Most ReadThe blood-brain barrier (BBB) is a dynamic interface for selective molecular trafficking between blood and brain parenchyma, playing a pivotal role in maintaining central nervous system homeostasis. Recent investigations have uncovered intricate regulatory networks governing BBB function, involving dynamic intercellular tight junction remodeling, signaling cascade activation, and multicomponent interactions within the neurovascular unit. This review systematically integrates current mechanistic understanding of BBB regulation and provides a critical evaluation of emerging interventional strategies, including nanotechnology-based drug delivery systems, gene editing, and traditional Chinese medicine formula interventions, with emphasis on their translational potential in the future. By integrating bench-to-bedside perspectives, this work aims to provide novel theoretical frameworks for developing precision therapies targeting BBB dysfunction in neurological disorders.
To observe colon tumor status in mice with azoxymethane/dextran sodium sulfate (AOM/DSS) -induced colitis-associated colorectal cancer (CAC) following autologous fecal microbiota transplantation (AFMT), and to investigate the anti-tumor effects and underlying mechanism of AFMT through its influence on tight junction proteins.
Female specific-pathogen-free BALB/c mice were divided randomly into blank control, CAC model, and AFMT intervention groups (n = 8 per group). CAC model mice received a single intraperitoneal injection of AOM (10 mg/kg), followed by drinking water containing 3.5% DSS for 7 days, followed by 0% DSS for 14 days, constituting one cycle; three cycles were performed to establish the CAC model. Mice in the AFMT group received daily AFMT (0.1 mL autologous fecal suspension) via gavage every other day concurrent with the CAC modeling protocol until cycle completion. Control mice received no special treatment. The general condition and body weight of the mice were monitored. Upon completion of the experiment, colon length was measured, tumor numbers were recorded, and colon pathology was examined. mRNA and protein expression levels of the tight junction proteins Occludin (OCLN) and Claudin-1 (CLDN1) in colorectal tumor tissue were detected by reverse transcription-polymerase chain reaction and Western blot, respectively. The fecal microbiota composition in each group was analyzed using 16S rRNA gene sequencing.
Compared with the blank control group, the CAC model group showed significantly shortened colon length (P< 0.0001) and a marked increase in tumor number. After AFMT intervention, the shortening of colon length was alleviated (P<0.01), and the number of tumors was reduced (P<0.05). Histological examination of mouse colon tissues revealed distorted crypt structures, reduced goblet cells, and increased inflammatory cell infiltration in the CAC model group(P< 0.01). After AFMT intervention, the crypt structure and goblet cells improved, and inflammatory cells decreased (P<0.05). Compared with the blank control group, the protein expression levels of Occludin and Claudin-1 in colorectal tumor tissues of the CAC model group were significantly decreased (P<0.05, P<0.01). After AFMT intervention, the protein expression levels of Occludin and Claudin-1 in colorectal tumor tissues significantly increased (P<0.05). As compared to the blank control group, the mRNA expression levels of OCLN and CLDN1 in the CAC model group were significantly downregulated (P <0.05); after AFMT intervention, their mRNA expression levels significantly recovered (P< 0.05). Compared with the blank control group, there was no statistically significant difference in the relative abundance of Firmicutes and Bacteroidota in the AFMT intervention group (P < 0.05). In the CAC model group, the relative abundance of Firmicutes decreased (P<0.05), while the relative abundance of Bacteroidota increased (P<0.05). Conclusions AFMT intervention can restore the relative abundance of Firmicutes and reduce the relative abundance of Bacteroroidota in the gut, effectively improve the aberrant expression of tight junction proteins within the tumor microenvironment, repair the intestinal barrier, regulate intestinal barrier function, alleviate intestinal inflammation, and consequently mitigate the pathological progression of CAC.
Post-translational modifications (PTMs) are crucial for regulating protein functions. As a novel PTM, lactylation has emerged as a recent research hotspot, participating in pathological processes such as tumor progression and inflammation; it dynamically regulates gene expression and protein activity, which is significant for metabolic-immune coordination. In degenerative osteoarthropathy (such as osteoarthritis and rheumatoid arthritis), cartilage metabolic imbalance is closely associated with dynamic changes in lactylation, involving pathological links such as cartilage matrix degradation, synovial inflammation, and abnormal bone remodeling. Current clinical interventions cannot block disease progression. This review systematically summarizes the molecular mechanisms of lactylation (including lactate metabolism as well as histone and non-histone lactylation), regulatory factors (enzymes, environment, and molecular tools), and its role in degenerative osteoarthropathy, covering expression changes in cartilage tissues, correlation with arthritis progression, and biomarker studies in clinical models. Lactylation affects joint degeneration by regulating glycolysis-oxidative phosphorylation balance, inflammatory factor expression, and extracellular matrix metabolism. Targeted regulation strategies (such as CRISPR editing and small-molecule inhibitors) hold promise as novel therapeutic approaches. Future research needs to overcome technical limitations in detection, decipher the dynamic lactylation network through interdisciplinary collaboration, and promote its clinical translation in early diagnosis, precise intervention, and personalized treatment.
