摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: Anxiety disorders leads to a decline in quality of life and increased risk of morbidity and mortality. The Baihe Dihuang decoction (BDD) is a classic Chinese medical formula that has been widely used to treat anxiety disorders for thousands of years in China. However, the pharmacodynamic material that is responsible for the antianxiety of BDD remains unclear. AIM OF THE STUDY: To screen the main ingredients of anti-anxiety in BDD based on the establishment of spectrum-effect relationship and verified experiment. METHODS: The UPLC-Q-TOF/MS technique was utilized to establish fingerprints of various fractions of BDD and identify the main compounds. The anti-anxiety effects of BDD were comprehensively evaluated through multiple assessments, including the open field test, elevated plus maze test, and neurotransmitters tests. Then, the spectrum-effect relationship was established through Pearson correlation analysis, gray correlation analysis, orthogonal partial least squares regression analysis. The spectrum-effect relationship results were confirmed through various measures on an anxiety condition cell model, induced by a corticosterone and lipopolysaccharide intervention. These measures included assessing neuronal cell viability, morphology, apoptosis, synaptic damage, and the expression of neurotransmitters and inflammatory factors. RESULTS: In the UPLC-Q-TOF-MS fingerprint, 46 common peaks were identified. The pharmacological results indicated that different fractions of BDD have strong effects on improving anxiety-like behavior and regulating neurotransmitters. Among them, butanol fraction has the highest comprehensive evaluation score of anti-anxiety efficacy, which is main active fraction of BDD for anti-anxiety. The analysis of the spectrum-effect relationship revealed that the 46 peaks exhibited varying degrees of correlation with the anti-anxiety efficacy indicators of BDD. Among them, 14 components have a high correlation with the anti-anxiety efficacy indicators, which may be the potential anti-anxiety efficacy components of BDD. The in vitro activity verification of active components verified our prediction, regaloside A, B, C, D, H, acteoside, and isoacteoside improved neuronal cell viability, cell morphology, apoptosis, and synaptic damage. Additionally, regaloside A, B, C, D, H and acteoside regulated the neurotransmitter levels, while regaloside A, B, C, D, acteoside and isoacteoside inhibited the levels of inflammatory cytokines. CONCLUSION: The butanol fraction was found to be the main active fraction of BDD, and 14 compounds were the major anxiolytic active components. The results of verifying the major active components were consistent with the predicted results of the spectrum-effect analysis. The developed spectrum-effect analysis in this study demonstrates high accuracy and reliability for screening active components in TCMs.
摘要：
The aim of this article is to introduce the roles and mechanisms of the JAK2/STAT3 pathway in various cardiovascular diseases, such as myocardial fibrosis, cardiac hypertrophy, atherosclerosis, myocardial infarction, and myocardial ischemiareperfusion. In addition, the effects of phytochemical ingredients and different natural plants, mainly traditional Chinese medicines, on the regulation of different cardiovascular diseases via the JAK2/STAT3 pathway are discussed. Surprisingly, the JAK2 pathway has dual roles in different cardiovascular diseases. Future research should focus on the dual regulatory effects of different phytochemical ingredients and natural plants on JAK2 to pave the way for their use in clinical trials.
期刊：
Journal of Drug Targeting,2024年32(1):1-20 ISSN：1061-186X
通讯作者：
Zhang, Liang;Ai, K
作者机构：
[Qu, Qirui; Zhang, Liang; Zhao, Lingyun; Wu, Qingze; Ai, Kun; Qi, Fang; Ai, K; Zhang, L] Hunan Univ Chinese Med, Coll Acupuncture & Tuina & Rehabil, Changsha 410208, Peoples R China.;[Long, Yiying] Hunan Tradit Chinese Med Coll, Zhuzhou, Peoples R China.;[Liu, Li] Hunan Univ Chinese Med, Affiliated Hosp 1, Changsha, Peoples R China.
通讯机构：
[Ai, K ; Zhang, L] H;Hunan Univ Chinese Med, Coll Acupuncture & Tuina & Rehabil, Changsha 410208, Peoples R China.
关键词：
Rheumatoid arthritis;angiogenesis;miR based therapeutics;microRNAs;therapeutic target
摘要：
Vascular neogenesis, an early event in the development of rheumatoid arthritis (RA) inflammation, is critical for the formation of synovial vascular networks and plays a key role in the progression and persistence of chronic RA inflammation. microRNAs (miRNAs), a class of single-stranded, non-coding RNAs with approximately 21-23 nucleotides in length, regulate gene expression by binding to the 3' untranslated region (3'-UTR) of specific mRNAs. Increasing evidence suggests that miRNAs are differently expressed in diseases associated with vascular neogenesis and play a crucial role in disease-related vascular neogenesis. However, current studies are not sufficient and further experimental studies are needed to validate and establish the relationship between miRNAs and diseases associated with vascular neogenesis, and to determine the specific role of miRNAs in vascular development pathways. To better treat vascular neogenesis in diseases such as RA, we need additional studies on the role of miRNAs and their target genes in vascular development, and to provide more strategic references. In addition, future studies can use modern biotechnological methods such as proteomics and transcriptomics to investigate the expression and regulatory mechanisms of miRNAs, providing a more comprehensive and in-depth research basis for the treatment of related diseases such as RA.
