期刊：
Journal of Clinical Gastroenterology,2023年57(8):782-788 ISSN：0192-0790
通讯作者：
Tian, XF
作者机构：
[Huang, Caizhi; Tian, Xuefei; Tian, XF] Hunan Univ Chinese Med, Coll Integrated Chinese & Western Med, Dept Internal Med, Changsha, Peoples R China.;[Huang, Caizhi] Hunan Childrens Hosp, Dept Lab Med, Changsha, Peoples R China.;[Mei, Si] Hunan Univ Chinese Med, Dept Physiol, Changsha, Peoples R China.;[Zhang, Xue] Hunan Univ Chinese Med, Key Lab Tradit Chinese Med Mech Tumor Prevent & Tr, Changsha, Peoples R China.;[Tian, Xuefei; Tian, XF] Hunan Univ Chinese Med, Hunan Prov Univ, Key Lab Oncol Tradit Chinese Med, Changsha, Hunan, Peoples R China.
通讯机构：
[Tian, XF ] H;Hunan Univ Chinese Med, Coll Integrated Chinese & Western Med, Dept Internal Med, Changsha, Peoples R China.;Hunan Univ Chinese Med, Hunan Prov Univ, Key Lab Oncol Tradit Chinese Med, Changsha, Hunan, Peoples R China.
关键词：
gut microbiota, hepatocellular carcinoma, inflammation, dysbiosis
摘要：
Hepatocellular carcinoma (HCC) is an invasive primary liver cancer caused by multiple pathogenic factors and is a significant global health concern. With few effective therapeutic options, HCC is a heterogeneous carcinoma that typically arises in an inflammatory environment. Recent studies have suggested that dysbiotic gut microbiota is involved in hepatocarcinogenesis via multiple mechanisms. In this review, we discuss the effects of gut microbiota, microbial components, and microbiota-derived metabolites on the promotion and progression of HCC by feeding a persistent inflammatory milieu. In addition, we discuss the potential therapeutic modalities for HCC targeting the inflammatory status induced by gut microbiota. A better understanding of the correlation between the inflammatory milieu and gut microbiota in HCC may be beneficial for developing new therapeutic strategies and managing the disease.
摘要：
Evidence is mounting that abnormal vascular remodeling leads to many cardiovascular diseases (CVDs). This suggests that vascular remodeling can be a crucial target for the prevention and treatment of CVDs. Recently, celastrol, an active ingredient of the broadly used Chinese herb Tripterygium wilfordii Hook F, has attracted extensive interest for its proven potential to improve vascular remodeling. Substantial evidence has shown that celastrol improves vascular remodeling by ameliorating inflammation, hyperproliferation, and migration of vascular smooth muscle cells, vascular calcification, endothelial dysfunction, extracellular matrix remodeling, and angiogenesis. Moreover, numerous reports have proven the positive effects of celastrol and its therapeutic promise in treating vascular remodeling diseases such as hypertension, atherosclerosis, and pulmonary artery hypertension. The present review summarizes and discusses the molecular mechanism of celastrol regulating vascular remodeling and provides preclinical proof for future clinical applications of celastrol.
关键词：
Endotoxin-induced uveitis;traditional Chinese medicine;network pharmacology;Astragalus membranaceus;total flavonoids of Astragalus
摘要：
Objectives This study is aimed at identifying critical therapeutic targets of Astragalus membranaceus (Huangqi (HQ)) and investigating the effects and mechanisms of HQ treating uveitis. The potential drug targets of HQ and main active ingredients were obtained from the traditional Chinese medicine (TCM) systems pharmacology database and analysis platform (TCMSP, http://tcmspnw.com). Materials and Methods Cytoscape software was used to identify the disease targets of uveitis. Drug targets and disease targets were compared, and intersected hubs were applied for the active ingredient-target network and protein-protein-interaction (PPI) network construction. Signaling pathway enrichment annotation was performed to identify possible signaling involved in uveitis treatment. An endotoxin-induced uveitis (EIU) model was established, and the therapeutic effects of total flavonoids of Astragalus (TFA) on uveitis were investigated by examining the improvement of eye symptoms, histopathological alterations, and the levels of cytokines. Results Based on network pharmacological analysis, HQ could modulate the initiation and progression of uveitis by reducing the production of cytokines and regulating cell apoptosis via the NOD-like receptor (NLR), apoptosis, and toll-like receptor (TLR) signaling pathways. Based on animal experiments, high-dose TFA could reduce rat's iris congestion, reduce anterior chamber exudation and pus, restore pupil size, and decrease the release of inflammatory factors IFN-gamma and IL-10. Network pharmacological and experimental analyses revealed that TFA regulates the release of inflammatory factors through the NLR and TLR signaling pathways, thus regulating the immune system of EIU rats and ultimately relieving inflammation responses in uveitis rats.