Lung adenocarcinoma (LUAD) has a poor prognosis. This study aimed to screen core genes associated with the tumor microenvironment (TME) and programmed cell death (PCD) to provide new prognostic markers and therapeutic targets for LUAD, and to validate their cross-species conservation. Methods Based on RNA-seq data for LUAD and normal lung tissue in The Cancer Genome Atlas (TCGA) database, we assessed the TME and screened for differentially expressed genes (DEGs) using the ESTIMATE algorithm. Functional enrichment analysis (Gene Ontology/Kyoto Encyclopedia of Genes and Genomes), protein-protein interaction (PPI) networks, and univariate Cox regression analysis were performed on the DEGs. Cross-screening combining PPI networks, univariate Cox regression, and the PCD genome was employed to identify core prognostic genes, and their prognostic value and TME association were validated by survival analysis, gene set enrichment analysis (GSEA), and immune infiltration (CIBERSORT) analysis.
High immune/ESTIMATE scores were significantly associated with prolonged patient survival. The selected shared DEGs were primarily enriched in immune-related pathways. Cross-analysis identified CD19 and CD79A as core prognostic genes associated with PCD. Clinical-feature analysis showed that CD19 and CD79A expression were significantly higher in LUAD tumors than in normal lung tissues, but their expression levels decreased significantly with advancing TNM staging, closely associated with advanced staging, distant metastasis, and poor prognosis. Patients with high CD19/CD79A expression had significantly longer overall survival than those with low expression. Animal-model validation confirmed the cross-species conserved role of CD19/CD79A in tumor progression. GSEA indicated that the high-CD19/CD79Aexpression group was significantly enriched in immune activation pathways (e. g. , allograft rejection, complement response), while the low-expression group was enriched in metabolic (glycolysis, oxidative phosphorylation) and oncogenic pathways. CIBERSORT analysis confirmed that their expression levels were significantly positively correlated with TME immune activity. Conclusions CD19 and CD79A are overexpressed in LUAD tumor tissues, but their expression levels decrease with disease progression. High expression of CD19/CD79A is closely associated with a favorable prognosis and immune-activated TME, while low expression suggests a poor prognosis and immune suppression/oncogenic states. As genes associated with PCD, CD19/CD79A may serve as potential protective prognostic biomarkers and immunotherapeutic targets in LUAD, thereby providing a basis for understanding the immune mechanisms of LUAD and guiding the development of B cell-targeted therapeutic strategies.
The blood-brain barrier (BBB) plays a critical role in maintaining brain homeostasis. BBB dysfunction is closely associated with various neurodegenerative diseases and acute brain injuries, which impair brain defense mechanisms and can exacerbate the progression of pathological conditions. Nitric oxide (NO), an important biological signaling molecule, exerts a wide range of effects on the central nervous system, influencing both physiological and pathological states. This review summarizes the production and metabolism of NO and their effects on BBB permeability, followed by an introduction to the role of NO in pathological conditions such as cerebral ischemia-reperfusion injury, neurodegenerative diseases, and brain tumors. NO regulates BBB integrity through the regulation of tight junction proteins and vascular endothelial growth factor receptor 2 (VEGFR2). The review also delves into the potential of NO as a therapeutic target in drug delivery and gene therapy, and explores its potential to enhance drug penetration across the BBB. These explorations provide novel perspectives for future therapeutic strategies.
