The pharmacological effects of the natural product triptonoterpene have been scarcely documented. In our preliminary investigations, we identified that triptonoterpene possesses the capacity to impede the invasion and migration of gastric cancer (GC) cells. We are committed to further exploring the potential extensive effects of triptonoterpene on GC and to clarifying its exact mechanism of action. This study was designed to examine the influence and underlying mechanisms of triptonoterpene on apoptosis in GC cells. Treatment with triptonoterpene effectively inhibited the proliferation of GC cells. We noted that triptonoterpene was capable of inducing apoptosis in GC cells, a process mediated through the mitochondrial pathway. Additionally, triptonoterpene was found to inhibit the polymerization of the actin cytoskeleton. The presence of triptonoterpene also disrupted the ROCK/LIMK/cofilin signaling pathway in GC cells. We hypothesize that triptonoterpene may trigger the mitochondrial apoptosis pathway by modulating the actin cytoskeleton. By employing Latrunculin A (LAT-A, an actin filament disruptor) and BMS-5 (a LIMK inhibitor) to manipulate actin dynamics, we observed that both LAT-A and BMS-5 enhanced triptonoterpene-induced apoptosis and the accumulation of reactive oxygen species (ROS), and intensified the decline in mitochondrial membrane potential (MMP). Intriguingly, we discovered that GC cells treated with triptonoterpene exhibited mitochondrial fragmentation and colocalization of cofilin-1 with mitochondria. Western blot analysis further revealed that triptonoterpene facilitated the translocation of cofilin-1 from the cytoplasm to the mitochondria. Finally, the results of our in vivo experiments indicated that triptonoterpene significantly inhibited the proliferation of xenograft tumors and induced tumor cell apoptosis. This study provides experimental evidence for the development of triptonoterpene and explores new pathways for cancer treatment.

Metabolomics and 16S rDNA sequencing have shown great potential in elucidating complex mechanisms associated with diseases. Currently, there is little research on the omics of gastric cancer and it lacks effective biomarkers. Objective Based on plasma metabolomics and 16S rDNA sequencing to evaluate the changes in metabolites and fecal microbiota of advanced gastric cancer. Method Firstly, plasma metabolomics was used to screen for differential metabolites and metabolic pathways in gastric cancer. Then, 16S rDNA sequencing was performed on fecal samples to study the differential intestinal microbiota in gastric cancer patients. Finally, conduct a correlation analysis between them. Result A total of 152 differential metabolites were identified, and we screened 10 of them. All metabolites were enriched into 42 differential metabolic pathways, of which 13 have P values less than 0.05. 16S rDNA sequencing showed significant differences in 4 microbial communities at the phylum level. There are significant differences in 23 communities at the genus level. We focus on Lactobacillales, Lactobacillus, Streptococcus, Veillonella, Bacilli and Megasphaera. Correlation analysis shows that the intestinal microbiota and plasma metabolites jointly affect the occurrence and development of gastric cancer. Conclusion For the first time, we comprehensively used plasma metabolomics and 16S rDNA sequencing to reveal the changes and correlations between metabolites and intestinal microbiota in advanced gastric cancer. We have discovered new potential biomarkers for gastric cancer. This deepens our understanding of the physiological and pathological mechanisms of advanced gastric cancer and helps to improve the diagnosis and treatment of advanced gastric cancer.