摘要：
We describe a graphene oxide (GO)-based bioassay for the fluorometric determination of norA gene transcription (mRNA) in methicillin-resistant Staphylococcus aureus (MRSA). This approach is based on Nb.BbvCI-assisted target recycling (NATR) and T7 exonuclease (T7 Exo)-triggered cascade dual-recycling signal amplification (TTCDRSA). The system included GO, a capture probe (CP), an assistant probe (AP), two carboxyfluorescein (FAM)-labeled hairpins (HP1 and HP2), endonuclease Nb.BbvcI, and exonuclease T7. In the presence of a target, AP, together with the target RNA, can hybridise with CP via partial complementarity to one another and open its hairpin structure to form a triple complex that is recognised by Nb.BbvCI. Once the CP is cleaved, the released AP and target RNA can walk on the carboxylated graphene oxide (CGO) surface to bind with another CP which induces the next round of cleavage, accumulating many trigger probes (TPs). The TPs then activate TTCDRSA with the assistance of T7 Exo, HP1, and HP2 to produce large amounts of free FAMs. These free FAMs are repelled by GO and exhibit enhanced fluorescence signals at excitation/emission wavelengths of 480/514 nm. The limit of detection (LOD) of the bioassay was calculated to be 0.37 fM, and the linear range of the method ranged from 1 fM to 1 nM. More importantly, the bioassay also exhibited high sensitivity and selectivity for target RNA detection in real samples, which may open a new promising avenue for monitoring drug efflux and studying the mechanisms of drug actions.
作者机构：
[Zhang, Hongning; Zhang, Jian; Chen, Wen; Hu, Xiang; Yuan, Changyue; Hu, X; Huang, Shulan; Su, Na] Hunan Normal Univ, Coll Life Sci, State Key Lab Dev Biol Freshwater Fish, Changsha 410081, Peoples R China.;[Chen, Wen] Hunan Univ Chinese Med, Med Sch, Key Lab Vasc Biol & Translat Med, Changsha 410208, Peoples R China.;[Xiang, Shuanglin; Su, Na] Hunan Normal Univ, Coll Life Sci, Engn Res Ctr Antibodies Expt Anim Hunan Prov, Changsha 410081, Peoples R China.
通讯机构：
[Xiang, SL ; Hu, X ] H;Hunan Normal Univ, Coll Life Sci, State Key Lab Dev Biol Freshwater Fish, Changsha 410081, Peoples R China.;Hunan Normal Univ, Coll Life Sci, Engn Res Ctr Antibodies Expt Anim Hunan Prov, Changsha 410081, Peoples R China.
摘要：
TNF α-induced protein 1 (TNFAIP1) was first identified in human umbilical vein endothelial cells and can be induced by tumor necrosis factor α (TNFα). Early studies have found that TNFAIP1 is involved in the development of many tumors and is closely associated with the neurological disorder Alzheimer’s disease. However, little is known about the expression pattern of TNFAIP1 under physiological conditions and its function during embryonic development. In this study, we used zebrafish as a model to illustrate the early developmental expression pattern of tnfaip1 and its role in early development. First, we examined the expression pattern of tnfaip1 during early zebrafish development using quantitative real-time PCR and whole mount in situ hybridization and found that tnfaip1 was highly expressed in early embryonic development and, subsequently, expression became localized to anterior embryonic structures. To investigate the function of tnfaip1 during early development, we constructed a model of a stably inherited tnfaip1 mutant using the CRISPR/Cas9 system. Tnfaip1 mutant embryos showed significant developmental delays as well as microcephaly and microphthalmia. At the same time, we found decreased expression of the neuronal marker genes tuba1b, neurod1, and ccnd1 in tnfaip1 mutants. Analysis of transcriptome sequencing data revealed altered expression of the embryonic development related genes dhx40, hspa13, tnfrsf19, nppa, lrp2b, hspb9, clul1, zbtb47a, cryba1a, and adgrg4a in the tnfaip1 mutants. These findings suggest an important role for tnfaip1 in the early development of zebrafish.
