection system,and their vascularization ability was evaluated to reveal their vascularization characteristics.METHODS:Human gingival epithelial cells were cultured from human gingival epithelium and human gingival fibroblasts,human gingival mesenchymal stem cells were cultured from human gingival lamina propria.Human gingival mesenchymal stem cells were induced to differentiate into vascular endothelial-like cells after monoclonal expansion culture.Human gingival epithelial cells,human gingival fibroblasts,and vascular endothelial-like cells were loaded with acellular vascular matrix-0.25%human-like collagen type Ⅰ scaffold to construct the vascularized oral mucosa equivalent.The layered structure of oral mucosa equivalent(experimental group)and the acellular vascular matrix-0.25%human-like collagen type Ⅰ scaffold(control group)were implanted subcutaneously into the back of nude mice,respectively.14 days later,the incision surface of the two groups was coated with biogel.The biogel surface of the experimental group was inoculated with human gingival epithelial cells,while the control group was not inoculated with cells.The samples were collected after 14 days of feeding.The layered structure of oral mucosa equivalent was observed by morphology.The neovascular-like structures in oral mucosa equivalents were labeled by immunohistochemistry and immunofluorescence with a more comprehensive expression profile of vascular endothelial cells,and the vascularization characteristics were analyzed.A laser capture microdissection system was used to capture the neovascularization structures in the oral mucosa equivalents specifically labeled by immunohistochemistry and analyze their vascularization characteristics.RESULTS AND CONCLUSION:(1)The morphology showed that the cell level of oral mucosa equivalent was clear,and the structure was similar to that of normal oral mucosa,that is,there were epithelioid structures,lamina-like structures,and vascular cavelike structures,and there were scattered erythrocytes in the vascular cavelike structures.(2)The results of EdU Apollo tracer seed cells in the oral mucosa equivalent group showed that human gingival epithelial cells labeled with EdU Apollo 488 showed green fluorescence expression.DAPI labeled human gingival fibroblasts showed blue fluorescence expression and formed lamina-like structures in vivo.EdU Apollo 567 labeled vascular endothelial-like cells showed red fluorescence expression and formed a vascular-like structure in vivo.(3)Vascular endothelial cell specific marker expression profile immunofluorescence labeling of vascular structure showed that compared with normal oral mucosa,the expressions of CD31,CD51,CD54,CD105,Tie-2,VWF,vascular endothelial growth factor receptor 1,and vascular endothelial growth factor receptor 2 in oral mucosa equivalents were increased(P<0.000 1).There were no significant changes in CD34 expression(P>0.05).(4)Compared with the specifically labeled oral mucosal vascular structures,the expression levels of CD51,CD54,CD105,Tie-2,VWF,vascular endothelial growth factor receptor 1,and vascular endothelial growth factor receptor 2 of the oral mucosa equivalents targeted by the laser capture microdissection system were increased(P<0.000 1).There were no significant changes in expression of CD31 and CD34(P>0.05).(5)The results showed that the oral mucosa equivalent reconstructed by three-dimensional cell stratification could achieve good vascularization,and its vascularization characteristics were consistent with the immunological function and characteristics of neovascularization.Vascularization helps three-dimensional cell layer reconstruction of oral mucosa equivalent regeneration.

