1.Mechanism of imperatorin in ameliorating doxorubicin resistance of breast cancer based on transcriptomics
Yiting LI ; Wei DONG ; Xinli LIANG ; Hu WANG ; Yumei QIU ; Xiaoyun DING ; Hao ZHANG ; Huiyun BAO ; Xianxi LI ; Xilan TANG
China Pharmacy 2025;36(5):529-534
OBJECTIVE To investigate the ameliorative effect and potential mechanism of imperatorin (IMP) on doxorubicin (DOX) resistance in breast cancer. METHODS The effects of maximum non-toxic concentration (100 μg/mL) of IMP combined with different concentrations of DOX (12.5, 25, 50, 75, 100 μg/mL) on the proliferation of MCF-7/DOX cells were determined by MTT method. MCF-7/DOX cells were divided into blank control group (1‰ dimethyl sulfoxide), DOX group (50 μg/mL), IMP+DOX group (100 μg/mL IMP+50 μg/mL DOX) and IMP group (100 μg/mL). mRNA and protein expressions of multidrug resistance protein 1 (MDR1) and multidrug resistance-associated protein 1 in each group were measured. The relevant pathways and targets involved in the improvement of DOX resistance in breast cancer cells by IMP were screened and validated by using transcriptome sequencing technology, along with gene ontology (GO) enrichment analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. RESULTS Compared with DOX alone, the combination of IMP and DOX reduced the half inhibitory concentration of DOX on MCF-7/DOX cells from 81.965 μg/mL to 43.170 μg/mL, the reverse fold was 1.90, and the mRNA expression of MDR1 was significantly down-regulated (P<0.05). The results of GO enrichment analyses and KEGG pathway enrichment analyses indicated that the reversal of DOX resistance in breast cancer by IMP was mainly associated with the regulation of biological processes such as detoxification, multiple biological processes, and cell killing. The main pathway involved was the p53 signaling pathway, and the key targets mainly included constitutively photomorphogenic protein 1 (COP1), cyclin E1 (CCNE1), growth arrest and DNA damage-inducible protein 45A E-mail:tangxilan1983@163.com (GADD45A) and GADD45B. The results of the verification experiments showed that compared with DOX group, there was a trend of up-regulation of COP1 mRNA, and significant down- regulation of CCNE1, GADD45A, and GADD45B mRNA expression in IMP+DOX group (P<0.05). CONCLUSIONS The effect of IMP in ameliorating DOX resistance in breast cancer is related to its regulation of COP1, CCNE1, GADD45A and GADD45B targets in the p53 signaling pathway.
2.Application of ARIMA model in predicting the incidence of hepatitis E in Yunnan Province
Bilian ZHU ; Yingmei TANG ; Zhengrong DING ; Jibo HE ; Weimin BAO ; Qinnian LI
Journal of Public Health and Preventive Medicine 2025;36(4):37-41
Objective To explore the application of the Autoregressive Integrated Moving Average (ARIMA) model in predicting the number of reported hepatitis E cases in Yunnan Province,to use this model to predict the incidence trend of hepatitis E, and to provide reference for the scientific prevention and control of hepatitis E. Methods Monthly reported cases of hepatitis E in Yunnan Province from 2012 to 2021 were collected. The ARIMA model was established using SPSS 27.0, and the model was validated and parameters were optimized with data from January 2022 to December 2022. The optimal fitting model was used to predict the incidence of hepatitis E in 2023. Results Hepatitis E incidence in Yunnan Province showed a certain seasonal distribution, with most cases concentrated from March to August. All parameters of ARIMA(3,1,4)(1,1,1)12 passed statistical tests. The Ljung-Box test showed statistic Q =10.050, P = 0.346, residual sequence was a white noise sequence, and goodness-of-fit index stationary R² was 0.591. The model extrapolation effect was verified with 2022 data, and MAPE was 14.747, indicating that the model extrapolation effect was effective. The number of hepatitis E cases in Yunnan Province in 2023 was expected to be 1,086. Conclusion The ARIMA (3,1,4)(1,1,1)12 model shows good fitting performance for hepatitis E cases in Yunnan Province and can effectively predict short-term disease trends, providing a theoretical basis for formulating prevention and control measures for hepatitis E.
3.Genome-wide DNA methylation and mRNA transcription analysis revealed aberrant gene regulation pathways in patients with dermatomyositis and polymyositis.
Hui LUO ; Honglin ZHU ; Ding BAO ; Yizhi XIAO ; Bin ZHOU ; Gong XIAO ; Lihua ZHANG ; Siming GAO ; Liya LI ; Yangtengyu LIU ; Di LIU ; Junjiao WU ; Qiming MENG ; Meng MENG ; Tao CHEN ; Xiaoxia ZUO ; Quanzhen LI ; Huali ZHANG
Chinese Medical Journal 2025;138(1):120-122
4.Effects of understory environmental factors on understory planting of medicinal plants.
