1.Microneedle-facilitated Portulaca oleracea L.-derived nanovesicles ameliorate atopic dermatitis by modulating macrophage M1/M2 polarization and inhibiting NF-κB and STING signaling pathways.
Meng LONG ; Jiaqi LI ; Yuecheng ZHU ; Hang RUAN ; Jing LI ; Fanjun XU ; Ruipeng LIU ; Tao YANG ; Yanqin SHI ; Nianping FENG ; Yongtai ZHANG
Acta Pharmaceutica Sinica B 2025;15(11):5966-5987
Clinical management of atopic dermatitis (AD) is challenged by its susceptibility to recurrence, side effects, and high costs. We found that Portulaca oleracea L.-derived nanovesicles (PDNV) exert anti-inflammatory effects by modulating macrophage M1/M2 polarization. These effects were achieved through pathways including inhibition of nuclear factor-κB (NF-κB) and stimulator of interferon genes (STING) protein expression in diseased tissues, demonstrating their potential to ameliorate AD symptoms. To increase the transdermal permeation of PDNV, dissolvable microneedles composed primarily of hyaluronic acid (HA) were developed as an adjunctive means of delivery. Meanwhile, polysaccharides of Portulaca oleracea L., which were synergistic with PDNV, were used as microneedle constituent materials to enhance the mechanical properties and physical stability of HA. This new means of delivery significantly improves the treatment of AD and also provides new options for the efficient utilization of plant extracellular vesicles and the treatment of AD. In addition, transcriptomic analysis of PDNV showed that the mRNAs of Portulaca oleracea L. are closest to those of ferns, which may shed light on related evolutionary and plant species identification studies.
2.Signatures of proteomics and glycoproteomics revealed liraglutide ameliorates MASLD by regulating specific metabolic homeostasis in mice.
Yuxuan CHEN ; Chendong LIU ; Qian YANG ; Jingtao YANG ; He ZHANG ; Yong ZHANG ; Yanruyu FENG ; Jiaqi LIU ; Lian LI ; Dapeng LI
Journal of Pharmaceutical Analysis 2025;15(11):101273-101273
Liraglutide (Lira), a glucagon-like peptide-1 (GLP-1) receptor agonist approved for diabetes and obesity, has shown significant potential in treating metabolic dysfunction-associated steatotic liver disease (MASLD). However, its systematic molecular regulation and mechanisms remain underexplored. In this study, a mouse model of MASLD was developed using a high-fat diet (HFD), followed by Lira administration. Proteomics and glycoproteomics were analyzed using label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS), while potential molecular target analysis was conducted via quantitative real-time polymerase chain reaction (qPCR) and Western blotting. Our results revealed that Lira treatment significantly reduced liver weight and serum markers, including alanine aminotransferase (ALT) and others, with glycosylation changes playing a more significant role than overall protein expression. The glycoproteome identified 255 independent glycosylation sites, emphasizing the impact of Lira on amino acid, carbohydrate metabolism, and ferroptosis. Simultaneously, proteomic analysis highlighted its effects on lipid metabolism and fibrosis pathways. 21 signature molecules, including 7 proteins and 14 N-glycosylation sites (N-glycosites), were identified as potential targets. A Lira hydrogel formulation (Lira@fibrin (Fib) Gel) was developed to extend drug dosing intervals, offering enhanced therapeutic efficacy in managing chronic metabolic diseases. Our study demonstrated the importance of glycosylation regulation in the therapeutic effects of Lira on MASLD, identifying potential molecular targets and advancing its clinical application for MASLD treatment.
3.Four Cases of Atypical Teratoid/Rhabdoid Tumor of Lateral Ventricles in Children
Jiaqi FENG ; Xinyao WANG ; Lei BAO ; Wenbin GUAN ; Yabing ZHOU ; Xiaoqiang WANG
Medical Journal of Peking Union Medical College Hospital 2024;15(3):655-660
Atypical teratoid/rhabdoid tumor (AT/RT) is a rare malignancy located primarily in infratentorial or subcortical areas with a poor prognosis, and rarely in the lateral ventricle with a very poor prognosis. So far, only 6 cases of AT/RT in lateral ventricle have been reported in China. This article reports the diagnosis and treatment of four children with AT/RT in the lateral ventricle, and discusses the clinical manifestations, differentiation and diagnosis, treatment and prognosis of the disease through literature review, in order to improve clinicians' understanding of the disease and reduce missed diagnosis and misdiagnosis.
