Effect of Celastrus Orbiculatus Extract on proliferation and apoptosis of human Burkitt lymphoma cells.

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.

Traditional Banxia Xiexin decoction inhibits invasion, metastasis, and epithelial mesenchymal transition in gastric cancer by reducing lncRNA TUC338 expression.

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.

Network analysis to explore the pharmacological mechanism of Shenmai injection in treating granulocytopenia and evidence-based medicine approach validation.

BACKGROUND: Shenmai injection is frequently utilized in China to clinically treat granulocytopenia in oncology patients following chemotherapy. Despite this, the drug's therapeutic benefits remain a topic of contention, and its active components and potential treatment targets have yet to be established. The present study utilizes a network pharmacology approach to investigate the drug's active ingredients and possible therapeutic targets, and to evaluate the effectiveness of Shenmai injection in treating granulocytopenia through meta-analysis. METHODS: In our subject paper, we utilized the TCMID database to investigate the active ingredients present in red ginseng and ophiopogon japonicus. To further identify molecular targets, we employed SuperPred, as well as OMIM, Genecards, and DisGeNET databases. Our focus was on targets associated with granulocytopenia. The DAVID 6.8 database was utilized to perform gene ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Additionally, a protein-protein interaction network was established. The resulting "drug-key component-potential target-core pathway" network was used to predict the mechanism of action of Shenmai injection in the treatment of granulocytopenia. In order to evaluate the quality of the studies included in our analysis, we utilized the Cochrane Reviewers' Handbook. We then conducted a meta-analysis of the clinical curative effect of Shenmai injection for granulocytopenia, utilizing the Cochrane Collaboration's RevMan 5.3 software. RESULTS: After conducting a thorough screening, the study identified 5 primary ingredients of Shenmai injection - ophiopogonoside a, ß-patchoulene, ginsenoside rf, ginsenoside re, and ginsenoside rg1-that can potentially target 5 essential proteins: STAT3, TLR4, PIK3CA, PIK3R1, and GRB2. Additionally, Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that Shenmai injection can be beneficial in treating granulocytopenia by interacting with pathways such as HIF-1 signaling, T-cell receptor signaling, PI3K-Akt signaling, chemokine signaling, and FoxO signaling. The results of meta-analysis indicate that the treatment group exhibited superior performance in terms of both efficiency and post-treatment leukocyte count when compared to the control group. CONCLUSION: In summary, studies in network pharmacology demonstrate that Shenmai injection exerts an impact on granulocytopenia via various components, targets, and mechanisms. Additionally, evidence-based studies provide strong support for the effectiveness of Shenmai injection in preventing and treating granulocytopenia.

The predictive value of prognosis and therapeutic response for STAT family in pancreatic cancer.

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.

Celastrus orbiculatus Thunb. extract inhibits EMT and metastasis of gastric cancer by regulating actin cytoskeleton remodeling.

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.

Triptonoterpene, a Natural Product from Celastrus orbiculatus Thunb, Has Biological Activity against the Metastasis of Gastric Cancer Cells.

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.

LncRNA-ENST00000543604 exerts a tumor-promoting effect via miRNA 564/AEG-1 or ZNF326/EMT and predicts the prognosis of and chemotherapeutic effect in colorectal cancer.

Objectives: Colorectal 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. Methods: Based 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. Results: In 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. Conclusions: Our 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.

Poria Acid, Triterpenoids Extracted from Poria cocos, Inhibits the Invasion and Metastasis of Gastric Cancer Cells.

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.

Hydroisomerization of n-Hexadecane Over Nickel-Modified SAPO-11 Molecular Sieve-Supported NiWS Catalysts: Effects of Modification Methods.

The complexation-excessive impregnation modification method, which was original in this study, and the ion-exchange method and the in situ modification method were used to synthesize Ni-modified SAPO-11 molecular sieves. With the Ni-modified SAPO-11 samples as support, the corresponding NiWS-supported catalysts for the hydroisomerization of n-hexadecane were prepared. The effects of Ni-modification on SAPO-11 characteristics and the active phase were studied. The structure, morphology, and acidity of SAPO-11, as well as the interaction between active metals and support, the morphology, dispersibility, and stacking number of the active phase, were all changed by Ni-modification methods. The complexation-excessive impregnation modification method deleted a portion of Al from SAPO-11 molecular sieves while simultaneously integrating Ni into the skeletal structure of the surface layer of SAPO-11 molecular sieves, considerably enhancing the acidity of SAPO-11 molecular sieves. Furthermore, during dealumination, ethylenediaminetetraacetic acid generated more mesoporous structures and increased the mesoporous volume of SAPO-11 molecular sieves. Because the complexation-excessive impregnation modification method increased the amount of Ni in the surface framework of the SAPO-11 molecular sieve, it has weakened the interaction between the active phase and the support, improved the properties of the active phase, and greatly improved the hydroisomerization performance of NiW/NiSAPO-11. The yield of i-hexadecane of NiW/NiSAPO-11 increased by 39.3% when compared to NiW/NiSAPO-11. It presented a realistic approach for increasing the acidity of SAPO-11, reducing the interaction between active metals and support, and improving the active phase stacking problem.

