摘要：
Objective: The use of immune checkpoint inhibitors (ICIs) provides promising strategies for hepatocellular carcinoma (HCC) treatment. This study aimed to explore impact and underlying mechanism of the combination therapy of quercetin and anti-programmed cell death 1 (anti-PD-1) antibody on HCC. Methods: Orthotopically transplanted HCC tumors in mice were treated with quercetin, anti-PD-1 antibody, or a combination of both therapies. Histopathological changes and programmed cell death ligand 1 (PD-L1) expression were characterized by hematoxylin and eosin (H&E) and immunohistochemistry (IHC) staining. The diversity and differences of gut microbiota (GM) were evaluated through 16S rRNA sequencing. Levels of macrophage immunity-related cytokines were quantified by enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (RT-qPCR), and Western blot. Results: Combination therapy reduced necrosis, fibrosis, and PD-L1 expression in liver tissues. Additionally, combination therapy reduced GM imbalance and increased abundance of Firmicutes, Actinobacteria, and Verrucomicrobiota at the phylum level as well as Dubosiella and Akkermansia at the genus level. Combination therapy improved macrophage immunity, raised the expressions of CD8a, CD4, CD11b, interleukin (IL)-10, and interferon (IFN)--y , and declined the expressions of IL-4, IL-6, toll-like receptor 4 (TLR4), an inhibitor of nuclear factor kB alpha (IkB alpha), and the NFkB subunit p65. Upon combination therapy, expressions of M2 macrophage-related genes arginase-1 (Arg-1), IL-10, transforming growth factor-beta (TGF-beta), and matrix metalloproteinase-9 (MMP-9) were upregulated. Instead, M1 macrophage-related genes IL-6, IL-12a, IL-1 beta, and tumor necrosis factor-alpha (TNF-alpha) were downregulated. Conclusions: Quercetin/anti-PD-1 antibody combination therapy reshaped HCC tumor microenvironment in mice in parallel with regulating the GM and macrophage immunity.
期刊：
FRONTIERS IN IMMUNOLOGY,2023年14:1205445 ISSN：1664-3224
通讯作者：
Zhang, SF
作者机构：
[Ou, Qinling; Zhang, SF; Zhang, Sifang; Chang, Yonglong; Nie, Kechao] Cent South Univ, Xiangya Hosp 2, Dept Integrated Tradit Chinese & Western Med, Changsha, Peoples R China.;[Ou, Qinling; Zhang, SF; Zhang, Sifang] Natl Clin Res Ctr Metab Dis, Changsha, Peoples R China.;[Zhou, Xuhui] Hunan Inst Mental Hlth, Brain Hosp Hunan Prov, Peoples Hosp Hunan Prov 2, Dept Addict Med, Changsha, Peoples R China.;[Liu, Jinhui] Hunan Univ Tradit Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha, Hunan, Peoples R China.
通讯机构：
[Zhang, SF ] C;Cent South Univ, Xiangya Hosp 2, Dept Integrated Tradit Chinese & Western Med, Changsha, Peoples R China.;Natl Clin Res Ctr Metab Dis, Changsha, Peoples R China.
摘要：
Rheumatoid arthritis (RA) is an autoimmune disease that currently has an unknown cause and pathogenesis, and is associated with many complications and a high disability rate. The neutrophil extracellular trap network (NETs) is a newly discovered mechanism that allows neutrophils to capture and kill pathogens. Multiple studies in recent years have highlighted its relevance to the progression of rheumatoid arthritis. Despite the growing number of studies indicating the crucial role of NETs in RA, there has been no bibliometric review of research hotspots and trends in this area. In this study, we retrieved articles related to NETs in RA from the Web of Science Core Collection (WoSCC) database from 1985 to 2023 and used visualization tools such as Citespace, VOSviewer, Tableau Public, and Microsoft Office Excel 2021 to analyze the data. After screening, we included a total of 416 publications involving 2,334 researchers from 1,357 institutions in 167 countries/regions, with relevant articles published in 219 journals. The U.S., China, and Germany are the top 3 countries/regions with 124, 57, and 37 publications respectively. Mariana J. Kaplan is the most published author, and journals such as Frontiers in Immunology and International Journal of Molecular Sciences have had a significant impact on research in this field. The clinical application of PAD enzymes and their inhibitors, and the drug development of NETs as therapeutic targets for RA is a trend for future research. Our study provides a comprehensive bibliometric analysis and summary of NETs in RA publications, which will aid researchers in conducting further scientific research.