BACKGROUND:Electronic patient-reported outcomes (ePROs)-based cancer symptom management presents an opportunity to improve patient outcomes by optimizing symptom detection and prompting clinician interventions in tertiary hospitals. However, real-world evidence is limited, especially in primary health care (PHC) settings, which are accompanied by more complex and unknown influencing factors. OBJECTIVE:We conducted a qualitative study to identify facilitators and barriers associated with the implementation of ePRO-based symptom management in China's PHC settings under the implementation science (IS) framework. We further developed strategies and recommendations for real-world practices and health policies. METHODS:This qualitative study was conducted from October to December 2023 in 9 purposively selected PHC institutions (5 urban and 4 rural) across 5 administrative districts of Yangzhou, Jiangsu Province, China. Community-dwelling patients with cancer, PHC providers, and medical supervisors participated in semistructured interviews and focus group discussions. We used 2 subframeworks under the IS framework-the Consolidated Framework for Implementation Research and Expert Recommendations for Implementing Change-to conduct data analysis and generate strategies. RESULTS:A total of 72 individuals were invited to participate in this study, including 35 community-dwelling patients with cancer (median 66, IQR 60-71.5 years; n=21, 60% men) and 23 PHC personnel (median 45, IQR 27-51 years; n=12, 52.17% men) who participated in semistructured interviews, and 14 medical supervisors (median 47.5, IQR 36.5-54 years; n=10, 71.43% men) who participated in focus group discussions. This study identified 29 barriers and 21 facilitators, and then developed 13 strategies. Crucial challenges include PHC providers' low self-efficacy and unclear role identification, coupled with community-dwelling patients' mistrust of primary care, cancer stigma, and fatalistic beliefs, which further reduce motivation; poor integration of ePRO with existing workflows and the absence of performance incentive mechanisms; a lack of nationwide standardized implementation guidelines and quality evaluation criteria; and outdated medical equipment and a limited range of medications. Common challenges included weak collaborative relationships and insufficient funding. CONCLUSIONS:Grounded in the IS framework, our study identifies 3 critical priorities for implementing ePRO-based cancer symptom management in PHC settings, including addressing individual-level motivational deficiencies among community-dwelling patients with cancer and PHC providers by resolving misconceptions, bridging knowledge gaps, and establishing supportive incentives; developing supportive medical partnerships and advancing tiered management systems to empower PHC settings; and creating standardized operational guidelines with clear workflows and implementing real-world data-driven regulatory feedback mechanisms to ensure quality control.

Abstract Background Celastrus orbiculatus has been used as a folk medicine in China for the treatment of many diseases. In the laboratory, the ethyl acetate extract of Celastrus orbiculatus (COE) displays a wide range of anticancer functions. However, the inhibition of the metastasis mechanism of COE in gastric cancer cells has not been investigated so far. Methods The present study was undertaken to determine if the anti-metastasis effect of COE was involved in inhibiting of epithelial–mesenchymal transition (EMT) of human gastric adenocarcinoma SGC-7901 cells. In vitro, a well-established experimental EMT model involving transforming growth factor β1 (TGF-β1) was applied. Viability, invasion and migration, protein and mRNA expression of tumor cells were analyzed by MTT assay, transwell assay, western blot and real-time PCR, respectively. The molecular targets of COE in SGC-7901 cells were investigated by two-dimensional gel electrophoresis (2-DE) and MALDI-TOF-TOF mass spectrometer. Overexpression of heat shock protein 27 (HSP27) was performed by transfected with the recombinant retroviral expression plasmid. In vivo, the anti-metastasis mechanisms of COE in the peritoneal gastric cancer xenograft model was explored and the effect was tested. Results The non-cytostatic concentrations of COE effectively inhibited TGF-β1 induced EMT process in SGC-7901 cells, which is characterized by prevented morphological changes, increased E-cadherin expression and decreased Vimentin, N-cadherin expression. Moreover, COE inhibited invasion and migration induced by TGF-β1. Using a comparative proteomics approach, four proteins were identified as differently expressed, with HSP27 protein being one of the most significantly down-regulated proteins induced by COE. Moreover, the activation of nuclear factor κB (NF-κB)/Snail signaling pathway induced by tumor necrosis factor-α (TNF-α) was also attenuated under the pretreatment of COE. Interestingly, overexpression of HSP27 significantly decreases the inhibitory effect of COE on EMT and the NF-κB/Snail pathway. Furthermore, COE significantly reduced the number of peritoneal metastatic nodules in the peritoneal gastric cancer xenograft model. Conclusions Taken together, these results suggest that COE inhibits the EMT by suppressing the expression of HSP27, correlating with inhibition of NF-κB/Snail signal pathways in SGC-7901 cells. Based on these results, COE may be considered a novel anti-cancer agent for the treatment of metastasis in gastric cancer.