4.Baihe Wuyaotang Ameliorates NAFLD by Enhancing mTOR-mediated Liver Autophagy
Rui WANG ; Tiantian BAN ; Lihui XUE ; Xinyi FENG ; Jiyuan GUO ; Jiaqi LI ; Shenghe JIANG ; Xiaolei HAN ; Baofeng HU ; Wenli ZHANG ; Naijun WU ; Shuang LI ; Yajuan QI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):66-77
ObjectiveTo investigate the therapeutic effect of Baihe Wuyaotang (BWT) on non-alcoholic fatty liver disease (NAFLD) and elucidate its underlying mechanism. MethodC57BL/6J mice were randomly assigned to six groups: normal control, model, positive drug (pioglitazone hydrochloride 1.95×10-3 g·kg-1), and low-, medium-, and high-dose BWT (1.3,2.5 and 5.1 g·kg-1). Following a 12-week high-fat diet (HFD) inducement, the mice underwent six weeks of therapeutic intervention with twice-daily drug administration. Body weight was monitored weekly throughout the treatment period. At the fifth week, glucose tolerance (GTT) and insulin tolerance (ITT) tests were conducted. Subsequently, the mice were euthanized for the collection of liver tissue and serum, and the subcutaneous adipose tissue (iWAT) and epididymal adipose tissue (eWAT) were weighed. Serum levels of total triglycerides (TG) and liver function indicators,such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), were determined. Histological examinations, including oil red O staining, hematoxylin-eosin (HE) staining, Masson staining, and transmission electron microscopy, were performed to evaluate hepatic lipid deposition, pathological morphology, and ultrastructural changes, respectively. Meanwhile, Western blot and real-time quantitative polymerase chain reaction (Real-time PCR) were employed to analyze alterations, at both gene and protein levels, the insulin signaling pathway molecules, including insulin receptor substrate 1/2/protein kinase B/forkhead box gene O1 (IRS1/2/Akt/FoxO1), glycogen synthesis enzymes phosphoenolpyruvate carboxy kinase (Pepck) and glucose-6-phosphatase (G6Pase), lipid metabolism-related genes stearoyl-coA desaturase-1 (SCD-1) and carnitine palmitoyltransferase-1 (CPT-1), fibrosis-associated molecules α-smooth muscle actin (α-SMA), type Ⅰ collagen (CollagenⅠ), and the fibrosis canonical signaling pathway transforming growth factor-β1/drosophila mothers against decapentaplegic protein2/3(TGF-β1/p-Smad/Smad2/3), inflammatory factors such as interleukin(IL)-6, IL-8, IL-11, and IL-1β, autophagy markers LC3B Ⅱ/Ⅰ and p62/SQSTM1, and the expression of mammalian target of rapamycin (mTOR). ResultCompared with the model group, BWT reduced the body weight and liver weight of NAFLD mice(P<0.05, P<0.01), inhibited liver lipid accumulation, and reduced the weight of white fat: it reduced the weight of eWAT and iWAT(P<0.05, P<0.01) as well as the serum TG content(P<0.05, P<0.01). BWT improved the liver function as reflected by the reduced ALT and AST content(P<0.05, P<0.01). It improved liver insulin resistance by upregulating IRS2, p-Akt/Akt, p-FoxO1/FoxO1 expressions(P<0.05). Besides, it improved glucose and lipid metabolism disorders: it reduced fasting blood glucose and postprandial blood glucose(P<0.05, P<0.01), improved GTT and ITT(P<0.05, P<0.01), reduced the expression of Pepck, G6Pase, and SCD-1(P<0.01), and increased the expression of CPT-1(P<0.01). The expressions of α-SMA, Collagen1, and TGF-β1 proteins were down-regulated(P<0.05, P<0.01), while the expression of p-Smad/Smad2/3 was downregulated(P<0.05), suggesting BWT reduced liver fibrosis. BWT inhibited inflammation-related factors as it reduced the gene expression of IL-6, IL-8, IL-11 and IL-1β(P<0.01) and it enhanced autophagy by upregulating LC3B Ⅱ/Ⅰ expression(P<0.05)while downregulating the expression of p62/SQSTM1 and mTOR(P<0.05). ConclusionBWT ameliorates NAFLD by multifaceted improvements, including improving IR and glucose and lipid metabolism, anti-inflammation, anti-fibrosis, and enhancing autophagy. In particular, BWT may enhance liver autophagy by inhibiting the mTOR-mediated signaling pathway.
