1.Network pharmacology, molecular docking, and animal experiments reveal mechanism of Zhizhu Decoction in regulating macrophage polarization to reduce adipose tissue inflammation in obese children.
Yong-Kai YIN ; Chang-Miao NIU ; Li-Ting LIANG ; Mo DAN ; Tian-Qi GAO ; Yan-Hong QIN ; Xiao-Ning YAN
China Journal of Chinese Materia Medica 2025;50(1):228-238
Network pharmacology and molecular docking were employed to predict the mechanism of Zhizhu Decoction in regulating macrophage polarization to reduce adipose tissue inflammation in obese children, and animal experiments were then carried out to validate the prediction results. The active ingredients and targets of Zhizhu Decoction were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The inflammation related targets in the adipose tissue of obese children were searched against GeneCards, OMIM, and DisGeNET, and a drug-disease-target network was established. STRING was used to construct a protein-protein interaction(PPI) network and screen for core targets. R language was used to carry out Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. AutoDock was used for the molecular docking between core targets and active ingredients. 24 SPF grade 6-week C57B/6J male mice were adaptively fed for 1 week, and 8 mice were randomly selected as the blank group. The remaining 16 mice were fed with high-fat diet for 8 weeks to onstruct a high-fat diet induced mouse obesity model. After successful modeling, the 16 mice were randomly divided into model group and Zhizhu Decoction group, with 8 mice in each group. Zhizhu Decoction group was intervened by gavage for 14 days, once a day. Blank group and model group were given an equal amount of sterile double distilled water(ddH_2O) by gavage daily. After the last gavage, serum and inguinal adipose tissue were collected from mice for testing. The morphology of inguinal adipose tissue was observed by hematoxylin-eosin(HE) staining, the levels of inflammatory factors interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA), and the protein expression of macrophage marker molecule nitric oxide synthase(iNOS) and epidermal growth factor like hormone receptor 1(F4/80) was detected by immunofluorescence staining. Network pharmacology predicted luteolin, naringenin, and nobiletin as the main active ingredients in Zhizhu Decoction and 15 core targets. KEGG pathway enrichment analysis revealed involvement in the key signaling pathway of nuclear factor κB(NF-κB). Molecular docking showed that the active ingredients of Zhizhu Decoction bound well to the core targets. Animal experiment showed that compared with the model group, Zhizhu Decoction reduced the distribution of inflammatory cytokines in the inguinal adipose tissue of mice, lowered the levels of TNF-α and IL-6 in the serum(P<0.05, P<0.01), and down-regulated the expression of iNOS and F4/80(P<0.05). The results showed that the active ingredients in Zhizhu Decoction, such as luteolin, naringenin, and nobiletin, inhibit the aggregation of macrophages in adipose tissue, downregulate their classic activated macrophage(M1) polarization, reduce the expression of inflammatory factors IL-6 and TNF-α, and thus improve adipose tissue inflammation in obese mice.
Animals
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Drugs, Chinese Herbal/pharmacology*
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Molecular Docking Simulation
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Adipose Tissue/immunology*
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Mice
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Male
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Humans
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Network Pharmacology
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Macrophages/immunology*
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Mice, Inbred C57BL
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Child
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Protein Interaction Maps/drug effects*
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Obesity/genetics*
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Inflammation/drug therapy*
2.Spermidine inactivates proteasome activity and enhances ferroptosis in prostate cancer.