ETHNOPHARMACOLOGICAL RELEVANCE:With the rapid development of China's economic level, great changes have taken place in people's diet structure, gout has become a common disease that puzzles people's health, seriously affects the realization of China's "Healthy China" strategic goal. Gouty arthritis (GA) is a common joint disease caused by chronic purine metabolism disorder. Currently, drugs used to treat GA are allopurinol and colchicine. However, these drugs can only temporarily relieve the clinical symptoms of GA with significant side effects. More and more basic and clinical studies have confirmed that Traditional Chinese medicine has definite curative effect on GA.AIM OF THE STUDY:To elucidate the potential molecular mechanism of Tongfengkang (TFK) in the treatment of GA, and to provide experimental basis for the search and development of efficient and low-toxicity Chinese medicine for GA treatment.MATERIALS AND METHODS:Aqueous extract of TFK (AETFK) were determined by liquid phase high resolution mass spectrometry and the possible effective constituents were screened out. Acute GA model rats were established to detect the anti-inflammatory and detumification effects of AETFK on GA and explore the potential mechanism. The effect of AETFK on serum uric acid and urinary uric acid levels in acute GA rats was determined by automatic biochemical analyzer, and the effect of AETFK on the expression of acute GA-related immunoinflammatory factors were determined by protein thermal fluorescence chip. The effect of AETFK on the concentration of neutrophils in the joint fluid of acute GA rats were determined by Reichs-Giemsa staining. The effect of AETFK on macrophage activation was detected by ELISA. In order to further investigate the mechanism of AETFK in the treatment of GA, a rat model of hyperuricemia was established to detect the effect of AETFK on the level of uric acid in hyperuricemia model rats. Biochemical indexes of liver and kidney and hematoxylin-eosin staining (HE) were used to evaluate the effects of AETFK on the organs, and to preliminatively evaluate the safety of ventilation confufang.RESULTS:Compared with the model group, the joint swelling degree of GA rats in AETFK treatment group were significantly reduced, and the levels of blood uric acid and urine uric acid were also significantly decreased. Protein thermal fluorescence microarray results showed that the levels of gout - related inflammatory factors in GA rats in AETFK treatment group were significantly lower than those in control group. Reichsen-giemsa staining and ELISA showed that AETFK could reduce the activation of macrophages and the accumulation of neutrophils in the joint fluid. The results of liver and kidney biochemical indexes and HE staining showed that no obvious tissue damage was observed in the organs of rats treated with AETFK.CONCLUSIONS:AETFK not only has significant anti-inflammatory effects on GA, but also can significantly reduce the level of blood uric acid in GA rats, without obvious toxic and side effects. These effects may be related to AETFK's inhibition of neutrophil enrichment and macrophage activation during early inflammation.

The lymphoma incidence rate is on the rise, with invasive forms particularly prone to relapse following conventional treatment, posing a significant threat to human life and wellbeing. Numerous studies have shown that traditional Chinese botanical drug medicine offers promising therapeutic benefits for various malignancies, with previous experimental findings indicating that Celastrus orbiculatus extract effectively combats digestive tract tumors. However, its impact on lymphoma remains unexplored. This study aims to investigate the impact and underlying mechanisms of COE on the proliferation and apoptosis of Burkitt lymphoma cells. We diluted COE in RPMI-1640 medium to create various working concentrations and introduced it to human Burkitt lymphoma Raji and Ramos cells. To evaluate cell viability, we used the CCK-8 assay, and we observed morphological changes using HE staining. We also conducted Annexin V-PI and JC-1 staining experiments to assess apoptosis. By combining the cell cycle experiment with the EDU assay, we gained insights into the effects of COE on DNA replication in lymphoma cells. Using Western blotting, we detected alterations in apoptosis-related proteins. In vivo experiments revealed that following COE intervention, tumor volume decreased, survival time was prolonged, spleen size reduced, and the expression of tumor apoptosis-related proteins changed. Our findings indicate that COE effectively inhibits lymphoma cell proliferation and promotes apoptosis by regulating these apoptosis-related proteins.

目的 分析乳腺癌患者健康信息需求现状并探讨其影响因素,为针对需求设计相关的教育内容提供依据.方法 2022年7月对江苏省扬州市中医院诊治的乳腺癌患者进行健康信息需求调查,采用乳腺癌患者需求量表评估其需求现状,采用描述性分析方法对乳腺癌患者健康信息需求进行分析,并对健康信息需求影响因素进行单、多因素分析.结果 纳入有效研究对象661例.健康信息需求总体条目均分(2.87±0.25)分,由高到低依次为康复信息、治疗信息、认知需求、情感需求、寻求希望、自我实现,条目均分分别为(3.20±0.31)、(3.11±0.28)、(2.97±0.22)、(2.51±0.18)、(2.14±0.16)、(1.96±0.20)分.多重线性回归分析结果显示年龄(β'=-0.074)、文化程度(β'=-0.365)、生育情况(β'=-0.177)、疾病分期(β'=0.133)、治疗阶段(β'=0.450)、是否保留乳房(β'=0.325)是乳腺癌患者健康信息需求的影响因素.结论 乳腺癌患者健康信息需求由高到低依次为康复信息、治疗信息、认知需求、情感需求、寻求希望、自我实现内容,需求现状受到多种因素影响,应当结合患者个体差异以及健康信息需求评估结果制订针对性健康教育方案,帮助患者提高疾病认知及治疗依从性,改善生存质量.