BACKGROUND: Tissue engineering holds promise for vascular repair and regeneration by mimicking the extracellular matrix of blood vessels. However, achieving a functional and thick vascular wall with aligned fiber architecture by electrospinning remains a significant challenge. METHODS: A novel electrospinning setup was developed that utilizes an auxiliary electrode and a spring. The impact of process parameters on fiber size and morphology was investigated. The structure and functions of the scaffolds were evaluated through material characterization and assessments of cellular biocompatibility. RESULTS: The new setup enabled controlled deposition of fibers in different designed orientations. The fabricated small-diameter vascular scaffolds consisted of an inner layer of longitudinally oriented fibers and an outer layer of circumferentially oriented fibers (L + C vascular scaffold). Key parameters, including rotational speed, the utilization of the auxiliary electrode, and top-to-collector distance (TCD) significantly influenced fiber orientation. Additionally, voltage, TCD, feed rate, needle size, auxiliary electrode and collector-auxiliary electrode distance affected fiber diameter and distribution. Mechanical advantages and improved surface wettability of L + C vascular scaffold were confirmed through tensile testing and water contact angle. Cellular experiments indicated that L + C vascular scaffold facilitated cell adhesion and proliferation, with human umbilical vein endothelial cells and smooth muscle cells attaching and elongating along the fiber direction of the inner and outer layer, respectively. CONCLUSION This study demonstrated the feasibility of fabricating fiber-aligned, thick-walled vascular scaffolds using a modified electrospinning setup. The findings provided insights into how the auxiliary electrode, specific collector influenced fiber deposition, potentially advancing biomimetic vascular scaffold engineering.

BACKGROUND:Previous studies have shown that 1,8-cineole has anti-inflammatory,antioxidation,antibacterial and anti-tumor effects.It has good anti-inflammatory effects in many diseases.OBJECTIVE:To investigate the effect of 1,8-cineole on inflammatory response in a rat model of experimental periodontitis.METHODS:Thirty Sprague-Dawley rats were assigned into normal control group,periodontitis control group and 1,8-cineole group with ten rats in each group according to the completely randomized digital table method.Except for the normal control group,rats in the other groups were induced into experimental periodontitis.The periodontitis model was constructed by the orthodontic ligature wire method.Eight weeks after modeling,in the 1,8-cineole group,1,8-cineole was placed into periodontal pockets,twice per day for 4 weeks.In the normal control group and the periodontitis control group,the same amount of normal saline was placed into periodontal pockets,twice per day for 4 weeks.After administration,general observation and periodontal clinical indicators were performed.Hematoxylin-eosin staining was used for periodontal histological evaluation.The expressions of inflammatory factors in the serum and gingiva at mRNA and protein levels were detected.RESULTS AND CONCLUSION:(1)Compared with the normal control group,rats in the periodontitis control group showed increased gingival bleeding index and periodontal probing depth(P<0.05),increased serum levels of interleukin 1β,tumor necrosis factor α,and interleukin 6(P<0.05),decreased serum level of interleukin 10(P<0.05),increased mRNA and protein levels of interleukin 1β,tumor necrosis factor α,and interleukin 6 in gingival tissue(P<0.05),and decreased mRNA and protein level of interleukin 10 in gingival tissue(P<0.05).Hematoxylin-eosin staining of periodontal tissues showed that compared with the normal control group,periodontal inflammation was obvious in the periodontitis control group.(2)Compared with the periodontitis control group,rats in the 1,8-cineole group showed decreased gingival bleeding index and periodontal probing depth(P<0.05),decreased serum levels of interleukin 1β,tumor necrosis factor α,and interleukin 6(P<0.05),increased serum level of interleukin 10(P<0.05),decreased mRNA and protein levels of interleukin 1β,tumor necrosis factor α,and interleukin 6 in gingival tissue(P<0.05),and increased mRNA and protein level of interleukin 10 in gingival tissue(P<0.05).Hematoxylin-eosin staining of periodontal tissues showed that compared with the periodontitis control group,periodontal inflammation was remarkably alleviated in the 1,8-cineole group.To conclude,1,8-cineole can attenuate the inflammatory response in the rat model of experimental periodontitis.

