1.Identification of GSK3 family and regulatory effects of brassinolide on growth and development of Nardostachys jatamansi.
Yu-Yan LEI ; Zheng MA ; Jing WEI ; Wen-Bing LI ; Ying LI ; Zheng-Ming YANG ; Shao-Shan ZHANG ; Jing-Qiu FENG ; Hua-Chun SHENG ; Yuan LIU
China Journal of Chinese Materia Medica 2025;50(2):395-403
This study identified 8 members including NjBIN2 of the GSK3 family in Nardostachys jatamansi by bioinformatics analysis. Moreover, the phylogenetic tree revealed that the GKS3 family members of N. jatamansi had a close relationship with those of Arabidopsis. RT-qPCR results showed that NjBIN2 presented a tissue-specific expression pattern with the highest expression in roots, suggesting that NjBIN2 played a role in root growth and development. In addition, the application of epibrassinolide or the brassinosteroid(BR) synthesis inhibitor(brassinazole) altered the expression pattern of NjBIN2 and influenced the photomorphogenesis(cotyledon opening) and root development of N. jatamansi, which provided direct evidence about the functions of NjBIN2. In conclusion, this study highlights the roles of BIN2 in regulating the growth and development of N. jatamansi by analyzing the expression pattern and biological function of NjBIN2. It not only enriches the understanding about the regulatory mechanism of the growth and development of N. jatamansi but also provides a theoretical basis and potential gene targets for molecular breeding of N. jatamansi with improved quality in the future.
Brassinosteroids/metabolism*
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Steroids, Heterocyclic/metabolism*
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Gene Expression Regulation, Plant/drug effects*
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Plant Proteins/metabolism*
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Phylogeny
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Nardostachys/metabolism*
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Plant Growth Regulators/pharmacology*
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Plant Roots/drug effects*
2.RBM14 enhances transcriptional activity of p23 regulating CXCL1 expression to induce lung cancer metastasis.
Wen ZHANG ; Yulin PENG ; Meirong ZHOU ; Lei QIAN ; Yilin CHE ; Junlin CHEN ; Wenhao ZHANG ; Chengjian HE ; Minghang QI ; Xiaohong SHU ; Manman TIAN ; Xiangge TIAN ; Yan TIAN ; Sa DENG ; Yan WANG ; Xiaokui HUO ; Zhenlong YU ; Xiaochi MA
Acta Pharmaceutica Sinica B 2025;15(6):3059-3072
Metastasis serves as an indicator of malignancy and is a biological characteristic of carcinomas. Epithelial-mesenchymal transition (EMT) plays a key role in the promotion of tumor invasion and metastasis and in the enhancement of tumor cell aggressiveness. Prostaglandin E synthase 3 (p23) is a cochaperone for heat shock protein 90 (HSP90). Our previous study showed that p23 is an HSP90-independent transcription factor in cancer-associated inflammation. The effect and mechanism of action of p23 on lung cancer metastasis are tested in this study. By utilizing cell models in vitro and mouse tail vein metastasis models in vivo, the results provide solid evidence that p23 is critical for promoting lung cancer metastases by regulating downstream CXCL1 expression. Rather than acting independently, p23 forms a complex with RNA-binding motif protein 14 (RBM14) to facilitate EMT progression in lung cancer. Therefore, our study provides evidence for the potential role of the RBM14-p23-CXCL1-EMT axis in the metastasis of lung cancer.
3.Baicalein attenuates lipopolysaccharide-induced myocardial injury by inhibiting ferroptosis via miR-299b-5p/HIF1-α pathway.
Wen-Yan ZHOU ; Jian-Kui DU ; Hong-Hong LIU ; Lei DENG ; Kai MA ; Jian XIAO ; Sheng ZHANG ; Chang-Nan WANG
Journal of Integrative Medicine 2025;23(5):560-575
OBJECTIVE:
Baicalein has been reported to have wide therapeutic effects that act through its anti-inflammatory activity. This study examines the effect and mechanism of baicalein on sepsis-induced cardiomyopathy (SIC).
METHODS:
A thorough screening of a small library of natural products, comprising 100 diverse compounds, was conducted to identify the most effective drug against lipopolysaccharide (LPS)-treated H9C2 cardiomyocytes. The core target proteins and their associated signaling pathways involved in baicalein's efficacy against LPS-induced myocardial injury were predicted by network pharmacology.
