1.Principles, technical specifications, and clinical application of lung watershed topography map 2.0: A thoracic surgery expert consensus (2024 version)
Wenzhao ZHONG ; Fan YANG ; Jian HU ; Fengwei TAN ; Xuening YANG ; Qiang PU ; Wei JIANG ; Deping ZHAO ; Hecheng LI ; Xiaolong YAN ; Lijie TAN ; Junqiang FAN ; Guibin QIAO ; Qiang NIE ; Mingqiang KANG ; Weibing WU ; Hao ZHANG ; Zhigang LI ; Zihao CHEN ; Shugeng GAO ; Yilong WU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(02):141-152
With the widespread adoption of low-dose CT screening and the extensive application of high-resolution CT, the detection rate of sub-centimeter lung nodules has significantly increased. How to scientifically manage these nodules while avoiding overtreatment and diagnostic delays has become an important clinical issue. Among them, lung nodules with a consolidation tumor ratio less than 0.25, dominated by ground-glass shadows, are particularly worthy of attention. The therapeutic challenge for this group is how to achieve precise and complete resection of nodules during surgery while maximizing the preservation of the patient's lung function. The "watershed topography map" is a new technology based on big data and artificial intelligence algorithms. This method uses Dicom data from conventional dose CT scans, combined with microscopic (22-24 levels) capillary network anatomical watershed features, to generate high-precision simulated natural segmentation planes of lung sub-segments through specific textures and forms. This technology forms fluorescent watershed boundaries on the lung surface, which highly fit the actual lung anatomical structure. By analyzing the adjacent relationship between the nodule and the watershed boundary, real-time, visually accurate positioning of the nodule can be achieved. This innovative technology provides a new solution for the intraoperative positioning and resection of lung nodules. This consensus was led by four major domestic societies, jointly with expert teams in related fields, oriented to clinical practical needs, referring to domestic and foreign guidelines and consensus, and finally formed after multiple rounds of consultation, discussion, and voting. The main content covers the theoretical basis of the "watershed topography map" technology, indications, operation procedures, surgical planning details, and postoperative evaluation standards, aiming to provide scientific guidance and exploration directions for clinical peers who are currently or plan to carry out lung nodule resection using the fluorescent microscope watershed analysis method.
2.Endovascular Treatment for Acute Posterior Circulation Tandem Lesions: Insights From the BASILAR and PERSIST Registries
Wei LI ; Mohamed F. DOHEIM ; Zhongming QIU ; Tan WANG ; Zhibin CHEN ; Wenjie ZI ; Qingwu YANG ; Haitao GUAN ; Hongyu QIAO ; Wenhua LIU ; Wei HU ; Xinfeng LIU ; Jinbo HUANG ; Zhongkui HAN ; Zhonglun CHEN ; Zhenqiang ZHAO ; Wen SUN ; Raul G. NOGUEIRA
Journal of Stroke 2025;27(1):75-84
Background:
and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT.
Methods:
Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery.
Results:
A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24).
Conclusion
Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.
3.Endovascular Treatment for Acute Posterior Circulation Tandem Lesions: Insights From the BASILAR and PERSIST Registries
Wei LI ; Mohamed F. DOHEIM ; Zhongming QIU ; Tan WANG ; Zhibin CHEN ; Wenjie ZI ; Qingwu YANG ; Haitao GUAN ; Hongyu QIAO ; Wenhua LIU ; Wei HU ; Xinfeng LIU ; Jinbo HUANG ; Zhongkui HAN ; Zhonglun CHEN ; Zhenqiang ZHAO ; Wen SUN ; Raul G. NOGUEIRA
Journal of Stroke 2025;27(1):75-84
Background:
and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT.
Methods:
Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery.
Results:
A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24).
Conclusion
Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.
4.Endovascular Treatment for Acute Posterior Circulation Tandem Lesions: Insights From the BASILAR and PERSIST Registries
Wei LI ; Mohamed F. DOHEIM ; Zhongming QIU ; Tan WANG ; Zhibin CHEN ; Wenjie ZI ; Qingwu YANG ; Haitao GUAN ; Hongyu QIAO ; Wenhua LIU ; Wei HU ; Xinfeng LIU ; Jinbo HUANG ; Zhongkui HAN ; Zhonglun CHEN ; Zhenqiang ZHAO ; Wen SUN ; Raul G. NOGUEIRA
Journal of Stroke 2025;27(1):75-84
Background:
and Purpose Limited evidence exists on the effectiveness of endovascular treatment (EVT) for acute posterior circulation tandem lesion (PCTL). This study aimed to explore the role of extracranial vertebral artery (VA) stenting in patients with PCTL stroke undergoing EVT.