目的:探讨胃癌组织中P2RX7的表达水平与胃癌脾虚毒蕴证的相关性,并探讨胃癌脾虚毒蕴证的危险因素.方法:收集胃癌新发病例的中医四诊资料,填写中医症状调查表,并进行辨证分型,收集患者的手术或胃镜石蜡切片进行免疫组织化学检测,采用x2检验、Pearson相关性分析和二分类Logistic回归分析方法研究P2RX7表达与胃癌脾虚毒蕴证的关系.结果:本研究共纳入80例胃癌患者.其中男42例,女38例;有肿瘤家族史者21例;P2RX7高表达者47例,低表达者33例;TNM分期为Ⅰ期者4例,Ⅱ期者19例,Ⅲ期者44例,Ⅳ期者13例;中医辨证为脾虚毒蕴证者36例,非脾虚毒蕴证者44例.胃癌脾虚毒蕴证患者的P2RX7蛋白表达水平显著高于胃癌非脾虚毒蕴证患者(P＜0.05),Pearson相关性分析显示P2RX7与脾虚毒蕴证存在相关性(R2=0.253,P＜0.01),Logistic回归分析显示P2RX7蛋白高表达和肿瘤家族史是胃癌患者脾虚毒蕴证的独立危险因素(P＜0.05).结论:胃癌脾虚毒蕴证患者的肿瘤组织中P2RX7显著高表达,胃癌患者肿瘤组织中P2RX7表达状态与脾虚毒蕴证相关,且P2RX7高表达是胃癌患者脾虚毒蕴证的独立危险因素.

ETHNOPHARMACOLOGICAL RELEVANCE:The traditional Chinese medicine herb Celastrus orbiculatus Thunb. is an important folk medicinal plant in China that has been used as an anti-inflammatory, antitumor, and analgesic in various diseases. Recent years, many studies have reported the significant effects of Celastrus orbiculatus Thunb. extract (COE) on gastric cancer. However, the specific mechanism by which COE regulates gastric cancer cytoskeleton remodeling and thus inhibits EMT has not yet been reported.AIM OF STUDY:To study the effect and mechanism of COE in inhibiting the epithelial-mesenchymal transition (EMT) and metastasis of gastric cancer cells, laying an experimental foundation for the clinical application and further development of COE.METHODS:The high-content cell dynamic tracking system was used to continuously track the trajectory of cell movement in real time. Through the high-content data, the average movement distance and movement speed of the cells are calculated. Additionally, the dynamic images of the cell movement in the high-content imaging system are derived to analyze the impact of COE on the movement of gastric cancer cells. Cytoskeleton staining experiment was performed to detect the effect of COE on the assembly of gastric cancer cell cytoskeleton proteins. Western blot was employed to detect the changes of EMT and metastasis-related proteins in the gastric cancer cells treated by COE. The effect of COE on the key regulatory protein Cofilin-1 (CFL1) of cell movement was examined by Western blot and protein degradation experiment. The effect of COE on EMT and metastasis of the gastric cancer cells lacking CFL1 was assessed by a transwell assay. The in vivo inhibitory effect of COE on EMT and metastasis of gastric cancer was determined by the animal living image system. IHC assays were used to detect the levels of EMT-related proteins in COE reversal in vivo.RESULT:The results showed that the movement distance and average movement speed of gastric cancer cells after COE treatment were significantly lower than those of the control group. Cytoskeleton staining experiments revealed that COE can significantly change the distribution of skeletal proteins in gastric cancer cells. Additionally, COE treatment significantly reduced the expression of Matrix metalloproteinases (MMP-2, MMP-9) and other proteins. Furthermore, COE can significantly accelerate the degradation of CFL1 protein, and both COE treatment and CFL1 deletion can significantly inhibit EMT and metastasis of gastric cancer cells. Lastly, the number of peritoneal metastases of gastric cancer cells was significantly reduced in animals after COE treatment. COE can reverse the levels of EMT-related proteins while reducing the expression levels of CFL1 protein in vivo.CONCLUSION:COE can significantly inhibit EMT and metastasis of gastric cancer cells in vivo and in vitro. This effect may be achieved by reducing the stability of CFL1 and inhibiting the assembly of actin in gastric cancer cells.

