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PHARMACEUTICAL BIOLOGY · 2023 · IF 3.8

Exploring the mechanisms of action of Zengye decoction (ZYD) against Sjogren’s syndrome (SS) using network pharmacology and animal experiment

Jiake Yu,Shuying Wang,Jie Yang,Wuxinrui Huang,Beikang Tang,Weijun Peng,Jing Tian

Context Zengye decoction (ZYD) has been considered to have a curative effect on Sjogren’s syndrome (SS). However, its therapeutic mechanisms remain obscure.Objectives This research explores the mechanisms of ZYD against SS.Materials and methods The active compounds and targets of ZYD were searched in the TCMSP and BATMAN-TCM databases. SS-related targets were obtained from the GeneCards database. The GO and KEGG enrichment analyses elucidated the molecular mechanisms. Animal experiments were performed using 8 C57BL/6 mice that served as the control group (physiological saline treatment) and 16 NOD mice randomly divided into the model group (physiological saline treatment) and the ZYD group (ZYD treatment) for 8 weeks to verify the therapeutic effects of ZYD on SS.Results Twenty-nine active compounds with 313 targets of ZYD and 1038 SS-related targets were screened. Thirty-two common targets were identified. β-Sitosterol and stigmasterol might be important components. GO analysis suggested that the action of ZYD against SS mainly involved oxidative stress, apoptotic processes, and tumor necrosis factor receptor superfamily binding, etc. KEGG analysis indicated the most significant signaling pathway was apoptosis-multiple species. Animal experiments showed that ZYD improved lymphocytic infiltration of the submandibular glands (SMGs), reduced the serum levels of TNF-α, IL-1β, IL-6, and IL-17, upregulated the expression of Bcl-2, and downregulated the expression of Bax and Caspase-3 in the model mice.Discussion and conclusion ZYD has anti-inflammatory and anti-apoptotic effects on SS, which provides a theoretical basis for the treatment of SS with ZYD.

CAS / MDL: 329-98-6
研究领域: 药理学 · 免疫学 · 中医药学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Food Bioscience · 2025 · IF 5.9

Chemical composition, antioxidant activity, α-glucosidase inhibitory activity, and metabolomic profiling of Dendrobium officinale across diverse growing regions and cultivation modes

Shu He,Zhengli Lu,Rurui Li,Chun Chen,Xiong Fu,Kin Weng Kong,Amin Ismail,Xuechun Zhang,Zhenxing Wang

This study evaluated the chemical composition and bioactivity of nine Dendrobium officinale from three cultivation modes (greenhouse, GC; understory, UC; and simulated wild, SWC) across China. Results demonstrated that UC-cultivated samples exhibited significantly higher flavonoid levels, antioxidant capacity, and α-glucosidase inhibition activity than those under GC/SWC modes. Using GC-IMS and UHPLC-TOF-MS, metabolomic profiling identified 27 volatile and 15 non-volatile biomarkers between different cultivation modes. Further KEGG analysis revealed the key signaling pathways of differential metabolites under different cultivation modes, including aminobenzoate degradation, phenylpropanoid biosynthesis, and phenylalanine metabolism. Overall, the cultivation mode significantly influences the chemical composition and biological activity of Dendrobium officinale , with the UC mode being relatively preferable. However, factors such as geographical distribution also play an important role. These findings provide actionable insights for quality control, cultivation optimization, and functional food/pharmaceutical applications of Dendrobium officinale .

研究领域: 生药学 · 植物科学 · 代谢组学 · 植物化学 · 功能食品研究 · 药学
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COMPUTERS IN BIOLOGY AND MEDICINE · 2024 · IF 7

Exploring molecular mechanisms of diazinon toxicity in HT22 hippocampal neurons through integrated miRNA and mRNA profiling

