1.Astrocytes in The Central Nervous System Regulate Myelination and Remyelination Through Multiple Mechanisms
Wen-Xiao XING ; Fu-Cheng LUO ; Tao LÜ
Progress in Biochemistry and Biophysics 2025;52(7):1792-1803
In the central nervous system (CNS), the myelin sheath, a specialized membrane structure that wraps around axons, is formed by oligodendrocytes through a highly coordinated spatiotemporal developmental program. The process begins with the directed differentiation of neural precursor cells into oligodendrocyte precursor cells (OPCs), followed by their migration, proliferation, differentiation, and maturation, ultimately leading to the formation of a multi-segmental myelin sheath structure. Recent single-cell sequencing research has revealed that this process involves the temporal regulation of over 200 key genes, with a regulatory network composed of transcription factors such as Sox10 and Olig2 playing a central role. The primary function of the myelin sheath is to accelerate nerve signal transmission and protect nerve fibers from damage. Its insulating properties not only increase nerve conduction speed by 50-100 times but also ensure the long-term functional integrity of the nervous system by maintaining axonal metabolic homeostasis and providing mechanical protection. The pathological effects of myelin sheath injury exhibit a cascade amplification pattern: acute demyelination leads to action potential conduction block, while chronic lesions may cause axonal damage and neuronal death in severe or long-term cases, ultimately resulting in irreversible neurological dysfunction with neurodegenerative characteristics. Multiple sclerosis (MS) is a neurodegenerative disease characterized by chronic inflammatory demyelination of the CNS. Clinically, the distribution of lesions in MS exhibits spatial heterogeneity, which is closely related to differences in the regenerative capacity of oligodendrocytes within the local microenvironment. Emerging evidence suggests that astrocytes form a dynamic “neural-immune-metabolic interface” and play a multidimensional regulatory role in myelin development and regeneration by forming heterogeneous populations composed of different subtypes. During embryonic development, astrocytes induce the targeted differentiation of OPCs in the ventricular region through the Wnt/β-catenin pathway. In the mature stage, they secrete platelet-derived growth factor AA (PDGF-AA) to establish a chemical gradient that guides the precise migration of OPCs along axonal bundles. Notably, astrocytes also provide crucial metabolic support by supplying energy substrates for high-energy myelin formation through the lactate shuttle mechanism. In addition, astrocytes play a dual role in myelin regulation. During the acute injury phase, reactive astrocytes establish a triple defense system within 72 h: upregulating glial fibrillary acidic protein (GFAP) to form scars that isolate lesions, activating the JAK-STAT3 regeneration pathway in oligodendrocytes via leukemia inhibitory factor (LIF), and releasing tumor necrosis factor-stimulated gene-6 (TSG-6) to inhibit excessive microglial activation. However, in chronic neurodegenerative diseases, the phenotypic transformation of astrocytes contributes to microenvironmental deterioration. The secretion of chondroitin sulfate proteoglycans (CSPGs) inhibits OPC migration via the RhoA/ROCK pathway, while the persistent release of reactive oxygen species (ROS) leads to mitochondrial dysfunction and the upregulation of complement C3-mediated synaptic pruning. This article reviews the mechanisms by which astrocytes regulate the development and regeneration of myelin sheaths in the CNS, with a focus on analyzing the multifaceted roles of astrocytes in this process. It emphasizes that astrocytes serve as central hubs in maintaining myelin homeostasis by establishing a metabolic microenvironment and signaling network, aiming to provide new therapeutic strategies for neurodegenerative diseases such as multiple sclerosis.
2.Determination of biological activity of teduglutide by a homogeneous time-resolved fluorescence method
Xiao-ming ZHANG ; Ran MA ; Li-jing LÜ ; Lü-yin WANG ; Ping LÜ ; Cheng-gang LIANG ; Jing LI
Acta Pharmaceutica Sinica 2025;60(1):211-217
In this study, we constructed a GLP-2R-HEK293 cell line and established a method for the determination of the
3.Antagonistic effect of Lactobacillus reuteri on testicular reproductive toxicity of neonicotinoid insecticides in mice.