Dan FENG ; Jian ZHANG ; Huanmin NIU ; Xiaoxue ZHENG ; Mengqi JIA ; Qiqi LU ; Jing WANG ; Wenxue GUO ; Qi SUN ; Huiqing YUAN ; Hongxiang LOU
Acta Pharmaceutica Sinica B 2025;15(4):2095-2113
The elevated polyamines, amine-rich molecules with diverse functions in pathophysiology processes, are implicated in contributing to tumorigenesis and progression. Whether and how they affect the efficacy of chemotherapy is incompletely understood. Our screening assays reveal that the supplement with a low dose of spermidine (Spd), one of the polyamines, enhances ferroptosis in prostate cancer cells as evidenced by increased lipid peroxidation and intracellular Fe2+ levels in vitro. Combination treatment with Spd and a low dose of ferroptosis inducer erastin synergistically augments anti-tumor efficacy with undetectable toxicity in mice. Analysis of RNA-seq data indicates that heme oxygenase 1 (HMOX1), an enzyme that catalyzes the cleavage of heme to release Fe2+, is significantly upregulated in response to Spd and erastin cotreatment. Spd mediated the hypusine modification of the eukaryotic initiation factor 5A (EIF5A) promotes the translation of the nuclear factor erythroid 2-related factor 2 (NRF2), subsequently leading to elevation of HMOX1. Moreover, Spd and erastin significantly inhibit proteasome activity which results in a decrease in proteasomal degradation of NRF2, although many proteasome-related genes are induced either by Spd or Spd plus erastin. Thus, in addition to its pro-oncogenic activity, the supplement of Spd improves antitumor activity in combination with ferroptosis inducers and offers an optional approach to cancer treatment.
3.Development and application of chiral separation technology based on chiral metal-organic frameworks.
Gege ZHU ; Li GE ; Xinyu LI ; Bing NIU ; Qin CHEN ; Dan ZHONG ; Xiaodong SUN
Journal of Pharmaceutical Analysis 2025;15(7):101176-101176
Chirality is not only a natural phenomenon but also a bridge between chemistry and life sciences. An effective way to obtain a single enantiomer is through racemates resolution. Recent literature shows that chiral metal-organic frameworks (CMOFs) have many applications in various fields because of their diverse topologies and functionalities. This review outlines the design idea and summarizes the latest synthesis strategies and applications of CMOFs. It highlights key advances and issues in the separation domain. In conclusion, the review provides perspectives on the challenges and prospective advancements of CMOFs materials and CMOFs-based separation technologies.
4.Differential analysis of biogas production in simulated experiments of aquitard layers in coal seam fire zones.
Daping XIA ; Yunxia NIU ; Jijun TIAN ; Haichao WANG ; Donglei JIA ; Dan HUANG ; Zhenzhi WANG ; Weizhong ZHAO
Chinese Journal of Biotechnology 2025;41(8):3064-3080
To explore the differences in biological gas production in the waterlogged zone of a coal seam fire-affected area, in this study the in-situ gas production experiment was conducted with the mine water from aquitard layers in coal seam fire zones in Xinjiang. The results showed that the biogas production first increased and then decreased with the increase in distance, and the highest gas production reached 216.55 mL. The changes in key metabolic pathways during the anaerobic fermentation of coal were analyzed, which showed that as the distance from the aquitard layer in the coal seam fire zone increased, the methanogenesis pathways gradually shifted from acetic acid decarboxylation and carbon dioxide reduction to acetic acid decarboxylation and methylamine methanogenesis. The significant variability in the in-situ mine water reservoir conditions contributed to the differences. In addition, the reservoir pressure and temperature increased as the distance from the fire zone became longer, and the salinity of the farthest mine water in the reverse fault was the highest due to the lack of groundwater supply. Pearson correlation analysis revealed significant correlations of microbial communities with key functional genes and the types and concentrations of ions. The ions significantly influencing microbial enzymatic metabolic activities included Al3+, Fe2+, Co2+, Ni2+, Cu2+, Zn2+, Mg2+, PO43-, and Mo6+. The differences in metabolic pathways were attributed to the integrated effects of a co-occurring environment with multiple ions. The gas production simulation experiments and metagenomic analyses provide data support for the practical application of in-situ biogas experiments, laying a foundation for engineering applications.