5.Low-dose ketamine attenuates microcirculatory deficits after traumatic brain injury in mice via microglial NF-κB/iNOS pathway
Guodong ZHANG ; Feng HE ; Yuanchao LI ; Gang ZHAO ; Jiaqi ZHANG ; Fengjie GUO ; Zhenguo CHENG
Chinese Journal of Neuromedicine 2024;23(1):10-17
Objective:To investigate the effect of low-dose ketamine on neuroinflammation and microcirculation in mice with traumatic brain injury (TBI).Methods:Sixty adult male C57BL/6 mice, weighing 22-28 g, were randomly divided into sham-operated group, TBI group, Sham+ketamine group, and TBI+ketamine group ( n=15). A controlled cortical impingement (CCI) method was used to establish TBI models in the later 2 groups. Sham+ketamine group and TBI+ketamine group were intraperitoneally injected with 30 mg/kg ketamine once daily for 3 d at 30 min after TBI; sham-operated group and TBI group were intraperitoneally injected same amount of saline at the same time points. Cerebral cortical blood flow in 6 mice from each group was measured by laser speckle contrast imaging (LSCI) before, immediately after, 30 min after, 1 d after and 3 d after modeling, respectively. Three d after modeling, immunohistochemical staining and immunofluorescent double label staining were used to detect the nuclear translocation of microglia markers, ionized calcin-antibody-1 (Iba-1) and nuclear factor (NF)-κB p65 in damaged cortical brain tissues in 6 mice from each group. The remaining 3 mice in each group were sacrificed and tissue plasma was extracted 3 d after modeling; levels of NF-κB p65, phosphorylated (p)-NF-κB p65, p-IκB and inducible nitric oxide synthase (iNOS) in cortical brain tissues were detected by Western blotting. Expressions of tumor necrosis factor-α (TNF-α), interleukin-1-β (IL-1β) and interleukin-6 (IL-6), iNOS, reactive oxygen species (ROS) and reactive nitrogen species (RNS) in cortical brain tissues were detected by ELISA. Results:LSCI indicated that, 3 d after modeling, relative blood flow in local cerebral microcirculation of TBI+ketamine group was significantly increased compared with that of TBI group ( P<0.05). Immunohistochemical staining indicated that compared with the sham-operated group and Sham+ketamine group, the TBI group and TBI+ketamine group had significantly increased number of Iba-1 positive cells in the cerebral cortex ( P<0.05); compared with the TBI group, the TBI+ketamine group had significantly decreased number of Iba-1 positive cells ( P<0.05). ELISA indicated that compared with the sham-operated group and Sham+ketamine group, the TBI group and TBI+ketamine group had significantly increased expressions of TNF-α, IL-1β, IL-6, iNOS, ROS and RNS in damaged cortical brain tissues ( P<0.05); compared with the TBI group, the TBI+ ketamine group had significantly decreased expressions of TNF-α, IL-1β, IL-6, iNOS, ROS and RNS in damaged cortical brain tissues ( P<0.05). Immunofluorescent double label staining indicated obviously inhibited NF-κB p65 nuclear translocation in TBI+ketamine group when it was compared with TBI group. Western blotting indicated that compared with the sham-operated group and Sham+ketamine group, the TBI+ketamine group had significantly increased iNOS, NF-κB p65, p-NF-κB p65 and P-IκB protein expressions in damaged cortical brain tissues ( P<0.05); compared with the TBI group, the TBI+ketamine group had significantly decreased protein expressions of iNOS, NF-κB p65, p-NF-κB p65 and p-IκB in damaged cortical brain tissues ( P<0.05). Conclusion:Low-dose ketamine reduces neuroinflammation and improves cerebral microcirculatory blood flow after open TBI, whose mechanism may be related to inhibition of microglia NF-κB/iNOS pathway.