RESULTS:
Baicalein was identified as the most potent protective agent in LPS-exposed H9C2 cardiomyocytes. It exhibited a dose-dependent inhibitory effect on cell injury and inflammation. In the LPS-induced septic mouse model, baicalein demonstrated a significant capacity to mitigate LPS-triggered myocardial deficits, inflammatory responses, and ferroptosis. Network pharmacological analysis and experimental confirmation suggested that hypoxia-inducible factor 1 subunit α (HIF1-α) is likely to be the crucial factor in mediating the impact of baicalein against LPS-induced myocardial ferroptosis and injury. By combining microRNA (miRNA) screening in LPS-treated myocardium with miRNA prediction targeting HIF1-α, we found that miR-299b-5p may serve as a regulator of HIF1-α. The reduction in miR-299b-5p levels in LPS-treated myocardium, compared to the control group, was reversed by baicalein treatment. The reverse transcription quantitative polymerase chain reaction, Western blotting, and dual-luciferase reporter gene analyses together identified HIF1-α as the target of miR-299b-5p in cardiomyocytes.
CONCLUSION
Baicalein mitigates SIC at the miRNA level, suggesting the therapeutic potential of it in treating SIC through the regulation of miR-299b-5p/HIF1-α/ferroptosis pathway. Please cite this article as: Zhou WY, Du JK, Liu HH, Deng L, Ma K, Xiao J, Zhang S, Wang CN. Baicalein attenuates lipopolysaccharide-induced myocardial injury by inhibiting ferroptosis via miR-299b-5p/HIF1-α pathway. J Integr Med. 2025; 23(5):560-575.
Flavanones/pharmacology*
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Animals
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MicroRNAs/genetics*
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Lipopolysaccharides
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Hypoxia-Inducible Factor 1, alpha Subunit/genetics*
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Ferroptosis/drug effects*
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Mice
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Myocytes, Cardiac/metabolism*
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Signal Transduction/drug effects*
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Rats
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Male
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Mice, Inbred C57BL
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Cardiomyopathies/etiology*
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Cell Line
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Sepsis/complications*
4.Spatiotemporal distribution of newly diagnosed echinococcosis patients in Qinghai Province from 2016 to 2022
Xinlu CUI ; Xiao MA ; Na LIU ; Jia LIU ; Wen LEI ; Shusheng WU ; Xianglan QIN ; Chunhua GONG ; Xiaojin MO ; Shijie YANG ; Ting ZHANG ; Li CAO
Chinese Journal of Schistosomiasis Control 2024;36(5):474-480
Objective To investigate the spatiotemporal distribution characteristics and potential influencing factors of newly diagnosed echinococcosis cases in Qinghai Province from 2016 to 2022, so as to provide insights into the formulation of the echinococcosis control strategy in Qinghai Province. Methods The number of individuals screened for echinococcosis, number of newly diagnosed echinococcosis cases, number of registered dogs and number of stray dogs were captured from the annual reports of echinococcosis control program in Qinghai Province from 2016 to 2022, and the detection of newly diagnosed echinococcosis cases was calculated. The number of populations, precipitation, temperature, wind speed, sunshine hours, average altitude, number of year-end cattle stock, number of year-end sheep stock, gross domestic product (GDP) per capita, and number of village health centers in each county (district) of Qinghai Province were captured from the Qinghai Provincial Statistical Yearbook, and county-level electronic maps in Qinghai Province were downloaded from the National Platform for Common Geospatial Information Services. The software ArcGIS 10.8 was used to map the distribution of newly diagnosed echinococcosis cases in Qinghai Province, and the spatial autocorrelation analysis of newly diagnosed echinococcosis cases was performed. In addition, the spacetime scan analyses of number of individuals screened for echinococcosis, number of newly diagnosed echinococcosis cases and geographical coordinates in Qinghai Province were performed with the software SaTScan 10.1.2, and the spatial stratified heterogeneity of the detection of newly diagnosed echinococcosis cases was investigated with the software GeoDetector. Results A total of 6 569 426 residents were screened for echinococcosis in Qinghai Province from 2016 to 2022, and 5 924 newly diagnosed echinococcosis cases were found. The detection of newly diagnosed echinococcosis cases appeared a tendency towards a decline over years from 2016 to 2022 (χ2 = 11.107, P < 0.01), with the highest detection in Guoluo Tibetan Autonomous Prefecture in 2017 (82.12/105). There were spatial clusters in the detection of newly diagnosed echinococcosis cases in Qinghai Province from 2016 to 2018 (Moran’s I = 0.34 to 0.65, all Z values > 1.96, all P values < 0.05), and the distribution of newly diagnosed echinococcosis cases appeared random distribution from 2019 to 2022 (Moran’s I = −0.09 to 0.04, all Z values < 1.96, all P values > 0.05). Local spatial autocorrelation analysis showed high-high clusters and low-low clusters in the detection of new diagnosed echinococcosis cases in Qinghai Province from 2016 to 2022, and space-time scan analysis showed that the first most likely cluster areas of newly diagnosed echinococcosis cases in Qinghai Province from 2016 to 2022 were mainly distributed in Yushu Tibetan Autonomous Prefecture and Guoluo Tibetan Autonomous Prefecture. GeoDetector-based analysis of the driving factors for the spatial stratified heterogeneity of detection of newly diagnosed echinococcosis cases in Qinghai Province showed that average altitude, number of village health centers, number of cattle and sheep stock, GDP per capita, annual average sunshine hours, and annual average temperature had a strong explanatory power for the spatial distribution of newly diagnosed echinococcosis cases, with q values of 0.630, 0.610, 0.600, 0.590, 0.588, 0.537 and 0.526, respectively. Conclusions The detection of newly diagnosed echinococcosis cases appeared a tendency towards a decline in Qinghai Province over years from 2016 to 2022, showing spatial clustering. Targeted control measures are required in cluster areas of newly diagnosed echinococcosis cases for further control of the disease.
