Background: Angiogenesis significantly contributes to breast cancer progression. While glyoxalase I (GLO1) has been extensively studied in endothelial cells related to cardiovascular and metabolic diseases, its role in breast cancer-associated endothelial cells (BCECs) remains unclear. Moreover, Additionally, a comprehensive analysis of GLO1 inhibitors is lacking. This study aims to systematically evaluate the pharmacological profiles of GLO1 inhibitors, identify those with potential effects on BCECs, and validate these findings experimentally. Materials and methods: Seventeen GLO1 inhibitors were analyzed using SwissADME and pkCSM for their pharmacological profiles. Target identification employed SwissTargetPrediction and SuperPred, and intersected with differentially expressed genes (DEGs) from the GSE80506 dataset to construct a BCECs-relevant target network. This network underwent enrichment analysis, expression correlation analysis, and molecular docking. Experimental validation was conducted using cellular assays and an aortic ring assay in mice. Results: Among 515 targets associated with the 17 GLO1 inhibitors, 36 were linked to BCECs regulation. Enrichment analysis highlighted the cell cycle as a pivotal pathway, with key targets including CCNA2, CCNE1, CDC25A, CDC25B, CDK6, CHEK1, PLK1, and TTK. Molecular docking indicated that Glyoxalase I inhibitor 6 plays a significant role in regulating these targets. Experimental assays demonstrated that this inhibitor arrested cells in the G0/G1 phase by modulating CCNA2 and CCNE1, suppressed BCECs proliferation, migration, and angiogenesis, and promoted cell death. Conclusions: GLO1 inhibitors exhibit significant regulatory effects on BCECs. Notably, Glyoxalase I inhibitor 6 effectively inhibits cell cycle progression, proliferation, migration, and angiogenesis in these cells, suggesting a promising therapeutic approach for targeting tumor-associated endothelial cells in breast cancer.

Background Triple-negative breast cancer is a particularly aggressive type of breast cancer that is closely associated with abnormal vascularization within the tumor. However, traditional anti-VEGF therapies and other treatments have limited efficacy. Tumor-associated macrophages (TAMs) induce and regulate tumor angiogenesis. In recent years, regulating TAMs polarization has become a hot topic for research with objectives to normalize tumor vasculature and improve drug delivery and the tumor microenvironment. Our previous studies have found that peritumoral electroacupuncture (EA) can regulate tumor angiogenesis, but the underlying mechanism remains unclear. Methods In this study, we examined the phenotype of TAMs and inflammatory factors to observe the effect of peritumoral electroacupuncture on the phenotypic polarization of TAMs. Based on this, we evaluated the structure and function of tumor vasculature. Finally, we conducted a preliminary exploration of the mechanism underlying the regulation of TAMs phenotypic polarization by peritumoral electroacupuncture. Results In this study, we found that peritumoral electroacupuncture could promote the phenotypic polarization of TAMs toward the M1 type, thereby reducing microvascular density in tumor tissue, increasing pericyte coverage, improving the stability of the basement membrane, promoting vascular maturation, and enhancing perfusion while reducing tissue hypoxia. Conclusions Peritumoral electroacupuncture can promote the phenotypic polarization of TAMs toward the M1 type, leading to normalization of tumor vascular structure and function. The mechanism may be related to the downregulation of glyoxalase-1 and subsequent activation of the MGO-AGEs/RAGE axis.

Emerging research suggested a potential role of immune cells in colorectal cancer (CRC) development. However, the causal relationship between immune phenotypes and CRC remains elusive. Hence, this two-sample Mendelian randomization (MR) study aimed to explore the causal association. In this study, a bidirectional, two-sample MR analysis and multivariate MR was conducted, leveraging public genetic data. Four types of immune phenotypes were employed. A comprehensive sensitivity analysis was carried out to validate the robustness, heterogeneity, and horizontal pleiotropy of the results, with Bonferroni correction applied for accurate interpretation. It was revealed that four immune cell phenotypes were significantly associated with CRC risk. Specifically, lymphocyte