6.Discussion on Traditional Chinese Medicine Theory and Pharmacological Mechanism of Xuanfei Baidu Prescription in Treatment of Viral Pneumonia
Yihao ZHANG ; Xin PENG ; Zheyu LUAN ; Yunfan WANG ; Jiaqi SHANG ; Jihong FENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):214-224
Viral pneumonia (VP) is an inflammatory disease caused by one or more viruses that infect the upper respiratory tract and spread downward. Causing varying degrees of pulmonary parenchymal damage, VP poses a serious threat to the society and public health. The treatment of VP now faces the dilemma of drug shortage, since Western medicine can only alleviate symptoms and lacks specific treatment methods. In traditional Chinese medicine (TCM), VP is assigned as an epidemic disease, with the etiology attributed to epidemic toxin and six excesses and the pathological factors of dampness, heat, toxin, deficiency, and stasis. The basic pathogenesis of VP is Yin-Yang imbalance, dysfunction of Zang-Fu organs, and healthy Qi deficiency. Accordingly, the treatment should follow the principle of replenishing healthy Qi and expelling pathogen. The treatment method of VP is mainly developed based on syndrome differentiation of six meridians, defense-Qi-nutrient-blood, and triple energizer. Xuanfei Baidu prescription (XFBD) is an effective prescription developed by Academician ZHANG Boli and Professor LIU Qingquan by literature research and selection of multi-component Chinese medicine. It is the product of modern research combined with TCM. XFBD is modified from Maxing Shigantang, Maxing Yigantang, Tingli Dazao Xiefeitang, Qianjin Weijingtang, and Buhuanjin Zhengqisan. It is mainly used to treat epidemic diseases with the syndrome of dampness toxin stagnating in the lung, with the effects of ventilating lung and resolving dampness, clearing heat and expelling pathogen, purging lung, and removing toxin, demonstrating the potential for the prevention and treatment of VP. This paper reviews the research progress of XFBD in combating VP in terms of the prescription composition, compatibility ideas, indications, and clinical new applications, as well as the pharmacological mechanisms of inhibiting virus, reducing inflammation, regulating immune system, ameliorating pulmonary fibrosis, and modulating intestinal flora. In addition, we put forward our thoughts and suggestions on the problems in the research, with a view to informing the clinical use of drugs and the basic research on the treatment of VP including COVID-19.
7.Progress of interruption of schistosomiasis transmission and prospects in Yunnan Province
Yun ZHANG ; Lifang WANG ; Xiguang FENG ; Mingshou WU ; Meifen SHEN ; Hua JIANG ; Jing SONG ; Jiayu SUN ; Chunqiong CHEN ; Jiaqi YAN ; Zongya ZHANG ; Jihua ZHOU ; Yi DONG ; Chunhong DU
Chinese Journal of Schistosomiasis Control 2024;36(4):422-427
Schistosomiasis was once hyper-endemic in Yunnan Province. Following concerted efforts for over 70 years, remarkable achievements have been made for schistosomiasis control in the province. In 2004, the Mid- and Long-term Plan for Schistosomiasis Prevention and Control in Yunnan Province was initiated in Yunnan Province, and the target for transmission control of schistosomiasis was achieved in the province in 2009. Following the subsequent implementation of the Outline for Key Projects in Integrated Schistosomiasis Control Program (2009—2015) and the 13th Five - year Plan for Schistosomiasis Control in Yunnan Province, no acute schistosomiasis had been identified in Yunnan Province for successive 12 years, and no local Schistosoma japonicum infections had been detected in humans, animals or Oncomelania hupensis snails for successive 6 years in the province by the end of 2020. The transmission of schistosomiasis was interrupted in Yunnan Province in 2020. This review summarizes the history of schistosomiasis, changes in schistosomiasis prevalence and progress of schistosomiasis control in Yunnan Province, and proposes the future priorities for schistosomiasis control in the province.