期刊：
BMC Complementary Medicine and Therapies,2024年24(1):1-12 ISSN：2662-7671
通讯作者：
Liqing Li<&wdkj&>Bin Liu<&wdkj&>Xiong Cai
作者机构：
[Zhaoli Su; Junping Zhu; Ye Lin; Yuanyuan Tang; Jiaming Wei] Department of Rheumatology, First Hospital, School of Chinese Medical Sciences, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China;[Yuanyuan Tang] College of Biology, Hunan University, Changsha, Hunan, 410082, China;[Zhaoli Su] The Central Research Laboratory, Hunan Traditional Chinese Medical College, Zhuzhou, China;[Zhaoli Su] Guangxi Provincial Key Laboratory of Preventive and Therapeutic Research in Prevalent Diseases in West Guangxi, Youjiang Medical University for Nationalities, Baise, Guangxi, 533000, China;[Liqing Li] The Central Research Laboratory, Hunan Traditional Chinese Medical College, Zhuzhou, China. liliqing87@qq.com
通讯机构：
[Liqing Li] T;[Bin Liu] C;[Xiong Cai] D;The Central Research Laboratory, Hunan Traditional Chinese Medical College, Zhuzhou, China<&wdkj&>Guangxi Provincial Key Laboratory of Preventive and Therapeutic Research in Prevalent Diseases in West Guangxi, Youjiang Medical University for Nationalities, Baise, China<&wdkj&>College of Biology, Hunan University, Changsha, China<&wdkj&>Department of Rheumatology, First Hospital, School of Chinese Medical Sciences, Hunan University of Chinese Medicine, Changsha, China
摘要：
BACKGROUND: Rheumatoid arthritis (RA) is a prevalent autoimmune disease marked by chronic synovitis as well as cartilage and bone destruction. Halofuginone hydrobromide (HF), a bioactive compound derived from the Chinese herbal plant Dichroa febrifuga Lour., has demonstrated substantial anti-arthritic effects in RA. Nevertheless, the molecular mechanisms responsible for the anti-RA effects of HF remain unclear. METHODS: This study employed a combination of network pharmacology, molecular docking, and experimental validation to investigate potential targets of HF in RA. RESULTS: Network pharmacology analyses identified 109 differentially expressed genes (DEGs) resulting from HF treatment in RA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses unveiled a robust association between these DEGs and the IL-17 signaling pathway. Subsequently, a protein-protein interaction (PPI) network analysis revealed 10 core DEGs, that is, EGFR, MMP9, TLR4, ESR1, MMP2, PPARG, MAPK1, JAK2, STAT1, and MAPK8. Among them, MMP9 displayed the greatest binding energy for HF. In an in vitro assay, HF significantly inhibited the activity of inflammatory macrophages, and regulated the IL-17 signaling pathway by decreasing the levels of IL-17C, p-NF-κB, and MMP9. CONCLUSION: In summary, these findings suggest that HF has the potential to inhibit the activation of inflammatory macrophages through its regulation of the IL-17 signaling pathway, underscoring its potential in the suppression of immune-mediated inflammation in RA.
摘要：
A549 cells were treated with different concentrations of anlotinib to create anlotinib‐resistant A549 cells (A549/anlotinib cells). miR‐181a‐3p mimics were transfected into A549/anlotinib cells. Meanwhile, A549 and A549/anlotinib cells were treated with β‐sitosterol at different concentrations. Cell Counting Kit‐8 (CCK‐8) was used to measure cell proliferation. The apoptosis level was detected by flow cytometry. Real‐time fluorescence quantitative PCR was used to detect the expression of miR‐181a‐3p. miR‐181a‐3p interaction with H/ACA ribonucleoprotein assembly factor (SHQ1) was predicted by miRDB and TargetScan Human databases and verified by luciferase reporter assay. The expressions of SHQ1, activating transcription factor 6 (ATF6) and glucose regulated protein 78 (GRP78) were detected by western blot. Our results show that β‐Sitosterol markedly promoted anlotinib‐resistant A549 cells apoptosis and inhibited the cell proliferation via activating SHQ1/UPR signaling via inhibiting miR‐181a‐3p. Abstract Anlotinib is used for the treatment of advanced non‐small cell lung cancer; however, the emergence of drug resistance limits its clinical application. β‐sitosterol may also be used to treat lung cancer, but there have been no studies evaluating β‐sitosterol against anlotinib‐resistant lung cancer. The purpose of this study was to determine the mechanism by which β‐sitosterol enhances the sensitivity of lung cancer cells to anlotinib. A549 cells were treated with different concentrations of anlotinib to generate anlotinib‐resistant cells (A549/anlotinib cells). miR‐181a‐3p mimics were transfected into A549/anlotinib cells. A549 and A549/anlotinib cells were treated with β‐sitosterol at various concentrations. The Cell Counting Kit‐8 (CCK‐8) assay was used to measure cell proliferation. Apoptosis was assessed by flow cytometry. Real‐time quantitative PCR was used to measure the expression of miR‐181a‐3p. The interaction of miR‐181a‐3p with the H/ACA ribonucleoprotein assembly factor (SHQ1) was predicted using the miRDB and TargetScan Human databases and verified with a luciferase reporter assay. The expression of SHQ1, activating transcription factor 6 (ATF6), and glucose‐regulated protein 78 (GRP78) were measured by western blot analysis. β‐Sitosterol effectively suppressed A549/anlotinib cell proliferation and promoted apoptosis. SHQ1 is a downstream target of miR‐181a‐3p. The expression of miR‐181a‐3p was inhibited; however, SHQ1 expression was increased by β‐sitosterol treatment of A549/anlotinib cells. The inhibition of SHQ1, ATF6, and GRP78 protein expression by β‐sitosterol in A549/anlotinib cells was rescued by increased miR‐181a‐3p. β‐Sitosterol markedly promotes anlotinib‐resistant A549 cell apoptosis and inhibits cell proliferation by activating SHQ1/UPR signaling through miR‐181a‐3p inhibition.