Previous evidence suggests that dietary intake can affect liver diseases; However, the causal relationship between dietary intake and liver diseases remains unclear. To investigate this, we conducted a bidirectional Mendelian randomization (MR) analysis to comprehensively assess the potential causal relationship between dietary intake and liver diseases. Two-sample bidirectional MR was performed based on genome-wide association studies summary data from the UK Biobank and FinnGen database. The primary analysis method for evaluating causal relationships was inverse-variance weighted. Supplementary analyses included MR-Egger and weighted median methods. Subsequently, sensitivity analyses were performed using Cochran Q test, MR-Egger intercept test, MR-PRESSO, RadialMR, and leave-one-out analysis to assess heterogeneity and horizontal pleiotropy. MR evidence indicated that genetically predicted poultry intake (adjusted odds ratio [OR] = 0.04, 95% confidence interval [CI] = 0.00-0.43, P = .007) and salad/raw vegetable intake (adjusted OR = 0.18, 95% CI = 0.04-0.83, P = .028) were directly associated with a reduced risk of cirrhosis. Conversely, there is no causal association between dietary intake and nonalcoholic fatty liver disease, alcoholic liver disease, or hepatocellular carcinoma. This study provides evidence supporting the impact of dietary intake on liver disease. Increased intake of poultry and salad/raw vegetables is associated with a reduced risk of cirrhosis. These findings can inform preventive and therapeutic strategies for cirrhosis.

Xiatianwu is a traditional Chinese medicine. This study investigates the function of Xiatianwu in treating HCC through database analyses and in vitro experiments. The active ingredients of Xiatianwu were identified from TCMSP and HERB databases and their targets were predicted by Swiss TargetPrediction. The HCC dataset was screened using the GEO database, and the differentially expressed genes between HCC and non-tumor liver tissues were analyzed to identify overlapping targets with Xiatianwu. The intersecting targets underwent enrichment analysis using R software to elucidate the molecular mechanisms of Xiatianwu against HCC. Core targets were identified using the PPI network and MCODE algorithm. Clinical relevance and disease prognosis in HCC were verified using the TCGA database. Meanwhile, binding affinities among components and targets were validated with molecular docking. Finally, the anti-HCC efficacy of the active ingredient was validated in vitro. Our findings revealed that eight active ingredients of Xiatianwu interacted with 11 key targets, providing anti-HCC efficacy. Molecular docking indicated that bicuculline and fumarine exhibited superior binding abilities. Bicuculline, a representative ingredient of Xiatianwu, was chosen for in vitro validation. Results demonstrated that bicuculline, in a dose-dependent manner inhibited HCC cell viability, reduced migration, suppressed the G0/M cell cycle, and decreased core protein expression. Xiatianwu demonstrates significant potential for clinical application in treating HCC. Bicuculline, a key active ingredient of Xiatianwu, exerts anti-HCC effects by inhibiting the cell cycle.

There is a commonality between jingjin (muscle region of meridian) and the fascial network for coordinating the balance in the body. The occurrence and the progression of tumor may disrupt the overall coordination between the fascial network and jingjin directly or indirectly, thereby, the impairment of this coordination may result in cancer pain. Rooted on the theory of overall balance of the fascial network, and combined with understanding of pain in jingjin theory, professor HUANG Jin-chang emphasizes the importance of "relaxing the knot" in treatment of cancer pain. It is recommended to select the fascia reaction point as the target point, in accordance with the principle of balance adjustment and apply various acupuncture and moxibustion therapies, such as Fu's subcutaneous needling, small-needle scalpel therapy, fire needling, and moxibustion.

Objective:To analyze the expression and clinical significance of SHC SH2-binding protein 1(SHCBP1)in lung adenocarcinoma(LUAD).Methods:Oncomine,TIMER,UALCAN,GEPIA,Kaplan-Meier plotter and STRING databases were used to explore the effect of SHCBP1 on progression and immune infiltration of LUAD.Results:Expression of SHCBP1 mRNA in LUAD tissue was significantly higher than that in normal lung tissue(P<0.05).Expression of SHCBP1 mRNA was significantly increased in LUAD patients with smoking history,nodal metastasis,late clinical stage and TP53 mutation(P<0.05).Survival analysis by GEPIA and Kaplan-Meier plotter databases showed that LUAD patients with high SHCBP1 mRNA expression had a lower overall survival rate(P<0.05).SHCBP1 mRNA was correlated with immune cell infiltration,immune cell markers and immune checkpoint expression in LUAD.Conclusion:High expression of SHCBP1 is related to poor prognosis and tumor immune infiltration of LUAD patients.