Methods:
Individual patient data were pooled from the BASILAR (EVT for Acute Basilar Artery Occlusion Study) and PERSIST (Posterior Circulation Ischemic Stroke) registries. Patients with PCTLs who underwent EVT were included in the present cohort and divided into the stenting and nonstenting groups based on the placement of extracranial VA stents. The primary efficacy outcome was the modified Rankin Scale (mRS) scores at 90 days and 1 year. Safety outcomes included 24-hour symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days and 1 year post-surgery.
Results:
A combined dataset of 1,320 patients with posterior circulation artery occlusion, including 263 (19.9%) with tandem lesions, of whom 217 (median age, 65 years; 82.9% male) met the inclusion criteria for the analysis. The stenting group had 84 (38.7%) patients, while the non-stenting group had 133 (61.3%). After adjustment for the potential confounders, extracranial VA stenting was associated with favorable shifts in mRS scores at both 90 days (adjusted common odds ratio [OR], 2.30; 95% confidence interval [CI], 1.23–4.28; P<0.01) and 1 year (adjusted OR [aOR], 2.04; 95% CI [1.05–3.97]; P=0.04), along with lower rate of mortality at both 90 days (aOR, 0.45; 95% CI [0.21–0.93]; P=0.01) and 1 year (aOR, 0.36; 95% CI [0.16–0.79]; P=0.01), with no significant difference in sICH incidence (aOR, 0.35; 95% CI [0.06–1.98]; P=0.24).
Conclusion
Extracranial VA stenting during EVT may improve functional outcomes and reduce mortality in patients with PCTL strokes.
5.Effect of Huangqin Qingre Chubi Capsules-containing Serum on CircRNA_0001543/NF-κB Expression in Co-cultured PBMCs and Human FLSs from Patients with Ankylosing Spondylitis
Yajun QI ; Jian LIU ; Qiao ZHOU ; Yuedi HU ; Xiang DING ; Chengzhi CONG ; Xu LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):87-95
ObjectiveThis study aims to explore the effects of Huangqin Qingre Chubi capsules-containing serum on the expression of CircRNA_0001543/nuclear factor-kappa B (NF-κB) in co-cultured peripheral blood mononuclear cells (PBMCs) and human fibroblast-like synoviocytes (FLSs) from patients with ankylosing spondylitis (AS). MethodsVenous blood was collected from patients with AS to isolate PBMCs. FLSs were co-cultured with AS patients' PBMCs, and FLSs were harvested after co-culture for subsequent experiments. The normal control group consisted of normal FLSs, while the model group comprised co-cultured AS PBMCs and FLSs to simulate AS pathology. The Huangqin Qingre Chubi capsules group involved adding Huangqin Qingre Chubi capsules-containing serum to the co-cultured cells(6.48 g·kg-1). To investigate the effect of HQC-containing serum on the viability of co-cultured cells, and the experiment was divided into the following groups based on the dilution concentration: blank group, 10% HQC group, 20% HQC group, and 30% HQC group.To study the influence of the optimal concentration of HQC-containing serum on cytokine and pathway indicators in each group, the experiment was divided into three groups: normal group, model group, and optimal concentration HQC-containing serum group.For the validation of the transfection efficiency of the CircRNA_0001543 interference plasmid, the experiment was divided into the following groups: blank group, si-NC group (with transfection reagent), si-circ_0001543-1 group (with transfection reagent and interference plasmid No. 1 targeting circ_0001543), si-circ_0001543-2 group (with transfection reagent and interference plasmid No. 2 targeting circ_0001543), and si-circ_0001543-3 group (with transfection reagent and interference plasmid No. 3 targeting circ_0001543).For the validation of the transfection efficiency of the CircRNA_0001543 overexpression plasmid, the experiment was divided into the following groups: blank group, OE-NC group (with transfection reagent), and OE-circ_0001543 group (with transfection reagent and overexpression plasmid targeting circ_0001543).To study the effects of CircRNA_0001543 interference/overexpression on cytokine and pathway indicators in each group, the experiment was divided into the following groups: si-NC group, si-CircRNA_0001543 group, OE-NC group, and OE-CircRNA_0001543 group. Enzyme-linked immunosorbent assay (ELISA) was used to detect levels of interleukin-1β (IL-1β), IL-10, IL-37, and tumor necrosis factor-α (TNF-α). Real-time quantitative polymerase chain reaction (Real-time PCR) was utilized to measure the expression of