作者机构：
[Xiong, Wu] Department of Burns and Plastic Surgery, the First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, China;[Zhang, Xi] Hunan Brain Hospital (Clinical Medical School of Hunan University of Chinese Medicine), Changsha, Hunan Province, China. Electronic address: cmxfyjzx2049@126.com;[Zhou, Jianda] Department of Plastic Surgery, the Third Xiangya Hospital, Central South University, Changsha, Hunan Province, China;[Chen, Jie] Department of Aesthetic Plastic Surgery, the First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, China;[Liu, Yu; Tan, Meixin; Wei, Yang; Huang, Hongyu; Si, Yuqi] College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan Province, China
通讯机构：
[Zhang, Xi] H;Hunan Brain Hospital (Clinical Medical School of Hunan University of Chinese Medicine), Changsha, Hunan Province, China. Electronic address:
摘要：
BACKGROUND AIMS: Treating chronic non-healing diabetic wounds and achieving complete skin regeneration has always been a critical clinical challenge. METHODS: In order to address this issue, researchers conducted a study aiming to investigate the role of miR-126-3p in regulating the downstream gene PIK3R2 and promoting diabetic wound repair in endothelial progenitor cell (EPC)-derived extracellular vesicles. The study involved culturing EPCs with astragaloside IV, transfecting them with miR-126-3p inhibitor or mock plasmid, interfering with high glucose-induced damage in human umbilical vein endothelial cells (HUVECs) and treating diabetic skin wounds in rats. RESULTS: The healing of rat skin wounds was observed through histological staining. The results revealed that treatment with miR-126-3p-overexpressing EPC-derived extracellular vesicles accelerated the healing of rat skin wounds and resulted in better tissue repair with slower scar formation. In addition, the transfer of EPC-derived extracellular vesicles with high expression of miR-126-3p to high glucose-damaged HUVECs increased their proliferation and invasion, reduced necrotic and apoptotic cell numbers and improved tube formation. In this process, the expression of angiogenic factors vascular endothelial growth factor (VEGF)A, VEGFB, VEGFC, basic fibroblast growth factor and Ang-1 significantly increased, whereas the expression of caspase-1, NRLP3, interleukin-1β, inteleukin-18, PIK3R2 and SPRED1 was suppressed. Furthermore, miR-126-3p was able to target and inhibit the expression of the PIK3R2 gene, thereby restoring the proliferation and migration ability of high glucose-damaged HUVEC. CONCLUSIONS: In summary, these research findings demonstrate the important role of miR-126-3p in regulating downstream genes and promoting diabetic wound repair, providing a new approach for treating chronic non-healing diabetic wounds.
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：
Frontiers in Immunology,2023年14:1209706 ISSN：1664-3224
通讯作者：
Wang, WJ;Kwak-Kim, J
作者机构：
[Chen, Zeyang] Qingdao Univ, Sch Med, Qingdao, Peoples R China.;[Chen, Zeyang; Wang, WJ; Wang, Wenjuan] Shanghai Jiao Tong Univ, Reprod Med Ctr, Xinhua Hosp, Sch Med, Shanghai, Peoples R China.;[Zhang, Yanan] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha, Peoples R China.;[Kwak-Kim, Joanne] Rosalind Franklin Univ Med & Sci, Chicago Med Sch, Clin Sci Dept, Reprod Med & Immunol,Obstet & Gynecol, Vernon Hills, IL 60064 USA.;[Kwak-Kim, Joanne] Rosalind Franklin Univ Med & Sci, Ctr Canc Cell Biol, Chicago Med Sch, Immunol & Infect, N Chicago, IL 60064 USA.
通讯机构：
[Kwak-Kim, J ] R;[Wang, WJ ] S;Shanghai Jiao Tong Univ, Reprod Med Ctr, Xinhua Hosp, Sch Med, Shanghai, Peoples R China.;Rosalind Franklin Univ Med & Sci, Chicago Med Sch, Clin Sci Dept, Reprod Med & Immunol,Obstet & Gynecol, Vernon Hills, IL 60064 USA.;Rosalind Franklin Univ Med & Sci, Ctr Canc Cell Biol, Chicago Med Sch, Immunol & Infect, N Chicago, IL 60064 USA.
