1.A new phenolic acid isolated from Salvia miltiorrhiza ameliorates OVA-induced allergic asthma by regulation of Th17/Treg cells and inflammation through the TLR4 pathway.
Zeng MENGNAN ; Wu YUANYUAN ; Ren YINGJIE ; Jiao XIANMIAN ; Chang FANGZHUO ; Wang YUANYUAN ; Feng WEISHENG ; Zheng XIAOKE
Chinese Journal of Natural Medicines (English Ed.) 2025;23(12):100007-100007
Salvia miltiorrhiza (S. miltiorrhiza) represents a crucial component of traditional Chinese medicine, demonstrating effects on blood circulation activation and stasis removal, and has been widely utilized in asthma treatment. This study isolated a novel phenolic acid (S1) from S. miltiorrhiza and investigated its anti-asthmatic activity and underlying mechanisms for the first time. An allergic asthma (AA) model was established using ovalbumin (OVA). The mechanism of S1's effects on AA was investigated using multi-factor joint analysis, flow cytometry, and co-culture systems to facilitate clinical asthma treatment. S1 (10 or 20 mg·kg-1) was administered daily to mice with OVA-induced AA (OVA-AA) during days 21-25. The study examined airway responsiveness, lung damage, inflammation, and levels of immunoglobulin E (IgE), PGD2, interleukins (IL-4, 5, 10, 13, 17A), tumor necrosis factor α (TNF-α), GM-CSF, CXCL1, CCL11, and mMCP-1. Additionally, mast cell (MC) activation and degranulation were explored, along with T helper type 17 (Th17)/Treg immune cells and TLR4 pathway biomarkers. The antagonistic activity of that specific antagonist of TLR4 (TAK-242) (1 µmol·L-1), a specific TLR4 blocker, against S1 (10 µmol·L-1) was examined in co-cultured 16HBE cells and bone marrow-derived cells (BMDCs) or splenic lymphocytes (SLs) induced with LPS (1 µg·mL-1) to elucidate the TLR4 pathway's mediating role. S1 demonstrated reduced airway responsiveness, lung damage, and inflammation, with downregulation of IgE, PGD2, interleukins, TNF-α, GM-CSF, CXCL1, CCL11, and mMCP-1. It also impeded MC activation and degranulation, upregulated IL-10, and influenced Th17/Treg immune cell transformation following OVA challenge. Furthermore, S1 inhibited the TLR4 pathway in OVA-AA mice, and TLR4 antagonism enhanced S1's positive effects. Analysis using an OVA-AA mouse model demonstrated that S1 alleviates AA clinical symptoms, restores lung function, and inhibits airway response. S1's therapeutic effects occur through regulation of Th17/Treg immune cells and inflammation, attributable at least partially to the TLR4 pathway. This study provides molecular justification for S1 in AA treatment.
2.Traditional Chinese medicine-facilitated redox-labile paclitaxel dimer nanoprodrug for efficient chemoimmunotherapy.
Fan LI ; Wenrui WANG ; Weisheng XU ; WanYing LI ; Yudi LU ; Rui WANG ; Zhonggui HE ; Zhihui FENG ; Jiabing TONG ; Zhenbao LI
Journal of Pharmaceutical Analysis 2025;15(9):101348-101348
Various therapeuti modailities have been engineered for lung cancer treatment, but their clinic application is severely impeded by the poor therapy efficiency and immunosuppressive microenvironment. Herein, we fabricated a library of small molecule redox-labile nanoparticles (NPs) (i.e., diPTX-2C NPs, diPTX-2S NPs, and diPTX-2Se NPs) by the self-assembly of dimer paclitaxel (PTX) prodrug, and then utilized these NPs with the traditional Chinese medicine (TCM) Qi-Yu-San-Long-Fang (Q) for effective chemoimmunotherapy on Lewis lung carcinoma (LLC)-bearing mice models. Under the high concentration of glutathione (GSH) and H2O2, diPTX-2Se NPs could specifically release PTX in cancer cells and exert a higher selectivity and toxicity than normal cells. In LLC tumor-bearing mice, oral administration of Q not only effectively downregulated programmed death ligand-1 (PD-L1) expression, but also remodeled the immunosuppressive tumor immune microenvironment via the increase of CD4+ T and CD8+ T cell proportion and the repolarization of M2 into M1 macrophages in tumor tissues, collectively achieving superior synergistic treatment outcomes in combination with intravenous PTX prodrug NPs. Besides, we found that the combination regimen also demonstrated excellent chemoimmunotherapeutic performances on low-dose small established tumor and high-dose large established tumor models. This study may shed light on the potent utilization of Chinese and Western-integrative strategy for efficient tumor chemoimmunotherapy.