CircRNA_0001543, IκBα, and NF-κB p65. ResultsAfter 48 hours, 30% Huangqin Qingre Chubi Capsules-containing serum significantly inhibited the proliferation of co-cultured PBMCs and FLSs, which was determined to be the optimal experimental drug-containing serum concentration. Compared with those in the normal group, the expressions of NF-κB p65 mRNA, IκBα mRNA, IL-1β, and TNF-α in the model group were significantly increased (P<0.01), while the expressions of CircRNA_0001543 mRNA, IL-10, and IL-37 were significantly decreased (P<0.01). Compared with those in the model group, the expressions of NF-κB p65 mRNA, IκBα mRNA, IL-1β, and TNF-α in the Huangqin Qingre Chubi Capsules-containing serum group were significantly decreased (P<0.05), and the expressions of CircRNA_0001543 mRNA, IL-10, and IL-37 were significantly increased (P<0.05), with the most prominent changes in the 30% drug-containing serum group (P<0.01). Compared with that in the si-NC group, the expression of CircRNA_0001543 was significantly reduced in the si-CircRNA_0001543 group (P<0.01). Compared with that in the OE-NC group, the expression of CircRNA_0001543 was significantly increased in the OE-CircRNA_0001543 group (P<0.01), indicating that the si-CircRNA_0001543 and OE-CircRNA_0001543 plasmids were successfully transfected. Based on the optimal drug-containing serum of Huangqin Qingre Chubi Capsules, si-CircRNA_0001543 transfection led to significantly increased expressions of NF-κB p65 mRNA, IκBα mRNA, IL-1β, and TNF-α and decreased the expressions of IL-10 and IL-37 (P<0.01). In contrast, OE-CircRNA_0001543 transfection significantly decreased the expressions of NF-κB p65 mRNA, IκBα mRNA, IL-1β, and TNF-α (P<0.01) and increased the expressions of IL-10 and IL-37 (P<0.01). ConclusionHuangqin Qingre Chubi capsules-containing serum can improve immune inflammation in AS by increasing the expression of CircRNA_0001543, regulating the NF-κB pathway, suppressing pro-inflammatory cytokines, and enhancing anti-inflammatory cytokine expression.
6.Exercise preconditioning alleviates motor deficits in MPTP-induced Parkinsonian mice by improving mitochondrial function.
Miao-Miao XU ; Dan-Ting HU ; Qiao ZHANG ; Xiao-Guang LIU ; Zhao-Wei LI ; Li-Ming LU
Acta Physiologica Sinica 2025;77(3):419-431
Parkinson's disease (PD) is a common neurodegenerative disorder mainly related to mitochondrial dysfunction of dopaminergic neurons in the midbrain substantia nigra. This study aimed to investigate the effects of exercise preconditioning on motor deficits and mitochondrial function in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. Eight-week-old male C57BL/6J mice were randomly divided into four groups: sedentary + saline (SS), sedentary + MPTP (SM), exercise + saline (ES), and exercise + MPTP (EM) groups. Mice in the ES and EM groups received 4 weeks of treadmill training, and then SM and EM groups were treated with MPTP for 5 days. Motor function was assessed by behavioral tests, and morphological and functional changes in dopaminergic neurons and mitochondria in the substantia nigra of the midbrain were evaluated using immunohistochemistry, Western blot, and transmission electron microscopy technology. The results showed that, compared with the SM group, the EM group exhibited significantly improved motor ability, up-regulated protein expression levels of tyrosine hydroxylase (TH) and dopamine transporter (DAT) in the midbrain, and down-regulated protein expression of α-synuclein (α-Syn) in the mitochondria of substantia nigra. Compared with the SM group, the EM group showed up-regulated protein expression levels of mitochondrial fusion proteins, including optical atrophy protein 1 (OPA1) and mitofusin 2 (MFN2), and biogenesis-related proteins, including peroxisome proliferator activated receptor gamma coactivator 1α (PGC-1α) and mitochondrial transcription factor A (TFAM), while the protein expression levels of dynamin-related protein 1 (DRP1) and mitochondrial fission protein 1 (FIS1) were significantly down-regulated. Compared with the SM group, the EM group showed significantly reduced damage to substantia nigra mitochondria, restored mitochondrial membrane potential and ATP production, and decreased levels of reactive oxygen species (ROS). These results suggest that 4-week treadmill pre-training can alleviate MPTP-induced motor impairments in PD mice by improving mitochondrial function, providing a theoretical basis for early exercise-based prevention of PD.