Abstract Background:: A plateau has been reached for conventional therapies in ovarian cancer as there is no definitive increase in overall survival. It is necessary to distinguish molecular subtypes based on multi-omics integration to take more targeted strategies to improve prognosis and increase therapeutic efficacy. Methods:: A total of 202 patients with mRNA, miRNA, DNA methylation, somatic mutation, and Reverse Phase Protein Array (RPPA) data were assembled into one multi-omics dataset and then developed a model via MOVICS. A total of 1028 OV samples with raw microarray data and clinicopathological information were obtained from the Gene Expression Omnibus (GEO) as a validation cohort. Then, a series of immune infiltration analyses were performed by GSVA, TIDE, EaSIeR, and ESTIMATE package. Lastly, Metascape was conducted to unravel activated signaling pathways, and the ChAMP package was used to identify potential biomarkers. Results:: 202 OV samples retrieved from the multi-omics TCGA cohort were categorized into two subgroups by MOVICS. Drug sensitivity analysis revealed that targeted therapy and immunotherapy are possibly considered as preferable approaches to prolong the survival of such patients as C2 while platinum-based drugs to C1. Furthermore, immune infiltration analysis revealed that there is a negative correlation between myeloid and neutrophil cells (MDSC) and prognosis and response to immunotherapy in C1. Immune-associated pathways were mainly enriched in C1 and metabolic-related pathways in C2. CRISPLD2, SLC12A8, STARD8, and DCHS1 were considered as potential targets to possibly improve the outcome by disrupting the immunosuppressive immunocytes by integration of DNA methylation and transcriptome expression. Conclusion:: The molecular subtypes based on integrated multi-omics provided novel insights into the molecular basis of immune recognition and immune regulation of cancer cells for predicting the prognosis of ovarian cancer and potential clinical therapeutic targets for OV.

目的 采用数据挖掘联合网络药理学分析中医药治疗放射性肺损伤的用药规律及其潜在作用机制.方法 计算机检索知网、万方、维普、中国生物医学文献服务系统自2000年1月至2021年6月发表的中医药治疗放射性肺损伤的相关文献,采用频数统计、关联规则分析等对纳入处方进行分析,筛选治疗放射性肺损伤的高频核心药组.运用网络药理学方法获取高频核心药组的有效活性成分并预测其作用靶点.通过公认的疾病数据库收集放射性肺损伤疾病靶点,然后将药物靶点与疾病靶点取交集,并对核心靶点进行蛋白互作网络分析和KEGG信号通路富集分析.结果 共筛选出符合条件文献154篇,含178首方剂,涉及214味中药,使用频次＞30次的中药21味.挖掘出高频药物间关联性最强的中药有6味,即为高频核心药组.高频核心药组与放射性肺损伤相关交集靶点97个,蛋白互作分析结果显示高频核心药组治疗放射性肺损伤的核心靶点可能是TP53、AKT1、INS等,KEGG通路富集结果涉及PI3K-Akt信号通路、HIF-1信号通路、MAPK信号通路等.结论 中医药治疗放射性肺损伤的以养阴益气为主,同时配合清热、化痰止咳平喘和活血化瘀.高频核心药组可能通过抑制炎性渗出、调节免疫平衡、减少肺组织细胞凋亡、修复损伤肺组织等方面治疗放射性肺损伤.

目的:评价头针疗法干预白内障超声乳化术后干眼的临床疗效.方法:采用前瞻性、随机对照的临床试验方法纳入白内障超声乳化+人工晶体植入术后干眼者共200例,分为头针组、药物组、对照组三组,其中头针组67例,药物组78例,对照组55例.头针组术后每日或隔日针1次,10～15次为1个疗程,疗程间休息5～7天;药物组滴用0.3％玻璃酸钠滴眼液,4次/日;对照组无针对干眼的药物及其他物理治疗措施.收集治疗前后5个时间点的临床主客观数据评价疗效.结果:头针和药物均可改善患者的主观症状评分,且头针疗法可改善患者的泪液分泌,三组治疗后泪液分泌有统计学差异(P<0.05).对照组与前两组同期指标比较,角膜染色无统计学差异(P>0.05),干眼问卷评分、泪液分泌和泪膜破裂时间均有统计学差异(P<0.05).结论:头针治疗白内障超声乳化术后干眼可明显改善患者临床症状及泪液分泌,远期疗效显著,为白内障术后干眼的治疗提供了新思路.