Jianan Li,Yan Sun,Haoran Bi

Diazinon (DZN), a persistent organophosphate insecticide, has been associated with neurotoxic effects, particularly in the hippocampus. However, the specific molecular mechanisms of DZN-induced hippocampal toxicity remain unknown. In this study, we analyzed the mRNA and miRNA expression patterns of HT22 cells following exposure to DZN (125 μM), and the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted subsequently. The integration of miRNA sequencing (miRNA-seq) and mRNA sequencing (mRNA-seq) data identified 33 differentially expressed miRNAs (DEMIs, 15 up-regulated and 18 down-regulated) and 271 differentially expressed mRNAs (DEMs, 69 up-regulated and 202 down-regulated) targeted by the DEMIs. Moreover, the 3 most central mRNAs (ITGAV, FN1, and EGFR) and 7 associated miRNAs (mmu-miR-700-5p, mmu-miR-26a-2-3p, mmu-miR-452-3p, mmu-miR-25-3p, mmu-miR-582-5p, mmu-miR-467a-5p, and mmu-miR-467b-5p) were screened and validated using quantitative real-time PCR. Furthermore, the GO analysis revealed that the identified DEMs were enriched in biological adhesion extracellular matrix, and growth factor binding, while the KEGG analysis suggested that the enriched DEMs were involved in ECM-receptor interaction, mTOR signaling pathway, MAPK signaling pathway, and AMPK signaling pathway. Our results may aid in elucidating the underlying mechanisms associated with DZN-induced hippocampal toxicity and provide valuable insights into the pathogenesis of neurotoxicity triggered by other organophosphorus pesticides.

研究领域: 神经毒理学 · 分子生物学 · 药理学
✓ 已验证 DOI PubMed 高影响因子
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Antioxidants · 2024 ·Vol. 13 ·期 9 ·1026 · IF 6

Tanshinone IIA Inhibits the Endoplasmic Reticulum Stress-Induced Unfolded Protein Response by Activating the PPARα/FGF21 Axis to Ameliorate Nonalcoholic Steatohepatitis

Dajin Pi,Zheng Liang,Jinyue Pan,Jianwei Zhen,Chuiyang Zheng,Wen Fan,Qingliang Song,Maoxing Pan,Qinhe Yang,Yupei Zhang

Nonalcoholic steatohepatitis (NASH) is a critical stage in the progression of nonalcoholic fatty liver disease (NAFLD). Tanshinone IIA (TIIA) is a tanshinone extracted from Salvia miltiorrhiza; due to its powerful anti-inflammatory and antioxidant biological activities, it is commonly used for treating cardiovascular and hepatic diseases. A NASH model was established by feeding mice a methionine and choline-deficient (MCD) diet. Liver surface microblood flow scanning, biochemical examination, histopathological examination, cytokine analysis through ELISA, lipidomic analysis, transcriptomic analysis, and Western blot analysis were used to evaluate the therapeutic effect and mechanism of TIIA on NASH. The results showed that TIIA effectively reduced lipid accumulation, fibrosis, and inflammation and alleviated endoplasmic reticulum (ER) stress. Lipidomic analysis revealed that TIIA normalized liver phospholipid metabolism in NASH mice. A KEGG analysis of the transcriptome revealed that TIIA exerted its effect by regulating the PPAR signalling pathway, protein processing in the ER, and the NOD-like receptor signalling pathway. These results suggest that TIIA alleviates NASH by activating the PPARα/FGF21 axis to negatively regulate the ER stress-induced unfolded protein response (UPR).

CAS / MDL: 568-72-9
研究领域: 药理学 · 肝病学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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LIFE SCIENCES · 2024 · IF 5.2

Liquiritin reduces chondrocyte apoptosis through P53/PUMA signaling pathway to alleviate osteoarthritis

Min Qiu,Liangyan Cheng,Jianbo Xu,Minwei Jin,Wenhua Yuan,Qinwen Ge,Kaiao Zou,Jiali Chen,Yuliang Huang,Ju Li,Liming Zhu,Bing Xu,Chunchun Zhang,Hongting Jin,Pinger Wang