[Corrigendum] DJ­1 promotes cell proliferation and tumor metastasis in esophageal squamous cell carcinoma via the Wnt/ß­catenin signaling pathway.

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that a pair of data panels featured between Figs. 4 and 7 contained overlapping data such that the data were derived from the same original source where they were intending to depict the results from experiments performed under different experimental conditions, and a pair of the data panels featured in Fig. 8 for the ß­catenin data also appeared to show overlapping data. The authors were able to re­examine their original data, and have identified the data that were intended to have been shown for these figure parts. The corrected versions of Fig. 4 (showing the correct data for the LV­DJ­1/migration experiment in Fig. 4A), Fig. 7 (showing the correct data for the LV­DJ­1 + XAV939/migration experiment) and Fig. 8 (showing the correct data for the LV­siRNA­DJ­1 experiment) are shown on the subsequent pages. The authors confirm that these inadvertent errors did not have any major impact on the conclusions reported in their paper, are grateful to the Editor of International Journal of Oncology for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [the original article was published in International Journal of Oncology 56: 1115­1128, 2020; DOI: 10.3892/ijo.2020.5005].

The TCM Prescription Yi-Fei-Jie-Du-Tang Inhibit Invasive Migration and EMT of Lung Cancer Cells by Activating Autophagy.

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.

Celastrus orbiculatus Extract Inhibits the Epithelial-Mesenchymal Transition Process by Transforming Growth Factor-ß Signaling Pathway in Gastric Cancer.

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-ß (TGF-ß) 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-ß signaling pathway. CONCLUSION: 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-ß signaling pathway.

Synthesis of Nickel In Situ Modified SAPO-11 Molecular Sieves and Hydroisomerization Performance of Their NiWS Supported Catalysts.

SAPO-11 molecular sieves were modified with different Ni contents by the in situ modification method. The Ni-modified SAPO-11 molecular sieves were used as the supports to prepare the corresponding NiW-supported catalysts for the hydroisomerization of n-hexadecane. The Ni-modified SAPO-11 and the corresponding NiW-supported catalysts were characterized by X-ray diffraction, scanning electron microscopy, N2 adsorption-desorption, NH3-temperature-programmed desorption, pyridine adsorbed infrared, high-resolution transmission electron microscopy, and X-ray photoelectron spectroscopy. The results showed that Ni in situ modification preserved the crystal structure of SAPO-11; increased the BET specific surface area, mesopore volume, and medium and strong Brønsted acid amount of SAPO-11; and increased the stacking number of the active phase of the catalysts. 3Ni-SAPO-11 possessed the largest BET specific surface area, mesopore volume, and medium and strong Brønsted acid amount. NiW/3Ni-SAPO-11 possessed the highest dispersion of the active phase and the highest sulfidation degree of the active metals. The results of the hydroisomerization of n-hexadecane showed that Ni in situ modification improved the catalytic activity and selectivity of the catalysts for the hydroisomerization of n-hexadecane to varying degrees. Especially, NiW/3Ni-SAPO-11 had the highest catalytic activity and isomer selectivity, and the maximum yield of isomeric hexadecane could reach 71.18%.

Effect of Fuzheng Qingdu Therapy for Metastatic Gastric Cancer is Associated With Improved Survival: A Multicenter Propensity-Matched Study.