摘要：
AIMS: Saikosaponin F (SsF) is one of the major active ingredients of Radix Bupleuri, an herb widely used in the treatment of depression. Studies have shown that dry eye disease often occurs together with depression. The aim of this study is to investigate whether SsF can improve depression-associated dry eye disease and explore the underlying mechanism. METHODS: Behavioral test was used to verify the effect of SsF on CUMS-induced depression-like behaviors in mice. Corneal fluorescein staining, phenol red cotton thread test and periodic acid-Schiff (PAS) staining were used to observe the effect of SsF on depression-associated dry eye disease. Western blot (WB) was performed to observe the expression of TAK1 protein and key proteins of NF-κB and MAPK (P38) inflammatory pathways in the hippocampus and cornea. Immunohistochemical staining was used to observe the expression of microglia, and immunoprecipitation was used to observe K63-linked TAK1 ubiquitination. Subsequently, we constructed a viral vector sh-TAK1 to silence TAK1 protein to verify whether SsF exerted its therapeutic effect based on TAK1. The expression of inflammatory factors such as IL-1β, TNF-α and IL-18 in hippocampus and cornea were detected by ELISA. Overexpression of TRIM8 (OE-TRIM8) by viral vector was used to verify whether SsF improved depression-associated dry eye disease based on TRIM8. RESULTS: SsF treatment significantly improved the depression-like behavior, increased tear production and restored corneal injury in depression-related dry eye model mice. SsF treatment downregulated TAK1 expression and TRIM8-induced K63-linked TAK1 polyubiquitination, while inhibiting the activation of NF-κB and MAPK (P38) inflammatory pathways and microglial expression. In addition, selective inhibition of TAK1 expression ameliorated depression-associated dry eye disease, while overexpression of TRIM8 attenuated the therapeutic effect of SsF on depression-associated dry eye disease. CONCLUSION: SsF inhibited the polyubiquitination of TAK1 by acting on TRIM8, resulting in the downregulation of TAK1 expression, inhibition of inflammatory response, and improvement of CUMS-induced depression-associated dry eye disease.
通讯机构：
[Liu, BY ] H;Hunan Acad Chinese Med, 58 Lushan Rd, Changsha 410007, Hunan, Peoples R China.
关键词：
Angiogenesis;Buyang huanwu decoction;Cerebral infarction;Glycolysis;Traditional Chinese medicine
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: Promoting the recovery of cerebral blood circulation after cerebral infarction (CI) is an important intervention. Buyang Huanwu decoction (BHD) is a classic prescription for treating CI that promotes angiogenesis. Cytoplasmic glycolysis ischaemic-region cells after CI may be highly activated to maintain metabolic activity under hypoxia. From the perspective of long-term maintenance of glycolytic metabolism in the ischaemic area after CI, it may be beneficial to promote angiogenesis and maintain glial cell activation and neuronal survival. In this context, the regulatory relationship of lncRNAs and miRNAs with mRNAs is worthy of attention. Mining the competitive binding relationships among RNAs will aid in the screening of key gene targets post-CI. In this study, network pharmacology and bioinformatics were used to construct a ceRNA network, screen key targets, and explore the effect of glycolysis on angiogenesis during BHD-mediated CI regulation. AIM OF THE STUDY: This study aimed to explore the effect of BHD on angiogenesis after glycolysis regulation in CI. MATERIALS AND METHODS: According to the 21 active BHD ingredients we identified by our research team, we conducted network pharmacology. BHD targets that can regulate glycolysis and angiogenesis after CI were screened from the GeneCards, CTD and OMIM databases. We retrieved CI-related datasets from the GEO database and screened for differentially expressed lncRNAs and miRNAs. LncRNA‒miRNA-mRNA/TF targeting relationships were screened and organized with the miRcode, miRDB, TargetScan, miRWalk, and TransmiR v2.0 databases. Cytoscape was used to construct an lncRNA‒miRNA-mRNA/TF ceRNA network. Through BioGPS, key mRNAs/TFs in the network were screened for enrichment analysis. Animal experiments were then conducted to validate some key mRNAs/TFs and enriched signalling pathways. RESULTS: PFKFB3 and other genes may help regulate glycolysis and angiogenesis through AMPK and other signalling pathways. The anti-CI effect of BHD may involve maintaining activation of genes such as AMPK and PFKFB3 in the ischaemic cortex, maintaining moderate glycolysis levels in brain tissue, and promoting angiogenesis. CONCLUSION: BHD can regulate glycolysis and promote angiogenesis after CI through multiple pathways and targets, in which AMPK signalling pathway activation may be important.
作者机构：
[Yi, Jian; Wang, Feiying; Ding, Rongzhen; Dai, Aiguo] Department of Respiratory Diseases, Medical School, Hunan University of Chinese Medicine, Changsha, China;[Yi, Jian; Wang, Feiying; Ding, Rongzhen; Dai, Aiguo] Hunan Provincial Key Laboratory of Vascular Biology and Translational Medicine, Changsha, China;[Ding, Rongzhen; Dai, Aiguo] Department of Respiratory Medicine, First Affiliated Hospital, Hunan University of Chinese Medicine, Changsha, China;[Sang, Shuliu] Shanghai University of Traditional Chinese Medicine, Shanghai, China;[Yi, Jian] Hunan Academy of Chinese Medicine, Changsha, China
摘要：
BACKGROUND: Lung adenocarcinoma (LUAD) with Pulmonary arterial hypertension (PAH) shows a poor prognosis. Detecting related genes is imperative for prognosis prediction. METHODS: The gene expression profiles of LUAD and PAH were acquired from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database, respectively. The co-expression modules associated with LUAD and PAH were evaluated using the Weighted Gene Co-Expression Network Analysis (WGCNA). The relationship between key gene expression with immune-cell infiltration and the tumor immune microenvironment (TIME) was evaluated. We confirmed the mRNA and protein levels in vivo and vitro. G6PD knockdown was used to conduct the colony formation assay, transwell invasion assay, and scratch wound assay of A549 cells. EDU staining and CCK8 assay were performed on G6PD knockdown HPASMCs. We identified therapeutic drug molecules and performed molecular docking between the key gene and small drug molecules. RESULTS: Three major modules and 52 overlapped genes were recognized in LUAD and PAH. We identified the key gene G6PD, which was significantly upregulated in LUAD and PAH. In addition, we discovered a significant difference in infiltration for most immune cells between high- and low-G6PD expression groups. The mRNA and protein expressions of G6PD were significantly upregulated in LUAD and PAH. G6PD knockdown decreased proliferation, cloning, and migration of A549 cells and cell proliferation in HPASMCs. We screened five potential drug molecules against G6PD and targeted glutaraldehyde by molecular docking. CONCLUSIONS: This study reveals that G6PD is an immune-related biomarker and a possible therapeutic target for LUAD and PAH patients.