Ding-Mei WEN ; Hong-Biao ZHANG ; Feng-Yuan QIN ; Chao-Qun XU ; Dou-Dou LI ; Bao-Lin GUO
China Journal of Chinese Materia Medica 2025;50(5):1164-1171
Understory planting of medicinal plants is a new planting mode that connects Chinese herbal medicine(CHM) with forest resources.The complex and variable understory environmental factors will inevitably affect the yield and quality of understory CHM.This research summarized the research progress on understory planting of medicinal plants based on forest types and environmental factors within the forest from the perspectives of understory light, air temperature and humidity, soil characteristics, and the interaction between crops within the forest.The results showed that the complex and variable light, temperature and humidity, and soil factors(such as fertility, acidity and alkalinity, and microorganisms) under the forest could affect the yield and quality of medicinal plants to varying degrees through physiological activities such as photosynthesis and respiration, resulting in a significant increase or decrease in yield and quality compared to open field cultivation.In addition, the competition or mutual benefit between different crops within the forest could lead to differences in the yield and quality of understory medicinal plants compared to open field cultivation.A reasonable combination of planting could achieve resource sharing and complementary advantages.Therefore, conducting systematic research on the effects of understory environmental factors on the yield and content of medicinal plants with different growth and development characteristics can provide theoretical guidance and technical references for formulating comprehensive strategies for understory planting of medicinal plants, such as selecting suitable medicinal plant varieties, optimizing planting density, and conducting reasonable forest management, thus contributing to the sustainable development and ecological protection of CHM.
Plants, Medicinal/growth & development*
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Forests
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Soil/chemistry*
;
Environment
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Ecosystem
;
Temperature
5.Research progress on molecular mechanisms of ginsenosides in alleviating acute lung injury.
Han-Yang ZHAO ; Xun-Jiang WANG ; Qiong-Wen XUE ; Bao-Lian XU ; Xu WANG ; Shu-Sheng LAI ; Ming CHEN ; Li YANG ; Zheng-Tao WANG ; Li-Li DING
China Journal of Chinese Materia Medica 2025;50(16):4451-4470
Acute lung injury(ALI) is a critical clinical condition primarily characterized by refractory hypoxemia and infiltration of inflammatory cells in lung tissue, which can progress into a more severe form known as acute respiratory distress syndrome(ARDS). Immune cells and inflammatory cytokines play important roles in the progression of the disease. Due to its unclear pathogenesis and the lack of effective clinical treatments, ALI is associated with a high mortality rate and severely affects patients' quality of life, making the search for effective therapeutic agents particularly urgent. Ginseng Radix et Rhizoma, the dried root of the perennial herb Panax ginseng from the Araliaceae family, contains active ingredients such as saponins and polysaccharides, which possess various pharmacological effects including anti-tumor activity, immune regulation, and metabolic modulation. In recent years, studies have shown that ginsenosides exhibit notable effects in reducing inflammation, ameliorating epithelial and endothelial cell injury, and providing anticoagulant action, indicating their comprehensive role in alleviating lung injury. This review summarizes the pathogenesis of ALI and the molecular mechanisms through which ginsenosides act at different stages of ALI development. The aim is to provide a scientific reference for the development of ginsenoside-based drugs targeting ALI, as well as a theoretical basis for the clinical application of Ginseng Radix et Rhizoma in the treatment of ALI.
Ginsenosides/pharmacology*
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Humans
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Acute Lung Injury/immunology*
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Animals
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Panax/chemistry*
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Drugs, Chinese Herbal
6.Quercetin Confers Protection against Sepsis-Related Acute Respiratory Distress Syndrome by Suppressing ROS/p38 MAPK Pathway.
Wei-Chao DING ; Juan CHEN ; Quan LI ; Yi REN ; Meng-Meng WANG ; Wei ZHANG ; Xiao-Hang JI ; Xin-Yao WU ; Shi-Nan NIE ; Chang-Bao HUANG ; Zhao-Rui SUN
Chinese journal of integrative medicine 2025;31(11):1011-1020
OBJECTIVE:
To identify the underlying mechanism by which quercetin (Que) alleviates sepsis-related acute respiratory distress syndrome (ARDS).