期刊：
Journal of Ethnopharmacology,2023年318(Pt A):116898 ISSN：0378-8741
通讯作者：
Feng, Zhitao;Ge, Jinwen;Mei, Zhigang
作者机构：
[Yang, Tong; Mei, Zhigang; Zhou, Yue] Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China;[Du, Lipeng; Liu, Xiaolu; Luo, Yanan] Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, College of Medicine and Health Sciences, China Three Gorges University, Yichang, 443002, Hubei, China;[Liu, Xiaolu] State Key Laboratory of Natural Medicines and School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009, Jiangsu, China;[Fu, Yang] Xiangyang Hospital of Traditional Chinese Medicine, Xiangyang, 441000, Hubei, China;[Zhang, Wenli] School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China
通讯机构：
[Mei, Zhigang; Feng, Zhitao] T;[Ge, Jinwen] K;Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, College of Medicine and Health Sciences, China Three Gorges University, Yichang, 443002, Hubei, China. Electronic address:;Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China. Electronic address:;Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, College of Medicine and Health Sciences, China Three Gorges University, Yichang, 443002, Hubei, China. Electronic address:
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: Cerebral ischemia-reperfusion injury (CIRI) is a complex pathophysiological process involving multiple factors, and becomes the footstone of rehabilitation after ischemic stroke. Sanpian decoction (SPD) has exhibited protective effects against CIRI, migraine, and other cerebral vascular diseases. However, the underlying mechanisms have not been completely elucidated. AIM OF THE STUDY: This study sought to explore the potential mechanisms underlying the effect of SPD against CIRI. MATERIALS AND METHODS: High-performance liquid chromatography (HPLC) and ultra-high-performance liquid chromatography (UPLC) were carried out to determine the chemical constituents of SPD. A network pharmacology approach combined with experimental verification was conducted to elucidate SPD's multi-component, multi-target, and multi-pathway mechanisms in CIRI occurrence. The pharmacodynamics of the decoction was evaluated by establishing the rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). In vivo and in vitro experiments were carried out, and the therapeutic effects of SPD were performed using 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining, and Nissl staining. We used terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and flow cytometry to evaluate cortex apoptosis. The quantification of mRNA and corresponding proteins were performed using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot respectively. RESULTS: Our research showed that pretreatment with SPD improved neurological function and inhibited CIRI. Network pharmacology revealed that the hypoxia-inducible factor-1 (HIF-1) signaling pathway and mitogen-activated protein kinase (MAPK) signaling pathway-mediated apoptosis may be associated with CIRI. In vivo and in vitro experiments, we confirmed that SPD increased cerebral blood flow, improved neural function, and reduced neural apoptosis via up-regulating the expression of sirtuin 1 (SIRT1) and down-regulating phospho-extracellular regulated protein kinases (p-ERK)/ERK and HIF-1α levels in CIRI rats. CONCLUSION: Taken together, the present study systematically revealed the potential targets and signaling pathways of SPD in the treatment of CIRI using in silico prediction and verified the therapeutic effects of SPD against CIRI via ameliorating apoptosis by regulating SIRT1/ERK/HIF-1α.