Aims The main pathological features of osteoarthritis (OA) include the degeneration of articular cartilage and a decrease in matrix synthesis. Chondrocytes, which contribute to matrix synthesis, play a crucial role in the development of OA. Liquiritin, an effective ingredient extracted from Glycyrrhiza uralensis Fisch., has been used for over 1000 years to treat OA. This study aims to investigate the impact of liquiritin on OA and its underlying mechanism. Materials and methods Gait and hot plate tests assessed mouse behavior, while Micro-CT and ABH/OG staining observed joint morphological changes. The TUNEL kit detected chondrocyte apoptosis. Western blot and immunofluorescence techniques determined the expression levels of cartilage metabolism markers COL2 and MMP13, as well as apoptosis markers caspase3, bcl2, P53, and PUMA. KEGG analysis and molecular docking technology were used to verify the relationship between liquiritin and P53. Key findings Liquiritin alleviated pain sensitivity and improved gait impairment in OA mice. Additionally, we found that liquiritin could increase COL2 levels and decrease MMP13 levels both in vivo and in vitro. Importantly, liquiritin reduced chondrocyte apoptosis induced by OA, through decreased expression of caspase3 expression and increased expression of bcl2 expression. Molecular docking revealed a strong binding affinity between liquiritin and P53. Both in vivo and in vitro studies demonstrated that liquiritin suppressed the expression of P53 and PUMA in cartilage. Significance This indicated that liquiritin may alleviate OA progression by inhibiting the P53/PUMA signaling pathway, suggesting that liquiritin is a potential strategy for the treatment of OA.

研究领域: 药理学 · 骨科 · 细胞生物学 · 分子生物学 · 生物医学工程
✓ 已验证 DOI PubMed 高影响因子
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CURRENT MICROBIOLOGY · 2025 ·Vol. 82 ·期 10 ·1-12 · IF 2.6

Transcriptomic Analysis Reveals Key Regulatory Genes and Pathways Involved in Macrophage Inflammation Induced by Hypervirulent Klebsiella pneumoniae Infection

Bi Jinli,Huang Xin,Meng Liqin,Li Jinghan,He Yu,Jin Jing,Li Taijie

Hypervirulent Klebsiella pneumoniae (hvKP) possesses multiple virulence factors and causes severe infections with elevated mortality rates. It induces a strong inflammatory response in the host, with macrophages playing a key role in defense and inflammation. However, the signaling pathways of macrophages involved in response to hvKP infection remain unclear. In this study, we developed a stable hvKP infection model in differentiated THP-1 macrophages, confirmed by CFU assay and LDH cytotoxicity assay, and subsequently performed transcriptomic profiling analysis of hvKP-infected cells to characterize infection-induced gene expression changes. Pathway and differential gene correlation network analyses identified 14 potential regulatory genes primarily involved in inflammation. These changes in gene expression were further validated by Reverse transcription quantitative PCR (RT-qPCR). KEGG and GO analyses revealed several key signaling pathways involved in inflammation and immune response, particularly the TNF, IL-17, NF-κB, and JAK-STAT pathways. Further analysis indicated that the NF-κB signaling pathway plays a central role in the inflammatory response to hvKP infection, whereas the TNF and IL-17 pathways act synergistically to upregulate pro-inflammatory cytokines and chemokines. Western blot analysis confirmed the expression of TRAF6 and NF-κB p65 protein during hvKP infection. This study provides valuable insights into the molecular mechanisms of macrophage responses to hvKP, offering potential targets for therapeutic intervention.

CAS / MDL: 1405-41-0
研究领域: 微生物学 · 免疫学 · 分子生物学 · 传染病学 · 基因组学 · 细胞生物学 · 生物信息学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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TOXICOLOGY AND APPLIED PHARMACOLOGY · 2022 · IF 4.46

Whole transcriptome analysis of long noncoding RNA in beryllium sulfate-treated 16HBE cells