OBJECTIVE: To evaluate the therapeutic effect of Traditional Chinese Medicine (TCM), specifically Fuzheng Qingdu (FZQD) therapy, on the survival time of metastatic GC patients. PATIENTS AND METHODS: Databases of medical records of 6 hospitals showed that 432 patients with stage IV GC were enrolled from March 1, 2012 to October 31, 2020. Propensity score matching (PSM) was used to reduce the bias caused by confounding factors in the comparison between the TCM and the non-TCM users. We used a Cox multivariate regression model to compare the hazard ratio (HR) value for mortality risk, and Kaplan-Meier survival curve for the survival time of GC patients. RESULTS: The same number of subjects from the non-TCM group were matched with 122 TCM-treated patients after PSM to evaluate their overall survival (OS) and progression-free survival (PFS). Median time of OS of TCM and non-TCM users were 16.53 and 9.10 months, respectively. TCM and non-TCM groups demonstrated a 1-year survival rate of 68.5% and 34.5%, 2-year survival rate of 28.6% and 3.5%, and 3-year survival rate of 17.8% and 0.0%, respectively. A statistical difference exists in OS between the 2 groups (χ2 = 33.39 and P < .0001). The PFS of TCM users was also longer than that of non-TCM users (χ2 = 4.95 and P = 0.026). Notably, Chinese herbal decoction, Shenmai and compound Kushen injections were commonly used for FZQD therapy. CONCLUSION: This propensity-matched study showed that FZQD therapy could improve the survival of metastatic GC patients.

Metabolomic Study on the Therapeutic Effect of the Jianpi Yangzheng Xiaozheng Decoction on Gastric Cancer Treated with Chemotherapy Based on GC-TOFMS Analysis.

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.

A Study on the Effect and Mechanism of Xiaoaiping (XAP) Injection and S-1 Combination Therapy in Inhibiting the Invasion and Metastasis of Human GC Cells.

BACKGROUND: This study aimed to determine the effect and mechanism of Xiaoaiping (XAP) injection combined with S-1 in inhibiting the invasion and metastasis of human GC cells. METHODS: BGC-823 and MGC-803 cells were incubated in vitro, and the effects of treatment on the cytotoxicity and proliferation of BGC-823 and MGC-803 cells were evaluated by MTT assay. Cell adhesion tests and Transwell assays were used to detect the effects of Xiaoaiping injection combined with S-1 on the metastatic ability of BGC-823 and MGC-803 cells. The expression of VEGF, Metalloproteinases (MMPs) and proteins related to the Epithelial-Mesenchymal Transition (EMT) were detected by Western blotting. Meanwhile, a tumour model was established in nude mice, and the effect of XAP combined with S-1 on BGC-823 cells in vivo was studied. RESULTS: Compared with the single drug group, the combination of XAP with S-1 increased the inhibition rate (P<0.05). The adhesion test showed that the combination group significantly inhibited the adhesion of BGC-823 and MGC-803 cells (P<0.05). The combination of XAP with S-1 reduced the migration and invasion potential of human GC BGC-823 and MGC-803 cells. Western blotting showed that the expression of VEGF, MMP-9, Ncadherin and vimentin was decreased and E-cadherin expression was increased in the combination group compared with these expression values in either the XAP or S-1 alone group (P<0.05). In vivo, we found that XAP combined with S-1 had a significant inhibitory effect on the growth of tumours compared with XAP or S-1 alone. Immunohistochemistry showed that XAP combined with S-1 was able to enhance the levels of E-cadherin and downregulate N-cadherin and vimentin. CONCLUSION: The combination of XAP with S-1 can enhance the inhibitory effect of a single drug on proliferation, invasion and metastasis. The mechanism may be related to the decrease in the expression of VEGF and MMP-9 proteins and the effect on EMT.

DJ­1 promotes cell proliferation and tumor metastasis in esophageal squamous cell carcinoma via the Wnt/ß­catenin signaling pathway.

DJ­1, an oncogene, has been reported to be an independent prognostic indicator of poor survival in patients with esophageal squamous cell carcinoma (ESCC). The aim of the present study was to investigate the role of DJ­1 in tumor cell proliferation and invasion in ESCC and its underlying mechanisms. It was observed that the expression level of DJ­1 was upregulated and positively associated with EMT biomarkers in 84 human ESCC tissue specimens. Overexpression and knockdown experiments demonstrated that DJ­1 was involved in proliferation, migration, invasion and EMT in ECA­109 cells in vitro and extensive peritoneal seeding in a peritoneal dissemination mice model. Furthermore, the present data revealed that DJ­1 could activate the Wnt/ß­catenin signaling pathway, which mediates the EMT and metastasis in ESCC. In conclusions, DJ­1 promoted proliferation, invasion, metastasis and the EMT in ESCC via activation of the Wnt/ß­catenin signal pathway. The present results suggested DJ­1 could represent a promising therapeutic target for the prevention and treatment of ESCC­related metastasis.

In silico screening and surface plasma resonance-based verification of programmed death 1-targeted peptides.