Background:Signal transducers and activators of transcription (STAT) proteins, well-known cytoplasmic transcription factors, were found to be abnormally expressed in various cancers and play essential parts in the initiation, progression and therapy resistance of cancer. Nevertheless, the functions of different STATs in pancreatic cancer (PC) and their relationship to the prognosis and immune infiltration as well as drug efficacy in PC patients have not been systematically elucidated.Methods:Expression, prognosis, genetic alterations and pathway enrichment analyses of the STAT family were investigated via Oncomine, GEPIA, Kaplan Meier-plotter, cBioPortal, Metascape and GSEA. Analysis of tumor immune microenvironment was conducted by ESTIMATE and TIMER. "pRRophetic" packages were used for analysis of chemotherapeutic response. Finally, the diagnostic and prognostic value of key STATs were further validated through public datasets and immunohistochemistry.Results:In this study, only STAT1 mRNA level was significantly increased in tumor tissues and highly expressed in PC cell lines via multiple datasets. PC patients with higher STAT1/4/6 expression had a worse overall survival (OS) and progression-free survival (PFS), while higher STAT5B expression was correlated with better prognosis in the TCGA cohort. The STATs-associated genes were enriched in pathways about the remodeling of tumor immune microenvironment. The STATs levels were significantly correlated with immune infiltration, except STAT6. The STAT1 was identified as a potential biomarker and its diagnostic and prognostic value were further validated at mRNA and protein levels. GSEA showed that STAT1 may be involved in the progression and immune regulations of PC. Moreover, STAT1 expression was significantly related to the level of immune checkpoint, and predicted immunotherapy and chemotherapy responses.Conclusion:STAT family members were comprehensively analyzed and STAT1 was identified as an effective biomarker for predicting the survival and therapeutic response, which could be beneficial to develop better treatment strategies.

Background:Banxia Xiexin decoction (BXD) is a classic traditional Chinese medicine (TCM) formula clinically used to treat chronic gastritis, gastric ulcers, gastric cancer, and many other gastrointestinal diseases. Long noncoding RNAs (lncRNAs) have been shown to play an important role in maintaining the malignant phenotype of tumors. However, no relevant studies have shown whether Banxia Xiexin decoction regulates and controls lncRNA TUC338, and the effect of TUC338 on the regulation of gastric cancer invasion and metastasis remains unclear.Purpose:To investigate the ability of the traditional Chinese medicine (TCM) Banxia Xiexin decoction (BXD) to inhibit the migration and invasion of human gastric cancer AGS cells by regulating the long noncoding RNA (lncRNA) TUC338.Methods:UHPLC‒MS/MS was used to analyze the chemical components of BXD. MTT was performed to determine the effects of BXD on the proliferation of AGS cells. qRT‒PCR was used to determine the expression of lncRNA TUC338 in gastric cancer tissues, paracarcinoma tissues, AGS human gastric cancer cells and GES-1 normal gastric mucosa cells and to evaluate the effects of BXD on the expression of lncRNA TUC338 in AGS cells. Lentiviral transfection was used to establish human gastric cancer AGS cells with knocked down lncRNA TUC338 expression. The effects of lncRNA TUC338 knockdown on the migration and invasion of AGS cells were observed by a scratch assay and Transwell migration assay, respectively. Western blotting was performed to analyze the effects of lncRNA TUC338 knockdown on epithelial-to-mesenchymal transition (EMT) in AGS cells. We performed quality control on three batches of BXD. We used UHPLC‒MS/MS to control the quality of three random batches of BXD used throughout the study.Results:Ninety-five chemical components were identified from the water extract of BXD, some of which have anticancer effects. The expression of TUC.338 in gastric cancer tissues was higher than that in para-carcinoma tissues. BXD inhibited the invasion and migration of gastric cancer cells by inhibiting the expression of lncRNA TUC338, which reduced EMT. After knockdown of lncRNA TUC338, the migration and invasion of AGS cells were reduced; the expression of the EMT-related protein E-cadherin was increased, and the expression of N-cadherin and vimentin was reduced.Conclusions:The present results suggest that BXD has potential as an effective treatment for gastric cancer through the inhibition of lncRNA TUC338 expression.