5.Effectiveness of Histopathological Examination of Ultrasound-guided Puncture Biopsy Samples for Diagnosis of Extrapulmonary Tuberculosis
Fei Wen GU ; Xia SHI ; Xin MA ; Lei Jun YU ; Chuan Jin XU ; Cheng Cheng QIAN ; Dong Zhi HU ; Hui ZHANG
Biomedical and Environmental Sciences 2024;37(2):170-177
Objective To evaluate the diagnostic value of histopathological examination of ultrasound-guided puncture biopsy samples in extrapulmonary tuberculosis(EPTB). Methods This study was conducted at the Shanghai Public Health Clinical Center.A total of 115 patients underwent ultrasound-guided puncture biopsy,followed by MGIT 960 culture(culture),smear,GeneXpert MTB/RIF(Xpert),and histopathological examination.These assays were performed to evaluate their effectiveness in diagnosing EPTB in comparison to two different diagnostic criteria:liquid culture and composite reference standard(CRS). Results When CRS was used as the reference standard,the sensitivity and specificity of culture,smear,Xpert,and histopathological examination were(44.83%,89.29%),(51.72%,89.29%),(70.11%,96.43%),and(85.06%,82.14%),respectively.Based on liquid culture tests,the sensitivity and specificity of smear,Xpert,and pathological examination were(66.67%,72.60%),(83.33%,63.01%),and(92.86%,45.21%),respectively.Histopathological examination showed the highest sensitivity but lowest specificity.Further,we found that the combination of Xpert and histopathological examination showed a sensitivity of 90.80%and a specificity of 89.29%. Conclusion Ultrasound-guided puncture sampling is safe and effective for the diagnosis of EPTB.Compared with culture,smear,and Xpert,histopathological examination showed higher sensitivity but lower specificity.The combination of histopathology with Xpert showed the best performance characteristics.
6.Determination of Isobutyl Chloroformate Residue in Agatroban by Derivatization-Gas Chromatography-Mass Spectrometry
Chong QIAN ; Bo-Kai MA ; Chuang NIU ; Shan-Shan LIU ; Wen-Wen HUANG ; Xin-Lei GOU ; Wei WANG ; Mei ZHANG ; Xue-Li CAO
Chinese Journal of Analytical Chemistry 2024;52(1):113-120
A derivatizaton method combined with gas chromatography-mass spectrometry(GC-MS)was established for detection of isobutyl chloroformate(IBCF)residue in active pharmaceutical ingredient of agatroban.The extraction and derivatization reagents,derivatization time,qualitative and quantitative ions were selected and optimized,respectively.The possible mechanism of derivatization and characteristic fragment ions fragmentation were speculated.The agatroban samples were dissolved and extracted by methanol,and the residual IBCF was derived with methanol to generate methyl isobutyl carbonate(MIBCB).After 24 h static derivatization at room temperature,IBCF was completely transformed into MIBCB,which could be used to indirectly detect IBCF accurately.The results showed that the linearity of this method was good in the range of 25-500 ng/mL(R2=0.9999).The limit of detection(LOD,S/N=3)was 0.75 μg/g,and the limit of quantification(LOQ,S/N=10)was 2.50 μg/g.Good recoveries(95.2%-97.8%)and relative standard deviations(RSDs)less than 3.1%(n=6)were obtained from agatroban samples at three spiked levels of IBCF(2.50,25.00,50.00 μg/g),which showed good accuracy of this method.Good precision of detection results was obtained by different laboratory technicians at different times,the mean value of spiked sample solution(25.00 μg/g)was 24.28 μg/g,and the RSD was 2.1%(n=12).The durability was good,minor changes of detection conditions had little effect on the results.Under the original condition and conditions with initial column temperature±5℃,heating rate±2℃/min,column flow rate±0.1 mL/min,the IBCF content of spiked sample solution(25.00 μg/g)was detected,the mean value of detection results was 24.16 μg/g,and the RSD was 2.2%(n=7).Eight batches of agatroban samples from two manufacturers were detected using the established method,and the results showed that no IBCF residue was detected in any of these samples.The agatroban samples could be dissolved by methanol,and then the IBCF residue could be simultaneously extracted and derived with methanol as well.This detection method had the advantages of simple operation,high sensitivity,low matrix effect and accurate quantification,which provided a new effective method for detection of IBCF residue in agatroban.