8.Analysis of nutritional status and related factors of school aged children with cerebral palsy in a welfare institution of Guangzhou
CHEN Jingyi, XIAO Jiaqi, GUO Feng, LIANG Quanquan, YANG Jiewen
Chinese Journal of School Health 2024;45(9):1238-1241
Objective:
To under the prevalence of malnutrition and its associated factors in school aged children with cerebral palsy, so as to provide a basis for relevant departments to formulate targeted policies.
Methods:
From July to August 2023, the researchers selected 333 children with cerebral palsy and 960 children with other diseases aged 6-18 years who were residents of a social welfare institution in Guangzhou, China. Their height and weight were measured and a nutritional status analysis was carried out using a cluster sampling method. Multivariate Logistic analysis was performed to analyze the relative factors and malnutrition status of school aged children with cerebral palsy.
Results:
The prevalence of growth retardation among school aged children with cerebral palsy was 74.5%, with rates of stunting, normal nutrition status, and overweight/obesity being 17.7%, 7.2%, and 0.6%, respectively. The results of the univariate analysis revealed statistically significant differences in the detection rate of malnutrition among school aged children with cerebral palsy based on gender, gross motor function classification system (GMFCS) grading, and the presence of swallowing disorders ( χ 2=6.02, 15.23, 32.16, P <0.05). The results of the multivariate Logistic regression analysis showed that gender ( OR=0.37, 95%CI =0.15-0.91), dysphagia (OR=4.10, 95%CI =1.39-12.12), and GMFCS classification ( OR=1.45, 95%CI =1.04-3.01) were influencing factors of malnutrition ( P <0.05).
Conclusions
The detection rate of malnutrition among children and adolescents with cerebral palsy in welfare institutions was found to be relatively high, and influenced by various factors. Corresponding nutritional interventions should be developed and implemented based on the risk factors of malnutrition in school aged children with cerebral palsy to improve their nutritional status.
9.Protective mechanism of Paeoniae Radix Alba against chemical liver injury based on network pharmacology, molecular docking, and in vitro experiments
Shuangqiao Liu ; Xin Liu ; Sijia Jiang ; Min Fu ; Jinxi Hu ; Jiaqi Liu ; Xiaoxu Fan ; Yingtong Feng ; Shujing Zhang ; Jingxia Wang
Journal of Traditional Chinese Medical Sciences 2024;11(1):55-66
Objective:
To explore and validate the potential targets of Paeoniae Radix Alba (P. Radix, Bai Shao) in protecting against chemical liver injury through network pharmacology, molecular docking technology, and in vitro cell experiments.
Methods:
Network pharmacology was used to identify the common potential targets of P. Radix and chemical liver injury. Molecular docking was used to fit the components, which were subsequently verified in vitro. A cell model of hepatic fibrosis was established by activating hepatic stellate cell (HSC)-LX2 cells with 10 ng/mL transforming growth factor-β1. The cells were exposed to different concentrations of total glucosides of paeony (TGP), the active substance of P. Radix, and then evaluated using the cell counting kit-8 assay, enzyme-linked immunosorbent assay, and western blot.
Results:
Analysis through network pharmacology revealed 13 key compounds of P. Radix, and the potential targets for preventing chemical liver injury were IL-6, AKT serine/threonine kinase 1, jun proto-oncogene, heat shock protein 90 alpha family class A member 1 (HSP90AA1), peroxisome proliferator activated receptor gamma (PPARG), PTGS2, and CASP3. Gene Ontology (GO) enrichment analysis indicated the involvement of response to drugs, membrane rafts, and peptide binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the main pathways involved lipid and atherosclerosis and chemical carcinogenesis-receptor activation. Paeoniflorin and albiflorin exhibited strong affinity for HSP90AA1, PTGS2, PPARG, and CASP3. Different concentrations of TGP can inhibit the expression of COL-Ⅰ, COL-Ⅲ, IL-6, TNF-α, IL-1β, HSP-90α, and PTGS2 while increasing the expression of PPAR-γ and CASP3 in activated HSC-LX2 cells.
Conclusion
P. Radix primarily can regulate targets such as HSP90AA1, PTGS2, PPARG, CASP3. TGP, the main active compound of P. Radix, protects against chemical liver injury by reducing the inflammatory response, activating apoptotic proteins, and promoting the apoptosis of activated HSCs.
