1.Establishment and Preliminary Analysis of GP73 Interactome Using Proximity-dependent Labeling Technology
Mu-Yi LIU ; Chang ZHANG ; Meng-Xin YANG ; Xin-Long YAN ; Lu-Ming WAN ; Cong-Wen WEI
Progress in Biochemistry and Biophysics 2026;53(3):711-723
ObjectiveProtein-protein interactions (PPIs) are fundamental to the execution of biological functions within living cells. However, traditional biochemical methods, such as co-immunoprecipitation (Co-IP), often fail to capture transient, weak, or membrane-associated interactions due to the stringent detergent requirements for cell lysis. Proximity labeling (PL) has emerged in recent years as a transformative technology for mapping the proteomes of specific subcellular compartments and identifying dynamic interactomes in situ. Golgi protein 73 (GP73, also known as GOLPH2), a resident type II Golgi transmembrane protein, is a well-recognized clinical biomarker for liver diseases, including hepatocellular carcinoma (HCC). Despite its clinical significance, the comprehensive physiological and pathological functions of GP73 remain partially understood. This study aims to establish an APEX2-mediated proximity labeling system specifically targeting GP73 to map its interactome in a living cellular environment, thereby providing new insights into its molecular roles and regulatory mechanisms. MethodsTo achieve spatial specificity, we first constructed a stable cell line expressing a fusion protein consisting of GP73 and the engineered soybean peroxidase APEX2. The localization of the GP73-APEX2 fusion protein was validated to ensure it correctly targeted the Golgi apparatus. The proximity labeling reaction was initiated by incubating the cells with biotin-phenol (BP) for 30 min, followed by a brief (1 min) treatment with1 mmol/L hydrogen peroxide (H2O2). This catalytic reaction converts BP into highly reactive, short-lived biotin-phenoxyl radicals that covalently attach to endogenous proteins within a small labeling radius of the GP73-APEX2 enzyme. Subsequently, the cells were quenched, and biotinylated proteins were enriched using high-affinity streptavidin-coated magnetic beads. The captured “neighbor” proteins were subjected to on-bead digestion and analyzed via liquid chromatography-tandem mass spectrometry (LC-MS/MS) for high-throughput identification. Rigorous bioinformatics analysis, including Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and protein-protein interaction network mapping, was performed to interpret the biological significance of the identified candidates. ResultsOur results demonstrate the successful establishment of a robust and sensitive APEX2-based proximity labeling system for GP73. We identified a total of 95 high-confidence interacting proteins that were significantly enriched in the GP73 proximity proteome compared to control groups. Bioinformatics analysis revealed that these interactors were predominantly associated with biological processes such as vesicular transport, protein localization, and, most notably, molecular functions related to “ribosome binding” and “translation regulation”. This suggested an unexpected role for the Golgi-resident GP73 in the cellular translation machinery. To validate these findings, we performed targeted biochemical assays which confirmed a direct interaction between GP73 and the subunits of the eukaryotic translation initiation factor 3 (eIF3) complex, specifically EIF3G and EIF3I. Furthermore, functional validation using the surface sensing of translation (SUnSET) assay—a non-radioactive method to monitor protein synthesis—revealed that the overexpression of GP73 significantly promoted global protein translation levels in the cell, whereas its depletion or inhibition resulted in reduced translation efficiency. ConclusionThis study successfully utilized APEX2-mediated proximity labeling to provide the first systematic map of GP73 interactome in living cells. Our findings uncover a novel, unconventional function of GP73 as a regulator of cellular protein translation, likely mediated through its interaction with the eIF3 complex. This discovery significantly broadens our understanding of the biological roles of GP73 beyond its traditional function in the Golgi apparatus and suggests that it may act as a bridge between Golgi-related trafficking and the protein synthesis machinery. Furthermore, the technical framework established in this study provides a valuable template for investigating other complex organelle-associated protein networks and resolving transient macromolecular interactions in various physiological and pathological contexts.