Programmed death 1 (PD-1) is a key immune checkpoint molecule. When it binds to programmed death-ligand 1 (PD-L1), it can negatively regulate the immune response. Therefore, blockade of the PD-1/PD-L1 interaction could unleash the power of immune system. Though successes achieved by anti-PD-1/PD-L1 antibody drugs in clinical for various cancers, many intrinsic limitations of the high molecular weight drugs require alternatives such as peptide drugs and chemical compounds. In this study, we described a novel in silico approach which was used to screen peptides from PDB database and aimed to identify peptides that have potential to bind the PD-L1 binding area of PD-1 molecule. Based on the docking poses, eight peptides were synthesized and measured for their binding abilities by surface plasma resonance technique. The KD values of the synthesized peptides ranged from 10.0 to 133.0 µM. Furthermore, the binding mechanism between PD-1 and the peptides was studied. In conclusion, we established a fast and reliable screening method for peptide discovery, which could be applied for identifying peptide inhibitors of various targets. The synthesized peptides could be served as starting points for designing PD-1 drug for cancer immunotherapy.

In Vitro and In Vivo Inhibitory Effect of Gujin Xiaoliu Tang in Non-Small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC) is a serious threat to people's health. This study aims to determine the possible effect of Gujin Xiaoliu Tang (GJXLT) on NSCLC, which is an empirical formula from Professor Dai-Han Zhou. In this study, chromatographic fingerprinting of GJXLT and A549 cell model in vitro and in vivo was established. We cultured A549 cells in vitro and found that GJXLT inhibited A549 cell growth and induced apoptosis. Compared with the control group, the expression of p-STAT3 and VEGF proteins in the GJXLT groups was decreased. Similar findings were also observed in vivo. First, GJXLT inhibited the growth of transplanted tumor and did not reduce the weight of the tumor-bearing mice in comparison with that of the control group. Then, the Ki-67 expression of transplanted tumor in the GJXLT groups was decreased. In addition, the apoptosis rate of transplanted tumor in the GJXLT groups was increased. Overall, our data showed that GJXLT inhibited A549 cell proliferation and induced apoptosis in vivo and in vitro. Furthermore, GJXLT inhibited the growth of lung cancer xenograft in nude mice model with no obvious side effects. The anti-tumor effect of GJXLT might also be related to the inhibition of p-STATS and VEGF expression in the JAK2/STAT3 pathway. Our results demonstrated the potential of GJXLT as a novel treatment for NSCLC.

Polypharmacological Profiles Underlying the Antitumor Property of Salvia miltiorrhiza Root (Danshen) Interfering with NOX-Dependent Neutrophil Extracellular Traps.

Danshen, the dried root of Salvia miltiorrhiza, one of the most investigated medicinal plants with well-defined phytochemical constituents, has shown prominent clinical outcomes for antioxidant, anti-inflammatory, and anticoagulant activities to attain vascular protection and additional benefits for cancer therapy. More recently, activation of neutrophil and excessive formation of neutrophil extracellular traps (NETs) have been observed in pathological conditions of metastatic cancers; thus, we hypothesized that suppression of NETs could account for an essential cellular event underlying Danshen-mediated reduction of the incidence of metastasis. Using an experimental pulmonary metastases model of red fluorescent protein- (RFP-) labeled gastric cancer cells in combination with macroscopic ex vivo live-imaging system, our data indicated that Danshen impaired the fluorescent intensity and quantity of metastatic nodules. Moreover, Danshen could prevent neutrophil trafficking to the metastatic sites with decreased plasma levels of neutrophil elastase (NE) and procoagulant potential featured by fibrinogen. We further established phorbol 12-myristate 13-acetate- (PMA-) induced NET formation of human neutrophils and screened representative active compounds derived from the hydrophilic and hydrophobic fractions of Danshen using qualitative and quantitative methods. As a result, we found that salvianolic acid B (Sal B) and 15,16-dihydrotanshinone I (DHT I) exhibited superior inhibitory activities on NET formation and significantly attenuated the levels of citrullinated histone H3 (citH3), a biomarker for NET formation. Multitarget biochemical assays demonstrated that Sal B and DHT I distinctly modulated the enzymatic cascade involved in NET formation. Sal B and DHT I could disrupt NET formation at the earlier stage by blocking the activities of myeloperoxidase (MPO) and NADPH oxidase (NOX), respectively. Lastly, combining treatment of Sal B and DHT I under subED50 doses displayed remarkable synergism effect on NET inhibition. Altogether, these data provide insight into how promiscuous compounds from herbal medicine can be effectively targeted NETs towards hematogenous metastasis of certain tumors.