从厥阴角度分析胰腺癌的核心病机,并结合胰腺癌的临床症状与病理特点,将其总结为厥阴脏寒、肝阳不足.基于乌梅丸主治厥阴脏寒的理解,根据胰腺癌的原发部位、转移灶和临床表现,在乌梅丸的基础上灵活加减用药,在临床可收到较好的疗效.

目的 基于网络药理学探讨宣白承气汤治疗急性呼吸窘迫综合征(ARDS)的可能作用机制.方法 检索TCMSP数据库获得宣白承气汤的活性成分及靶点,检索GeneCards、OMIM、TTD和DrugBank数据库获得ARDS的疾病靶点,得到药物-疾病共有靶点.通过STRING数据库构建蛋白互作(PPI)网络模型,通过Metascape和Reactome平台进行基因本体论(GO)分析和基因组的京都基因与基因组百科全书(KEGG)富集分析,运用Cytoscape 3.7.2软件构建药物成分-ARDS靶点-通路网络图,并利用AutoDockTools和Vina软件进行分子对接验证.结果 共获得大黄、苦杏仁和瓜蒌皮相关靶点93个,ARDS疾病靶点5416个,得到共有靶点51个.PPI分析结果示TNF、TP53、CASP3、PTGS2作用关系最强;GO分析得到生物过程主要富集条目20条、细胞组成9条、分子功能17条,主要生物学过程为丝裂原活化蛋白激酶(MAPK)级联反应的调控;KEGG富集的主要通路有核受体转录途径、白细胞介素4和白细胞介素13信号、通用转录途径等;网络拓扑分析示Eupatin为宣白承气汤治疗ARDS的主要活性成分,其次是(+)-catechin和Mutatochrome,PTGS2、ESR1、NR3C2、NOS2是其发挥作用的核心靶点;分子对接结果示Glabridin-PTGS2对接分数最高,大部分靶点与成分的结合活性较好.结论 宣白承气汤的核心成分Glabridin和Eupatin可能作用于TPGS2、TNF、TP53、CASP3等靶点,通过白细胞介素相关通路、MAPK信号通路、核受体转录途径等抑制炎症反应和氧化应激,调控基因表达,发挥治疗ARDS的作用.

目的:基于网络药理学及分子对接虚拟预测方法,探究余甘子治疗肝细胞癌的潜在分子机制.方法:通过公共数据库获取余甘子的有效活性成分及作用靶点,并筛选肝细胞癌相关靶点,构建"活性成分-靶点"关系图与PPI网络,进行GO分析和KEGG、Reactome通路富集,采用分子对接评价活性成分与核心靶点的结合活性.结果:共获得19个有效活性成分和12个重要靶点.通过GO分析获得了1794个细胞生物过程,而KEGG和Reactome富集分析分别涉及315和391个相关通路.结论:余甘子的主要有效活性成分为鞣花酸、木犀草素、槲皮素和山奈酚,可能作用于AKT1、MMP9、SRC、ESR1、PPARG和AR等关键靶点,调控内分泌抵抗、癌症中的蛋白多糖、癌症通路、受体酪氨酸激酶信号、白细胞介素信号通路、生长因子受体和第二信使信号转导、PI3 K/AKT信号通路等以治疗肝癌.除了直接的肿瘤相关信号通路,间接的炎症、代谢通路在抑制肝癌进展中发挥了重要作用.

To analyze the research status of acupuncture and moxibustion for cancer at home and abroad in the past 45 years by using bibliometric and scientific knowledge map methods，and explore the development trends in future. The literature of acupuncture and moxibustion for cancer was retrieved from CNKI and Web of Science (WOS) till December 31, 2020 since the database establishment, and CiteSpace and VOSviewer software were used to perform visual map analysis through cooperation network, keyword co-occurrence, keyword timeline, keyword emergence and other methods. Totally, 1 585 literature in CNKI and 1 564 literature in WOS were included, and the annual publication amount showed a fluctuating upward trend. Cooperation between countries was centered on China and the United States, and there was relatively little cooperation among different institutions. The analysis of keyword and cited literature showed that researches focused on the control of acupuncture and moxibustion therapy on cancer complications and adverse reactions of western medicine. The main research types in WOS were systematic review and randomized controlled trial (RCT), while in CNKI was review, depth studies on mechanism of acupuncture and moxibustion for cancer were rare. The concern about the quality of life of cancer patients may become research emphasis in the field of acupuncture and moxibustion for cancer in future, and the research scope tends to integrative and holistic oncology.