METHODS:
In vivo, C57BL/6 mice were assigned to sham, cecal ligation and puncture (CLP), and CLP+Que (50 mg/kg) groups (n=15 per group) by using a random number table. The sepsisrelated ARDS mouse model was established using the CLP method. In vitro, the murine alveolar macrophages (MH-S) cells were classified into control, lipopolysaccharide (LPS), LPS+Que (10 μmol/L), and LPS+Que+acetylcysteine (NAC, 5 mmol/L) groups. The effect of Que on oxidative stress, inflammation, and apoptosis in mice lungs and MH-S cells was determined, and the mechanism with reactive oxygen species (ROS)/p38 mitogen-activated protein kinase (MAPK) pathway was also explored both in vivo and in vitro.
RESULTS:
Que alleviated lung injury in mice, as reflected by a reversal of pulmonary histopathologic changes as well as a reduction in lung wet/dry weight ratio and neutrophil infiltration (P<0.05 or P<0.01). Additionally, Que improved the survival rate and relieved gas exchange impairment in mice (P<0.01). Que treatment also remarkedly reduced malondialdehyde formation, superoxide dismutase and catalase depletion, and cell apoptosis both in vivo and in vitro (P<0.05 or P<0.01). Moreover, Que treatment diminished the release of inflammatory factors interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 both in vivo and in vitro (P<0.05 or P<0.01). Mechanistic investigation clarifified that Que administration led to a decline in the phosphorylation of p38 MAPK in addition to the suppression of ROS expression (P<0.01). Furthermore, in LPS-induced MH-S cells, ROS inhibitor NAC further inhibited ROS/p38 MAPK pathway, as well as oxidative stress, inflammation, and cell apoptosis on the basis of Que treatment (P<0.05 or P<0.01).
CONCLUSION
Que was found to exert anti-oxidative, anti-inflammatory, and anti-apoptotic effects by suppressing the ROS/p38 MAPK pathway, thereby conferring protection for mice against sepsis-related ARDS.
Animals
;
Sepsis/drug therapy*
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Quercetin/therapeutic use*
;
Respiratory Distress Syndrome/enzymology*
;
p38 Mitogen-Activated Protein Kinases/metabolism*
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Mice, Inbred C57BL
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Reactive Oxygen Species/metabolism*
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Apoptosis/drug effects*
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Male
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Oxidative Stress/drug effects*
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MAP Kinase Signaling System/drug effects*
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Lung/drug effects*
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Mice
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Lipopolysaccharides
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Macrophages, Alveolar/pathology*
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Inflammation/pathology*
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Protective Agents/therapeutic use*
7.An anti-complement homogeneous polysaccharide from Houttuynia cordata ameliorates acute pneumonia with H1N1 and MRSA coinfection through rectifying Treg/Th17 imbalance in the gut-lung axis and NLRP3 inflammasome activation.
Xinxing LI ; Wenxin DING ; Yan LU ; Haiyan ZHU ; Weilian BAO ; Yang LIU ; Jiaren LYU ; Lishuang ZHOU ; Hong LI ; Jiyang LI ; Daofeng CHEN
Acta Pharmaceutica Sinica B 2025;15(6):3073-3091
The coinfection of respiratory viruses and bacteria is a major cause of morbidity and mortality worldwide, despite the development of vaccines and powerful antibiotics. As a macromolecule that is difficult to absorb in the gastrointestinal tract, a homogeneous polysaccharide from Houttuynia cordata (HCPM) has been reported to exhibit anti-complement properties and alleviate influenza A virus (H1N1)-induced lung injury; however, the effects of HCPM without in vitro antiviral and antibacterial activities on more complicated pulmonary diseases resulting from viral-bacterial coinfection remains unclear. This study established a representative coinfection murine pneumonia model infected with H1N1 (0.2 LD50) and methicillin-resistant Staphylococcus aureus (MRSA, 107 CFU). HCPM significantly improved survival rate and weight loss, and ameliorated gut-lung damage and inflammatory cytokine production. Interestingly, the therapeutic effect of HCPM on intestinal damage preceded that in the lungs. Mechanistically, HCPM inhibited the overactivation of the intestinal complement (C3a and C5a) and suppressed the activation of the NLR family pyrin domain-containing 3 (NLRP3) pathway, which contributes to the regulation of the Treg/Th17 cell balance in the gut-lung axis. The results indicate the beneficial effects of an anti-complement polysaccharide against viral-bacterial coinfection pneumonia by modulating crosstalk between multiple immune regulatory networks.
8.Progress and challenges of functionalized bacterial encapsulation: A novel biotechnology for next-generation biotherapeutics.