Biofuels
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Coal
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Methane/biosynthesis*
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Fires
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Groundwater
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Coal Mining
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Fermentation
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China
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Anaerobiosis
5.Renal leukocyte chemokine type 2 amyloidosis: a clinicopathological analysis of fifteen cases
Xiangyang WANG ; Weixia HAN ; Siyu CHEN ; Dan NIU ; Xinyu WANG ; Chen WANG
Chinese Journal of Pathology 2024;53(8):809-815
Objective:To investigate the clinicopathological features of renal leukocyte chemokine type 2 amyloidosis (ALECT2).Methods:The prevalence, clinical characteristics, renal histopathological features, and renal outcome of 15 patients with ALECT2 by kidney biopsy were collected in the Department of Kidney Pathology, Shanxi Medical University Second Hospital, Taiyuan, China from January 1993 to December 2023. Immunohistochemistry and mass spectrometry for amyloid proteins were carried out.Results:Fifteen patients with ALECT2 were included in the study, representing 12.93% (15/116) of the renal biopsy-proven amyloidosis cases. There were 5 males and 10 females. The median age at diagnosis was 61 years. All patients had various degrees of proteinuria; 7 patients had nephrotic syndrome; 3 patients had renal insufficiency; 7 patients had microscopic hematuria. Renal biopsy showed that strongly orangophilic amyloid proteins distributed mainly in the renal cortical interstitium, vascular walls, the glomerular mesangium and/or glomerular basement membrane. Eight cases were diagnosed with ALECT2 alone and 7 cases combined with other renal diseases, including 4 cases with membranous nephropathy, 2 cases with IgA nephropathy, and 1 case with subacute tubular interstitial nephropathy. ALECT2 patients with concurrent renal disease showed a higher proteinuria level than those without (3.48 g/24 h versus 4.58 g/24 h). All patients were corroborated by immunohistochemistry to exhibit the specific location of LECT2 in the amyloid fibrils. Mass spectrometry analysis revealed LECT2 polypeptide in 9 patients. Except two patients with worsening renal function, the others showed stable renal function during the mean follow-up period of 12.5 months.Conclusions:ALECT2 is the second common type of renal amyloidosis in our center. The majority of ALECT2 patients show concurrent renal diseases, with a high rate of membranous nephropathy. Amyloid deposits distribute mainly in the cortical interstitium of the kidney, the glomerular mesangium and vascular walls. Mass spectrometry is the most sensitive and specific method for detecting LECT2 amyloidosis.
6.Evaluation of performance of disposable medical protective clothing for resistance to infective agent penetration
Ke-Yang LIU ; Yan FENG ; Juan ZHANG ; Yue NIU ; Dan QIN ; Yong-Fu HUANG ; Guang-Yong HU
Chinese Medical Equipment Journal 2024;45(5):16-21
Objective To evaluate the performance of the disposable medical protective clothing in blocking the penetration of infectious agents,in order to provide data support for the setting of such performance indexes when the GB 19082 is revised.Methods Totally 10 batches of different brands and models of protective clothing were selected,and tests were carried out for penetration resistance to synthetic blood,phage,wet microorganisms,dry microorganisms and contaminated liquid aerosol and particle filtration efficiency according to YY/T 0700-2008,YY/T 0689-2008,YY/T 0506.6-2009,GB 19082-2009,YY/T 0506.5-2009 and YY/T 1799-2020.Results There were 2 batches of protective clothing with anti-synthetic blood penetration performance level 2,3,4,5 and 6,respectively;all the protective clothing had the highest level 6 for anti-wet microorganisms penetration,part of whom had the levels for the resistance to phage penetration lower than those for preventing anti-synthetic blood penetration;all of the protective clothing had the particle filtration efficiencies higher than 95%,and had the highest level 3 for anti-dry microorganisms penetration;there're 5 batches of protective clothing with the highest level 3 for contaminated liquid aerosol penetration,1 batch with level 2 and the remained 4 batches with undetermined levels,which all had an average logarithmic reduction higher than 4.5 after penetration.Conclusion Particle filtration efficiency and resistance to phage penetration may be involved in the requirements for resistance to infective agent penetration in revised GB 19082 for evaluating the ability of protective clothing materials to block microorganisms in airborne particles and liquid contaminants.[Chinese Medical Equipment Journal,2024,45(5):16-21]
