AIMS:Breast cancer (BC) is by far seen as the most common malignancy globally, with 2.261 million patients newly diagnosed, accounting for 11.7% of all cancer patients, according to the Global Cancer Statistics Report (2020). The luminal A subtype accounts for at least half of all BC diagnoses. According to TCM theory, Bushen Huoxue Decoction (BSHXD) is a prescription used for cancer treatment that may influence luminal A subtype breast cancer (LASBC). OBJECTIVES:To analyze the clinical efficacy and underlying mechanisms of BSHXD in LASBC. MATERIALS AND METHODS:Network pharmacology and in vitro experiments were utilized to foresee the underlying mechanism of BSHXD for LASBC. RESULTS:According to the bioinformatics analysis, BSHXD induced several proliferation and apoptosis processes against LASBC, and the presumed targets of active components in BSHXD were mainly enriched in the HIF-1 and PI3K/AKT pathways. Flow cytometry assay and western blotting results revealed that the rate of apoptosis enhanced in a dose-dependent manner with BSHXD concentration increasing, respectively. BSHXD notably downregulated the expressions of HIF-1α, P-PI3K, PI3K, P-AKT and AKT proteins. However, adding an HIF-1α agonist restored those protein levels. CONCLUSION:The study proved that the mechanism of BSHXD in LASBC may be connected to suppressing proliferation by inhibiting the activity of the HIF-1α/PI3K/AKT signaling pathway and promoting apoptosis via the Caspase cascade in LASBC cells.

Excessive hepatic lipid accumulation and inflammatory injury are significant pathological manifestations of nonalcoholic fatty liver disease (NAFLD). Our previous research discovered that diosgenin, a natural steroidal saponin derived from Chinese herbs, can reduce hepatic lipid accumulation and steatosis; however, the exact mechanism remains unclear. This study aimed to investigate the protective mechanisms of diosgenin against NAFLD. We utilized network pharmacology and molecular docking approaches to identify the pathways through which diosgenin improves NAFLD. In high-fat diet (HFD)-fed rats, we measured biochemical markers in the serum and liver. Liver histopathology was assessed using HE and oil-red O staining. In free fatty acids (FFAs)-induced HepG2 cells, we employed the cell transfection overexpression method to verify the regulatory relationship of the identified pathways. The mechanisms in vitro and in vivo were examined using quantitative polymerase chain reaction and Western blot analyses. Bioinformatics analysis indicated that the mTOR-FASN/HIF-1α/RELA/VEGFA pathway may be the target pathway for diosgenin in alleviating NAFLD. Diosgenin inhibited hepatic lipid accumulation and pro-inflammatory cytokines in HFD-fed rats, and reduced intracellular lipid accumulation as well as TG, TC, IL-1β, and TNF-α levels in FFAs-induced HepG2 cells. Mechanistically, diosgenin downregulated the expression of p-mTOR, FASN, HIF-1α, RELA, and VEGFA, which are associated with lipid synthesis and inflammation. Overexpression of mTOR abolished the beneficial effects of diosgenin on lipid reduction and inflammation, as well as its inhibitory effects on the expression of FASN, HIF-1α, RELA, and VEGFA. In conclusion, diosgenin alleviates NAFLD through mTOR-mediated inhibition of lipid accumulation and inflammation.

Breast cancer (BC) is an important cause of cancer-related death in the world. As a subtype of BC with the worst prognosis, triple-negative breast cancer (TNBC) is a serious threat to human life and health. In recent years, there has been an increasing amount of research aimed at designing and developing nanomaterials for the diagnosis and treatment of TNBC. The purpose of this study was to comprehensively evaluate the current status and trend of the application of nanomaterials in TNBC through bibliometric analysis. Studies focusing on nanomaterials and cancer were searched from the Web of Science core collection (WOSCC) database, and relevant literature meeting the inclusion criteria was selected for inclusion in the study. VOSviewer and CiteSpace were used to perform bibliometric and visual analysis of the included publications. A total of 2338 studies were included. Annual publications have increased from 2010 to 2024. China, the United States and India were the leading countries in the field, accounting for 66.1%, 11.5% and 7.2% of publications, respectively. The Chinese Academy of Sciences and Li Yaping were the most influential institutions and authors, respectively. Journal of Controlled Release was considered the most productive journal. Cancer Research was considered to be the most co-cited journal. Drug delivery and anti-cancer mechanisms related to nanomaterials were considered to be the most widely studied aspects, and green synthesis and anti-cancer mechanisms were also recent research hotspots. In this study, the characteristics of publications were summarized, and the most influential countries, institutions, authors, journals, hot spots and trends in the application of nanomaterials in cancer were identified. These findings provide valuable insights into the current state and future direction of this dynamic field.