关键词：
memory regulatory T cells;reproductive immunology;Pregnancy;Recurrent pregnancy loss;gestational diabetes mellitus;Preeclampsia
摘要：
Pregnancy requires the process of maternal immune tolerance to semi-allogeneic embryos. In contrast, an overreactive maternal immune system to embryo-specific antigens is likely to result in the rejection of embryos while damaging the invading placenta, such that the likelihood of adverse pregnancy outcomes can be increased. Regulatory T cells (Tregs) are capable of suppressing excessive immune responses and regulating immune homeostasis. When stimulating Tregs, specific antigens will differentiate into memory Tregs with long-term survival and rapid and powerful immune regulatory ability. Immunomodulatory effects mediated by memory Tregs at the maternal-fetal interface take on critical significance in a successful pregnancy. The impaired function of memory Tregs shows a correlation with various pregnancy complications (e.g., preeclampsia, gestational diabetes mellitus, and recurrent pregnancy losses). However, the differentiation process and characteristics of memory Tregs, especially their role in pregnancy, remain unclear. In this study, a review is presented in terms of memory Tregs differentiation and activation, the characteristics of memory Tregs and their role in pregnancy, and the correlation between memory Tregs and pregnancy complications. Furthermore, several potential therapeutic methods are investigated to restore the function of memory Tregs in accordance with immunopathologies arising from memory Tregs abnormalities and provide novel targets for diagnosing and treating pregnancy-associated diseases.
作者机构：
[Yu Yi-Pin; Sheng Dan; Zhong Li-Qin; Tan Duo-Ting] Hunan Univ Chinese Med, Grad Sch, Changsha 410208, Peoples R China.;[Liang, H; Hu Zhi-Xi; Liang Hao; Yang Liu] Hunan Univ Chinese Med, Inst TCM Diagnost, Changsha 410208, Peoples R China.;[Huang Ru-Jia] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha 410208, Peoples R China.
通讯机构：
[Liang, H ] H;Hunan Univ Chinese Med, Inst TCM Diagnost, Changsha 410208, Peoples R China.
作者机构：
[Chen L.; Deng C.; Yan H.] College of Integrated Traditional Chinese and Western Medicine, Medical School, Hunan University of Chinese Medicine, Changsha, 410208, China;[Ren R.] School of Mathematics, Southwest Jiaotong University, Chengdu, 611756, China
通讯机构：
[Deng, C.] C;College of Integrated Traditional Chinese and Western Medicine, China
作者机构：
[Da-Yuan Zhong; De-Liang Liu; Xue-Ming Ou; Ping-Wen Liu; Jia-Rong Li; Xiang-Bo Kong; Jia-Qi Chen] Department of Neurosurgery, Nanhai Hospital of Traditional Chinese and Western Medicine, Jinan University, Foshan 528200, China.;Institute of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China.;[Hong-Sheng Luo] Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.;[Yi-Hui Deng] College of Integrative Medicine, Hunan University of Chinese Medicine, Changsha 410208, China.;[Huan-Jie Li] Preventive Treating Disease Center, Foshan Hospital of Traditional Chinese Medicine, Foshan 528099, China.
通讯机构：
[De-Liang Liu] D;Department of Neurosurgery, Nanhai Hospital of Traditional Chinese and Western Medicine, Jinan University, Foshan 528200, China.