Animals
;
Male
;
Physical Conditioning, Animal/physiology*
;
Mice
;
Mice, Inbred C57BL
;
Mitochondria/physiology*
;
Dopaminergic Neurons
;
MPTP Poisoning/physiopathology*
;
Substantia Nigra
;
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
;
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
7.Identification of blood-entering components of Anshen Dropping Pills based on UPLC-Q-TOF-MS/MS combined with network pharmacology and evaluation of their anti-insomnia effects and mechanisms.
Xia-Xia REN ; Jin-Na YANG ; Xue-Jun LUO ; Hui-Ping LI ; Miao QIAO ; Wen-Jia WANG ; Yi HE ; Shui-Ping ZHOU ; Yun-Hui HU ; Rui-Ming LI
China Journal of Chinese Materia Medica 2025;50(7):1928-1937
This study identified blood-entering components of Anshen Dropping Pills and explored their anti-insomnia effects and mechanisms. The main blood-entering components of Anshen Dropping Pills were detected and identified by UPLC-Q-TOF-MS/MS. The rationality of the formula was assessed by using enrichment analysis based on the relationship between drugs and symptoms, and core targets of its active components were selected as the the potential anti-insomnia targets of Anshen Dropping Pills through network pharmacology analysis. Furthermore, protein-protein interaction(PPI) network, Gene Ontology(GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were performed on the core targets. An active component-core target network for Anshen Dropping Pills was constructed. Finally, the effects of low-, medium-, and high-dose groups of Anshen Dropping Pills on sleep episodes, sleep duration, and sleep latency in mice were measured by supraliminal and subliminal pentobarbital sodium experiments. Moreover, total scores of the Pittsburgh sleep quality index(PSQI) scale was used to evaluate the changes before and after the treatment with Anshen Dropping Pills in a clinical study. The enrichment analysis based on the relationship between drugs and symptoms verified the rationality of the Anshen Dropping Pills formula, and nine blood-entering components of Anshen Dropping Pills were identified by UPLC-Q-TOF-MS/MS. The network proximity revealed a significant correlation between eight components and insomnia, including magnoflorine, liquiritin, spinosin, quercitrin, jujuboside A, ginsenoside Rb_3, glycyrrhizic acid, and glycyrrhetinic acid. Network pharmacology analysis indicated that the major anti-insomnia pathways of Anshen Dropping Pills involved substance and energy metabolism, neuroprotection, immune system regulation, and endocrine regulation. Seven core genes related to insomnia were identified: APOE, ALB, BDNF, PPARG, INS, TP53, and TNF. In summary, Anshen Dropping Pills could increase sleep episodes, prolong sleep duration, and reduce sleep latency in mice. Clinical study results demonstrated that Anshen Dropping Pills could decrease total scores of PSQI scale. This study reveals the pharmacodynamic basis and potential multi-component, multi-target, and multi-pathway effects of Anshen Dropping Pills, suggesting that its anti-insomnia mechanisms may be associated with the regulation of insomnia-related signaling pathways. These findings offer a theoretical foundation for the clinical application of Anshen Dropping Pills.
Animals
;
Drugs, Chinese Herbal/administration & dosage*
;
Tandem Mass Spectrometry/methods*
;
Sleep Initiation and Maintenance Disorders/metabolism*
;
Mice
;
Network Pharmacology
;
Male
;
Chromatography, High Pressure Liquid
;
Humans
;
Protein Interaction Maps/drug effects*
;
Sleep/drug effects*
;
Female
;
Adult
8.Phase changes and quantity-quality transfer of raw material, calcined decoction pieces, and standard decoction of Ostreae Concha (Ostrea rivularis).