BACKGROUND:In previous studies,the equivalent structure of three-dimensional cell reconstruction of tissue engineering oral mucosa is similar to normal oral mucosa,including epithelial-like structure,lamina propria-like structure,and vascular lumen-like structure,and has initially achieved the establishment of vascular equivalent,but its vascularization characteristics are not very clear.OBJECTIVE:Vascular-like structures of vascularized oral mucosa equivalent were obtained by targeting vascular endothelial cells specific marker expression profiles correlated with laser capture microdissection system,and their vascularization ability was evaluated to reveal their vascularization characteristics.METHODS:Human gingival epithelial cells were cultured from human gingival epithelium and human gingival fibroblasts,human gingival mesenchymal stem cells were cultured from human gingival lamina propria.Human gingival mesenchymal stem cells were induced to differentiate into vascular endothelial-like cells after monoclonal expansion culture.Human gingival epithelial cells,human gingival fibroblasts,and vascular endothelial-like cells were loaded with acellular vascular matrix-0.25%human-like collagen type Ⅰ scaffold to construct the vascularized oral mucosa equivalent.The layered structure of oral mucosa equivalent(experimental group)and the acellular vascular matrix-0.25%human-like collagen type Ⅰ scaffold(control group)were implanted subcutaneously into the back of nude mice,respectively.14 days later,the incision surface of the two groups was coated with biogel.The biogel surface of the experimental group was inoculated with human gingival epithelial cells,while the control group was not inoculated with cells.The samples were collected after 14 days of feeding.The layered structure of oral mucosa equivalent was observed by morphology.The neovascular-like structures in oral mucosa equivalents were labeled by immunohistochemistry and immunofluorescence with a more comprehensive expression profile of vascular endothelial cells,and the vascularization characteristics were analyzed.A laser capture microdissection system was used to capture the neovascularization structures in the oral mucosa equivalents specifically labeled by immunohistochemistry and analyze their vascularization characteristics.RESULTS AND CONCLUSION:(1)The morphology showed that the cell level of oral mucosa equivalent was clear,and the structure was similar to that of normal oral mucosa,that is,there were epithelioid structures,lamina-like structures,and vascular cavelike structures,and there were scattered erythrocytes in the vascular cavelike structures.(2)The results of EdU Apollo tracer seed cells in the oral mucosa equivalent group showed that human gingival epithelial cells labeled with EdU Apollo 488 showed green fluorescence expression.DAPI labeled human gingival fibroblasts showed blue fluorescence expression and formed lamina-like structures in vivo.EdU Apollo 567 labeled vascular endothelial-like cells showed red fluorescence expression and formed a vascular-like structure in vivo.(3)Vascular endothelial cell specific marker expression profile immunofluorescence labeling of vascular structure showed that compared with normal oral mucosa,the expressions of CD31,CD51,CD54,CD105,Tie-2,VWF,vascular endothelial growth factor receptor 1,and vascular endothelial growth factor receptor 2 in oral mucosa equivalents were increased(P<0.000 1).There were no significant changes in CD34 expression(P>0.05).(4)Compared with the specifically labeled oral mucosal vascular structures,the expression levels of CD51,CD54,CD105,Tie-2,VWF,vascular endothelial growth factor receptor 1,and vascular endothelial growth factor receptor 2 of the oral mucosa equivalents targeted by the laser capture microdissection system were increased(P<0.000 1).There were no significant changes in expression of CD31 and CD34(P>0.05).(5)The results showed that the oral mucosa equivalent reconstructed by three-dimensional cell stratification could achieve good vascularization,and its vascularization characteristics were consistent with the immunological function and characteristics of neovascularization.Vascularization helps three-dimensional cell layer reconstruction of oral mucosa equivalent regeneration.