The present study aimed to investigate the effect of diosgenin on mammalian target of rapamycin(mTOR), fatty acid synthase(FASN), hypoxia inducible factor-1α(HIF-1α), and vascular endothelial growth factor A(VEGFA) expression in liver tissues of rats with non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin on lipogenesis and inflammation in NAFLD. Forty male SD rats were divided into a normal group(n=8) fed on the normal diet and an experimental group(n=32) fed on the high-fat diet(HFD) for the induction of the NAFLD model. After modeling, the rats in the experimental group were randomly divided into an HFD group, a low-dose diosgenin group(150 mg·kg~(-1)·d~(-1)), a high-dose diosgenin group(300 mg·kg~(-1)·d~(-1)), and a simvastatin group(4 mg·kg~(-1)·d~(-1)), with eight rats in each group. The drugs were continuously given by gavage for eight weeks. The levels of triglyceride(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), alanine transaminase(ALT), and aspartate transaminase(AST) in the serum were detected by the biochemical method. The content of TG and TC in the liver was detected by the enzyme method. Enzyme-linked immunosorbent assay(ELISA) was used to measure interleukin 1β(IL-1β) and tumor necrosis factor α(TNF-α) in the serum. Lipid accumulation in the liver was detected by oil red O staining. Pathological changes of liver tissues were detected by hematoxylin-eosin(HE) staining. The mRNA and protein expression levels of mTOR, FASN, HIF-1α, and VEGFA in the liver of rats were detected by real-time fluorescence-based quantitative polymerase chain reaction(PCR) and Western blot, respectively. Compared with the normal group, the HFD group showed elevated body weight and levels of TG, TC, LDL-C, ALT, AST, IL-1β, and TNF-α(P<0.01), increased lipid accumulation in the liver(P<0.01), obvious liver steatosis, up-regulated mRNA expression levels of mTOR, FASN, HIF-1α, and VEGFA(P<0.01), and increased protein expression levels of p-mTOR, FASN, HIF-1α, and VEGFA(P<0.01). Compared with the HFD group, the groups with drug treatment showed lowered body weight and levels of TG, TC, LDL-C, ALT, AST, IL-1β, and TNF-α(P<0.05, P<0.01), reduced lipid accumulation in the liver(P<0.01), improved liver steatosis, decreased mRNA expression levels of mTOR, FASN, HIF-1α, and VEGFA(P<0.05, P<0.01), and declining protein expression levels of p-mTOR, FASN, HIF-1α, and VEGFA(P<0.01). The therapeutic effect of the high-dose diosgenin group was superior to that of the low-dose diosgenin group and the simvastatin group. Diosgenin may reduce liver lipid synthesis and inflammation and potentiate by down-regulating the mTOR, FASN, HIF-1α, and VEGFA expression, playing an active role in preventing and treating NAFLD.

Context: Echinacoside (ECH) is a natural anti-cancer compound and is of great value in cancer treatment. However, the mechanism underlying this effect on breast cancer (BC) was unclear.Objective: To explore the mechanism of ECH treating BC by network pharmacology and experimental validation.Materials & methods: Several databases were searched to screen potential targets of ECH and obtain information on targets related to BC. STRING was applied to construct a Protein-protein interaction (PPI) network. DAVID was applied for Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Gene Expression Profiling Interactive Analysis (GEPIA) was searched for the relationship between the expression profile and overall survival of major targets in normal breast and BC tissues. Finally, the results of network pharmacology analysis were validated by experiments.Results: Seventeen targets of ECH overlapped with targets in BC. Ten hub targets were determined through PPI. By GO and KEGG analysis 15 entries and 25 pathways were obtained, in which phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), hypoxia inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) played greater roles. Validation of key targets in the GEPIA database showed that PIK3R1 and PIK3CD remained consistent with the results of the study. Experiments in vitro showed ECH inhibited proliferation, induced apoptosis and reduced mRNA levels and protein expression of PI3K, AKT, hypoxia inducible factor-1 alpha (HIF-1 alpha) and vascular endothelial growth factor A (VEGFA) in MCF-7 cells. Furthermore, experiments in vivo revealed that ECH significantly reduced tumor growth, promoted apoptosis and decreased the related mRNA levels and protein expression, suggesting ECH works on BC by regulating PI3K/AKT/HIF-1 alpha/VEGF signaling pathway.Discussion & conclusion: In summary, ECH played an important role in anti-BC by regulating PI3K/AKT/HIF-1 alpha/ VEGF signaling pathway. Furthermore, ECH had multi-target and multi-pathway effects, which may be a promising natural compound for treating BC.