Hong-Yi ZHANG ; Jing-Wei ZHOU ; Jia-Wen LIU ; Wen-Bo FEI ; Shi-Ru HUANG ; Yu-Mei CHEN ; Chong-Yang LI ; Fei-Fei LI ; Qiao-Ling MA ; Fu WANG ; Yuan HU ; You-Ping LIU ; Shi-Lin CHEN ; Lin CHEN ; Hong-Ping CHEN
China Journal of Chinese Materia Medica 2025;50(5):1209-1223
The phase changes and quantity-quality transfer of 17 batches of Ostreae Concha(Ostrea rivularis) during the raw material-calcined decoction pieces-standard decoction process were analyzed. The content of calcium carbonate(CaCO_3), the main component, was determined by chemical titration, and the extract yield and transfer rate were calculated. The CaCO_3 content in the raw material, calcined decoction pieces, and standard decoction was 94.39%-98.80%, 95.03%-99.22%, and 84.58%-90.47%, respectively. The process of raw material to calcined decoction pieces showed the yield range of 96.85% to 98.55% and the CaCO_3 transfer rate range of 96.92% to 99.27%. The process of calcined decoction pieces to standard decoction showed the extract yield range of 2.86% to 5.48% and the CaCO_3 transfer rate range of 2.59% to 5.13%. The results of X-ray fluorescence(XRF) assay showed that the raw material, calcined decoction pieces, and standard decoction mainly contained Ca, Na, Mg, Si, Br, Cl, Al, Fe, Cr, Mn, and K. The chemometric results showed an increase in the relative content of Cr, Fe, and Si from raw material to calcined decoction pieces and an increase in the relative content of Mg, Al, Br, K, Cl, and Na from calcined decoction pieces to standard decoction. X-ray diffraction(XRD) was employed to establish XRD characteristic patterns of the raw material, calcined decoction pieces, and standard decoction. The XRD results showed that the main phase of all three was calcite, and no transformation of crystalline form or generation of new phase was observed. Fourier transform infrared spectroscopy(FTIR) was employed to establish the FTIR characteristic spectra of the raw material, calcined decoction pieces, and standard decoction. The FTIR results showed that the raw material had internal vibrations of O-H, C-H, C=O, C-O, and CO■ groups. Due to the loss of organic matter components after calcination, no information about the vibrations of C-H, C=O, and C-O groups was observed in the spectra of calcined decoction pieces and standard decoction. In summary, this study elucidated the quantity-quality transfer and phase changes in the raw material-calcined decoction pieces-standard decoction process by determining the CaCO_3 content, calculating the extract yield and transfer rate, and comparing the element changes, FTIR characteristic spectra, and XRD characteristic pattern. The results were reasonable and reliable, laying a foundation for the subsequent process research and quality control of the formula granules of calcined Ostreae Concha(O. rivularis Gould), and providing ideas and methods for the quality control of the whole process of raw material-decoction pieces-standard decoction-formula granules of Ostreae Concha and other testacean traditional Chinese medicine.
Drugs, Chinese Herbal/isolation & purification*
;
Calcium Carbonate/analysis*
;
Quality Control
9.Ecliptasaponin A ameliorates DSS-induced colitis in mice by suppressing M1 macrophage polarization via inhibiting the JAK2/STAT3 pathway.
Minzhu NIU ; Lixia YIN ; Tong QIAO ; Lin YIN ; Keni ZHANG ; Jianguo HU ; Chuanwang SONG ; Zhijun GENG ; Jing LI
Journal of Southern Medical University 2025;45(6):1297-1306
OBJECTIVES:
To investigate the effect of ecliptasaponin A (ESA) for alleviating dextran sulfate sodium (DSS)-induced inflammatory bowel disease (IBD) in mice and the underlying mechanism.
METHODS:
Twenty-four male C57BL/6 mice (8-10 weeks old) were equally randomized into control group, DSS-induced IBD model group, and DSS+ESA (50 mg/kg) treatment group. Disease activity index (DAI), colon length and spleen index of the mice were measured, and intestinal pathology was examined with HE staining. The expressions of inflammatory mediators (TNF-α, IL-6, and iNOS) in the colon mucosa were detected using ELISA and RT-qPCR, and intestinal barrier integrity was assessed using AB-PAS staining and by detecting ZO-1 and claudin-1 expressions using immunofluorescence staining and Western blotting. In cultured RAW264.7 macrophages, the effects of treatment with 50 μmol/L ESA, alone or in combination with 20 μmol/L RO8191 (a JAK2/STAT3 pathway activator), on M1 polarization of the cells induced by LPS and IFN-γ stimulation and expressions of JAK2/STAT3 pathway proteins were analyzed using flow cytometry and Western blotting.