Long non-coding RNA (lncRNA) contains rich information and functions. The research on Traditional Chinese Medicine (TCM) targeting lncRNA mainly involves tumors, cardiovascular diseases, endocrine and metabolic related diseases, osteoporosis and other diseases, which are used to explore the mechanism of TCM and the differetiation of TCM syndromes or constitution, etc. LncRNA has important application prospects in the field of TCM. The study of lncRNA may provide new ways and technical methods for the research of modern TCM.

ObjectivesColorectal cancer(CRC) is a common malignant tumor. Recent studies have found that lncRNAs play an important role in the occurrence and development of colorectal cancer.MethodsBased on high-throughput sequencing results of fresh CRC tissues and adjacent tissues, we identified lncRNA-ENST00000543604 (lncRNA 604) as the research object by qRT-PCR in CRC tissues and cells. We explored the mechanism of lncRNA 604 action by using luciferin reporter, qRT-PCR and Western blot assays. Kaplan-Meier survival analysis and a Cox regression model were used to analyze the correlation of lncRNA 604 and its regulatory molecules with the prognosis of and chemotherapy efficacy in CRC patients.ResultsIn this study, we found that the expression levels of lncRNA 604 were increased in CRC. LncRNA 604 could promote CRC cell proliferation and metastasis through the miRNA 564/AEG-1 or ZNF326/EMT signaling axis in vivo and in vitro. LncRNA 604 could predict the prognosis of CRC and was an independent negative factor. LncRNA 604 exerted a synergistic effect with miRNA 564 or ZNF326 on the prognosis of CRC. LncRNA 604 could improve chemoresistance by increasing the expression of AEG-1, NF-κB, and ERCC1.ConclusionsOur study demonstrated that lncRNA 604 could promote the progression of CRC via the lncRNA 604/miRNA 564/AEG-1/EMT or lncRNA 604/ZNF326/EMT signaling axis. LncRNA 604 could improve chemoresistance by increasing drug resistance protein expression.

Cancer is one of the greatest threats to human health. Gastric cancer (GC) is the fifth most common malignant tumor in the world. Invasion and metastasis are the major difficulties in the treatment of GC. Herbal medicines and their extracts have a lengthy history of being used to treat tumors in China. The anti-tumoral effects of the natural products derived from herbs have received a great deal of attention. Our previous studies have shown that the traditional Chinese herb Celastrus orbiculatus Thunb extract (COE) can inhibit the invasion and metastasis of GC cells, but the specific anti-cancer components of COE are still unclear. Dozens of natural products from COE have been isolated and identified by HPLC spectroscopy in our previous experiments. Triptonoterpene is one of the active ingredients in COE. In this study, we focused on revealing whether Triptonoterpene has an excellent anti-GC effect and can be used as an effective component of Celastrus orbiculatus Thunb in the treatment of tumors. We first observed that Triptonoterpene reduces GC cell proliferation through CCK-8 assays and colony formation experiments. The cell adhesion assays have shown that Triptonoterpene inhibits adhesion between cells and the cell matrix during tumor invasion. In addition, the cell migration assay has shown that Triptonoterpene inhibits the invasion and migration of GC cells. The high-connotation cell dynamic tracking experiment has also shown the same results. The effects of Triptonoterpene on epidermal mesenchymal transition (EMT)-related and matrix metalloproteinases (MMPs)-related proteins in gastric cancer cells were detected by Western blots. We found that Triptonoterpene could significantly inhibit the changes in EMT-related and invasion and metastasis-related proteins. Altogether, these results suggest that Triptonoterpene is capable of inhibiting the migration and invasion of GC cells. Triptonoterpene, as a natural product from Celastrus orbiculatus Thunb, has significant anti-gastric cancer effects, and is likely to be one of the major equivalent components of Celastrus orbiculatus Thunb.