摘要：
Background: Traditional Chinese medicine (TCM) has been shown to be effective in treating ischemic stroke (IS), and the combination of Angelicae Sinensis Radix (ASR) and Astragali Radix (AR) is a core TCM prescription that is widely acknowledged for its efficacy in IS treatment. This study utilized network pharmacology methods to explore the molecular mechanisms underlying the therapeutic effects of Angelicae Sinensis Radix and Astragali Radix in IS treatment, with preliminary validation conducted through molecular docking. Methods: Information on the structure, targets, main biological functions, and pathways of the active components in Angelicae Sinensis Radix and Astragali Radix was collected using databases such as PubChem, PharmMapper, UniProt, and GeneCards. The results were visualized using software such as Cytoscape 3.6.1, Ledock, and pymol. Results: We retrieved 20 active components and 149 targets associated with the compatibility of Angelicae Sinensis Radix and Astragali Radix from various databases, and GeneCards database was used to search 3350 IS-related gene targets, including 78 key targets of Angelicae Sinensis Radix and Astragali Radix for the treatment of IS. Enrichment analysis of these 78 targets using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed the involvement of 48 GO terms in the treatment of IS, mainly in biological processes such as metabolism, biological regulation, and stress response. The composition of biological devices such as supercavitary membrane, cell fluid, and extracellular space was also involved. The biological functions mainly included protein binding, ion binding, hydrolytic enzyme activity, and others. The identified pathways were estrogen signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, PI3K-AKT signaling pathway, RAP1 signaling pathway, P53 signaling pathway, PPAR signaling pathway, FOXO signaling pathway, RAS signaling pathway, prolactin signaling pathway, HIF-1 signaling pathway, and TNF signaling pathway. Molecular docking analysis showed that the 17 key active components of Angelicae Sinensis Radix and Astragali Radix had strong binding activity with 13 IS key targets. Conclusion: Through the application of network pharmacology methods, it was found that the use of Angelicae Sinensis Radix and Astragali Radix for treating ischemic stroke mainly targets the MAPK and PI3K-AKT signaling pathways, involving several crucial compounds and genes. Nevertheless, additional in vitro and in vivo studies are needed to verify these findings.
作者：
Jin Ding;Wen Sheng;Wei Fu;Meixin Lin;Bonan Li;...
期刊：
中医科学杂志(英文),2023年10(4):484-492 ISSN：2095-7548
通讯作者：
Xing Zhou<&wdkj&>Qinghu He
作者机构：
School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 430000, China;Andrology Laboratory, Hunan University of Chinese Medicine, Changsha, 430000, China;[Wei Fu; Meixin Lin] Department of Andrology Clinic, Affiliated Bao'an Hospital of Traditional Chinese Medicine, The Seventh Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518133, China;Hunan University of Medicine, Huaihua, 418000, China;[Jin Ding] School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 430000, China<&wdkj&>Andrology Laboratory, Hunan University of Chinese Medicine, Changsha, 430000, China<&wdkj&>Department of Andrology Clinic, Affiliated Bao'an Hospital of Traditional Chinese Medicine, The Seventh Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518133, China
通讯机构：
[Xing Zhou; Qinghu He] S;School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 430000, China<&wdkj&>Andrology Laboratory, Hunan University of Chinese Medicine, Changsha, 430000, China<&wdkj&>School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 430000, China<&wdkj&>Andrology Laboratory, Hunan University of Chinese Medicine, Changsha, 430000, China<&wdkj&>Hunan University of Medicine, Huaihua, 418000, China
关键词：
Male infertility;Oxidative damage;Traditional Chinese medicine;Guilu Erxian glue;Autophagy;Keap1/Nrf2 pathway
摘要：
To explore the effects and underlying mechanisms of Guilu Erxian glue (GLEXG) on oxidative damage in a mouse GC-1 spermatogonial (MGS) cell model.
A cellular model for oxidative damage was created using MGS cells exposed to hydrogen peroxide (H2O2). Cell viability was assessed using the cell counting kit-8 assay, while reactive oxygen species (ROS) and malondialdehyde (MDA) levels were measured via flow cytometry and enzyme-linked immunosorbent assay, respectively. Western blotting and immunofluorescence techniques were employed to quantify the relative expression levels of sequestosome-1 (p62), nuclear factor erythroid 2-related factor 2 (Nrf2), microtubule-associated protein light chain 3β (LC3B), and Kelch-like ECH-associated protein 1 (Keap1). Quantitative real-time PCR was used to evaluate Keap1 mRNA expression. Transmission electron microscopy (TEM) was conducted to observe structural changes in autophagy-related vesicles.