3.miR-18a-5p Regulates Colorectal Cancer Proliferation and Progression by Targeting RORA
Yifeng CHEN ; Shuai WANG ; Mingming CHAI ; Di ZHANG ; Chunxia WANG ; Lixia ZHAO ; Honglai ZHANG ; Xiongfei YANG ; Weisheng ZHANG ; Tao WANG
Cancer Research on Prevention and Treatment 2024;51(8):667-677
Objective To investigate the mechanism and clinical significance of miR-18a-5p and retinoid acid receptor-related orphan receptor-α(RORA)in the proliferation and progression of colorectal cancer(CRC)cells.Methods The expressions of miR-18a-5p and RORA in CRC cells and tissues were detected via qRT-PCR,FISH,and IHC.Cell proliferation capability was detected through EdU and CFSE assay,cell apoptosis by flow cytometry assay,and cell migration and invasion abilities by cell scratch and Transwell invasion assays,respectively.The targeted regulation of miR-18a-5p on RORA was further verified via dual-luciferase reporter assay,cell function rescue test,RT-PCR,and Western blot assay.Finally,bioinformatics was used to explore the molecular mechanism of miR-18a-5p promoting malignant proliferation,invasion,and progression of CRC via regulating RORA.Results miR-18a-5p exhibited a high expression in CRC tissues and cells(P<0.05)and promoted the proliferation,migration,and invasion of CRC cells(P<0.05).In addition,RORA served as the target gene of miR-18a-5p,and its overexpression effectively reduced the promoting function of miR-18a-5p in the malignant biological phenotype of CRC cells(P<0.05).The expression of RORA in CRC tissues showed a significantly positively correlation with the infiltration of CD8+T cells and the expression of its surface marker protein CD8A.Conclusion The targeted regulation of RORA by miR-18a-5p promotes the proliferation and progression of CRC.The miR-18a-5p/RORA regulatory pathway possibly contributes to the immune microenvironment of CRC,which can be a potential therapeutic target for CRC.
4.Analysis of volatile constituents in different parts of Huai chrysanthemum by GC-MS combined with stoichiometry
Mengzhen GUO ; Meng LI ; Xiaoyan DENG ; Shuyan LIU ; Xiaolan WANG ; Xiaoya SUN ; Jingke ZHANG ; Xiaoke ZHENG ; Weisheng FENG
China Pharmacist 2024;27(2):209-219
Objective To analyze and identify the volatile constituents in different parts(flowers,stems and leaves)of Huai chrysanthemumin,and to lay a theoretical foundation for the comprehensive utilization for it.Methods The volatile oil in different parts of Huai chrysanthemumin were extracted by hydrodistillation,respectively.Their constituents were analyzed by gas chromatography-mass spectrometry(GC-MS).The compounds were identified by library search and literature screening.The relative percentage of each compound was obtained by the area normalization method.The differences in their chemical compositions were analyzed by Venn diagram,principal component analysis(PCA)and cluster heat map analysis.Results A total of 62 volatile chemical components were identified from different parts of Huai chrysanthemumin,including monoterpenes,sesquiterpenes,and their derivatives,as well as a small amount of aliphatic compounds.32,42 and 40 volatile components were detected from the flowers,stems and flowers,respectively.Furthermore 17 volatile components were shared by three parts,whereas 5,6 and 16 volatile components were unique to the flowers,stems and leaves,respectively.The results of stoichiometric analysis showed that both PCA and cluster heat map analysis could separate the flowers,stems and leaves,and their volatile components were different.Conclusion The types and contents of the volatile oil in the stems,leaves and flowers of Huai chrysanthemumin have certain variability,which provide a scientific basis for the further medicinal or industrial exploitation of different parts of Huai chrysanthemumin.