摘要：
Objectives: The nuclear factor-kappa B (NF-kappa B) signaling pathway plays an important role in regulating tubular epithelial-mesenchymal transition (EMT), an indispensable cellular programme for driving organ fibrosis and tumor progression. Liuwei Dihuang Decoction (LWD) is an effective Chinese formula for treating chronic renal failure. Methods: First, by using morphological examination, immunofluorescence staining assay, RT-qPCR, and Western blot analysis, in vitro experiments were designed to analyze NF-kappa B and EMT markers (including Snail, alpha-SMA, and E-cadherin) in transforming growth factor-beta 1 (TGF-beta 1) induced renal tubular epithelial cells (HK-2) and to detect the expression levels of LWD-CS co-treatment. Then, the recombinant lentiviral vector was overexpressed and knocked down by NF kappa B and transfected into HK-2 cells. Cells were treated with TGF-beta 1 (10 ng/ml) with blank serum or LWD-containing serum, respectively, and the expression of these molecules in the NF-kappa B/Snail signaling pathway was further evaluated. Results: Our results confirmed that TGF-beta 1 could induce EMT, nuclear translocation of NF-kappa B p65, and activate the NF-kappa B/Snail signaling pathway in HK-2 cells. Furthermore, NF-kappa B knocked-down dramatically increases the TGF-beta 1-induced mRNA and protein expression level of E-cadherin and reduces the level of Snail and alpha-SMA; this is reversed by NF-kappa B overexpression. LWD can decrease the EMT levels through the NF-kappa B/Snail signaling activation in TGF-beta 1-induced EMT of HK-2 cells. Conclusion: The present study provides evidence suggesting a novel mechanism that LWD exerts anti-fibrosis effects through inhibiting activation of the NF-kappa B/Snail signaling pathway and consequently downregulating the TGF-beta 1-induced EMT in renal tubular epithelial cells.
作者机构：
[Huang, Jiawang; Ma, Xinyue; Li, Ling; Liao, Zexuan; Liu, Zhuolin] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha 410208, Peoples R China.;[Feng, Zhiying; Wang, Kangyu] Hunan Univ Chinese Med, Coll Tradit Chinese Med, Changsha 410208, Peoples R China.;[Ning, Yi; Lu, Fangguo] Hunan Univ Chinese Med, Med Sch, Changsha 410208, Peoples R China.;[Li, Ling; Liu, Zhuolin] Hunan Univ Chinese Med, Hunan Prov Key Lab Integrated Tradit Chinese & Wes, Changsha 410208, Peoples R China.
通讯机构：
[Li, L ] H;Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha 410208, Peoples R China.;Hunan Univ Chinese Med, Hunan Prov Key Lab Integrated Tradit Chinese & Wes, Changsha 410208, Peoples R China.
摘要：
Influenza is an acute viral respiratory infection that has caused high morbidity and mortality worldwide. Influenza A virus (IAV) has been found to activate multiple programmed cell death pathways, including ferroptosis. Ferroptosis is a novel form of programmed cell death in which the accumulation of intracellular iron promotes lipid peroxidation, leading to cell death. However, little is known about how influenza viruses induce ferroptosis in the host cells. In this study, based on network pharmacology, we predicted the mechanism of action of Maxing Shigan decoction (MXSGD) in IAV-induced ferroptosis, and found that this process was related to biological processes, cellular components, molecular function and multiple signaling pathways, where the hypoxia inducible factor-1(HIF-1) signaling pathway plays a significant role. Subsequently, we constructed the mouse lung epithelial (MLE-12) cell model by IAV-infected in vitro cell experiments, and revealed that IAV infection induced cellular ferroptosis that was characterized by mitochondrial damage, increased reactive oxygen species (ROS) release, increased total iron and iron ion contents, decreased expression of ferroptosis marker gene recombinant glutathione peroxidase 4 (GPX4), increased expression of acyl-CoA synthetase long chain family member 4 (ACSL4), and enhanced activation of hypoxia inducible factor-1 alpha (HIF-1 alpha), induced nitric oxide synthase (iNOS) and vascular endothelial growth factor (VEGF) in the HIF-1 signaling pathway. Treatment with MXSGD effectively reduced intracellular viral load, while reducing ROS, total iron and ferrous ion contents, repairing mitochondrial results and inhibiting the expression of cellular ferroptosis and the HIF-1 signaling pathway. Finally, based on animal experiments, it was found that MXSGD effectively alleviated pulmonary congestion, edema and inflammation in IAV-infected mice, and inhibited the expression of ferroptosis-related protein and the HIF-1 signaling pathway in lung tissues.