Background: Poria cocos (P. cocos) is an important medicinal fungus in traditional Chinese medicine. Poria acid (PA), a triterpenoid compound, is an effective component of traditional Chinese medicine P. cocos. This experiment investigated the anti-gastric cancer biological activity of PA in vitro. Methods: The effect of PA on the viability of gastric cancer cells was detected by the thiazolyl blue (MTT) assay. Cell adhesion assays were used to detect changes in the adhesion of cells treated after PA (0, 20, 40, and 80 µmol/L). The ability of cell invasion and migration were detected by Transwell assays and wound healing assays. A high-content imaging system was used to dynamically record the motility of the gastric cancer cells after PA (0, 20, 40, and 80 µmol/L) treatment. Western blotting was used to detect the expression of epithelial–mesenchymal transformation (EMT), invasion and migration related proteins. Results: The MTT assay showed that the proliferation of gastric cancer cells was significantly inhibited after PA treatment. Cell adhesion experiments showed that the adhesion of gastric cancer cells was significantly decreased after PA treatment. Compared with the control group, the wound healing area of the gastric cancer cells treated with different concentrations of PA decreased. The Transwell assay showed that the number of gastric cancer cells passing through the cell membrane were significantly reduced after PA treatment. In addition, after PA treatment, the cells’ movement distance and average movement speed were significantly lower than those of the control group. Finally, PA can significantly alter the expression of EMT-related proteins E-cadherin, N-cadherin, and Vimentin and decreased the expressions of metastasis-related proteins matrix metalloproteinase (MMP) 2, MMP-9 and tissue inhibition of matrix metalloproteinase (TIMP)1 in the gastric cancer cells. Conclusions: Triterpenoids from P. cocos have significant biological activity against gastric cancer, and the mechanism may be involved in the process of epithelial–mesenchymal transformation.

目的:探讨和评价中药外敷、耳穴揿针及耳穴压豆中医外治技术联合三阶梯止痛治疗对晚期癌痛患者临床相关症状的干预效果.方法:选取本院肿瘤内科2020年7月至2021年8月收治的合并中、重度癌性疼痛、负性情绪、睡眠障碍及心理痛苦等相关症状的晚期癌症患者90例,按照中医外治护理干预措施的不同分为A组、B组、C组(每组30例).其中,A组单纯接受中西医药物治疗方案,针对疼痛程度遵循三阶梯止痛原则给予口服止痛药及抗焦虑药物;B组在A组治疗方案上联合院内制剂"抗癌止痛膏"中药穴位外敷;C组在B组治疗方案上联合耳穴揿针及耳穴压豆.对比三组患者干预4周后的癌性疼痛程度(NRS)、消极情绪(综合性医院焦虑抑郁量表HAD)、失眠(睡眠质量匹兹堡指标PSQI)及心理痛苦(DT)的缓解程度.结果:干预前,三组患者NRS、HAD、PSQI及DT得分比较,均无明显差异(P>0.05);干预4周,三组患者疼痛程度均有明显缓解,三组缓解程度差异不明显(P>0.05);A组干预前后的HAD、PSQI、DT评分无明显变化(P>0.05);B、C两组干预后的HAD得分均明显低于本组干预前,C组较B组的降低幅度更明显(P<0.05);干预后的B组PSQI及DT评估得分与干预前比较变化不明显(P>0.05),干预后的C组PSQI及DT评估得分较与干预前差异明显(P<0.05),且显著优于B组相应项目(P<0.001).结论:三阶梯止痛方案联合中药穴位外敷、耳穴揿针及耳穴压豆中医外治干预措施,可以明显缓解晚期癌痛患者癌痛、失眠及心理痛苦等临床相关症状,多种措施联合应用,效果更为显著.

BACKGROUND Gastric cancer is the fifth most common tumor and has the third-highest mortality rate among various malignant tumors, and the survival rate of patients is low. Celastrus orbiculatus extract (COE) has been shown to inhibit the activity of a variety of tumors. In this study, we examined the inhibition of the epithelial-mesenchymal transition (EMT) process in gastric cancer cells by COE through the transforming growth factor-β(TGF-β) signaling pathway. METHODS COE was first diluted to various concentrations and then used to treat SGC-7901, BGC-823, MGC-803, and AGS cells. Cell proliferation was assessed by an MTT (thiazole blue) assay. Transwell assays were used to assess cell invasion and migration. The high-content imaging technology was used to further observe the effects of the drug on cell invasion and migration. Western blotting was used to assess the effects of the drug on the expression of EMT and Smad2/3 signaling pathway-related proteins. RESULTS We found that COE inhibited the migration and invasion of AGS gastric cancer cells in a dose-dependent manner. Consequently, COE decreased the expression of EMT-related proteins and proteins related to the Smad2/3 signaling pathway in gastric cancer cells, inhibiting the migration and invasion of gastric cancer cells, and this effect occurred through the TGF-β signaling pathway. SUMMARY We investigated that COE could inhibit the proliferation of gastric cancer cells and inhibit invasion and metastasis by inhibiting the EMT process at the molecular level and its effect on the TGF-β signaling pathway.