摘要：
OBJECTIVES: Statistics on the rate of unconventional lymph node metastases (ULNM) at the time of one-stage radical surgery in tongue cancer patients. To assess whether an extended neck dissection group with additional removal of ULNs has a lower rate of neck recurrence compared to the traditional neck dissection group. MATERIALS AND METHODS: A total of 336 patients with TSCC who underwent radical surgery were recruited and underwent traditional or extended neck dissection. Compared to traditional neck dissection, the aim of extended neck dissection is designed to additional resect ULNs. RESULTS: In total, 180 patients underwent extended neck dissection, while 156 underwent traditional neck dissection. The incidence of ULNM was 11.67% (21/180) in patients treated with extended neck dissection. The incidence of ipsilateral neck recurrence was 9.49% and 0.56% in patients who underwent traditional and extended neck dissection, respectively (p = 0.0001). CONCLUSIONS: Extended neck dissection is effective for preventing neck recurrence in TSCC patients with ULNs. CLINICAL RELEVANCE: ULNM may be the main cause of neck recurrence after neck dissection in patients with tongue cancer. A better prognosis may be achieved by additional resection of ULNs on the basis of traditional neck dissection.
关键词：
Nonspecific orbital inflammation (NSOI);Gln-Metabolism genes (GlnMgs);Lasso regression;SVM-RFE;Bioinformatics
摘要：
Nonspecific orbital inflammation (NSOI) is an idiopathic, persistent, and proliferative inflammatory condition affecting the orbit, characterized by polymorphous lymphoid infiltration. Its pathogenesis and progression have been linked to imbalances in tumor metabolic pathways, with glutamine (Gln) metabolism emerging as a critical aspect in cancer. Metabolic reprogramming is known to influence clinical outcomes in various malignancies. However, comprehensive research on glutamine metabolism's significance in NSOI is lacking. This study conducted a bioinformatics analysis to identify and validate potential glutamine-related molecules (GlnMgs) associated with NSOI. The discovery of GlnMgs involved the intersection of differential expression analysis with a set of 42 candidate GlnMgs. The biological functions and pathways of the identified GlnMgs were analyzed using GSEA and GSVA. Lasso regression and SVM-RFE methods identified hub genes and assessed the diagnostic efficacy of fourteen GlnMgs in NSOI. The correlation between hub GlnMgs and clinical characteristics was also examined. The expression levels of the fourteen GlnMgs were validated using datasets GSE58331 and GSE105149. Fourteen GlnMgs related to NSOI were identified, including FTCD, CPS1, CTPS1, NAGS, DDAH2, PHGDH, GGT1, GCLM, GLUD1, ART4, AADAT, ASNSD1, SLC38A1, and GFPT2. Biological function analysis indicated their involvement in responses to extracellular stimulus, mitochondrial matrix, and lipid transport. The diagnostic performance of these GlnMgs in distinguishing NSOI showed promising results. This study successfully identified fourteen GlnMgs associated with NSOI, providing insights into potential novel biomarkers for NSOI and avenues for monitoring disease progression.
摘要：
Oxidative stress is an important mechanism of aging, and in turn, aging can also aggravate oxidative stress, which leads to a vicious cycle. In the process of the brain converting light into visual signals, the eye is stimulated by harmful blue-light radiation directly. Thus, the eye is especially vulnerable to oxidative stress and becomes one of the organs most seriously involved during the aging process. Cataracts, age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), and dry eye are inextricably linked to the aging process and oxidative stress. Chlorogenic acid (CGA) has been demonstrated to have antioxidant and anti-inflammatory activities, and its validity has been established experimentally in numerous fields, including cardiovascular disease, metabolic disorders, cancers, and other chronic diseases. There has previously been evidence of CGA's therapeutic effect in the field of ophthalmopathy. Considering that many ophthalmic drugs lead to systemic side effects, CGA may act as a natural exogenous antioxidant for patients to take regularly, controlling their condition while minimizing side effects. In this paper, in vitro and in vivo studies of CGA in the treatment of age-related eye diseases are reviewed, and the prospects of CGA's antioxidant application for the eye are discussed. The aim of this review is to summarize the relevant knowledge and provide theoretical support for future research.
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: Huzhang-Guizhi herb pair (HGHP), composed of Polygonum cuspidatum (Huzhang [HZ] in Chinese, the root of Polygonum cuspidatum Sieb. & Zucc.) and Ramulus Cinnamomi (Guizhi [GZ] in Chinese, the dried twig of Cinnamomum cassia Presl.), is a popular herb pair commonly used to treat arthritis and involved in many Chinese prescriptions. In order to reveal the influence of GZ on HZ on bioavailability, the pharmacokinetic behaviors and tissue distribution variations of the three analytes from HZ were detected between oral administration of HZ and HGHP extracts to rats. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomly assigned to two groups for pharmacokinetics study and eight groups for tissues distribution research with the equivalent dose of 18g crude HZ/kg. Assays for analytes from HZ (polydatin, resveratrol, emodin) were developed and validated using high performance liquid chromatography with ultraviolet detection (HPLC-UV). RESULTS: Part pharmacokinetic parameters including area under the concentration-time curve (AUC), the maximum plasma concentration (C(max)), biological half-life (t(1/2)), mean residence time (MRT), time to peak concentration (T(max)), clearance rate/bioavailability (CL/F) and volume of distribution/bioavailability (Vd/F) showed significant difference (P<0.05) after oral administration of HGHP, as compared to those of HZ. The three analytes could be detected in heart, liver, spleen, lung, kidney and brain. Compared with the HZ group, AUC(0-t) of polydatin in heart, liver and kidney increased significantly (p<0.05) while that in spleen decreased significantly (p<0.05); AUC(0-t) of resveratrol in all detected tissues increased conspicuously (p<0.05) in the HGHP group; AUC(0-t) of emodin in heart, liver, spleen, lung, and kidney increased conspicuously (p<0.05), and decreased obviously (p<0.05) in brain in the HGHP group. CONCLUSIONS: GZ could strongly influence the pharmacokinetic parameters and tissue distribution characteristics of polydatin, resveratrol and emodin in rats when administrated with HZ or HGHP extracts. It might provide a reference for further explanation of the compatibility mechanism and the clinical application of HGHP.