Shaoxiong Chen,Zhanbing Sun,Weihua Deng,Guilan Li,Xiuli Liu,Zhaohui Zhang

Beryllium and its compounds can cause pulmonary interstitial fibrosis through mechanisms that are not yet clear. Long non-coding RNA (lncRNA) is implicated in various diseases. The molecular toxicity of beryllium sulfate (BeSO 4 ) was investigated through the RNA-seq analysis of the lncRNA and mRNA whole-transcriptome of BeSO 4 -treated 16HBE cells. A total of 1014 lncRNAs (535 upregulated and 479 downregulated) and 4035 mRNAs (2224 upregulated and 1811 downregulated) were found to be significantly dysregulated (|logFC| ≥> 2.0, p  < 0.05) in the BeSO 4 -treated groups when compared with the control group. Five differentially expressed lncRNAs and mRNAs were verified by qRT-PCR. KEGG analysis showed that lncRNA regulates the ECM receiver interaction and PI3K/AKT signaling pathways, etc. In addition, H19:17, lnc-C5orf13–1:1, lnc-CRYAA-17:1, lnc-VSTM5–1:11, and lnc-THSD7A-7:1 may regulate BeSO 4 -induced 16HBE cytotoxicity through ceRNA mechanism. The results of this study will provide some theoretical support for the study of the toxic mechanism of beryllium and its compounds.

CAS / MDL: 7787-56-6
研究领域: 毒理学 · 分子生物学 · 基因组学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Frontiers in Pharmacology · 2021 · IF 5.811

Integrated Proteomics and Metabolomics Link Acne to the Action Mechanisms of Cryptotanshinone Intervention

Zhu Zhaoming,Chen Tingting,Wang Zhuxian,Xue Yaqi,Wu Wenfeng,Wang Yuan,Du Qunqun,Wu Yufan,Zeng Quanfu,Jiang Cuiping,Shen Chunyan,Liu Li,Zhu Hongxia,Liu Qiang

The label-free methods of proteomic combined with metabolomics were applied to explore the mechanisms of Cryptotanshinone (CPT) intervention in rats with acne. The model group consisted of rats given oleic acid (MC), then treated with CPT, while control groups did not receive treatment. The skin samples were significantly different between control, model and CPT-treated groups in hierarchical clustering dendrogram. Obvious separations of the skin metabolic profiles from the three groups were found through PCA scoring. In total, 231 and 189 differentially expressed proteins (DEPs) were identified in MC and CPT groups, respectively. By the KEGG analysis, five protein and metabolite pathways were found to be significantly altered. These played important roles in response to oleic acid-induced acne and drug treatment. CPT could negatively regulate glycolysis/gluconeogenesis and histidine metabolisms to decrease keratinocyte differentiation and improve excessive keratinization and cellular barrier function. CPT could down-regulate the IL-17 signaling pathway and regulate the acne-driven immune response of sebum cells. The biosynthesis of unsaturated fatty acids metabolism, glycerophospholipid metabolism and linoleic acid pathways could significantly alter sebum production and control sebaceous gland secretion after CPT treatment. The gap junction was up-regulated after CPT treatment and the skin barrier turned back to normal. Krt 14, Krt 16 and Krt 17 were significantly down-regulated, decreasing keratinization, while inflammatory cell infiltration was improved by down-regulation of Msn, up-regulation of linoleic acid and estrogen pathways after CPT treatment. These results propose action mechanisms for the use of CPT in acne, as a safe and potential new drug.

CAS / MDL: 56-81-5 25618-55-7
研究领域: 药理学 · 分子生物学 · 皮肤科 · 系统生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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BMC Complementary Medicine and Therapies · 2024 ·Vol. 24 ·期 1 ·1-15 · IF 3.3

Molecular mechanism of resveratrol promoting differentiation of preosteoblastic MC3T3-E1 cells based on network pharmacology and experimental validation