Ying ZHANG ; Yuwei WU ; Xinyu ZHAO ; Qinghua YE ; Lulu CAO ; Ming LIU ; Bao GAO ; Qinya NIU ; Nuo CHEN ; Zixuan DUAN ; Yu DING ; Juan WANG ; Moutong CHEN ; Ying LI ; Qingping WU
Acta Pharmaceutica Sinica B 2025;15(10):5167-5191
The disturbance of the human microbiota influences the occurrence and progression of many diseases. Live therapeutic bacteria, with their genetic manipulability, anaerobic tendencies, and immunomodulatory properties, are emerging as promising therapeutic agents. However, their clinical applications face challenges in maintaining activity and achieving precise spatiotemporal release, particularly in the harsh gastrointestinal environment. This review highlights the innovative bacterial functionalized encapsulation strategies developed through advances in physicochemical and biological techniques. We comprehensively review how bacterial encapsulation strategies can be used to provide physical barriers and enhanced adhesion properties to live microorganisms, while introducing superior material properties to live bacteria. In addition, this review outlines how bacterial surface coating can facilitate targeted delivery and precise spatiotemporal release of live bacteria. Furthermore, it elucidates their potential applications for treating different diseases, along with critical perspectives on challenges in clinical translation. This review comprehensively analyzes the connection between functionalized bacterial encapsulation and innovative biomedical applications, providing a theoretical reference for the development of next-generation bacterial therapies.
9.Downregulation of Serum PTEN Expression in Mercury-Exposed Population and PI3K/AKT Pathway-Induced Inflammation
Peng MEI ; Min En DING ; Yang Hao YIN ; Xue Xue DING ; Huan WANG ; Feng Jian WANG ; Lei HAN ; Dong Heng ZHANG ; Li Bao ZHU
Biomedical and Environmental Sciences 2024;37(4):354-366
Objective This study investigated the impact of occupational mercury(Hg)exposure on human gene transcription and expression,and its potential biological mechanisms. Methods Differentially expressed genes related to Hg exposure were identified and validated using gene expression microarray analysis and extended validation.Hg-exposed cell models and PTEN low-expression models were established in vitro using 293T cells.PTEN gene expression was assessed using qRT-PCR,and Western blotting was used to measure PTEN,AKT,and PI3K protein levels.IL-6 expression was determined by ELISA. Results Combined findings from gene expression microarray analysis,bioinformatics,and population expansion validation indicated significant downregulation of the PTEN gene in the high-concentration Hg exposure group.In the Hg-exposed cell model(25 and 10 μmol/L),a significant decrease in PTEN expression was observed,accompanied by a significant increase in PI3K,AKT,and IL-6 expression.Similarly,a low-expression cell model demonstrated that PTEN gene knockdown led to a significant decrease in PTEN protein expression and a substantial increase in PI3K,AKT,and IL-6 levels. Conclusion This is the first study to report that Hg exposure downregulates the PTEN gene,activates the PI3K/AKT regulatory pathway,and increases the expression of inflammatory factors,ultimately resulting in kidney inflammation.
10.Efficacy of two-staged laparoscopic Fowler-Stephens surgery through the Hay's triangle approach for the treat-ment of high cryptorchidism in children
Yan DING ; Jian-Da WANG ; Li-Bao SUN
Journal of Regional Anatomy and Operative Surgery 2024;33(3):260-264
Objective To analyze the efficacy of two-staged laparoscopic Fowler-Stephens surgery through the Hay's triangle approach for the treatment of high cryptorchidism in children.Methods The clinical data of 116 children with high cryptorchidism in our hospital were retrospectively analyzed,among which 43 children who underwent laparoscopic testicular extraction and fixation through the Hay's triangle approach were selected as the control group,and 73 children who underwent two-staged laparoscopic Fowler-Stephens surgery through the Hay's triangle approach were selected as the study group.The changes of sex hormone levels and testicular function before and after surgery were compared between the two groups.All patients were followed up for 6 months,and the testicular volume was reviewed and the occurrences of complications were recorded.Results There was no significant difference in the testicular volume before and after surgery between the two groups(P>0.05),and there was no significant difference in the total incidence of postoperative complications between the two groups(P>0.05).After surgery,the levels of serum follicle-stimulating hormone(FSH),estradiol(E2)and luteinizing hormone(LH)in the two groups were significantly lower than those before surgery(P<0.05),and the levels of serum testosterone(T),anti-Mullerian hormone(AMH),inhibin B(INHB)and INHB/FSH were significantly higher than those before surgery(P<0.05).However,there was no significant difference between the two groups(P>0.05).Conclusion The two-staged Fowler-Stephens surgery is effective in the treatment of high-risk cryptorchidism.It can establish a good collateral circulation by disconnection of spermatic cord vessels and gubernaculum testis,and the testis can be lowered to a satisfactory position in the scrotum.


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