BACKGROUND:Previous studies have shown that 1,8-cineole has anti-inflammatory,antioxidation,antibacterial and anti-tumor effects.It has good anti-inflammatory effects in many diseases.OBJECTIVE:To investigate the effect of 1,8-cineole on inflammatory response in a rat model of experimental periodontitis.METHODS:Thirty Sprague-Dawley rats were assigned into normal control group,periodontitis control group and 1,8-cineole group with ten rats in each group according to the completely randomized digital table method.Except for the normal control group,rats in the other groups were induced into experimental periodontitis.The periodontitis model was constructed by the orthodontic ligature wire method.Eight weeks after modeling,in the 1,8-cineole group,1,8-cineole was placed into periodontal pockets,twice per day for 4 weeks.In the normal control group and the periodontitis control group,the same amount of normal saline was placed into periodontal pockets,twice per day for 4 weeks.After administration,general observation and periodontal clinical indicators were performed.Hematoxylin-eosin staining was used for periodontal histological evaluation.The expressions of inflammatory factors in the serum and gingiva at mRNA and protein levels were detected.RESULTS AND CONCLUSION:(1)Compared with the normal control group,rats in the periodontitis control group showed increased gingival bleeding index and periodontal probing depth(P<0.05),increased serum levels of interleukin 1β,tumor necrosis factor α,and interleukin 6(P<0.05),decreased serum level of interleukin 10(P<0.05),increased mRNA and protein levels of interleukin 1β,tumor necrosis factor α,and interleukin 6 in gingival tissue(P<0.05),and decreased mRNA and protein level of interleukin 10 in gingival tissue(P<0.05).Hematoxylin-eosin staining of periodontal tissues showed that compared with the normal control group,periodontal inflammation was obvious in the periodontitis control group.(2)Compared with the periodontitis control group,rats in the 1,8-cineole group showed decreased gingival bleeding index and periodontal probing depth(P<0.05),decreased serum levels of interleukin 1β,tumor necrosis factor α,and interleukin 6(P<0.05),increased serum level of interleukin 10(P<0.05),decreased mRNA and protein levels of interleukin 1β,tumor necrosis factor α,and interleukin 6 in gingival tissue(P<0.05),and increased mRNA and protein level of interleukin 10 in gingival tissue(P<0.05).Hematoxylin-eosin staining of periodontal tissues showed that compared with the periodontitis control group,periodontal inflammation was remarkably alleviated in the 1,8-cineole group.To conclude,1,8-cineole can attenuate the inflammatory response in the rat model of experimental periodontitis.

BACKGROUND: Tissue engineering holds promise for vascular repair and regeneration by mimicking the extracellular matrix of blood vessels. However, achieving a functional and thick vascular wall with aligned fiber architecture by electrospinning remains a significant challenge. METHODS: A novel electrospinning setup was developed that utilizes an auxiliary electrode and a spring. The impact of process parameters on fiber size and morphology was investigated. The structure and functions of the scaffolds were evaluated through material characterization and assessments of cellular biocompatibility. RESULTS: The new setup enabled controlled deposition of fibers in different designed orientations. The fabricated small-diameter vascular scaffolds consisted of an inner layer of longitudinally oriented fibers and an outer layer of circumferentially oriented fibers (L + C vascular scaffold). Key parameters, including rotational speed, the utilization of the auxiliary electrode, and top-to-collector distance (TCD) significantly influenced fiber orientation. Additionally, voltage, TCD, feed rate, needle size, auxiliary electrode and collector-auxiliary electrode distance affected fiber diameter and distribution. Mechanical advantages and improved surface wettability of L + C vascular scaffold were confirmed through tensile testing and water contact angle. Cellular experiments indicated that L + C vascular scaffold facilitated cell adhesion and proliferation, with human umbilical vein endothelial cells and smooth muscle cells attaching and elongating along the fiber direction of the inner and outer layer, respectively. CONCLUSION This study demonstrated the feasibility of fabricating fiber-aligned, thick-walled vascular scaffolds using a modified electrospinning setup. The findings provided insights into how the auxiliary electrode, specific collector influenced fiber deposition, potentially advancing biomimetic vascular scaffold engineering.

BACKGROUND: Tissue engineering holds promise for vascular repair and regeneration by mimicking the extracellular matrix of blood vessels. However, achieving a functional and thick vascular wall with aligned fiber architecture by electrospinning remains a significant challenge. METHODS: A novel electrospinning setup was developed that utilizes an auxiliary electrode and a spring. The impact of process parameters on fiber size and morphology was investigated. The structure and functions of the scaffolds were evaluated through material characterization and assessments of cellular biocompatibility. RESULTS: The new setup enabled controlled deposition of fibers in different designed orientations. The fabricated small-diameter vascular scaffolds consisted of an inner layer of longitudinally oriented fibers and an outer layer of circumferentially oriented fibers (L + C vascular scaffold). Key parameters, including rotational speed, the utilization of the auxiliary electrode, and top-to-collector distance (TCD) significantly influenced fiber orientation. Additionally, voltage, TCD, feed rate, needle size, auxiliary electrode and collector-auxiliary electrode distance affected fiber diameter and distribution. Mechanical advantages and improved surface wettability of L + C vascular scaffold were confirmed through tensile testing and water contact angle. Cellular experiments indicated that L + C vascular scaffold facilitated cell adhesion and proliferation, with human umbilical vein endothelial cells and smooth muscle cells attaching and elongating along the fiber direction of the inner and outer layer, respectively. CONCLUSION This study demonstrated the feasibility of fabricating fiber-aligned, thick-walled vascular scaffolds using a modified electrospinning setup. The findings provided insights into how the auxiliary electrode, specific collector influenced fiber deposition, potentially advancing biomimetic vascular scaffold engineering.