5.Effect of deliberate practice combined with intensive training in cardiopulmonary resuscitation teaching for nurses receiving standardized training
Weiping WANG ; Qiuying DENG ; Chuanren LING ; Weisheng CHEN ; Haihui FANG ; Liqun HUANG
Chinese Journal of Medical Education Research 2024;23(1):123-127
Objective:To investigate the mid- and long-term training effect of deliberate practice combined with intensive training in cardiopulmonary resuscitation (CPR) teaching for nurses receiving standardized training.Methods:A total of 160 nurses who received the first year of standardized training in Guangdong Provincial Hospital of Traditional Chinese Medicine from July 2020 to March 2021 were enrolled as subjects, and they were randomly divided into experimental group and control group, with 80 nurses in each group. The nurses in the control group received the mode of single deliberate practice, and those in the experimental group received deliberate practice combined with intensive training at months 0, 3, and 6. Assessment was performed for the two groups before and after training,with objective indicators and subjective evaluation as the assessment criteria. Objective score was determined by the immediate objective feedback provided by the electronic display of Resusci Anne ? QCPR, and subjective score was determined by the same group of examiners based on the evaluation of cardiopulmonary resuscitation performed by trainees,including environment evaluation, judgment of consciousness, judgment of respiration, initiation of emergency treatment system, re-evaluation after resuscitation, and overall evaluation. SPSS 18.0 was used for the independent samples t-test, the non-parametric test, and the chi-squares test. Results:After training, there were significant differences between the experimental group and the control group in the objective indicators of the percentage of correct compression (CC%) [85.500 (77.50, 93.00) vs. 81.00 (71.75, 89.00), Z=-2.49, P=0.013] and the proportion of correct ventilation (V%) [84.00 (75.00, 92.75) vs. 80.00 (64.00, 90.25), Z=-2.15, P=0.031]. Both groups had significant improvements in objective and subjective indicators after training (all P<0.05). Conclusions:Deliberate practice combined with intensive training at an interval of 3 months can effectively improve the mid- and long-term CPR skills of nurses receiving standardized training and is more suitable for high-level muscle memory training.
6.Relationship between PI3K/Akt/mTOR signal pathway and autophagy regulation and related diseases
Weisheng LI ; Tingting WANG ; Wenqiang HE
Chongqing Medicine 2024;53(13):2047-2052
Phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamy-cin(mTOR)signaling pathway is an important regulating pathway for metabolism,proliferation and survival in cells,and plays a pivotal role in maintaining cellular homeostasis.This signaling pathway participates in the occurrence and development process of multiple diseases by mediating the cellular autophagy,such as tumors,neurodegenerative disorders(ND)and metabolic diseases.This paper reviews the role of PI3K/Akt/mTOR signaling pathway in autophagy regulation in order to better understand the regulatory mechanisms of cellular metabolism and survival,moreover investigate the role of this signal pathway in multiple diseases and direc-tion of the future study to provide reference for explore the new disease treatment methods.
7.Progress of T1 Mapping and Its Application in Evaluating Myocardial Fibrosis
Dandan LI ; Qian WANG ; Jing XU ; Weisheng ZHANG
Chinese Journal of Medical Imaging 2024;32(9):966-971
T1 mapping is a widely-used magnetic resonance technology in recent years.By quantifying the T1 value and extracellular volume of myocardial tissue,T1 mapping can evaluate the cardiovascular diseases leading to myocardial fibrosis.The basic principle,scanning sequence and application of T1 mapping are reviewed in diseases leading to myocardial fibrosis,mainly including:myocardial infarction,hypertrophic cardiomyopathy,dilated cardiomyopathy,congenital heart disease,aortic stenosis,hypertensive heart disease,diabetic cardiomyopathy,uremic cardiomyopathy,heart failure with preserved ejection fraction,heart transplantation,etc.