期刊：
Journal of Ethnopharmacology,2024年319(Pt 3):117343 ISSN：0378-8741
通讯作者：
Wang, Xianwen;He, YC
作者机构：
[Wang, Xianwen; He, Yingchun; Liu, Liu; Zhou, Fangliang; Tang, Le; Wang, Wen; Xu, Runshi; Lin, Ting] Hunan Univ Chinese Med, Changsha 410208, Peoples R China.;[Zhou, Fangliang; Tang, Le; Wang, Wen; He, Yingchun; He, Lan] Hunan Univ Chinese Med, Hunan Prov Engn & Technol Res Ctr Prevent & Treatm, Changsha 410208, Peoples R China.;[Lin, Ting] Hunan Univ Chinese Med, Hunan Prov Key Lab Prevent & Treatment Ophthalmol, Changsha 410208, Peoples R China.;[Wang, Wen; He, Lan] Hunan Univ Chinese Med, Affiliated Hosp 1, Changsha 410007, Peoples R China.
通讯机构：
[Wang, XW; He, YC ] H;Hunan Univ Chinese Med, Changsha 410208, Peoples R China.
关键词：
Nasopharyngeal carcinoma;Network pharmacology;Non-targeted-metabolomics;Traditional Chinese medicine;Yiqi Jiedu formula
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: Yiqi Jiedu formula (YQJDF), rooted in the traditional Chinese medicinal principle of "tonifying qi and detoxifying", is remarkably efficacious in the clinical treatment of nasopharyngeal carcinoma (NPC). Previous studies have shed light on some of its anti-NPC effects and mechanisms, but the responsible pharmacological substances and their precise mechanisms of action remain unclear. AIM OF THE STUDY: The purpose of this study was to identify components of YQJDF that entered the bloodstream and to investigate their mechanisms of action against NPC through network pharmacology and serum metabolomics. MATERIAL AND METHODS: Components of YQJDF in serum were identified using liquid chromatography-tandem mass spectrometry. With these serum species as the focus of our research, network pharmacology analysis was used to identify active compounds and target genes that might mediate the efficacy of YQJDF in the treatment of NPC. Following establishment of an NPC xenograft model in nude mice, a non-targeted metabolomics approach was adopted to identify significant serum metabolites and metabolic pathways influenced by YQJDF. RESULTS: Thirty-six components of YQJDF were identified, primarily consisting of alkaloids, phenylpropanoids, and flavonoids. Notably, pathways such as PI3K/AKT, factors associated with Epstein-Barr virus infection, IL-17 signaling, and lipid metabolism, were highlighted as potential therapeutic targets of YQJDF during NPC treatment. Additionally, our findings suggested that YQJDF modified the metabolism of arginine and proline in the serum of mice bearing nasopharyngeal tumor grafts. CONCLUSIONS: This study identified the primary active components of YQJDF, highlighting its holistic role in the treatment of NPC through multiple targets and pathways. Furthermore, our findings provided a roadmap for future research into the mechanism of YQJDF in the therapy of NPC, setting the stage for its clinical application.
摘要：
Objective: To investigate the effect of isorhamnetin on the pathology of rheumatoid arthritis (RA). Methods: Tumor necrosis factor (TNF)- alpha -induced fibroblast-like synoviocytes (FLS) was exposed to additional isorhamnetin (10, 20 and 40 mu mol/L). Overexpression vectors for matrix metalloproteinase-2 (MMP2) or MMP9 or SRC were transfected to explore their roles in isorhamnetin-mediated RA-FLS function. RA-FLS viability, migration, and invasion were evaluated. Moreover, a collagen-induced arthritis (CIA) rat model was established. Rats were randomly divided to sham, CIA, low-, medium-, and high-dosage groups using a random number table (n=5 in each group) and administed with normal saline or additional isorhamnetin [2, 10, and 20 mg/(kg<middle dot>day)] for 4 weeks, respectively. Arthritis index was calculated and synovial tissue inflammation was determined in CIA rats. The levels of MMP2, MMP9, TNF-alpha, interleukin-6 (IL-6), and IL-1 beta, as well as the phosphorylation levels of SRC, extracellular regulated kinase (ERK), and cyclic adenosine monophosphate response element-binding (CREB), were detected in RA-FLS and synovial tissue. Molecular docking was also used to analyze the binding of isorhamnetin to SRC. Results: In in vitro studies, isorhamnetin inhibited RA-FLS viability, migration and invasion (P<0.05). Isorhamnetin downregulated the levels of MMP2, MMP9, TNF-alpha, IL-6, and IL-1 beta in RA-FLS (P<0.05). The overexpression of either MMP2 or MMP9 reversed isorhamnetin-inhibited RA-FLS migration and invasion, as well as the levels of TNF-alpha, IL-6, and IL-1 beta (P<0.05). Furthermore, isorhamnetin bound to SRC and reduced the phosphorylation of SRC, ERK, and CREB (P<0.05). SRC overexpression reversed the inhibitory effect of isorhamnetin on RA-FLS viability, migration and invasion, as well as the negative regulation of MMP2 and MMP9 (P<0.05). In in vivo studies, isorhamnetin decreased arthritis index scores (P<0.05) and alleviated synovial inflammation. Isorhamnetin reduced the levels of MMP2, MMP9, TNF-alpha, IL-6, and IL-1 beta, as well as the phosphorylation of SRC, ERK, and CREB in synovial tissue (P<0.05). Notably, the inhibitory effect of isorhamnetin was more pronounced at higher concentrations (P<0.05). Conclusion: Isorhamnetin exhibited anti-RA effects through modulating SRC/ERK/CREB and MMP2/MMP9 signaling pathways, suggesting that isorhamnetin may be a potential therapeutic agent for RA.