7.Impact of rehabilitation exercise intervention mode based on cardiac function classification on clinical effect and quality of life in CHF patients
Juan LI ; Hui CAO ; Lin-Na HUI ; Yan-Ling WANG ; Dan NIU ; Yan-Rong ZHANG ; Ya-Ni ZHANG ; Xia DU ; Wen-Ting LI
Chinese Journal of cardiovascular Rehabilitation Medicine 2024;33(3):270-276
Objective:To explore the impact of rehabilitation exercise intervention mode based on cardiac function classification on clinical effect and quality of life(QOL)in patients with chronic heart failure(CHF).Methods:A total of 160 CHF patients who visited our hospital from Dec 2021 to Jan 2023 were selected,and 154 cases were fi-nally enrolled.According to the random number table method,patients were divided into study group and control group with 77 cases in each group.Control group received routine nursing program,while the study group received rehabilitation exercise intervention based on cardiac function classification on the basis of control group,both groups were intervened for three months.Clinical total effective rate,and cardiopulmonary function,serum oxidative stress indicators and MLHFQ score before and after intervention were compared between two groups.Results:Total effective rates of study subgroups of class Ⅱ and Ⅲ were significantly higher than those of control group(class Ⅱ:100.00%vs.83.78%;class Ⅲ:97.37%vs.80.00%)(P<0.05 both).Compared with control subgroup of classⅢ after intervention,there were significant rise in peak VO2[(16.98±2.03)ml·min-1·kg-1 vs.(18.61±2.41)ml·min-1·kg-1],LVEF[(41.73±4.53)%vs.(48.03±5.22)%]and 6MWD[(351.34±61.00)m vs.(391.53±64.42)m](P<0.01 all);and significant reductions in LVEDd[(57.55±3.91)mm vs.(53.18±3.07)mm],LVESd[(35.90±2.91)mm vs.(30.50±2.67)mm],levels of LPO[(6.00±0.99)mg/L vs.(3.95±0.61)mg/L],MPO[(3.83±0.58)mg/L vs.(2.03±0.28)mg/L],and MLHFQ total score[(57.05±4.57)points vs.(45.29±3.94)points]in study subgroup of class Ⅲ(P=0.001 all).Compared with control subgroup of class Ⅱ after intervention,there were significant rise in peak VO2,LVEF and 6MWD,and significant reductions in LVEDd,LVESd,levels of LPO,MPO and MLHFQ score in study subgroup of class Ⅱ,P<0.05 or<0.01.There was no significant difference in the incidence rate of adverse events during follow-up between two groups(3.90%vs.6.49%,P=0.717).Conclusion:Rehabilitation exercise intervention based on cardiac function classifi-cation can significantly improve cardiopulmonary function,inhibit oxidative stress response in vivo and improve quality of life in CHF patients,which is worthy of promotion and application in clinical practice.
8.Application value of intravoxel incoherent motion and dynamic contrast-enhanced MRI in prognostic staging evaluation of early-stage rectal adenocarcinoma
Yaxin CHAI ; Yongchao NIU ; Dan SONG
Journal of Practical Radiology 2024;40(8):1291-1295
Objective To explore the application value and diagnostic efficiency of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)and intravoxel incoherent motion(IVIM)in prognostic staging of early-stage rectal adenocarcinoma.Methods Eighty-one patients with early-stage rectal adenocarcinoma confirmed by surgery were retrospectively selected.They were examined by high-resolution MRI,IVIM and DCE-DWI before operation.According to prognostic staging criteria,they were divided into stageⅠ and stage Ⅱ A groups.The quantitative parameters of DCE-MRI and IVIM were obtained by GenIQ or MITK software respectively.The differences of parameter values between the two groups were compared by independent sample t-test or Mann-Whitney U test,and the diagnostic efficiency was analyzed.Results The values of rate constant(Kep),volume transfer constant(Ktrans)and pseudo diffusion coefficient(D*)in stage Ⅰ group were lower than stage Ⅱ A group(P<0.05).The f value in stage Ⅰ group was higher than stage Ⅱ A group(P<0.05).D*and Kep values were included in the binary logistic regression equation.The receiver operating characteristic(ROC)curves of D*,Kep values and their joint prediction probability values were obtained,and the area under the curve(AUC)were 0.791,0.770 and 0.852 respectively.The sensitivities were 90.91%,66.67%and 81.82%respectively.The specificities were 66.67%,83.33%and 79.17%respectively.Conclusion D*and Kep values have the potential to be imaging indicators of prognostic staging of early-stage rectal adenocarcinoma,and to guide the selection of clinical treatment schemes.