He Yu,Liu Fei,He Mingjuan,Long Fayu,Hu Ding,Chen Jingwen,Fang Miao,Wang Zhenlong

The purpose of this study was to investigate the mechanism by which resveratrol (Res) inhibits apoptosis and promotes proliferation and differentiation of pre-osteoblastic MC3T3-E1 cells, laying the groundwork for the treatment of osteoporosis (OP). The TCMSP database was used to find the gene targets for Res. The GeneCards database acquire the gene targets for OP. After discovering the potential target genes, GO, KEGG, and Reactome enrichment analysis were conducted. Verifying the major proteins involved in apoptosis can bind to Res using molecular docking. CCK8 measured the proliferative activity of mouse pre-osteoblasts in every group following Res intervention. Alkaline phosphatase staining (ALP) and alizarin red staining to measure the ability of osteogenic differentiation. RT-qPCR to determine the expression levels of Runx2 and OPG genes for osteogenic differentiation ability of cells. Western blot to measure the degree of apoptosis-related protein activity in each group following Res intervention. The biological processes investigated for GO of Res therapeutic OP involved in cytokine-mediated signaling pathway, negative regulation of apoptotic process, Aging, extrinsic apoptotic signaling pathway in absence of ligand, according to potential therapeutic target enrichment study. Apoptosis, FoxO signaling pathway, and TNF signaling pathway are the primary KEGG signaling pathways. Recactome pathways are primarily engaged in Programmed Cell Death, Apoptosis, Intrinsic Apoptotic Pathway, and Caspase activation via extrinsic apoptotic signaling pathways. This research established a new approach for Res treatment of OP by demonstrating how Res controls the apoptosis-related proteins TNF, IL6, and CASP3 to suppress osteoblast death and increase osteoclastogenesis.

研究领域: 药理学 · 细胞生物学 · 分子生物学 · 生物信息学 · 骨生物学 · 网络医学
✓ 已验证 DOI 高影响因子
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SCIENCE OF THE TOTAL ENVIRONMENT · 2019 · IF 5.589

C9–13 chlorinated paraffins cause immunomodulatory effects in adult C57BL/6 mice

Xia Wang,Jianbo Zhu,Baida Kong,Bingnan He,Lai Wei,Yuanxiang Jin,Yudong Shan,Weitao Wang,Chunqiang Pan,Zhengwei Fu

Short-chain chlorinated paraffins (SCCPs, C 10–13 ) were listed as persistent organic pollutants (POPs) by the Stockholm Convention in 2017 and pose extensive exposure risks to humans. To our knowledge, there have been no studies reporting the immmunomodulatory effects of SCCPs until now. C 9 -CPs have also been shown to be present in the environment. In this study, adult male C57BL/6 mice were exposed to 1, 10, or 100 mg/kg/d C 9–13 -CPs by gavage for 28 d. The results showed that compared to those of the controls, exposure to C 9–13 -CPs led to increased spleen weight, delimited germinal centers, enhanced energy metabolism, and elevated glutathione content, but no variation in the malonaldehyde level in the spleen was observed. Exposure to C 9–13 -CPs also increased the populations of splenic lymphocytes, T lymphocytes, NK cells, and the ratio of the CD3 + /CD19 + subsets and CD4 + /CD8 + subsets compared to those of the controls. RNA-seq revealed 424 differentially expressed genes (DEGs) (fold change ≥ 1.5, FDR < 0.05) in the spleen between the control group and the 100 mg/kg/d C 9–13 -CPs-treated group. KEGG analysis demonstrated that folate biosynthesis, pathways in cancer and thyroid hormone signaling were the three most significantly enriched pathways, and despite not reaching statistical significance, some immune-related pathways were also enriched in the KEGG functional enrichment analysis, including the chemokine signaling pathway (FDR < 0.0584), the NF-κB signaling pathway (FDR < 0.0663), Th17 cell differentiation (FDR < 0.0839), and the Jak-STAT signaling pathway. Moreover, compared to those of the controls, exposure to C 9–13 -CPs enhanced the Concanavalin A (Con A)-stimulated cultured splenocyte proliferation, while the exposure showed no effect on the splenocyte proliferation that was stimulated by lipopolysaccharides (LPS). Taken together, these results demonstrated that subacute exposure to C 9–13 -CPs could have immunomodulatory effects in mice. The present study helps to provide an understanding of the comprehensive health risks posed by C 9–13 -CPs.

CAS / MDL: 11028-71-0
研究领域: 毒理学 · 免疫学 · 分子生物学 · 环境科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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