作者机构：
[Kuang, Gaoyan; Lu, Min; Xu, Xiaotong; Wen, Zhi] Hunan Univ Chinese Med, Hosp 1, Dept Joint Orthoped, Changsha 410000, Hunan, Peoples R China.;[Qiu, Liguo; Wen, Zhi; Liu, Enxu] Hunan Univ Chinese Med, Changsha, Hunan, Peoples R China.;[Jiang, Yong; Wu, Yuyuan] Tradit Chinese Med Hosp Huaihua, Dept Pediat Orthoped, Huaihua, Hunan, Peoples R China.
通讯机构：
[Lu, M ] H;Hunan Univ Chinese Med, Hosp 1, Dept Joint Orthoped, Changsha 410000, Hunan, Peoples R China.
关键词：
aneurysmal bone cyst (ABC);autogenous fibula transplantation;case report
摘要：
RATIONALE: Aneurysmal bone cyst (ABC) is a rare primary or secondary tumor that usually occurs in young women aged between 10 and 20 years, mostly in the long tubular bone and spine. However, there are no definite standards for its clinical treatment. To our knowledge, this is the first report of a young female patient with distal radius ABC who was successfully treated with tumor resection and autogenous fibular head transplantation. PATIENT CONCERNS: A 28-year-old married Chinese young woman presented to our hospital with swelling and pain in her right wrist for 2 years and aggravation of wrist movement restriction for 1 week. DIAGNOSES: Pathological biopsy confirmed ABC. INTERVENTIONS: We performed a pathological examination of the tumor on the right wrist and preliminarily confirmed the diagnosis of ABC. The right wrist joint was reconstructed by total surgical resection of the ABC tumor in the right wrist joint and autogenous fibular head transplantation. OUTCOMES: During follow-up within 7 years, good right wrist function was confirmed. The tumor did not recur, the swelling of the right wrist disappeared, the joint pain and limitation of movement significantly improved, and the function of the right wrist was not impaired in daily activities. Radiography showed that the fracture had healed. LESSONS: Our results suggest that autofibular head transplantation is an effective treatment for reconstruction of wrist function in adult patients with ABC of the distal radius.
摘要：
is an early event of brain injury after subarachnoid hemorrhage (SAH). Whether the macrophage mediators in resolving inflammation 1 (MaR1) is involved in SAH pathogenesis is unknown. In this study, 205 male Sprague-Dawley rats were subjected to SAH via endovascular perforation in the experimental and control groups. MaR1 was dosed intranasally at 1 h after SAH, with LGR6 siRNA and KG -501, GSK-J4 administered to determine the signaling pathway. Neurobehavioral, histological and biochemical data were obtained from the animal groups with designated treatments. The results showed: (i) The leucine-rich repeat containing G protein-coupled receptor 6 (LGR6) was decreased after SAH and reached to the lowest level at 24 h after SAH. Jumonji d3 (JMJD3) protein levels tended to increase and peaked at 24 h after SAH. LGR6 and JMJD3 expression were co-localized with microglia. (ii) MaR1 administration mitigated short-term neurological deficits, brain edema and long-term neurobehavioral performance after SAH, and attenuated microglial activation and neutrophil infiltration. (iii) Knockdown of LGR6, inhibition of CREB phosphorylation or JMJD3 activity abolished the antineuroinflammatory effect of MaR1 on the expression of CREB, CBP, JMJD3, IRF4, IRF5, IL -1b, IL -6 and IL -10, thus prevented microglial activation and neutrophil infiltration. Together, the results show that MaR1 can activate LGR6 and affect CREB/JMJD3/IRF4 signaling to attenuate neuroinflammation after SAH, pointing to a potential pharmacological utility in this disorder.(c) 2024 IBRO. Published by Elsevier Inc. All rights reserved.
期刊：
Drug Design, Development and Therapy,2024年18:699-717 ISSN：1177-8881
通讯作者：
Guo, C
作者机构：
[Zhou, Xuqing; Guo, C; Wang, Xu; Guo, Chun; Lei, Shihui; Yang, Yi] Hunan Univ Chinese Med, Hosp 1, Expt Ctr Med Innovat, Changsha 410007, Hunan, Peoples R China.;[Zhou, Xuqing; Guo, C; Wang, Xu; Guo, Chun] Hunan Univ Chinese Med, Clin Coll Tradit Chinese Med 1, Changsha 410007, Hunan, Peoples R China.;[Li, Jiaqi; He, Ying; Yang, Hua] Hunan Agr Univ, Coll Biosci & Biotechnol, Changsha 410128, Hunan, Peoples R China.;[Zhang, Mengxue; Zhou, Desheng] Hunan Univ Chinese Med, Hosp 1, Dept Neurol, Changsha 410007, Hunan, Peoples R China.
通讯机构：
[Guo, C ] H;Hunan Univ Chinese Med, Hosp 1, Expt Ctr Med Innovat, Changsha 410007, Hunan, Peoples R China.;Hunan Univ Chinese Med, Clin Coll Tradit Chinese Med 1, Changsha 410007, Hunan, Peoples R China.