The cellular model of oxidative damage induced by H2O2 showed reduced cell viability along with elevated levels of ROS and MDA. Treatment with 10% GLEXG-enriched serum significantly enhanced cell viability (P = .0002) while decreasing ROS and MDA levels (P = .0105 and P = .0033, respectively). In rapamycin-treated MGS cells, GLEXG treatment substantially upregulated the relative protein expression of p-mTOR, Nrf2, and p62 (all P < .01), and downregulated the expression of Keap1 and the LC3B-II/LC3B-I ratio (P = .002 and P = .0043, respectively). It also lowered ROS and MDA levels. TEM analysis revealed that GLEXG treatment considerably reduced the number of abnormally enlarged autolysosomes in rapamycin-treated MGS cells. In Keap1-siRNA-transfected MGS cells, the siRNA-Keap1-2311 knockdown site demonstrated higher efficiency. Furthermore, GLEXG treatment in these Keap1-siRNA-transfected cells notably upregulated the relative protein expression of Nrf2 and p62, decreased Keap1 expression and the LC3B-II/LC3B-I ratio, and reduced ROS and MDA levels.
GLEXG effectively mitigated oxidative damage in the MGS cell model by inhibiting autophagy through the Keap1/Nrf2 pathway.
摘要：
To investigate the role of miR-140/BCL2L2 axis on the formation of intracranial aneurysms. The expression of miR-140 in the serum of patients with intracranial aneurysms and healthy volunteers was detected. CCK-8 assay and Annexin V-FITC/PI double staining flow cytometry were used to evaluate the effect of miR-140 knockdown on the proliferation and apoptosis of human brain vascular smooth muscle cells (HBVSMCs). Meanwhile, the relationship between miR-140 and BCL2L2 was examined. MiR-140 was found to be upregulation in intracranial aneurysm patients. MiR-140 knock-out significantly inhibited the apoptosis of HBVSMCs and promoted cell proliferation. BCL2L2 was a direct target gene of miR-140 and suppressed its expression. Knockdown of miR-140 alleviates the development of intracranial aneurysms. MiR-140/BCL2L2 axis promotes the progression of intracranial aneurysms by regulating apoptosis of HBVSMCs. Therefore, miR-140 is a potential therapeutic target for intracranial aneurysms.
作者机构：
[He, Chunxiang; Li, Ze; Song, Zhenyan; Cheng, Shaowu; Song, ZY; Cheng, SW; Yang, Miao; Yu, Wenjing; Deng, Sisi] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.;[He, Chunxiang; Li, Ze; Song, Zhenyan; Cheng, Shaowu; Song, ZY; Zhong, Dayuan; Yu, Jingping; Cheng, SW; Yang, Miao; Yu, Wenjing; Deng, Sisi] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha 410208, Hunan, Peoples R China.;[Yu, Jingping] Baoshan Coll Tradit Chinese Med, Baoshan 678000, Yunnan, Peoples R China.;[Zhong, Dayuan] Guangdong Prov Hosp Integrated Tradit Chinese & We, Foshan 528000, Guangdong, Peoples R China.
通讯机构：
[Song, ZY; Cheng, SW ] H;Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.;Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha 410208, Hunan, Peoples R China.
关键词：
Alzheimer’s disease;RAGE;TLR4/NF-κB signaling pathway;neuroinflammation;traditional Chinese medicine
摘要：
The purpose of this study is to investigate the therapeutic effect of Qi Fu Yin (QFY) on Alzheimer's disease (AD) both computationally and experimentally. Network pharmacology analysis and molecular docking were conducted to identify potential targets and signaling pathways involved in QFY treating AD. Streptozotocin-induced AD rat model was used to verify important targets and predicted pathways. The components of QFY were identified using liquid chromatography-tandem mass spectrometry. The results indicate that the potential targets of QFY are highly enriched for anti-inflammatory pathways. Molecular docking analysis revealed stable structures formed between QFY's active compounds, including stigmasterol, β-sitosterol, and isorhamnetin, and the identified targets. In vivo, QFY improved cognitive memory in AD rats and reduced the mRNA expression levels of toll-like receptor 4 (TLR4), the receptor for advanced glycation end products (AGER), and the inflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the brains of AD rats. Furthermore, QFY effectively reduced nuclear translocation of nuclear factor-kappa B (NF-κB) and inhibited NF-κB and microglia activation. In conclusion, QFY can ameliorate neuroinflammation in AD model rats, partly via the inhibition of TLR4 and RAGE/NF-κB pathway and microglia activation, thereby enhancing learning and memory in AD model rats.