目的:利用网络药理学预测补肾活血汤干预乳腺癌内分泌治疗相关骨质疏松的潜在作用机制,并通过体外细胞模型进行实验验证.方法:首先通过网络药理学筛选补肾活血汤的主要有效化学成分和作用靶点,进一步获取乳腺癌内分泌治疗相关骨质疏松相关的疾病靶点.将二者的共同靶点信息进行基因本体(GO)功能注释和京都基因与基因组百科全书(KEGG)通路富集分析.其次利用生存分析网站(Kaplan-Meier Plotter)对关键靶点进行生存分析.最后通过体外实验噻唑蓝(MTT)比色法评估细胞增殖抑制活性,蛋白免疫印迹法(Western blot)验证关键靶点及通路,并使用实时荧光定量聚合酶链式反应(Real-time PCR)评估关键靶点mRNA表达.结果:网络药理学研究共获得补肾活血汤活性成分716个,关键靶点249个,补肾活血汤和乳腺癌内分泌治疗相关骨质疏松的共同靶点135个,其中蛋白激酶B(Akt)1、低氧诱导因子-1α(HIF-1α)是两个关键靶点,靶点共涉及生物过程531种,细胞组成62种,分子功能162种,参与乳腺癌、内分泌抵抗等细胞信号通路145条;靶点有效地富集在磷脂酰肌醇3-激酶(PI3K)/Akt和低氧诱导因子(HIF)-1两条信号通路.体外实验中,MTT比色法显示,与空白组比较,22.5、45、90 g·L-1及45、90、180 g·L-1质量浓度的补肾活血汤作用48 h后分别能不同程度的降低人Luminal A型乳腺癌细胞系MCF-7和T47D细胞增殖率和细胞运动能力.将0、15、60 g·L-1 的补肾活血汤干预MCF-7细胞48 h,Western blot实验表明,与空白组比较,不同质量浓度的补肾活血汤作用于MCF-7细胞中磷酸化(p)-PI3K、PI3K、p-Akt、Akt和HIF-1α蛋白相对表达水平均降低(P＜0.05,P＜0.01),且呈浓度依赖性.采用Real-time PCR检测关键靶点HIF-1α的mRNA表达,结果显示,与空白组比较随浓度升高MCF-7细胞中HIF-1α的mRNA表达显著降低(P＜0.01),且呈浓度依赖性.结论:补肾活血汤通过PI3K/Akt/HIF-1信号通路作用于关键靶点Akt1、HIF1A,进而干预乳腺癌内分泌治疗相关的骨质疏松.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. Our previous studies have found that Shuangyu Tiaozhi Decoction (SYTZD) could produce an improvement in NAFLD-related indicators, but the underlying mechanism associated with this improvement remains unclear. The study aimed to investigate the potential mechanism of SYTZD against NAFLD through network pharmacology and experimental verification. The components of SYTZD and SYTZD drug containing serum were analyzed using ultra-performance liquid chromatography to quadrupole/time-of-flight mass spectrometry (UPLC-Q/TOF-MS). Active components and targets of SYTZD were screened by the traditional Chinese medical systems pharmacology (TCMSP) and encyclopedia of traditional Chinese medicine (ETCM) databases. NAFLD-related targets were collected from the GeneCards and DisGeNET databases. The component-disease targets were mapped to identify the common targets of SYTZD against NAFLD. Protein–protein interaction (PPI) network of the common targets was constructed for selecting the core targets. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the core targets was performed using the database for annotation, visualization, and integrated discovery (DAVID) database. Furthermore, animal and cell models were constructed for validating the predictions of network pharmacology. Lipid accumulation, liver histopathology, insulin resistance, and core gene expression were measured by oil red O staining, hematoxylin and eosin staining, insulin tolerance test, real-time quantitative polymerase chain reaction, and Western blotting, respectively. Two components and 22 targets of SYTZD against NAFLD were identified by UPLC-Q/TOF-MS and relevant databases. PPI analysis found that ESR1, FASN, mTOR, HIF-1α, VEGFA, and GSK-3β might be the core targets of SYTZD against NAFLD, which were mainly enriched in the thyroid hormone pathway, insulin resistance pathway, HIF-1 pathway, mTOR pathway, and AMPK pathway. Experimental results revealed that SYTZD might exert multiple anti-NAFLD mechanisms, including improvements in lipid deposition, inflammation, and insulin resistance. SYTZD treatment led to decreases in the lipid profiles, hepatic enzyme levels, inflammatory cytokines, and homeostatic model assessment for insulin resistance (HOMA-IR). SYTZD treatment affected relative mRNA and protein levels associated with various pathways. Our findings reveal that SYTZD could alleviate NAFLD through a multi-component, multi-target, and multi-pathway mechanism of action.