Zhen-Han XU ; Pei-Gen CHEN ; Jin-Tao GUO ; Lin-Yan LÜ ; Hai-Cheng CHEN ; Gui-Hua LIU
National Journal of Andrology 2025;31(2):131-137
OBJECTIVE:
To explore the effect of Lactobacillus reuteri on testicular injury in mice exposed to neonicotinoid insecticides (NNI).
METHODS:
Fifteen C57BL/6 male mice were randomly divided into control group (CTRL group), exposure group (NNI group) and Lactobacillus intervention group (NNI-L group). The mice in CTRL group were given 0.02ml/g of 0.5% carboxymethyl cellulose sodium solution by gavage for 14 days. The mice in NNI group were given 0.02 ml/g of NNI mixture by gavage for 14 days. The mice in NNI-L group were given 0.02 ml/g of NNI mixture by gavage and 5×108cfu/ml of Lactobacillus reuteri powder solution for 14 days. Then, the histomorphology and function of testicle were evaluated by hematoxylin-eosin staining, immunofluorescence staining and RNA sequencing.
RESULTS:
Compared with CTRL group, the thickness of testicular seminiferous epithelium in the NNI group was significantly thinner. And the decline in the number of spermatogenic cells and sperm was observed. And the expression of spermatogonial stem cell marker UCHL1 was down-regulated which was significantly improved in NNI-L group compared with the NNI group. The abnormal expressions of hormone and sperm methylation related genes in testis of NNI group were detected by RNA sequencing, with significant down-regulation being found in NPFF and IGF2. While the expression of HSD3B8 was significantly up-regulated. The abnormal expression of these genes could be significantly improved after oral administration of Lactobacillus reuteri.
CONCLUSION
Testicular spermatogenesis and endocrine function can be damaged by NNI exposure. And oral administration of Lactobacillus reuteri protects testis from the adverse effects of NNI toxicity.
Animals
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Male
;
Limosilactobacillus reuteri
;
Testis/pathology*
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Mice
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Mice, Inbred C57BL
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Insecticides/toxicity*
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Neonicotinoids/toxicity*
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Probiotics
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Spermatogenesis/drug effects*
4.Research progress in the fungal bioluminescence pathway.
Lei LÜ ; Ke CHENG ; Zhitao XU ; Shijie AN ; Dang XU ; Hao DU
Chinese Journal of Biotechnology 2025;41(7):2545-2558
The fungal bioluminescence pathway (FBP) catalyzes the oxidation of endogenous caffeic acid to produce green bioluminescence through an enzymatic cascade. Genetic engineering of FBP into plants creates autoluminescent specimens that circumvent the substrate limitations of conventional reporter systems. These transgenic plants serve dual functions as aesthetic displays and versatile biosensing platforms, enabling applications in real-time gene expression monitoring, continuous environmental surveillance, and non-invasive bioimaging, offering novel opportunities for horticultural production, environmental conservation, and bioengineering applications. This review synthesizes current advances in plant FBP engineering and explores how machine learning approaches can optimize autoluminescent phenotypes, thereby accelerating innovation in agricultural biotechnology, environmental sensing, and synthetic biology applications.