2.Efficacy comparison of goniosynechialysis versus trabeculectomy combined with phacoemulsification in the treatment of glaucoma complicated with cataract
Zhentong LIU ; Nannan TIAN ; Xiangci MENG ; Yan ZHANG
International Eye Science 2026;26(3):405-409
AIM: To compare the clinical efficacy of goniosynechialysis versus trabeculectomy combined with cataract phacoemulsification in treating glaucoma complicated with cataract.METHODS:From January 2019 to January 2024, patients with glaucoma complicated with cataract diagnosed in our hospital were included as the study subjects. They were assigned into trabeculectomy group and goniosynechialysis group based on different surgical methods. The trabeculectomy group was treated with cataract phacoemulsification combined with trabeculectomy, while the goniosynechialysis group was treated with cataract phacoemulsification combined with goniosynechialysis. The improvement of visual acuity, anterior chamber depth, chamber angle width, intraocular pressure, whole en face vessel density within the optic disc head and in the peripapillary region, and complications were compared between two groups.RESULTS: A total of 120 patients(120 eyes)with glaucoma combined with cataract were included in this study, among which 60 eyes were in the trabeculectomy group and 60 eyes in the goniosynechialysis group. The age of the trabeculectomy group was 60.72±6.16 years, including 28 males and 32 females. The age of the goniosynechialysis group was 61.04±6.24 years, including 31 males and 29 females. At 3 mo after surgery, the visual acuity of patients in both groups improved significantly, and the improvement of visual acuity in the goniosynechialysis group was significantly better than that in the trabeculectomy group(all P<0.01). At 3 mo after surgery, the anterior chamber depth and chamber angle width of patients in both groups were higher than those before surgery, and with the goniosynechialysis group being higher than the trabeculectomy group(all P<0.01), while the intraocular pressure was lower than that before surgery, and with the goniosynechialysis group being lower than the trabeculectomy group(all P<0.01). Before surgery, there was no significant difference in the whole en face vessel density within the optic disc head between the two groups(P>0.05), however, the whole en face vessel density within the optic disc head in both groups on 1 d after surgery were significantly lower than before surgery(all P<0.05); and compared with 1 d after surgery, there was a significant increase at 1 wk, 1, and 3 mo after surgery(all P<0.05); the whole en face vessel density within the optic disc head in the goniosynechialysis group was significantly higher than that in the trabeculectomy group at various time points after surgery(all P<0.05). However, there was no significant difference in the whole en face vessel density in the peripapillary region between the two groups before surgery and various time points after surgery(all P>0.05). Within 3 mo after surgery, the incidence of complications in the goniosynechialysis group(8.3%)was significantly lower than that in the trabeculectomy group(21.7%; P<0.05).CONCLUSION:Goniosynechialysis combined with phacoemulsification is more effective than trabeculectomy combined with phacoemulsification in the treatment of patients with glaucoma complicated with cataract in improving the visual acuity and whole en face vessel density within the optic disc head of patients, increasing the anterior chamber depth and chamber angle width, reducing intraocular pressure and the risk of complications. It has high safety and ideal short-term efficacy.
3.Influencing factors of work alienation among Chinese nurses: A meta-analysis
Yan MENG ; Hailong ZHANG ; Linjun ZHU ; Yupin HAN ; Simeng GU
Journal of Environmental and Occupational Medicine 2026;43(3):354-362
Background Work alienation is a subjectively negative psychological state characterized by detachment from one's job and its environment. Due to heavy workloads, high-intensity tasks, low compensation, as well as pressures related to promotion, nurses are particularly susceptible to work alienation. Objective To meta-analyze the primary factors affecting work alienation of nurses in China, providing an evidence-based foundation for improving nursing management and nurses' physical and mental health. Methods A systematic search was conducted across multiple databases, including PubMed, Embase, the Cochrane Library, Web of Science, CNKI, VIP, Wanfang Data, and DBM, for cross-sectional studies on work alienation and its influencing factors among nurses in China published from inception to December 2024. Two researchers independently conducted literature screening, data extraction, and risk of bias assessment for the included studies. Meta-analysis was performed using Stata 15.0 and RevMan 5.4 software. Pooled effect sizes were calculated using either fixed-effects or random-effects models based on the magnitude of heterogeneity. Results A total of 27 studies involving 13 028 nurses were included in the meta-analysis, from which 11 influencing factors of work alienation were identified. The pooled score for work alienation among nurses in China was 34.79 (95%CI: 32.56, 37.01). Subgroup analysis revealed that the emergency department reported the highest score (36.81, 95%CI: 31.64, 41.98), followed by the intensive care unit (34.99, 95%CI: 32.27, 37.72) and internal medicine department (33.90, 95%CI: 29.10, 38.71). Significant factors influencing work alienation included length of work experience [standardized mean difference (SMD)=0.32, 95%CI: 0.02, 0.61], professional title (SMD=0.30, 95%CI: 0.16, 0.44), monthly income (SMD=0.38, 95%CI: 0.14, 0.62), psychological capital (SMD=–0.41, 95%CI:–0.52, –0.29), work stress (SMD=0.54, 95%CI: 0.49, 0.58), attitude toward aggression and violence management (SMD=–0.38, 95%CI:–0.44, –0.32), and organizational climate (SMD=–0.47, 95%CI: –0.57, –0.36) (P <0.05). Sensitivity analysis confirmed the robustness of the meta-analysis results, and no significant publication bias was detected. Conclusion Nurses in China exhibit a high level of work alienation, particularly in high-acuity settings like emergency and intensive care unit departments compared to general departments. Shorter work experience (<5 years), lower professional title, lower monthly income (<5 000 CNY), and greater work stress are positively correlated with work alienation. In contrast, psychological capital, proactive attitudes toward managing aggression and violence, and a supportive organizational climate are negatively correlated. These findings indicate a need for nursing managers to develop targeted strategies based on these multifaceted factors to mitigate alienation among nursing staff.