8.Characteristics of avian leukosis virus infection and polymorphism analysis of re-ceptor gene sequence in Qingyuan Ma chickens
Xiaoxue ZHENG ; Xueli SHU ; Hongmei WANG ; Mingchao GAO ; Mingcheng YU ; Yibin LI ; Ming LIAO ; Weisheng CAO
Chinese Journal of Veterinary Science 2024;44(7):1380-1386,1393
In order to understand the characteristics of avian leukosis virus(ALV)infection and the polymorphisms of receptor genes Tva,Tvb and NHE1 sequences in different Qingyuan Ma chick-en breeding farms,the isolation and identification of exogenous ALV virus,receptor gene amplifi-cation and sequencing analysis were carried out in five Qingyuan Ma chicken breeding farms.The results of virus isolation and subtype identification showed that the positive rate of exogenous ALV virus isolation in farms A,B and C was less than 5%,among which there was ALV-J infection alone in farm A,mixed infection with ALV-J and ALV-K in farm B,ALV-K infection a-lone in farm C,and no exogenous ALV infection was detected in farm D and E.Polymorphism anal-ysis of recipient genes showed that there were different frequencies of Tvar3,Tvar4 and Tvbr3 re-sistance alleles in A-E farms,and the distribution frequency of Tvar3 was 0.2-0.6,the distribution frequency of Tvar4 was 0.3-0.7,and the distribution frequency of Tvbr3 was 0.1-0.7.In addition,there were Tvar5 resistance alleles in both B and D farms,with a distribution frequency of 0.2.A to-tal of 18 SNP mutations occurred in the NHE1 receptor gene sequence,and further analysis showed that positions 1 279,1 361,1 369,1 406,1 442,and 1 912 were non-synonymous mutations,which could cause changes in amino acids.The study suggested that there were differences in the exogenous ALV and its subtypes among the five Qingyuan Ma chicken breeders,and each farm should have a more targeted and unique purification strategy.The distribution of Tva and Tvb re-sistance alleles at different frequencies,along with the occurrence of 6 non-synonymous mutations in the NHE1 gene,indicate that Qingyuan Ma chicken have the potential of genetic resistance breeding.
9.Mechanisms of Qinghua Liangxue Huluo Decoction in preventing acute radiation enteritis in rats through the PI3K/Akt pathway
Lin ZHU ; Ting ZHANG ; Huafang YIN ; Weisheng SHEN ; Yu LI ; Jian WANG ; Weidong SHEN
Chinese Journal of Radiological Medicine and Protection 2024;44(7):571-577
Objective:To explore the regulatory effects of Qinghua Liangxue Huluo Decoction on oxidative stress and inflammation in acute radiation enteritis in rats, as well as its impact on the PI3K/Akt pathway. Methods:A total of 36 SD rats were randomly divided into four groups using block randomization, namely the control, model, low-dose group (6.17 g/kg), and high-dose (24.68 g/kg) groups, with nine rats in each group. These rats were exposed to X-ray irradiation at a dose of 17.5 Gy to induce acute radiation enteritis, followed by continuous intragastric administration for seven days pre- and post-irradiation. Seven days post-irradiation, the perianal and fecal conditions of rats in each group were observed, and rectal tissues were collected and ground. Enzyme-linked immunosorbent assay (ELISA) was employed to assess the activity of superoxide dismutase (SOD), catalase (CAT) expression, and malondialdehyde (MDA) levels indicative of lipid peroxidation. Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to analyze the mRNA expression of tumor necrosis factor-ɑ (TNF-ɑ), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in the rectal tissues of each group. Additionally, Western blot was conducted to examine the expression of proteins associated with the PI3K/Akt signaling pathway in rectal tissues. The IEC-6 cells were categorized into the control, radiation, blank, and drug administration groups, with all these groups except for the control group subjected to 10 Gy single irradiation. ELISA was then employed to determine the concentrations of SOD, CAT, MDA, TNF-ɑ, IL-6, and IL-1β in