摘要：
BACKGROUND: Annao Pingchong decoction (ANPCD) is a traditional Chinese decoction which has definite effects on treating intracerebral hemorrhage (ICH) validated through clinical and experimental studies. However, the impact of ANPCD on oxidative stress (OS) after ICH remains unclear and is worth further investigating. AIM: To investigate whether the therapeutic effects of ANPCD on ICH are related to alleviating OS damage and seek potential targets for its antioxidant effects. MATERIALS AND METHODS: The therapeutic candidate genes of ANPCD on ICH were identified through a comparison of the target genes of ANPCD, target genes of ICH and differentially expressed genes (DEGs). Protein-protein interaction (PPI) network analysis and functional enrichment analysis were combined with targets-related literature to select suitable antioxidant targets. The affinity between ANPCD and the selected target was verified using macromolecular docking. Subsequently, the effects of ANPCD on OS and the selected target were further investigated through in vivo experiments. RESULTS: Forty-eight candidate genes were screened, in which silent information regulator sirtuin 1 (SIRT1) is one of the core genes that has antioxidant effects and ICH significantly affected its expression. The good affinity between 6 compounds of ANPCD and SIRT1 was also demonstrated by macromolecular docking. The results of in vivo experiments demonstrated that ANPCD significantly decreased modified neurological severity scoring (mNSS) scores and serum MDA and 8-OHdG content in ICH rats, while significantly increasing serum SOD and CAT activity, complicated with the up-regulation of ANPCD on SIRT1, FOXO1, PGC-1α and Nrf2. Furthermore, ANPCD significantly decreased the apoptosis rate and the expression of apoptosis-related proteins (P53, cytochrome c and caspase-3). CONCLUSION: ANPCD alleviates OS damage and apoptosis after ICH in rats. As a potential therapeutic target, SIRT1 can be effectively regulated by ANPCD, as are its downstream proteins.
期刊：
International Journal of Cardiology,2024年395:131400 ISSN：0167-5273
通讯作者：
Guo, ZH
作者机构：
[Zheng, Huizhen; Yin, Ziwei; Luo, Xi; Zhou, Yingli] Hunan Univ Chinese Med, Affiliated Hosp 1, Dept Cardiol, Changsha 410007, Peoples R China.;[Zheng, Huizhen; Yin, Ziwei; Zhang, Fei; Luo, Xi; Guo, Zhihua; Zhou, Yingli] Hunan Univ Chinese Med, Coll Chinese Med, Changsha 410208, Peoples R China.;[Guo, Zhihua] Coll Intelligent Tradit Chinese Med Diag & Prevent, Hunan Key Lab, Changsha 410208, Peoples R China.
通讯机构：
[Guo, ZH ] H;Hunan Univ Chinese Med, Coll Chinese Med, Changsha 410208, Peoples R China.
关键词：
Cross-sectional study;Heart failure;NHANES;Population-based study;Risk factors;Systemic immune-inflammation index
摘要：
BACKGROUND: Heart failure (HF) is a disease closely associated with inflammation, and the systemic immune-inflammation index (SII) is a novel inflammatory marker. Therefore, this study aims to explore the relationship between SII and HF. METHODS: We used National Health and Nutrition Examination Survey data from 1998 to 2018 to include adults who reported a diagnosis of HF and complete information on the calculation of SII. SII was calculated as platelet count × neutrophil count/lymphocyte count. We used multiple logistic regression models to examine the association between SII and HF and explored possible influencing factors by subgroup analysis. In addition, we performed smoothed curve fitting and threshold effect analysis to describe the nonlinear relationship. RESULTS: The population-based study involved a total of 48,155 adults ages 20-85. Multivariate logistic regression showed that participants with the highest SII had a statistically significant 32% increased risk of HF prevalence compared to those with the lowest SII (OR=1.32; 95% CI, 1.06-1.65, P=0.0144) in a fully adjusted model. Subgroup analysis revealed no significant interactions between SII and specific subgroups (p>0.05 for all interactions). Furthermore, the association between SII and HF was non-linear; the inflection point was 1104.78 (1000 cells/μl). CONCLUSIONS: Based on our findings, elevated SII levels were found to be strongly associated with the risk of HF, and SII was nonlinearly associated with HF. To validate these findings, a larger prospective investigation is needed to support the results of this study and investigate potential problems.
作者机构：
[Zhang, Weili; Jin-si-han, E-er-man-bie-ke; Lu, ZH; Lian, Shaopu; Li, Yuan; Lu, Zhenhai; Feng, Cheng; Wang, Hao] Sun Yat Sen Univ Canc Ctr, Dept Colorectal Surg, Guangzhou 510515, Guangdong, Peoples R China.;[He, Meng; He, M] Chinese Acad Med Sci & Peking Union Med Coll, Natl Clin Res Ctr Canc, Canc Hosp, Dept Radiat Oncol,Natl Canc Ctr, Shenzhen 518116, Guangdong, Peoples R China.;[He, Meng; He, M] Chinese Acad Med Sci & Peking Union Med Coll, Shenzhen Hosp, Shenzhen 518116, Guangdong, Peoples R China.;[Chen, QF; Chen, Qifeng] Sun Yat Sen Univ Canc Ctr, Dept Minimally Invas Intervent Therapy, Liver Canc Study & Serv Grp, Guangzhou 510060, Guangdong, Peoples R China.;[Tai, Yi] Sun Yat Senen Univ Canc Ctr, Dept Musculoskeletal Oncol, Guangzhou 510515, Guangdong, Peoples R China.
通讯机构：
[Chen, QF ; Lu, ZH ] S;[He, M ] C;Sun Yat Sen Univ Canc Ctr, Dept Colorectal Surg, Guangzhou 510515, Guangdong, Peoples R China.;Chinese Acad Med Sci & Peking Union Med Coll, Natl Clin Res Ctr Canc, Canc Hosp, Dept Radiat Oncol,Natl Canc Ctr, Shenzhen 518116, Guangdong, Peoples R China.;Chinese Acad Med Sci & Peking Union Med Coll, Shenzhen Hosp, Shenzhen 518116, Guangdong, Peoples R China.