4.Genetic analysis and prenatal diagnosis of structural brain abnormalities associated with TUBB gene c.155A>G variant.
Yifan LIU ; Wei SONG ; Xinlian WANG ; Yan RUAN ; Meng ZHANG ; Yujiao CHEN ; Yan LIU ; Puqing ZHANG ; Li WANG ; Yousheng YAN
Chinese Journal of Medical Genetics 2026;43(2):136-142
OBJECTIVE:
To explore the genotype-phenotype correlation in a Chinese family with structural brain abnormalities due to variant of the TUBB gene.
METHODS:
A family undergoing prenatal diagnosis at Beijing Obstetrics and Gynecology Hospital in October 2024 was selected as the study subject. Clinical data were collected. Amniotic fluid sample was subjected to chromosomal copy number variation sequencing (CNV-seq). Trio whole-exome sequencing (Trio-WES) was carried out on the amniotic fluid and parental blood samples, and candidate variant was verified by Sanger sequencing. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2023-KY-076-01).
RESULTS:
Both prenatal ultrasound and fetal MRI showed deviation of brain midline, unilateral lateral ventriculomegaly, and bilateral gyral asymmetry. Trio-WES revealed that the fetus has harbored a maternally derived heterozygous missense variant of the TUBB gene [NM_178014.4: c.155A>G (p.N52S)]. Sanger sequencing confirmed that the woman and a previously terminated fetus both harbored the same variant. Both the proband and two fetuses exhibited similar neuroimaging abnormalities including midline deviation and asymmetrical gyri. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PM2_Supporting+PS2_Moderate+PS3).
CONCLUSION
The heterozygous c.155A>G (p.N52S) variant was the TUBB gene probably underlay the pathogenesis of the structural brain abnormalities in this family. Above findings have expanded the phenotypic spectrum associated with the variant and facilitated the prenatal diagnosis for this family.
Humans
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Female
;
Pregnancy
;
Prenatal Diagnosis
;
Tubulin/genetics*
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Adult
;
Brain/diagnostic imaging*
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Male
;
Pedigree
;
DNA Copy Number Variations/genetics*
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Exome Sequencing
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Genetic Association Studies
;
Magnetic Resonance Imaging
5.Mechanism of miR-21 targeting inhibition of the PTEN/AKT/mTOR pathway in ameliorating chronic renal fibrosis in mice
Jiao QI ; Shanshan XU ; Qige QI ; Yan MENG ; Jianrong ZHAO ; Liying ZHANG
Acta Universitatis Medicinalis Anhui 2026;61(2):217-224
ObjectiveTo investigate the mechanism through which miR‑21 improves chronic renal fibrosis in mice via targeted modulation of the phosphatase and tensin homolog (PTEN)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. MethodsThirty‑two chronic kidney disease model mice were randomly divided into four groups (n=8 each group): model group, miR‑21 overexpression group, miR‑21 inhibition group, and miR‑21 inhibition + MK‑2206 group. Eight healthy mice were included as the control group. The miR‑21 overexpression, miR‑21 inhibition, and miR‑21 inhibition + MK‑2206 groups received tail‑vein injections of lentivirus (50 μL, 1×10⁸ TU per mouse) once weekly for three weeks. The control and model groups were injected with an equal volume of empty vector (LV‑NC). The miR‑21 inhibition + MK‑2206 group additionally received gavage of the AKT/mTOR pathway inhibitor MK‑2206 (480 mg/kg) once weekly for three weeks. The expressions of miR‑21, 24 