10.Prediction of potential geographic distribution of Oncomelania hupensis in Yunnan Province using random forest and maximum entropy models
Zongya ZHANG ; Chunhong DU ; Yun ZHANG ; Hongqiong WANG ; Jing SONG ; Jihua ZHOU ; Lifang WANG ; Jiayu SUN ; Meifen SHEN ; Chunqiong CHEN ; Hua JIANG ; Jiaqi YAN ; Xiguang FENG ; Wenya WANG ; Peijun QIAN ; Jingbo XUE ; Shizhu LI ; Yi DONG
Chinese Journal of Schistosomiasis Control 2024;36(6):562-571
Objective To predict the potential geographic distribution of Oncomelania hupensis in Yunnan Province using random forest (RF) and maximum entropy (MaxEnt) models, so as to provide insights into O. hupensis surveillance and control in Yunnan Province. Methods The O. hupensis snail survey data in Yunnan Province from 2015 to 2016 were collected and converted into O. hupensis snail distribution site data. Data of 22 environmental variables in Yunnan Province were collected, including twelve climate variables (annual potential evapotranspiration, annual mean ground surface temperature, annual precipitation, annual mean air pressure, annual mean relative humidity, annual sunshine duration, annual mean air temperature, annual mean wind speed, ≥ 0 ℃ annual accumulated temperature, ≥ 10 ℃ annual accumulated temperature, aridity and index of moisture), eight geographical variables (normalized difference vegetation index, landform type, land use type, altitude, soil type, soil textureclay content, soil texture-sand content and soil texture-silt content) and two population and economic variables (gross domestic product and population). Variables were screened with Pearson correlation test and variance inflation factor (VIF) test. The RF and MaxEnt models and the ensemble model were created using the biomod2 package of the software R 4.2.1, and the potential distribution of O. hupensis snails after 2016 was predicted in Yunnan Province. The predictive effects of models were evaluated through cross-validation and independent tests, and the area under the receiver operating characteristic curve (AUC), true skill statistics (TSS) and Kappa statistics were used for model evaluation. In addition, the importance of environmental variables was analyzed, the contribution of environmental variables output by the models with AUC values of > 0.950 and TSS values of > 0.850 were selected for normalization processing, and the importance percentage of environmental variables was obtained to analyze the importance of environmental variables. Results Data of 148 O. hupensis snail distribution sites and 15 environmental variables were included in training sets of RF and MaxEnt models, and both RF and MaxEnt models had high predictive performance, with both mean AUC values of > 0.900 and all mean TSS values and Kappa values of > 0.800, and significant differences in the AUC (t = 19.862, P < 0.05), TSS (t = 10.140, P < 0.05) and Kappa values (t = 10.237, P < 0.05) between two models. The AUC, TSS and Kappa values of the ensemble model were 0.996, 0.954 and 0.920, respectively. Independent data verification showed that the AUC, TSS and Kappa values of the RF model and the ensemble model were all 1, which still showed high performance in unknown data modeling, and the MaxEnt model showed poor performance, with TSS and Kappa values of 0 for 24%(24/100) of the modeling results. The modeling results of 79 RF models, 38 MaxEnt models and their ensemble models with AUC values of > 0.950 and TSS values of > 0.850 were included in the evaluation of importance of environmental variables. The importance of annual sunshine duration (SSD) was 32.989%, 37.847% and 46.315% in the RF model, the MaxEnt model and their ensemble model, while the importance of annual mean relative humidity (RHU) was 30.947%, 15.921% and 28.121%, respectively. Important environment variables were concentrated in modeling results of the RF model, dispersed in modeling results of the MaxEnt model, and most concentrated in modeling results of the ensemble model. The potential distribution of O. hupensis snails after 2016 was predicted to be relatively concentrated in Yunnan Province by the RF model and relatively large by the MaxEnt model, and the distribution of O. hupensis snails predicted by the ensemble model was mostly the joint distribution of O. hupensis snails predicted by RF and MaxEnt models. Conclusions Both RF and MaxEnt models are effective to predict the potential distribution of O. hupensis snails in Yunnan Province, which facilitates targeted O. hupensis snail control.


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