cell supernatants, while Western blot was utilized to assess the expression of PI3K/Akt signaling pathway-related proteins in each group.Results:Compared to the model group, rats in the low-dose and high-dose groups exhibited a trend toward normal perianal and fecal conditions, increased SOD activity ( t = 4.86, 8.50, P < 0.05), elevated CAT expression ( t = 8.72, 14.28, P<0.05), and decreased MDA level ( t = 6.94, 10.66, P < 0.05). Furthermore, the mRNA expression of TNF-ɑ, IL-6, and IL-1β in rectal tissues was significantly inhibited in both low-dose and high-dose groups ( t = 5.60, 2.95, 4.31, 9.16, 4.66, 13.35, P < 0.05), along with lower p-PI3K/PI3K and p-Akt/Akt ratios in rectal tissues compared to the model group ( t = 22.35, 13.56, 18.23, 13.85, P < 0.05). Compared to the radiation group, the drug administration groups (10% drug-containing serum) exhibited increased SOD and CAT expressions ( t = 6.85, 10.44, P < 0.05), as well as decreased MDA expression ( t = 10.44, P < 0.05), in the supernatant. Furthermore, compared to the radiation group, this group displayed significantly inhibited TNF-ɑ, IL-6, and IL-1β concentrations in the cell supernatant ( t = 12.07, 6.87, 14.80, P < 0.05), while lowering p-PI3K/PI3K and p-Akt/Akt ratios in cells ( t = 10.95, 5.59, P < 0.05). Conclusions:Qinghua Liangxue Huluo Decoction demonstrates the potential for mitigating oxidative stress-induced injury and suppressing the expressions of inflammatory factors in rats with acute radiation enteritis. The mechanism behind the potential is likely associated with the negative regulation of the PI3K/Akt signaling pathway.
10.Regulation of Th17/Treg immune imbalance by β-sitosterol in an OVA-induced allergic asthma rat model
Jufang JIA ; Mengnan ZENG ; Beibei ZHANG ; Ru WANG ; Meng LIU ; Pengli GUO ; Qinqin ZHANG ; Fengyu ZHANG ; Xiaoke ZHENG ; Weisheng FENG
Chinese Journal of Immunology 2023;39(12):2477-2482
Objective:To explore the interventional effect of β-sitosterol on ovalbumin(OVA)-induced allergic asthma rats and its potential mechanism.Methods:SD male rats were randomly divided into normal group(CON),model group(M),positive drug dexamethasone group(DEX,0.075 mg/kg)and β-sitosterol group(Sit,50 mg/kg).A rat model of allergic asthma was estab-lished by intraperitoneal injection of OVA with aluminum hydrogen solution,and nebulized inhalation of OVA to stimulate.Rats were given intragastric administration 30 min before aerosol challenge,and after continuous administration for 7 days,the indicators of cough and asthma and tracheal phenol red excretion were detected.HE staining was used to observe pathological changes of lung tis-sue.Flow cytometry was used to detect reactive oxygen species(ROS)generation,apoptosis level and ratios of Th17 and Treg cells in peripheral blood.Biochemical method was used to detect contents of MDA,and activities of T-SOD and GSH-Px in rat lung tissues.ELISA was used to detect levels of Th17 and Treg-related cytokines(TNF-α,IL-4,IL-6,IL-17A,and IL-35).Results:Compared with model group,β-sitosterol significantly prolonged the incubation period of cough and gasp in rats with allergic asthma,reduced the frequency of cough and gasping,and promoted the excretion of phenol red in trachea;significantly reduced inflammatory infiltration in lung tissue of asthmatic rats;observably reduced MDA content in lung tissue,ROS of primary lung cell and apoptosis levels of asthmatic rats,increased the activities of T-SOD and GSH-Px;markedly reduced proportion of Th17 cells and levels of pro-inflammatory cyto-kines TNF-α,IL-4,IL-6 and IL-17A,increased proportion of Treg cells and levels of anti-inflammatory cytokine IL-35.Conclusion:β-sitosterol can ameliorate airway inflammation and oxidative damage in OVA-induced allergic asthmatic rats,and its mecha-nism may be related to the regulation of β-sitosterol on Th17/Treg immune imbalance and oxidative stress response.

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