h urinary protein, serum creatinine (Scr), blood urea nitrogen (BUN), and renal tissue levels of collagen Ⅰ, collagen Ⅲ, α‑smooth muscle actin (α‑SMA), and PTEN protein, as well as p‑AKT/AKT and p‑mTOR/mTOR ratios, were compared among groups. HE staining was used to observe pathological changes in renal tissue, and Masson staining was used to observe the degree of renal fibrosis. A dual‑luciferase assay was performed to verify the targeting relationship between miR‑21 and PTEN. ResultsCompared with the model group, miR‑21 expression in renal tissue increased in the miR‑21 overexpression group (P<0.05) and decreased in the miR‑21 inhibition group (P<0.05). Compared with the model group, the miR‑21 overexpression group showed increased 24 h urinary protein, Scr, BUN, and renal tissue expression of collagen Ⅰ, collagen Ⅲ, and α‑SMA (all P<0.05), while these indicators decreased in the miR‑21 inhibition group (P<0.05). Compared with the miR‑21 inhibition group, the miR‑21 inhibition + MK‑2206 group exhibited lower 24‑h urinary protein, Scr, BUN, and renal tissue expression of Collagen Ⅰ, Collagen Ⅲ, and α‑SMA (all P<0.05). Compared with the model group, the miR‑21 overexpression group showed decreased PTEN protein expression (P<0.05) and increased p‑AKT/AKT and p‑mTOR/mTOR ratios (P<0.05), while the miR‑21 inhibition group showed increased PTEN expression (P<0.05) and decreased p‑AKT/AKT and p‑mTOR/mTOR ratios (P<0.05). Compared with the miR‑21 inhibition group, the miR‑21 inhibition + MK‑2206 group had lower p‑AKT/AKT and p‑mTOR/mTOR ratios (P<0.05), with no significant difference in PTEN protein expression. HE and Masson staining showed normal kidney structure and almost no fibrosis in the control group. The model group exhibited glomerular enlargement, capillary loop adhesion, and focal fibrosis. The miR-21 overexpression group showed severe destruction of glomerular structure, accompanied by extensive fibrosis and renal tubular atrophy. The pathological changes and degree of fibrosis were alleviated in the miR-21 inhibition group. The miR-21 inhibition + MK-2206 group showed only mild pathological changes and mild fibrosis, with the interstitium being largely normal. Compared with PTEN-WT + NC mimics 1, the relative luciferase activity in the PTEN-WT + miR-21 mimics group decreased (P<0.001). There was no statistically significant difference in relative luciferase activity between PTEN-WT + NC mimics group and PTEN-MUT + miR-21 mimics group. ConclusionmiR‑21 may improve renal function indicators and alleviate renal fibrosis in chronic kidney disease mice via targeted modulation of PTEN and subsequently inhibiting the AKT/mTOR pathway.
6.Discriminating Tumor Deposits From Metastatic Lymph Nodes in Rectal Cancer: A Pilot Study Utilizing Dynamic Contrast-Enhanced MRI
Xue-han WU ; Yu-tao QUE ; Xin-yue YANG ; Zi-qiang WEN ; Yu-ru MA ; Zhi-wen ZHANG ; Quan-meng LIU ; Wen-jie FAN ; Li DING ; Yue-jiao LANG ; Yun-zhu WU ; Jian-peng YUAN ; Shen-ping YU ; Yi-yan LIU ; Yan CHEN
Korean Journal of Radiology 2025;26(5):400-410
Objective:
To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer.
Materials and Methods:
A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs.
Results:
All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027).
Conclusion
The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.
7.Correlation between differences in starch gelatinization, water distribution, and terpenoid content during steaming process of Curcuma kwangsiensis root tubers by multivariate statistical analysis.