摘要：
Hepatocellular carcinoma (HCC) has high morbidity and mortality, and effective therapies are lacking. Gallic acid (GA), a natural phenolic compound derived from plants, has been reported to prevent the onset and progression of various cancers. However, there is limited elaboration on the potential mechanisms and anticancer effects of GA on hepatocellular carcinoma. Inducing ferroptosis of tumor cells has become one of the most promising ways to eradicate tumor cells. However, the effect of GA on HCC ferroptosis remains unknown. We evaluated the impact of GA on cell viability, migration, and mitochondrial morphology in HepG2 cells. Our study identified a critical role of GA in inducing ferroptosis in HepG2 cells. Mechanistically, we found that GA could inhibit the expression of a ferroptosis-related protein SLC7A11 and GPX4 in HepG2, by blocking β-catenin transport from nuclear to the cytoplasm, thus inducing the inactivation of the Wnt/β-catenin pathway. Our study has confirmed that GA is a novel ferroptosis inducer of HC, suggesting GA could be a promising candidate for the clinical treatment of HCC.
期刊：
Journal of Pharmacy and Pharmacology,2023年75(5):666-676 ISSN：0022-3573
通讯作者：
Biao Tang
作者机构：
[Wang, Linlin; Xiao, Lan; Kang, Zhineng; Xiao, Qian; Tang, Biao] Hunan Univ Chinese Med, Basic Res Ctr Integrated Chinese & Western Med Pre, Changsha, Peoples R China.;[Tang, Biao] Hunan Univ Chinese Med, Med Sch, Xiangzui Rd, Changsha, Hunan, Peoples R China.
通讯机构：
[Biao Tang] B;Basic Research Center of Integrated Chinese & Western Medicine for Prevention & Treatment of Vascular Diseases, Hunan University of Chinese Medicine , Changsha , China
摘要：
OBJECTIVES: This study aimed to observe the effect of the combination of astragaloside IV (AST IV) and Panax notoginseng saponins (PNS) on cerebral ischaemia-reperfusion injury (CIRI) and explore the specific mechanism of the nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated combination of AST IV and PNS against CIRI based on ferroptosis and inflammatory response. METHODS: The therapeutic effect and mechanism of AST IV and PNS were evaluated by constructing a Sprague-Dawley rat middle cerebral artery ischaemia-occlusion-reperfusion model. The specific mechanism of the combination of AST IV and PNS against CIRI was revealed through the combined intervention of the Nrf2-specific inhibitor brusatol. KEY FINDINGS: After AST IV and PNS treatment, the cerebral infarction area of the rats was reduced; behavioural performance was improved; Fe2+, malondialdehyde, lipid peroxidation, interleukin-6, interleukin-1β, tumour necrosis factor-α and myeloperoxidase levels were reduced; and glutathione and glutathione peroxidase 4 levels were increased. In addition, the expression of Nrf2 was significantly increased, the combined treatment was more effective than the single treatment, and the Nrf2 inhibitor brusatol could reverse the effects of the combined intervention of AST IV and PNS. CONCLUSIONS: The findings of this study suggest that combining AST IV and PNS attenuates CIRI by activating Nrf2 to inhibit ferroptosis and inflammatory responses.
期刊：
Frontiers in Cardiovascular Medicine,2023年10 ISSN：2297-055X
通讯作者：
Zhong, Yancheng;Tuo, Q
作者机构：
[Zhong, Yancheng; Tuo, Qinhui; Chen, Wen; Zhong, YC; Hu, Bo] Hunan Univ Chinese Med, Med Sch, Hunan Key Lab Vasc Biol & Translat Med, Changsha, Peoples R China.
通讯机构：
[Tuo, Q ; Zhong, YC] H;Hunan Univ Chinese Med, Med Sch, Hunan Key Lab Vasc Biol & Translat Med, Changsha, Peoples R China.
关键词：
Cardiovascular disease (CVD);LncRNA - long noncoding RNA;gasdermins (GSDMs);pyroptosis;Inflammatory
摘要：
Cardiovascular disease (CVD) is the leading cause of death worldwide. Pyroptosis is a unique kind of programmed cell death that varies from apoptosis and necrosis morphologically, mechanistically, and pathophysiologically. Long non-coding RNAs (LncRNAs) are thought to be promising biomarkers and therapeutic targets for the diagnosis and treatment of a variety of diseases, including cardiovascular disease. Recent research has demonstrated that lncRNA-mediated pyroptosis has significance in CVD and that pyroptosis-related lncRNAs may be potential targets for the prevention and treatment of specific CVDs such as diabetic cardiomyopathy (DCM), atherosclerosis (AS), and myocardial infarction (MI). In this paper, we collected previous research on lncRNA-mediated pyroptosis and investigated its pathophysiological significance in several cardiovascular illnesses. Interestingly, certain cardiovascular disease models and therapeutic medications are also under the control of lncRNa-mediated pyroptosis regulation, which may aid in the identification of new diagnostic and therapy targets. The discovery of pyroptosis-related lncRNAs is critical for understanding the etiology of CVD and may lead to novel targets and strategies for prevention and therapy.