摘要：
Autoimmune diseases are affected by complex pathophysiology involving multiple cell types, cytokines, antibodies and mimicking factors. Different drugs are used to improve these autoimmune responses, including nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, antibodies, and small molecule drugs (DMARDs), which are prevalent clinically in the treatment of rheumatoid arthritis (RA), etc. However, low cost-effectiveness, reduced efficacy, adverse effects, and patient non-response are unattractive factors driving the development of new drugs such as iguratimod. As a new disease-modifying antirheumatic drug, iguratimod has pharmacological activities such as regulating autoimmune disorders, inflammatory cytokines, regulating immune cell activation, differentiation and proliferation, improving bone metabolism, and inhibiting fibrosis. In recent years, clinical studies have found that iguratimod is effective in the treatment of RA, SLE, IGG4-RD, Sjogren ‘s syndrome, ankylosing spondylitis, interstitial lung disease, and other autoimmune diseases and rheumatic diseases. The amount of basic and clinical research on other autoimmune diseases is also increasing. Therefore, this review systematically reviews the latest relevant literature in recent years, reviews the research results in recent years, and summarizes the research progress of iguratimod in the treatment of related diseases. This review highlights the role of iguratimod in the protection of autoimmune and rheumatic bone and related immune diseases. It is believed that iguratimod’s unique mode of action and its favorable patient response compared to other DMARDs make it a suitable antirheumatic and bone protective agent in the future.
期刊：
Cancer Cell International,2023年23(1):1-15 ISSN：1475-2867
通讯作者：
Sheng, W;Li, YQ
作者机构：
[Xu, Wenjing] Hunan Univ Chinese Med, Affiliated Hosp 1, Dept Dermatol, Changsha 410021, Peoples R China.;[Ding, Jin] Guangzhou Univ Chinese Med, Shenzhen Baoan Tradit Chinese Med Hosp, Dept Androl, Shenzhen 518133, Peoples R China.;[Li, Bonan; Sheng, W; Sheng, Wen; Kuang, Shida; Zhu, Congxu; Sun, Tiansong] Hunan Univ Chinese Med, Androl Lab, Changsha 410208, Peoples R China.;[Kuang, Shida] Hunan Univ Chinese Med, Sch Tradit Chinese Med, Changsha 410208, Peoples R China.;[Li, Bonan; Sheng, W; Sheng, Wen; Zhu, Congxu; Sun, Tiansong] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha 410208, Peoples R China.
通讯机构：
[Sheng, W ; Li, YQ ] H;Hunan Univ Chinese Med, Androl Lab, Changsha 410208, Peoples R China.;Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha 410208, Peoples R China.;Hunan Univ Chinese Med, Med Sch, Changsha 410208, Peoples R China.
摘要：
Docetaxel (DTX) resistance reduces therapeutic efficacy in prostate cancer (PCa). Accumulating reports support the role of phytochemicals in the reversal of DTX resistance. This study aimed to determine whether Epimedium brevicornu and Curcuma zedoaria extracts (ECe), specially icariin-curcumol, attenuates DTX resistance and explore their potential mechanisms. Regulatory pathways were predicted between ECe active ingredients and PCa using network pharmacology. DTX-resistant cell LNCaP/R were established based on DTX-sensitive LNCaP, and xenograft models were further established. Active ingredients in ECe by HLPC-MS were identified. The binding of icariin and curcumol to the target was analyzed by molecular docking. Biochemical experiments were applied to determine the possible mechanisms by which Icariin-Curcumol regulates DTX sensitivity. Akt1 and the PI3K-Akt signaling pathway were predicted as the primary functional target between drug and PCa. ECe and DTX inhibited xenograft tumor growth, inflammation, cell viability and promoted apoptosis. Icariin and curcumol were detected in ECe, and icariin and curcumol docked with Akt1. ECe, Icariin-Curcumol and DTX downregulated AR, PSA, PI3K, Akt1, mTOR, and HIF-1ɑ. Moreover, ECe, Icariin-Curcumol and DTX increased glucose and PDH, decreased lactic acid, ATP and LDH, and downregulated c-Myc, hnRNPs, VEGF, PFK1, and PKM2. Notably, the anti-PCa effect of DTX was attenuated compared to ECe or Icariin-Curcumol in the LNCaP/R model. The combined effect of Icariin-Curcumol and DTX was superior to that of DTX. Our data support that Icariin-Curcumol reverses DTX resistance by inhibiting the PI3K-Akt signaling and the Warburg effect, providing new ideas for improving therapeutic measures for PCa.