Fungi/genetics*
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Plants, Genetically Modified/metabolism*
;
Genetic Engineering
;
Biosensing Techniques
;
Luminescent Measurements
;
Caffeic Acids/metabolism*
;
Luminescence
5.Mechanism by which sanguis draconis flavones regulating ROS/TXNIP pathway-mediated pyroptosis to ameliorate cerebral ischemia-reperfusion injury in rats
Chao-Xia ZHU ; Zhi-Ying LI ; Xiao-Fei LÜ ; Qian ZHAO ; Bao-Cang CHENG ; Hui-Jie YANG ; Li-Ping ZHOU ; Li-Min ZENG
Acta Anatomica Sinica 2025;56(6):673-680
Objective To explore the mechanism by which the sanguis draconis flavones(SDF)regulates the reactive oxygen species(ROS)/thioredoxin-interacting protein(TXNIP)pathway to mediate cell pyroptosis and improve cerebral ischemia-reperfusion injury(CIRI)in rats.Methods The experimental rats were randomly divided into the control group(Ctrl),the CIRI group,the low-dose SDF group(SDF-L),the high-dose SDF group(SDF-H),and the SDF-H+ROS/TXNIP pathway activator,trimethylamine oxide(TMAO)group(SDF-H+TMAO).Among them,except for the control group,the remaining rats all needed to establish the CIRI rat model by the modified suture method.Zea Longa scoring was performed on rats from each group.ELISA was used to detect the levels of serum inflammatory factors interleukin(IL)-1β,IL-18 and oxidative stress-related factors superoxide dismutase(SOD),malondialdehyde(MDA),glutathione peroxidase(GSH-Px).Flow cytometry was used to measure the ROS levels.Cerebral edema was detected.Cerebral infarction was detected by 2,3,5-triphenyl tetrazolium chloride(TTC)staining.HE staining was used to detect the pathological changes of brain tissue.Immunohistochemistry was used to detect the expression of pyrolytic effector protein dermolin D(GSDMD).Western blotting was used to detect the expression of proteins related to the ROS/TXNIP pathway.Results Compared with the control group,a large area of cerebral infarctions were observed in the brain tissue of the CIRI group,accompanied by mild hemorrhage and obvious infiltration of inflammatory cells.Neuronal cells underwent degeneration and necrosis,with sparse and disordered arrangement.The phenomena of nuclear condensation and nucleolus lysis were obvious.The Zea Longa score,cerebral infarction volume,brain tissue water content,levels of IL-1β,IL-18,ROS,MDA,and the expressions of GSDMD,TXNIP,nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),apoptosis-related punctate protein(ASC),and Caspase-1 increased,while the activities of SOD and GSH-Px decreased(P<0.05).Compared with the CIRI group,the pathological damage of brain tissues in the SDF-L group and the SDF-H group was significantly improved.The Zea Longa score,cerebral infarction volume,brain tissue water content,levels of IL-1β,IL-18,ROS,MDA,and the expressions of GSDMD,TXNIP,NLRP3,ASC,and Caspase-1 decreased.The activities of SOD and GSH-Px increased(P<0.05);TMAO treatment partially reversed the improvement effect of SDF on CIRI in rats.Conclusion SDF ameliorates cerebral CIRI in rats by inhibiting ROS/TXNIP pathway-mediated pyroptosis.
6.New advances in stroke therapy targeting the CREB signaling pathway and the potential for herbal interventions
Cui-cui CHENG ; Yu-juan LIANG ; Xing LI ; Ming LÜ ; Yan ZHU
Acta Pharmaceutica Sinica 2024;59(6):1538-1545
cAMP response element binding protein (CREB) is an eukaryotic intranuclear protein widely expressed in a variety of organs, and its activation increases the transcriptional activity of downstream genes and promotes the expression of related genes. The neuronal function of CREB is related to many intracellular processes, such as proliferation, differentiation, survival, long-term synaptic potentials, neurogenesis and neuronal plasticity. Increasing evidence has demonstrated that CREB plays an important role in the stroke development and therefore, it may serve as a potential target for stroke therapy. Since some herbal medicines as well as their active ingredients regulate the CREB signaling, this article will summarize the role of CREB signaling pathway in stroke pathophysiology. The research progress of traditional Chinese medicine and its active ingredients modulating CREB activity will also be discussed, with the aim of providing the basis and reference for the future research and development of natural medicines against stroke.