Yan LIANG ; Meng-Na YANG ; Xiao-Li QIN ; Zhi-Yong ZHANG ; Zhong-Nan SU ; Hou-Kang CAO ; Ke-Feng ZHANG ; Ming-Wei WANG ; Bo LI ; Shuo LI
China Journal of Chinese Materia Medica 2025;50(10):2684-2694
To elucidate the mechanism by which steaming affects the quality of Curcuma kwangsiensis root tubers, methods such as LSCM, RVA, dual-wavelength spectrophotometry, LF-NMR, and LC-MS were employed to qualitatively and quantitatively detect changes in starch gelatinization characteristics, water distribution, and material composition of C. kwangsiensis root tubers under different steaming durations. Based on multivariate statistical analysis, the correlation between differences in gelatinization parameters, water distribution, and terpenoid material composition was investigated. The results indicate that steaming affects both starch gelatinization and water distribution in C. kwangsiensis. During the steaming process, transformations occur between amylose and amylopectin, as well as between semi-bound water and free water. After 60 min of steaming, starch gelatinization and water distribution reached an equilibrium state. The content of amylopectin, the amylose-to-amylopectin ratio, and parameters such as gelatinization temperature, viscosity, breakdown value, and setback value were significantly correlated(P≤0.05). Additionally, the amylose-to-amylopectin ratio was significantly correlated with total free water and total water content(P≤0.05). Steaming induced differences in the material composition of C. kwangsiensis root tubers. Clustering of primary metabolites in the OPLS-DA model was distinct, while secondary metabolites were classified into 9 clusters using the K-means clustering algorithm. Differential terpenoid metabolites such as(-)-α-curcumene were significantly correlated with zerumbone, retinal, and all-trans-retinoic acid(P<0.05). Curcumenol was significantly correlated with isoalantolactone and ursolic acid(P<0.05), while all-trans-retinoic acid was significantly correlated with both zerumbone and retinal(P<0.05). Alpha-tocotrienol exhibited a significant correlation with retinal and all-trans-retinoic acid(P<0.05). Amylose was extremely significantly correlated with(-)-α-curcumene, curcumenol, zerumbone, retinal, all-trans-retinoic acid, and α-tocotrienol(P<0.05). Amylopectin was significantly correlated with zerumbone(P<0.05) and extremely significantly correlated with(-)-α-curcumene, curcumenol, zerumbone, retinal, all-trans-retinoic acid, and 9-cis-retinoic acid(P<0.01). The results provide scientific evidence for elucidating the mechanism of quality formation of steamed C. kwangsiensis root tubers as a medicinal material.
Curcuma/chemistry*
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Starch/chemistry*
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Multivariate Analysis
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Water/chemistry*
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Terpenes/analysis*
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Plant Roots/chemistry*
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Plant Tubers/chemistry*
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Drugs, Chinese Herbal/chemistry*
8.Mechanism related to bile acids metabolism of liver injury induced by long-term administration of emodin.
Jing-Zhuo TIAN ; Lian-Mei WANG ; Yan YI ; Zhong XIAN ; Nuo DENG ; Yong ZHAO ; Chun-Ying LI ; Yu-Shi ZHANG ; Su-Yan LIU ; Jia-Yin HAN ; Chen PAN ; Chen-Yue LIU ; Jing MENG ; Ai-Hua LIANG
China Journal of Chinese Materia Medica 2025;50(11):3079-3087
Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage*
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Bile Acids and Salts/metabolism*
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Animals
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Male
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Liver/injuries*
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Chemical and Drug Induced Liver Injury/genetics*
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Drugs, Chinese Herbal/adverse effects*
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Humans
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Rats, Sprague-Dawley
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Mice
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Rats
9.Establishment of different pneumonia mouse models suitable for traditional Chinese medicine screening.