目的 探讨脓肿期肉芽肿性小叶性乳腺炎(GLM)与哺乳期乳腺炎(LM)的中医用药规律及差异.方法 筛选自建库至2021年12月发表在中国生物医学文献服务系统、中国知网、万方数据库和维普网中关于中医药治疗脓肿期GLM、LM的文献,应用中医传承计算平台分析脓肿期GLM、LM核心用药及组方规律,并比较两者差异.结果 治疗脓肿期GLM、LM的方剂中,前10位高频次药物有7味相同,3味不同.两者四气、五味、归经比较,脓肿期GLM、LM的用药均寒温并用,以苦、甘味药为主.脓肿期GLM的温性、甘味用药占比高于脓肿期LM;两者用药归经均以肝、胃、肺经为主;用药分类中均以清热、补虚、化痰、活血化瘀类药物为主,脓肿期GLM的补虚、化痰、活血化瘀类药物用药占比高于脓肿期LM.进一步分析得到脓肿期GLM潜在药对6个,脓肿期LM潜在药对7个,并各得到一组核心药物组合.结论 脓肿期GLM和LM均以清热解毒、托里排脓为治疗原则,脓肿期LM需加强扶正补虚之功,并佐以化痰、活血之品;脓肿期LM则需加强清热凉血之功.

Objective: To evaluate clinical efficacy by traditional Chinese combined with western therapy to treat upper extremity edema after breast cancer surgery. The clinical efficacy was described by the effective rate and the change of peripheral diameter of the affected limb. Methods: National Knowledge Internet (CNKI), Wan Fang Digital Journals (Wan Fang), VIP Chinese periodical service platform (VIP), Chinese biomedical literature service system (CBM), PubMed and EMBASE were searched on computer. And clinical randomized controlled trials (RCT) of the treatment of upper extremity edema after breast cancer surgery with integration of Chinese and western treatment were selected. The time was from January 2011 to May 2020. Upper extremity edema after breast cancer surgery was the first key word and the second was traditional Chinese combined with western therapy. Note Express was used to screen and extract literature. Bias risks of all the literature included in the study were evaluated and analyzed by RevMan5.3 software. Results: 10 randomized controlled clinical tests, 644 patients in conformity to the inclusion criteria, 9 for the observation of curative effectiveness, 5 of changes in limb circumference. 322 cases were included in the observation group and the same number of cases in the control group, all of which were in Chinese. The results expressed that the curative effect in the observation group was 91.1％, and it was higher than the curative effect in the control group treated by single western treatment obviously, and it was only 68.9％ [95％ CI (1.22, 1.44), Z = 6.55, P < 0.00001]. The peripheral diameter shrinking degree of the affected limb in the observation group was also clearly higher than that in the control group which was healed by simple western treatment[95％ CI (-0.98, -0.64), Z = 9.40, P < 0.00001]. Conclusion: Traditional Chinese combined with western therapy treating upper extremity edema after the surgery of breast cancer had a notable clinical effect, which treated the disease and effectively lessened the peripheral diameter of the affected limb. The method was worthy of clinical application. However, owing to the low quality of the included documents, further discussion and learning were still needed.