7.Correlation Analysis and Comparison of Adult CE-Chirp ABR Response Threshold and Pure Tone Hearing Threshold
He-Ying CHENG ; Yun-Ge ZHANG ; Yan CHEN ; Sun YIN ; Ming LÜ ; Chun-Xiao LI
Journal of Forensic Medicine 2024;40(1):15-19
Objective To study the application of CE-Chirp in the evaluation of hearing impairment in forensic medicine by testing the auditory brainstem response(ABR)in adults using CE-Chirp to ana-lyze the relationship between the V-wave response threshold of CE-Chirp ABR test and the pure tone hearing threshold.Methods Subjects(aged 20-77 with a total of 100 ears)who underwent CE-Chirp ABR test in Changzhou De'an Hospital from January 2018 to June 2019 were selected to obtain the V-wave response threshold,and pure tone air conduction hearing threshold tests were conducted at 0.5,1.0,2.0 and 4.0 kHz,respectively,to obtain pure tone listening threshold.The differences and statistical differences between the average pure tone hearing threshold and V-wave response threshold were compared in different hearing levels and different age groups.The correlation,differences and statistical differences between the two tests at each frequency were analyzed for all subjects.The lin-ear regression equation for estimating pure tone hearing threshold for all subjects CE-Chirp ABR V-wave response threshold was established,and the feasibility of the equation was tested.Results There was no statistical significance in the CE-Chirp ABR response threshold and pure tone hearing threshold dif-ference between different hearing level groups and different age groups(P>0.05).There was a good correlation between adult CE-Chirp ABR V-wave response threshold and pure tone hearing threshold with statistical significance(P<0.05),and linear regression analysis showed a significant linear correla-tion between the two(P<0.05).Conclusion The use of CE-Chirp ABR V-wave response threshold can be used to evaluate subjects'pure tone hearing threshold under certain conditions,and can be used as an audiological test method for forensic hearing impairment assessment.
8.Comparison of the microbiota diversity between autogenous and anautogenous Culex pipiens pallens
Jingjing LEI ; Wenxiang LÜ ; Wenqian WANG ; Haifang WANG ; Xiuxia GUO ; Peng CHENG ; Maoqing GONG ; Lijuan LIU
Chinese Journal of Schistosomiasis Control 2024;36(1):52-58
Objective To investigate the microbiota composition and diversity between autogenous and anautogenous Culex pipiens pallens, so as to provide insights into unraveling the pathogenesis of autogeny in Cx. pipiens pallens. Methods Autogenous and anautogenous adult Cx. pipiens pallens samples were collected at 25 ℃, and the hypervariable regions of the microbial 16S ribosomal RNA (16S rRNA) gene was sequenced on the Illumina NovaSeq 6000 sequencing platform. The microbiota abundance and diversity were evaluated using the alpha diversity index, and the difference in the microbiota structure was examined using the beta diversity index. The microbiota with significant differences in the abundance between autogenous and anautogenous adult Cx. pipiens pallens samples was identified using the linear discriminant analysis effect size (LEfSe). Results The microbiota in autogenous and anautogenous Cx. pipiens pallens samples belonged to 18 phyla, 28 classes, 70 orders, 113 families, and 170 genera, and the dominant phyla included Proteobacteria, Bacteroidetes, and so on. At the genus level, Wolbachia was a common dominant genus, and the relative abundance was (77.6 ± 11.3)% in autogenous Cx. pipiens pallens samples and (47.5 ± 8.5)% in anautogenous mosquito samples, while Faecalibaculum (0.4% ± 0.1%), Dubosiella (0.5% ± 0.0%) and Massilia (0.5% ± 0.1%) were specific species in autogenous Cx. pipiens pallens samples. Alpha diversity analysis showed that higher Chao1 index and ACE index in autogenous Cx. pipiens pallens samples than in anautogenous samples (both P values > 0.05), and lower Shannon index (P > 0.05) and Simpson index (P < 0.05) in autogenous Cx. pipiens pallens samples than in anautogenous samples. LEfSe analysis showed a total of 48 significantly different taxa between autogenous and anautogenous Cx. pipiens pallens samples (all P values < 0.05). Conclusion There is a significant difference in the microbiota diversity between autogenous and anautogenous Cx. pipiens pallens.