7.Clinical observation of goserelin combined with estradiol valerate in the treatment of endometriosis in patients of childbearing age after laparoscopic surgery
Huiling WANG ; Ning MA ; Lei QIAO ; Jun YANG ; Zhengfang WEN
China Pharmacy 2024;35(14):1748-1752
OBJECTIVE To observe the efficacy and safety of goserelin combined with estradiol valerate in the treatment of endometriosis (EMs) in patients of childbearing age after laparoscopic surgery. METHODS The clinical data of 144 patients with EMs of childbearing age who underwent laparoscopic surgery in our hospital from January 2020 to December 2022 were collected retrospectively, and those patients were divided into control group (70 cases) and combination group (74 cases) based on different postoperative medication regimens. Control group was given Acetate goserelin sustained-release implant on the 1st to 5th day of their first menstrual cycle after laparoscopic surgery, while combination group was additionally given Estradiol valerate tablets on the basis of control group. The short-term and long-term efficacy of 2 groups were observed; preoperative and postoperative pain scores, ovarian reserve function, and the incidence of adverse reactions were all recorded in 2 groups. RESULTS There was no statistically significant difference in short-term total effective rate, 1-year postoperative recurrence rate and the incidence of decreased libido, vaginal dryness, gastrointestinal reactions, rash, or arrhythmia between two groups (P>0.05). The natural pregnancy rate of combination group was significantly higher than control group at 1 year after surgery, while the incidence E-mail:wanghuiling0518@126.com of early miscarriage, hot flashes and sweating, emotional fluctuations, insomnia and fatigue, joint muscle pain, dizziness and headache were significantly lower than control group (P<0.05). However, at 6 months after surgery, pain scores and the levels of anti-Müllerian hormone, follicle stimulating hormone, luteinizing hormone, estradiol of both groups were significantly lower than before surgery in the same group, while the number of antral follicle count was significantly higher than before surgery in the same group; the levels of anti-Müllerian hormone, luteinizing hormone, estradiol, and the number of antral follicles in the combination group were significantly higher than control group, while pain score and follicle stimulating hormone level were significantly lower than control group (P<0.05). CONCLUSIONS The combination of goserelin and estradiol valerate after laparoscopic surgery has a significant therapeutic effect and good safety in the treatment of EMs of childbearing age.
8.Relationship of triglyceride-glucose index and its derivatives with blood pressure abnormalities in adolescents:an analysis based on a restricted cubic spline model
Mei TIAN ; Xiao-Yan MA ; Ling-Ling TONG ; Lei-Na JIA ; Wen-Qing DING
Chinese Journal of Contemporary Pediatrics 2024;26(1):54-61
Objective To explore the relationship of triglyceride-glucose index(TyG),triglyceride-glucose-body mass index(TyG-BMI),and triglyceride-glucose-waist circumference index(TyG-WC)with blood pressure abnormalities in adolescents,providing theoretical basis for the prevention and control of hypertension in adolescents.Methods A stratified cluster sampling method was used to select 1 572 adolescents aged 12 to 18 years in Yinchuan City for questionnaire surveys,physical measurements,and laboratory tests.Logistic regression analysis and restricted cubic spline analysis were employed to examine the relationship of TyG,TyG-BMI,and TyG-WC with blood pressure abnormalities in adolescents.Results Multivariable logistic regression analysis revealed that after adjusting for confounding factors,the groups with the highest quartile of TyG,TyG-BMI,and TyG-WC had 1.48 times(95%CI:1.07-2.04),3.71 times(95%CI:2.67-5.15),and 4.07 times(95%CI:2.89-5.73)higher risks of blood pressure abnormalities compared to the groups with the lowest quartile,respectively.Moreover,as the levels of TyG,TyG-BMI,and TyG-WC increased,the risk of blood pressure abnormalities gradually increased(P<0.05).A non-linear dose-response relationship was observed between TyG-BMI and the risk of blood pressure abnormalities(Poverall trend<0.001,Pnon-linearity=0.002).Linear dose-response relationships were found between TyG and the risk of blood pressure abnormalities(Poverall trend<0.001,Pnon-linearit =0.232),and between TyG-WC and the risk of blood pressure abnormalities(Poverall trend<0.001,Pnon-linearity=0.224).Conclusions Higher levels of TyG and its derivatives are associated with an increased risk of blood pressure abnormalities in adolescents,with linear or non-linear dose-response relationships.