摘要：
Neutrophil extracellular traps (NETs) have been categorized as a form of inflammatory cell death mode of neutrophils (NETosis) involved in natural immunity and the regulation of adaptive immunity. More and more studies revealed the ability of NETs to reshape the tumor immune microenvironment (TIME) by limiting antitumor effector cells, which may impair the efficacy of immunotherapy. To explore whether NETs-related genes make vital impacts on Colon carcinoma (COAD), we have carried out a systematic analysis and showed several findings in the present work. First, we obtained the patient's data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset, aiming to detect two NETs-associated subtypes by consensus clustering. For the purpose of annotating the roles of NETs-related pathways, gene ontology enrichment analyses were adopted. Next, we constructed a 6 novel NETs-related genes score using the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model. We found that the NETs risk score was notably upregulated in COAD patient samples, and its levels were notably correlated with tumor clinicopathological and immune traits. Then, according to NETs-associated molecular subtypes and the risk signature, this study compared immune cell infiltration calculated through the estimate, CIBERSORT, TIMER, ssGSEA algorithms, tumor immune dysfunction, as well as exclusion (TIDE). Furthermore, we confirm that MPO(myeloperoxidase) was significantly upregulated in COAD patient samples, and its levels were significantly linked to tumor malignancy and clinic outcome. Moreover, multiplex immunohistochemistry (mIHC) spatial analysis confirmed that MPO was closely related to Treg and PD-1 + Treg in spatial location which suggested MPO may paly an important role in TIME formation. Altogether, the obtained results indicated that a six NETs-related genes prognostic signature was conducive to estimating the prognosis and response of chemo-/immuno-therapy of COAD patients.
期刊：
Frontiers in Bioscience-Landmark,2023年28(10):271 ISSN：2768-6701
通讯作者：
Yu, Lili;Wu, QB;Fan, XM
作者机构：
[Luo, Dan; Wang, Jue; Liang, Yuling; Yu, Lili; Wu, Qibiao] Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Fac Chinese Med, Taipa 999078, Macao, Peoples R China.;[Luo, Dan; Fan, Xianming; Wang, Wenjun; Gui, Xuemei; Yan, Jie; Fang, Mengying; Liang, Yuling; Chen, Mengqin] Southwest Med Univ, Affiliated Hosp, Dept Resp & Crit Care Med, Luzhou 646099, Sichuan, Peoples R China.;[Luo, Dan; Fan, Xianming; Wang, Wenjun; Gui, Xuemei; Yan, Jie; Fang, Mengying; Liang, Yuling; Chen, Mengqin] Southwest Med Univ, Affiliated Hosp, Inflammat & Allerg Dis Res Unit, Luzhou 646099, Sichuan, Peoples R China.;[Shao, Le] Hunan Univ Chinese Med, Hosp 1, Ctr Med Res & Innovat, Changsha 410021, Hunan, Peoples R China.;[Wu, Qibiao] Guangdong Univ Technol, Guangdong Hong Kong Macao Joint Lab Contaminants, Guangzhou 510520, Peoples R China.
通讯机构：
[Yu, LL; Wu, QB ] M;[Fan, XM ] S;Macau Univ Sci & Technol, State Key Lab Qual Res Chinese Med, Fac Chinese Med, Taipa 999078, Macao, Peoples R China.;Southwest Med Univ, Affiliated Hosp, Dept Resp & Crit Care Med, Luzhou 646099, Sichuan, Peoples R China.;Southwest Med Univ, Affiliated Hosp, Inflammat & Allerg Dis Res Unit, Luzhou 646099, Sichuan, Peoples R China.
摘要：
BACKGROUND: Lung cancer is the main cause of cancer-related death, with epithelial-mesenchymal transition (EMT) playing an important role in the development of this disease. The EMT-related genes Polypeptide N-Acetylgalactosaminyltransferase 3 (GALNT3) and 2'-5'-Oligoadenylate Synthetase 1 (OAS1) are involved in numerous tumor processes. Although these genes have been extensively studied in cancer, they have yet to be analyzed by multi-omics in lung adenocarcinoma (LUAD). METHODS: EMT-related genes were identified by R and Venn diagram. Cox regression and Kaplan-Meier analysis were performed to evaluate patient survival, and the Gene Expression Profiling Interactive Analysis (GEPIA) database was used for correlation analysis. GeneCards and R packages were used to explore gene characterization and functional annotation. The Tumor Immune Estimation Resource (TIMER), Human Protein Atlas (HPA), University of Alabama at Birmingham Cancer (UALCAN), and The Cancer Genome Atlas (TCGA) databases were used to investigate gene expression, which was then confirmed by RT-PCR. Clinicopathological analysis was carried out using the UALCAN database. Functional mechanisms and multi-omics analysis were performed using DNA Methylation Interactive Visualization Database (DNMIVD), Targetscan, TIMER, Tumor-immune System Interactions Database (TISIDB) and cBioportal. Diagnostic values were calculated using ROC curve analysis. RESULTS: A total of 320 EMT-related genes were identified in LUAD. Their characteristics were confirmed in the Database for Annotation, Visualization and Integrated Discovery (DAVID) database by the intersection of 855 and 3600 different genes from the Gene Expression Omnibus (GEO) and EMTome databases, respectively. Expression of the EMT-related genes GALNT3 and OAS1 was associated with the prognosis of LUAD patients. A positive correlation was observed between the expression of GALNT3 and OAS1, and their expression was higher in LUAD tissue than in normal lung tissue. This was confirmed using RT-PCR. Multi-omics analysis revealed that GALNT3 and OAS1 expression was associated with gene mutation and methylation, cellular immune infiltration, and several immune subtypes. A miRNA-GALNT3/OAS1 regulatory network was also found. Receiver operating characteristic (ROC) curve analysis found that GALNT3 and OAS1 expression combined had superior diagnostic value to that of each marker alone. CONCLUSIONS: GALNT3 and OAS1 expression are associated with immune cell infiltration and poor prognosis in LUAD. Their combined expression has high diagnostic value; hence, GALNT3 and OAS1 may be valuable biomarkers for the early detection of LUAD.