Xing-Nan YUE ; Jia-Yin HAN ; Chen PAN ; Yu-Shi ZHANG ; Su-Yan LIU ; Yong ZHAO ; Xiao-Meng ZHANG ; Jing-Wen WU ; Xuan TANG ; Ai-Hua LIANG
China Journal of Chinese Materia Medica 2025;50(15):4089-4099
In this study, lipopolysaccharide(LPS), ovalbumin(OVA), and compound 48/80(C48/80) were administered to establish non-infectious pneumonia models under simulated clinical conditions, and the correlation between their pathological characteristics and traditional Chinese medicine(TCM) syndromes was compared, providing the basis for the selection of appropriate animal models for TCM efficacy evaluation. An acute pneumonia model was established by nasal instillation of LPS combined with intraperitoneal injection for intensive stimulation. Three doses of OVA mixed with aluminum hydroxide adjuvant were injected intraperitoneally on days one, three, and five and OVA was administered via endotracheal drip for excitation on days 14-18 to establish an OVA-induced allergic pneumonia model. A single intravenous injection of three doses of C48/80 was adopted to establish a C48/80-induced pneumonia model. By detecting the changes in peripheral blood leukocyte classification, lung tissue and plasma cytokines, immunoglobulins(Ig), histamine levels, and arachidonic acid metabolites, the multi-dimensional analysis was carried out based on pathological evaluation. The results showed that the three models could cause pulmonary edema, increased wet weight in the lung, and obvious exudative inflammation in lung tissue pathology, especially for LPS. A number of pyrogenic cytokines, inclading interleukin(IL)-6, interferon(IFN)-γ, IL-1β, and IL-4 were significantly elevated in the LPS pneumonia model. Significantly increased levels of prostacyclin analogs such as prostaglandin E2(PGE2) and PGD2, which cause increased vascular permeability, and neutrophils in peripheral blood were significantly elevated. The model could partly reflect the clinical characteristics of phlegm heat accumulating in the lung or dampness toxin obstructing the lung. The OVA model showed that the sensitization mediators IgE and leukotriene E4(LTE4) were increased, and the anti-inflammatory prostacyclin 6-keto-PGF2α was decreased. Immune cells(lymphocytes and monocytes) were decreased, and inflammatory cells(neutrophils and basophils) were increased, reflecting the characteristics of "deficiency", "phlegm", or "dampness". Lymphocytes, monocytes, and basophils were significantly increased in the C48/80 model. The phenotype of the model was that the content of histamine, a large number of prostacyclins(6-keto-PGE1, PGF2α, 15-keto-PGF2α, 6-keto-PGF1α, 13,14-D-15-keto-PGE2, PGD2, PGE2, and PGH2), LTE4, and 5-hydroxyeicosatetraenoic acid(5S-HETE) was significantly increased, and these indicators were associated with vascular expansion and increased vascular permeability. The pyrogenic inflammatory cytokines were not increased. The C48/80 model reflected the characteristics of cold and damp accumulation. In the study, three non-infectious pneumonia models were constructed. The LPS model exhibited neutrophil infiltration and elevated inflammatory factors, which was suitable for the efficacy study of TCM for clearing heat, detoxifying, removing dampness, and eliminating phlegm. The OVA model, which took allergic inflammation as an index, was suitable for the efficacy study of Yiqi Gubiao formulas. The C48/80 model exhibited increased vasoactive substances(histamine, PGs, and LTE4), which was suitable for the efficacy study and evaluation of TCM for warming the lung, dispersing cold, drying dampness, and resolving phlegm. The study provides a theoretical basis for model selection for the efficacy evaluation of TCM in the treatment of pneumonia.
Animals
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Disease Models, Animal
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Mice
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Pneumonia/genetics*
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Medicine, Chinese Traditional
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Male
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Humans
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Cytokines/immunology*
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Female
;
Lipopolysaccharides/adverse effects*
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Lung/drug effects*
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Drugs, Chinese Herbal
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Ovalbumin
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Mice, Inbred BALB C
10.Mechanism of traditional Chinese medicine treatment of hepatic fibrosis by restoring circadian rhythms.
Meng-Ru ZHANG ; Ruo-Nan JIANG ; Shu-Hua XIONG ; Hong-Yan WU ; De-Song KONG ; Li CHEN
China Journal of Chinese Materia Medica 2025;50(16):4407-4414
Hepatic fibrosis is a key pathological process in the development of chronic liver disease to cirrhosis, and its core mechanism involves the activation of hepatic stellate cells(HSC) and abnormal deposition of extracellular matrix(ECM). Although existing treatments, such as antiviral drugs, can delay disease progression, they have the problem of single therapeutic targets and cannot reverse fibrosis. Accordingly, multidimensional intervention strategies are urgently needed. Recent studies have shown that circadian rhythm disorders aggravate hepatic fibrosis by regulating metabolism, immunity, and inflammation. Traditional Chinese medicine(TCM) plays a unique role in restoring the circadian clock via multi-target and holistic regulation. This paper establishes a three-dimensional network by systematically integrating biological clock, metabolism, and immunity for the first time to elucidate the scientific connotation of the theory of time-concerned treatment of TCM, and proposes a new strategy for the development of time-targeted compound prescriptions, providing innovative ideas for the treatment of hepatic fibrosis.
Humans
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Liver Cirrhosis/metabolism*
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Drugs, Chinese Herbal/therapeutic use*
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Circadian Rhythm/drug effects*
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Animals
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Medicine, Chinese Traditional
;
Hepatic Stellate Cells/drug effects*

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