9.Effect of reading man flap in repair of surgical defect of skin and soft tissue tumors of head and face
Peng WANG ; Lei MA ; Qiang WEN
Journal of Clinical Medicine in Practice 2024;28(24):63-67
Objective To observe the effect of reading man flap in repairing surgical defects of skin and soft tissue tumors of the head and face. Methods A total of 120 patients with surgical defects of skin and soft tissue tumors of the head and face were randomly divided into control group (treated with fatty pedicle flap repair) and study group (treated with reading man flap repair), with 60 cases in each group. The incision healing rate, flap survival rate, flap repair effect, and quality of life were compared between the two groups. Results There were no significant differences in the incision healing rate and flap survival rate between the two groups (
10.Antiviral Efficacy and Mechanism of BD-77 Against Novel Coronavirus SARS-CoV-2
Lei BAO ; Qinhai MA ; Shanshan GUO ; Ronghua ZHAO ; Wen XIA ; Zihan GENG ; Jing SUN ; Yanyan BAO ; Zhou XU ; Shenglong YAN ; Jinxin XIAO ; Huarong CHEN ; Chenggang HUANG ; Xiaolan CUI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(13):45-51
ObjectiveThe human angiotensin converting enzyme2 (hACE2) transgenic mouse model was used to clarify the antiviral efficacy of BD-77 against a novel coronavirus SARS-CoV-2 and explore the action mechanism of BD-77 against SARS-CoV-2. MethodSARS-CoV-2 Omicron and Delta variant strains-infected VeroE6 cell models were established and administered with BD-77 to observe the antiviral effect of BD-77 in vitro. A kit was used to detect the effect of BD-77 in vitro on the binding of spike S protein of SARS-CoV-2 virus (Delta/Omicron) to angiotensin converting enzyme2 (ACE2). Chromatography was adopted to detect the binding of BD-77 to the S protein and N protein of the novel coronavirus. hACE2 transgenic C57BL/6 mice were divided into a blank control group, SARS-CoV-2 infection group, BD-77 administration groups of 37.5 mg·kg-1 and 75 mg·kg-1, with eight mice in each group. The pneumonia model of SARS-CoV-2-infected hACE2 transgenic mice was built to observe the survival of the mice, detect the virus titer of the lung tissue of the mice, and observe the lesions in the lung tissue. ResultBD-77 had a certain inhibitory effect on Omicron and Delta variant strains in vitro, with median inhibitory concentration (IC50) of 526.3 mg·L-1 and 653.0 mg·L-1, respectively. BD-77 had no significant inhibitory effect on the binding of the S protein of WT, Omicron, and Delta variant strains of SARS-CoV-2 to ACE2 and had no binding effect with the S protein and N protein of the novel coronavirus. No mice in the blank group died, while the mortality rate of SARS-CoV-2-infected mice was 75%. There was a large amount of virus replication in the lung tissue of the mice and large areas of inflammatory infiltration in the lung tissue and interstitium. Compared with the model group, BD-77 administration groups of 37.5 mg·kg-1 and 75 mg·kg-1 could reduce the mortality of mice, significantly lower the virus titer in the lung tissue of mice (P<0.05), and improve lung lesions. ConclusionBD-77 demonstrated significant inhibitory effects against SARS-CoV-2 virus in vitro and in vivo. However, its mechanism of action did not involve direct inhibition of the virus itself or intervention in the virus-host binding process. This finding suggests that the mechanism of action of BD-77 needs to be thoroughly investigated and elucidated by further experiments.


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