RESULTS:
In the mouse models of DSS-induced IBD, ESA treatment significantly alleviated body weight loss and colon shortening, reduced DAI, spleen index and histological scores, and ameliorated inflammatory cell infiltration in the colon tissue. ESA treatment also suppressed TNF‑α, IL-6 and iNOS expressions, protected the goblet cells and the integrity of the mucus and mechanical barriers, and upregulated the expressions of ZO-1 and claudin-1. ESA treatment obviously decreased CD86+ M1 polarization in the mesenteric lymph nodes of IBD mice and in LPS and IFN-γ-induced RAW264.7 cells, and significantly reduced p-JAK2 and p-STAT3 expressions in both the mouse models and RAW264.7 cells. Treatment with RO8191 caused reactivation of JAK2/STAT3 and strongly attenuated the inhibitory effect of ESA on CD86+ polarization in RAW264.7 cells.
CONCLUSIONS
ESA alleviates DSS-induced colitis in mice by suppressing JAK2/STAT3-mediated M1 macrophage polarization and mitigating inflammation-driven intestinal barrier damage.
Animals
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Mice
;
Janus Kinase 2/metabolism*
;
STAT3 Transcription Factor/metabolism*
;
Mice, Inbred C57BL
;
Male
;
Dextran Sulfate
;
Macrophages/cytology*
;
Colitis/metabolism*
;
Saponins/pharmacology*
;
Signal Transduction/drug effects*
;
RAW 264.7 Cells
;
Triterpenes/pharmacology*
;
Interleukin-6/metabolism*
10.Pinostrobin targets the PI3K/AKT/CCL2 axis in intestinal epithelial cells to inhibit intestinal macrophage infiltration and alleviate dextran sulfate sodium-induced colitis in mice.
Keni ZHANG ; Tong QIAO ; Lin YIN ; Ju HUANG ; Zhijun GENG ; Lugen ZUO ; Jianguo HU ; Jing LI
Journal of Southern Medical University 2025;45(10):2199-2209
OBJECTIVES:
To investigate the mechanism through which pinostrobin (PSB) alleviates dextran sulfate sodium (DSS)-induced colitis in mice.
METHODS:
C57BL/6 mice were randomized into control group, DSS model group, and PSB intervention (30, 60, and 120 mg/kg) groups. Colitis severity of the mice was assessed by examining body weight changes, disease activity index (DAI), colon length, and histopathology. The expressions of tight junction proteins ZO-1 and claudin-1 in the colon tissues were examined using immunofluorescence staining, and macrophage infiltration and polarization were analyzed with flow cytometry. ELISA and RT-qPCR were used for detecting the expressions of inflammatory factors (TNF‑α and IL-6) and chemokines (CCL2, CXCL10, and CX3CL1) in the colon tissues, and PI3K/AKT phosphorylation levels were analyzed with Western blotting. In cultured Caco-2 and RAW264.7 cells, the effect of PSB on CCL2-mediated macrophage migration was assessed using Transwell assay. Network pharmacology analysis was performed to predict the key pathways that mediate the therapeutic effect of PSB.
RESULTS:
In DSS-induced mouse models, PSB at 60 mg/kg optimally alleviated colitis, shown by reduced weight loss and DAI scores and increased colon length. PSB treatment significantly upregulated ZO-1 and claudin-1 expressions in the colon tissues, inhibited colonic macrophage infiltration, and promoted the shift of macrophage polarization from M1 to M2 type. In cultured intestinal epithelial cells, PSB significantly inhibited PI3K/AKT phosphorylation and suppressed chemokine CCL2 expression. PSB treatment obviously blocked CCL2-mediated macrophage migration of RAW264.7 cells, which could be reversed by exogenous CCL2. Network pharmacology analysis and rescue experiments confirmed PI3K/AKT and CCL2 signaling as the core targets of PSB.
CONCLUSIONS
PSB alleviates DSS-induced colitis in mice by targeting intestinal epithelial PI3K/AKT signaling, reducing CCL2 secretion, and blocking macrophage chemotaxis and migration, highlighting the potential of PSB as a novel natural compound for treatment of inflammatory bowel disease.
Animals
;
Mice
;
Mice, Inbred C57BL
;
Phosphatidylinositol 3-Kinases/metabolism*
;
Colitis/drug therapy*
;
Dextran Sulfate
;
Proto-Oncogene Proteins c-akt/metabolism*
;
Macrophages
;
Chemokine CCL2/metabolism*
;
Humans
;
Signal Transduction/drug effects*
;
Caco-2 Cells
;
RAW 264.7 Cells
;
Epithelial Cells/drug effects*
;
Intestinal Mucosa/metabolism*

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