9.HVPG minimally invasive era: exploration based on forearm venous approach
Jitao WANG ; Lei LI ; Meng NIU ; Qingliang ZHU ; Zhongwei ZHAO ; Kohei KOTANI ; Akira YAMAMOTO ; Haijun ZHANG ; Shuangxi LI ; Dan XU ; Ning KANG ; Xiaoguo LI ; Kunpeng ZHANG ; Jun SUN ; Fazong WU ; Hailong ZHANG ; Dengxiang LIU ; Muhan LYU ; Jiansong JI ; Norifumi KAWADA ; Ke XU ; Xiaolong QI
Chinese Journal of Hepatology 2024;32(1):35-39
Objective:The transjugular or transfemoral approach is used as a common method for hepatic venous pressure gradient (HVPG) measurement in current practice. This study aims to confirm the safety and effectiveness of measuring HVPG via the forearm venous approach.Methods:Prospective recruitment was conducted for patients with cirrhosis who underwent HVPG measurement via the forearm venous approach at six hospitals in China and Japan from September 2020 to December 2020. Patients' clinical baseline information and HVPG measurement data were collected. The right median cubital vein or basilic vein approach for all enrolled patients was selected. The HVPG standard process was used to measure pressure. Research data were analyzed using SPSS 22.0 statistical software. Quantitative data were used to represent medians (interquartile ranges), while qualitative data were used to represent frequency and rates. The correlation between two sets of data was analyzed using Pearson correlation analysis.Results:A total of 43 cases were enrolled in this study. Of these, 41 (95.3%) successfully underwent HVPG measurement via the forearm venous approach. None of the patients had any serious complications. The median operation time for HVPG detection via forearm vein was 18.0 minutes (12.3~38.8 minutes). This study confirmed that HVPG was positively closely related to Child-Pugh score ( r = 0.47, P = 0.002), albumin-bilirubin score ( r = 0.37, P = 0.001), Lok index ( r = 0.36, P = 0.02), liver stiffness ( r = 0.58, P = 0.01), and spleen stiffness ( r = 0.77, P = 0.01), while negatively correlated with albumin ( r = -0.42, P = 0.006). Conclusion:The results of this multi-centre retrospective study suggest that HVPG measurement via the forearm venous approach is safe and feasible.
10.Spiral Microfluidic for Particle Focusing by Stabilization and Acceleration of Secondary Flow
Han-Jie BAI ; Zhi-Hui LIN ; Shi-Chao GUO ; Dan-Dan LONG ; Yan-Bing NIU ; Lei ZHAO ; Shao-Fei SHEN
Chinese Journal of Analytical Chemistry 2024;52(4):504-512
Inertial microfluidics,as a microfluidic technology with the ability to precisely manipulate particles and cells with high throughput,has attracted widespread attention.However,challenges remain in achieving particle focusing with insensitivity to flow rates in large-scale channels,mainly due to the instability of secondary flows within the inertial microfluidic chip.This study developed a microstructure-assisted ultra-low aspect ratio spiral microchannel,which utilized the stability and acceleration of secondary flows to achieve inertial particle focusing.The research results demonstrated successful particle focusing within a 1 mm-wide spiral channel chip,for different diameter sizes(7.3 μm and 15.5 μm),within a wide range of flow rates(0.5-3 mL/min).The focusing efficiencies for these particles were measured to be above 94%and 99%,respectively.Additionally,it was observed that the particle focusing position was approximately 100 μm away from the channel walls,significantly larger than other inertial focusing chips.Consequently,by incorporating ordered microstructures within the spiral channel chip,the stability and enhancement of secondary flows were achieved,resulting in flow rate and particle size-insensitive inertial focusing.Compared to traditional methods of inertial focusing,this design had advantages of not requiring additional sheath flow operations,and boasted high throughput and ease of manufacturing.This innovative structure opened up vast prospects for the development of portable inertial microfluidic chips,and could be used in the fields such as cell analysis and detection,flow cytometry,and online sample processing.

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