Yi-Fei-Jie-Du-Tang (YFJDT) is a traditional Chinese medicine formulation. Our previous studies have demonstrated that YFJDT can be used to treat non-small-cell lung cancer (NSCLC), but its protective effect against NSCLC and its mechanisms remain unclear. In the present study, we evaluated the protective effects and potential mechanisms of YFJDT on a tumor-bearing mouse lung cancer model and A549 cell model. Tumor-bearing mice and A549 cells were treated with YFJDT, tumors were measured during the experiment, and tumor tissues and cell supernatants were collected at the end of the experiment to assess the levels of autophagy and epithelial-mesenchymal transition (EMT)-related proteins. The results showed that YFJDT treatment reduced tumor volume and mass, increased the expression of the autophagy marker LC3, and inhibited EMT-related proteins compared with the model group. Cell survival was reduced in the YFJDT-treated groups compared with the model group, and YFJDT also reduced the migration and invasion ability of A549 cells in a dose-dependent manner. Western blotting detected that YFJDT also upregulated FAT4 in the tumor tissue and A549 cells and downregulated the expression of vimentin. Meanwhile, apoptosis in both tissues and cells was greatly increased with treatment of YFJDT. We further interfered with FAT4 expression in cells and found that the inhibitory effect of YFJDT on EMT was reversed, indicating that YFJDT affects EMT by regulating FAT4 expression. Taken together, results of this study suggested that the inhibitory effect of YFJDT on EMT in lung cancer tumors is through upregulating FAT4, promoting autophagy, and thus inhibiting EMT in cancer cells.

毒邪是对导致脏腑功能紊乱、气血阴阳失调的多种病理因素的总体概括,总属于现代中医病因病理学范畴,其致病症状不一,病症繁多.毒邪的产生、发展和清除均与脾的运化功能密切相关,脾主运化作为脾藏象发挥功能的重要基础,主导物质和能量的新陈代谢.本文试从脾主运化理论角度,分析毒邪形成及损伤机体的病因病理,明确"脾主运化"功能在机体清除毒邪过程中的重要性.

Objective. This study aimed to find new biomarkers of prognosis and metabolomic therapy for gastric carcinoma (GC) treated with chemotherapy and investigate the metabolic mechanism of the Jianpi Yangzheng Xiaozheng (JPYZXZ) decoction in the treatment of GC. Methods. First, 36 patients with GC were randomly assigned to the treatment (chemotherapy plus JPYZXZ) and control (chemotherapy alone) groups. The clinical efficacy, side effects, and quality of life of patients in the two groups were evaluated after treatment. Then, the serum samples taken from 16 randomly selected patients (eight treatment cases and eight control cases with no evident pattern characters) and eight healthy volunteers were tested to identify the differential metabolite under the gas chromatography-time-of-fight mass spectrometry platform. The relevant metabolic pathways of differential substances were analyzed using multidimensional statistical analysis. Results. JPYZXZ combined with chemotherapy resulted in a lower risk of leucopenia, thrombocytopenia, and gastrointestinal reaction (P < 0.05). Additionally, patients in the treatment group showed a higher Karnofsky (KPS) scale (P < 0.05). Compared with healthy persons, patients with GC were found to have 26 significant differential metabolites after chemotherapy; these metabolites are mainly involved in 12 metabolic pathways, such as valine, leucine, and isoleucine biosynthesis. JPYZXZ primarily influences the pentose phosphate pathway; glutathione metabolism; glyoxylate and dicarboxylate metabolism; porphyrin and chlorophyll metabolism; and glycine, serine, and threonine metabolism of patients with GC treated with chemotherapy. Conclusions. The metabolic characteristics of patients with GC after chemotherapy are mainly various amino acid metabolic defects, especially L-glutamine, L-leucine, L-alloisoleucine, and L-valine. These defects lead to a series of problems, such as decreased tolerance and effectiveness of chemotherapy, increased side effects, decreased immunity, and shortened survival time. In addition, the remarkable upregulation of the gluconolactone level in patients with GC suggests the high proliferative activity of GC cells. Thus, gluconolactone may be used as a potential prognostic and diagnostic evaluation index. Moreover, JPYZXZ can reduce the incidence of ADRs and improve the life quality of patients by the correction of L-glutamine, L-leucine, L-alloisoleucine, and L-valine metabolism deficiency. In addition, gluconolactone metabolism is inhibited by JPYZXZ. Such inhibition may be one of the antitumor mechanisms of JPYZXZ.