Background As global environmental pollutants, chronic low-dose exposure to microplastics (MPs) is increasingly recognized for its potential risks to the nervous system. However, the molecular mechanisms linking MPs to major depressive disorder (MDD) remain unclear. Objective To investigate the mechanistic link between chronic environmentally relevant-dose MPs exposure and MDD using bioinformatics, machine learning, and molecular docking approaches, and to identify key targets and evaluate their diagnostic value. Methods Potential MPs-related targets were retrieved from the Comparative Toxicogenomics Database (CTD). Differentially expressed genes in MDD were identified using the GSE98793 dataset (128 patients and 64 healthy controls, aged 18-75 years) from the Gene Expression Omnibus (GEO). MDD-related targets were integrated from multiple databases and intersected with MPs-related genes to identify common targets. A protein-protein interaction network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), and hub genes were identified via six algorithms in CytoHubba. Immune infiltration analysis was performed using single-sample gene set enrichment analysis (ssGSEA) with the Bindea signature to evaluate 19 immune cell types. A competitive endogenous RNA (ceRNA) network was constructed using multiple databases. Molecular docking was performed using AutoDock Vina to evaluate binding affinities between MPs monomers and hub gene-encoded proteins. A diagnostic model was developed and validated using the GSE76826 late-onset MDD cohort (94 patients and 47 controls, age ≥50 years). Least absolute shrinkage and selection operator (Lasso) regression was applied to identify core genes, followed by single-gene gene set enrichment analysis (SG-GSEA). Results A total of 52 common MPs-MDD targets were identified. Six key genes, namely interleukin-1β (IL1B), tumor necrosis factor (TNF), interleukin 6 (IL6), peroxisome proliferator-activated receptor gamma (PPARG), catenin beta 1 (CTNNB1), and chemokine ligand 2 (CCL2), were identified and found to be enriched in neuroinflammatory responses, lipid metabolism disorders, and the Wnt/β-catenin signaling pathway. Construction of the ceRNA network revealed that 32 microRNAs (miRNAs) and 27 circular RNAs (circRNAs) had regulatory relationships with these key genes. The immune infiltration analysis showed increased peripheral eosinophils and decreased Th17 cells in MDD patients (P < 0.05). The results of molecular docking demonstrated stable binding between bisphenol A (BPA) and PPARG (ΔG=–5.82 kcal·mol⁻¹), and between styrene and IL6 (ΔG=–5.61 kcal·mol⁻¹). The diagnostic model showed excellent performance for PPARG in late-onset MDD (AUC=0.942, 95%CI: 0.899, 1.000), with a combined model AUC of 0.954 (95%CI: 0.862, 1.000). The Lasso regression model further identified CCL2 and PPARG as core regulatory genes of MPs-MDD. The SG-GSEA indicated that CCL2 was associated with immune-inflammatory pathways and mitochondrial dysfunction, while PPARG was linked to neuroplasticity and proteostasis. Conclusion Chronic low-dose MPs exposure may contribute to MDD pathogenesis through a multidimensional "immune-metabolic-neural" regulatory network. CCL2 and PPARG may serve as potential biomarkers for environmentally associated MDD, providing new molecular insights into the link between environmental pollution and neuropsychiatric disorders.