9.A reporter gene assays for bioactivity determination of human chorinonic gonadotropin
Ying HUANG ; Xiao-ming ZHANG ; He-yang LI ; Lü-yin WANG ; Hui ZHANG ; Ping LÜ ; Jing LI ; Xiang-dong GAO ; Cheng-gang LIANG
Acta Pharmaceutica Sinica 2024;59(2):432-438
This study constructed a LHCGR-CRE-luc-HEK293 transgenic cell line according to the activation of the cAMP signaling pathway after recombinant human chorionic gonadotropin binding to the receptor. The biological activity of recombinant human chorionic gonadotropin was assayed using a luciferase assay system. The relative potency of the samples was calculated using four-parameter model. And the method conditions were optimized to validate the specificity, relative accuracy, precision and linearity of the method. The results showed that there was a quantitative potency relationship of human chorinonic gonadotropin (hCG) in the method and it was in accordance with the four-parameter curve. After optimization, the conditions were determined as hCG dilution concentration of 2.5 μg·mL-1, dilution ratio of 1∶4, cell number of 10 000-15 000 cells/well, and induction time of 6 h. The method had good specificity, relative accuracy with relative bias ranging from -8.9% to 3.4%, linear regression equation correlation coefficient of 0.996, intermediate precision geometric coefficient of variation ranging from 3.3% to 15.0%, and linearity range of 50% to 200%. This study successfully established and validated a reporter gene method to detect hCG biological activity, which can be used for hCG biological activity assay and quality control.
10.Predictive value of GCS-F score combined with arterial lactate for prognosis of elderly patients with spontaneous cerebral hemorrhage
Tengyu CHE ; Xin HE ; Lei LÜ ; Jie CHENG ; Xu ZHAO ; Changxiang CHEN
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(10):1187-1191
Objective To investigate the predictive value of Glasgow coma scale(GCS)-Full Out-line of UnResponsiveness(FOUR)scale(GCS-F)score and arterial lactate level for prognosis of intracerebral hemorrhage(ICH)in elderly patients.Methods A total of 278 elderly ICH patients admitted to Neurosurgical Intensive Care Unit of the Affiliated Hospital of North China Universi-ty of Science and Technology from January 2022 to January 2024 were retrospectively recruited.According score at 90 d after onset,95 of them were assigned into good prognosis group and 183 into poor prognosis group.Basic information,vital signs at admission,pupils,laboratory indica-tors,GCS score and other clinical data were compared between the two groups.Binary logistic re-gression analysis was used to analyze the risk factors of poor prognosis in elderly ICH patients.ROC curve was drawn to analyze the prognostic value of GCS-F score(including eye opening re-sponse and limb movement in GCS,and brainstem response in FOUR scale)combined with lac-tate level in elderly ICH patients.Results Significantly higher blood pressure,elevated levels of blood glucose,creatinine and arterial lactic acid,increased percentages of supratentorial and sub-tentorial bleeding,and larger blood loss,while obviously lower GCS score and GCS-F score were observed in the poor prognosis group than the good prognosis group(P<0.05,P<0.01).In the analyses for poor prognosis rate of ICH patients at different levels,the poor prognosis rate of se-vere GCS-F patients was significantly higher than that of patients with same level of GCS score(P<0.05).Binary logistic regression analysis showed that GPS-F score(OR=1.762,95%CI:1.507-2.061,P=0.000)and arterial lactate level(OR=0.536,95%CI:0.385-0.746,P=0.000)were risk factors for 90-day poor prognosis in elderly ICH patients.ROC curve analysis indicated that the AUC value of arterial lactate,GCS score and GCS-F score in predicting 90-day poor prog-nosis in elderly ICH patients was 0.713(95%CI:0.650-0.775),0.827(95%CI:0.774-0.880)and 0.876(95%CI:0.828-0.925),respectively,and the AUC value of GCS-F score combined with arterial lactic acid was 0.919(95%CI:0.886-0.953),which was significantly higher than that of GCS score,GCS-F score and arterial lactic acid alone(P<0.01).Conclusion GCS-F score has better performance than GCS score in predicting 90-day poor prognosis in elderly ICH pa-tients,especially for severe patients.The GPS-F score combined with arterial lactate level shows the best predictive effectiveness for elderly ICH patients.

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