We conducted a systematic review of the construction method and pathological mechanisms of animal and cellular models for diminished ovarian reserve (DOR), to provide a theoretical basis for understanding its pathophysiological mechanisms and references for future drug development and therapeutic strategies. We carried out extensive retrieval and analysis of the recent literature to identify the detailed diverse modeling approaches (including pharmaceutical induction, environmental factors, natural factors, and composite factors) and explored the roles of their mechanisms in DOR pathogenesis. The pathogenesis of DOR involves multiple factors, including oxidative stress, apoptosis and autophagy dysregulation, impaired angiogenesis, and imbalances in follicular development and the immune microenvironment. Studies also revealed intrinsic correlations among key signaling pathways in DOR models. Although existing DOR modeling method can effectively replicate Western medicine pathological features, models incorporating traditional Chinese medicine (TCM) syndrome characteristics remain scarce. Given the unique advantages of TCM in regulating the complex pathological network of DOR, future research is needed to prioritize the construction of TCM syndrome-oriented DOR models. This will support investigations into the scientific basis of TCM's multi-target regulatory mechanisms and provide a robust theoretical foundation for clinical applications.
To investigate the mechanism of remifentanil (Rem) on myocardial fibrosis in rats with dilated cardiomyopathy (DCM) in relation to the interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3)/glutathione peroxidase 4 (GPX4) pathway.
A DCM rat model was established by intraperitoneal injection of 2.5 mg/kg doxorubicin. The rats were then divided into Model, low-dose (Rem-L, 2 μg/kg), medium-dose (Rem-M, 4 μg/kg), and high-dose Rem groups (Rem-H, 8 μg/kg), and a high-dose Rem+Colivelin (STAT3 activator, Rem-H+Colivelin, 8 μg/kg Rem+1 mg/kg Colivelin) group (n=12 rats per group). Another 12 normal Wistar rats were set as a Control group. After continuous administration for 4 weeks, left ventricular end systolic diameter (LVESD), left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD), and left ventricular fractional shortening (LVFS) were measured by ultrasound. Type Ⅰcollagen (Col Ⅰ), transforming growth factor-β1 (TGF-β1), and type Ⅲ collagen (Col Ⅲ) expression in myocardial tissue were detected by immunohistochemistry. Pathological changes in myocardial tissue were detected by Masson and hematoxylin/eosin staining. IL-6/STAT3/GPX4 pathway-related proteins were detected by Western blot. Results Compared with the Control group, rats in the Model group showed obvious increases in LVEDD, LVESD, ColⅠ((123.62±10.78) vs (76.53±6.12)), ColⅢ, TGF-β1, IL-6, and phospho-STAT3Tyr705/STAT3((0.95± 0.05) vs (0.46± 0.92)) in myocardial tissue, and decreases in LVEF((52.19 ± 4.88) % vs (76.78 ± 6.97) %), LVFS, SLC7A11, and GPX4 ((0.11 ± 0.01) vs (0.43 ± 0.04)) (P<0.05), inflammatory infiltration, collagen accumulation, and myocardial fibrosis. Compared with the Model group, rats in the Rem-M and Rem-H groups showed reduced LVEDD, LVESD, ColⅠ((98.74±7.28)、(84.27±7.13) vs (123.62±10.78)), ColⅢ, TGF-β1, IL-6, and p-STAT3Tyr705/STAT3((0.81±0.06)、(0.57±0.04) vs (0.95±0.05)) in myocardial tissue, increases in LVEF((69.85± 6.13) %、(72.83± 6.55) % vs(52.19± 4.88)%), LVFS, SLC7A11, and GPX4((0.24± 0.02)、(0.36±0.02) vs (0.11 ± 0.01)) (P<0.05), and improvements in myocarditis injury and fibrosis. Colivelin was able to reverse the improving effect of Rem on myocardial fibrosis in DCM rats.
Rem may reduce collagen accumulation and improve myocardial fibrosis and cardiac function in DCM rats by adjusting the IL-6/STAT3/GPX4 pathway.
To explore the mechanism by which melanotan-II (MT-II) improves social deficits in a Shank3 gene-deficient autism model.
Rats were divided into control and Shank3-deficient model groups (n = 18 per group) treated by microinjection of empty or Shank3-interfering lentivirus, respectively, into the right lateral ventricle of neonatal rats. Shank3-deficient rats were further divided randomly into two groups: Shank3+saline (Sh3-Sal) and Shank3+ MT-II (Sh3-MT-II) groups (n = 9 per group). Similarly, control rats were divided into control+saline (V-Sal) and control+MT-II (V-MT-II) groups (n=9 per group). On day 28, rats in the V-MT-II and Sh3-MT-II groups received intraperitoneal (i. p.) injections of MT-II (3.3 mg/kg), while rats in the V-Sal and Sh3-Sal groups received i. p. saline (3.3 mL/kg). Behavioral changes were assessed using the open-field test, grooming behavior analysis, three-chamber social test, and the Morris water maze test. mRNA and protein expression levels of hypothalamic oxytocin (OXT), OXT receptor (OXTR), and melanocortin receptor 4 (MC4R) were detected by reverse transcription-polymerase chain reaction and Western blot, respectively.