目的:系统评价中医与西医结合治疗乳腺癌术后出现上肢水肿的疗效,临床效果用有效率和患肢周径的变化来描述.方法:借助计算机网络检索中国知网(CNKI)、万方(Wan Fang)、维普(VIP)网、中国生物医学文献服务系统(CBM)、PubMed、Embase,检索筛选中西医结合治疗乳腺癌术后上肢水肿的临床随机对照试验(RCT),查阅时间范围是2011年1月～2020年5月,检索关键词是乳腺癌术后上肢水肿、中西医治疗,管理软件Note Express用来进行文献筛选和数据提取,Meta分析借助于软件RevMan5.3操作,研究中所有需要的文献指标均被采纳.结果:10篇临床随机对照试验,644例患者符合纳入标准,9篇为治疗有效率观察,5项是患肢周径的变化研究,观察组322例,对照组322例,纳入的文献全部为中文文献.研究结果表明,对照组(单纯西医治疗)对于乳腺癌术后上肢水肿治疗的有效率为68.9％,明显低于观察组(中西医结合治疗)有效率91.1％[95％CI(1.22,1.44),Z=6.55,P<0.00001];观察组(中西医结合治疗)患肢周径减小程度明显高于对照组(单纯西医治疗)[95％CI(-0.98,-0.64),Z=9.40,P<0.00001].结论:中西医结合方法治疗乳腺癌术后上肢水肿的临床效果显著,可以明显提高水肿缓解率,有效减小患肢周径,在临床上值得推广和使用.但是,由于纳入文献的质量较低,因此仍需要进一步的研究与学习.

Background : Triple-negative breast cancer (TNBC) progresses at a rapid pace. Chemotherapy is a major clinical application. However, resistance and metastases are key barriers to chemotherapy. Xiaojin pills (XJP) have been used clinically for treating TNBC for decades. However, the potential molecular mechanisms of the effect of XJP on breast cancer is still not understood. Methods: The cell viability was analyzed using Cell Counting Kit-8 (CCK-8). Flow cytometry was used to detect apoptosis, and the migration and invasion abilities of TNBC were assessed using Transwell assay. For molecular mechanisms, the protein expression levels were determined by Western blot analysis. The expression of β-catenin in the Wnt/β-serial protein (β-catenin) pathway was detected with immunofluorescence (IF). Results: XJP inhibited the viability and proliferation of the TNBC cell line in vitro . Flow cytometry analysis showed that apoptosis increased in both MDA-MB-231 and MDA-MB-468 cells induced by XJP. The expression of the proteins associated with invasion, for example, matrix metalloproteinase (MMP) and MMP9, was reduced. Among epithelial–mesenchymal transition markers, E-cadherin was upregulated and N-cadherin was downregulated. The apoptosis-related proteins caspase-8, caspase-3, caspase-9, and Parp were all upregulated. Additionally, XJP effectively suppressed the expression of β-catenin, which belonged to the Wnt/β-catenin pathway. Conclusions: These results suggested that XJP suppressed the progression of TNBC cells by suppressing apoptosis, invasion, EMT, and Wnt/β-catenin pathway.

Background: With the development of Traditional Chinese Medicine (TCM), comprehensive traditional Chinese therapy is often used to treat Granulomatous Lobular Mastitis (GLM), but the effectiveness and risk are still controversial. This study is aimed to evaluate the efficacy of comprehensive therapy of traditional Chinese medicine on GLM. Methods: Articles in both international databases (PubMed, EMBASE, Cochrane Library, Web of Science and Clinicaltrials.gov) and Chinese databases (Chinese National Knowledge Internet (CNKI), Chinese Biomedical Databases (CBM), VIP Chinese periodical service platform and Wan Fang Digital Journals)) were searched. Original studies which reported the effective rate and/or recurrence rate and/or maximum diameter of the mass of comprehensive traditional Chinese therapy were included. The 95% confidence interval (95% CI) for effective rate, recurrence rate and maximum diameter of the mass were calculated and analyzed by review manager 5.3. Results: Eight eligible trials with 309 cases and 265 controls were included, six in Chinese and two in English. Statistical analysis suggested a statistical difference in effective rate ( RR = 0.86, 95% CI [0.74, 1.00], P = 0.047 ) between comprehensive traditional Chinese therapy group and control. Meanwhile, there was statistical difference found in recurrence rate between comprehensive traditional Chinese therapy and western medicine therapy ( RR = 3.09, 95% CI [1.50, 6.40], P = 0.002 ). Besides, no statistical difference existed in maximum diameter of the mass between the two therapies ( RR = -5.25, 95% CI [-125.42, 114.93], P = 0.93). Conclusion: Although there was no significant difference in the reduction of breast mass size between comprehensive traditional Chinese therapy and western medicine alone, comprehensive traditional Chinese therapy demonstrated the efficacy in improving the effective rate and reducing the recurrence rate. For GLM patients, comprehensive traditional Chinese therapy could be a potential option.