In the three-chamber social test, Sh3-Sal group rats showed no significant social preference compared with the time spent with stranger rat 1 (P>0.05). In contrast, after MT-II intervention, Sh3-MT-II group rats spent significantly longer with stranger rat 2 (P<0.01). In the Morris water maze test, rats in the Sh3-Sal group exhibited significant learning and memory impairments compared with the V-Sal group (P<0.05), while MT-II intervention significantly improved the learning and memory performance of the Sh3-MT-II group (P<0.01). The open field and grooming tests revealed that Sh3-Sal group rats spent significantly longer in the peripheral zone of the open field and exhibited increased grooming behavior compared with the V-Sal group (P<0.01). However, MT-II did not significantly alter the center time or self-grooming behavior compared with the Sh3-Sal group (P>0.05). mRNA expression levels of OXT, OXTR, and MC4R were significantly higher in the Sh3-MT-II group than in the Sh3-Sal group (P<0.05,P<0.01). Hypothalamic OXT protein expression was significantly increased in the Sh3-MT-II group compared with the Sh3-Sal group (P<0.05), while hypothalamic SHANK3 protein expression was significantly decreased in both the Sh3-Sal and Sh3-MT-II groups compared with the V-Sal group (P<0.05,P<0.01), and protein expression levels of OXTR and MC4R showed no significant changes (P>0.05).
The melanocortin receptor agonist MT-II may ameliorate social deficits in Shank3-deficient autistic rats by activating the hypothalamic OXT system. This suggests that targeting the OXT/MC4R pathway could be a potential therapeutic strategy for social deficits in patients with autism spectrum disorder.
Animal experiment courses are a crucial practical component in the life sciences field. Traditional teaching, however, often overemphasizes theoretical instruction, leading to insufficient skill development, poor ethical and safety awareness, detachment from real-world applications, and a lack of innovation training. To address these challenges, this study introduced an outcome-based education (OBE) concept, constructing a student-ability-centered animal experimentation curriculum system. Three dimensional objective were established based on this OBE: mastering foundational knowledge, proficiency in experimental skills, and enhancing comprehensive qualities. A closed-loop framework of "content conception-program design-process implementation-experience summarization" was adopted. Using authentic research projects as the vehicle, theoretical knowledge, practical skills, and research capability cultivation were integrated through project database construction, process-oriented evaluation, and team-collaboration models. Practice demonstrated that the OBE model significantly enhanced students' knowledge mastery, skill proficiency, and teaching satisfaction, effectively fostering their team collaboration, problem-solving, and innovative thinking abilities. This study shows that project-driven teaching under the OBE concept can resolve the structural dilemmas of traditional experimental teaching, thus providing an effective pathway for enhancing the quality of animal experimentation courses and cultivating high-caliber scientific research talent.
Inflammatory pain and depression are clinically common disorders with a high comorbidity rate. They mutually exacerbate their pathological processes and severely reduce the quality of life of patients. The pathogenesis of the comorbidity of inflammatory pain and depression is highly complex, posing significant challenges for clinical diagnosis and treatment. Recent studies have revealed that sustained activation of neuroinflammation is a central pathological link in the comorbidity of inflammatory pain and depression. As a non-pharmacological intervention, exercise can effectively improve both pain and depressive symptoms in patients with comorbidity. However, its specific mechanisms of action remain incompletely elucidated. This article summarizes recent research advances on the effects of exercise in inhibiting central inflammation, modulating the balance of microglial M1/M2 polarization, regulating neuronal excitatory-inhibitory homeostasis, and promoting hippocampal neurogenesis. It systematically reviews the molecular and neural mechanisms by which exercise modulates neuroinflammation to treat the comorbidity of inflammatory pain and depression, with the aim of providing a theoretical basis and practical guidance for clinical exercise therapy.
No. 86 Xueyuan South Road, Haidian District, Beijing
010-62199257
qkjq@cast.org.cn
Copyright © 2025 China Association for Science and Technology. All rights reserved. For all open access content, the relevant licensing terms apply.
Sponsored by the Office of the Leading Group for Cybersecurity and Informatization of CAST, and supported by Science and Technology Review Publishing House
