Discussion on the anti-tumor metastasis mechanism of Notoginseng Radix et Rhizoma based on internet pharmacology / 国际中医中药杂志

Objective:To analyze and explore the possible mechanism of anti-tumor metastasis of Notoginseng Radix et Rhizoma using Internet pharmacology. Methods:The active components and targets of Notoginseng Radix et Rhizoma were screened by retrieving Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP). GeneCards database was used to screen the anti-tumor metastasis-related targets, and compounds and disease targets were under mapping analysis. Key targets of Notoginseng Radix et Rhizoma for anti-tumor metastasis were screened through Venn map. With the help of Cytoscape 3.7.2 software, a compound-disease network diagram was constructed. String platform was used to build a PPI network. Bioconductor was used to enrich the target genes for KEGG signaling pathway and GO biological process analysis. Results:Totally 119 active components were selected from Notoginseng Radix et Rhizoma. There were 8 eligible active components, corresponding to 162 related targets, 121 targets related to anti-tumor metastasis, and 30 key targets screened by PPI network, including AKT1, MAPK1, JUN, RELA, IL6, etc. GO enrichment analysis mainly involved biological processes such as cytokine receptor binding, heme binding, RNA polymerase Ⅱ transcription factor binding, ubiquitin protein ligase binding, and steroid hormone receptor activity. 149 signal pathways related to Notoginseng Radix et Rhizoma anti-tumor metastasis were obtained by KEGG enrichment analysis, mainly involving multiple signal pathways, such as AGE-RAGE and PI3K-Akt, and hepatitis B, Kaposi's sarcoma-associated herpes virus infection, human cytomegalovirus infection and other viral infections and various tumors. Conclusion:Notoginseng Radix et Rhizoma can pass multiple active components, such as ginsenoside f2, ginsenoside rh2 β-, sitosterol, stigmasterol and quercetin, and multiple targets, such as AKT1, MAPK1, JUN, RELA and IL6, acting on multiple pathways such as PI3K-Akt, thereby playing the role of anti-tumor metastasis.

Research progress of anti-tumor effect and mechanism of CDDO and its derivatives / 中国药房

2-cyano-3，12-dioxooleana-1，9 （11）-dien-28-oic acid （CDDO） is a compound synthesized by taking oleanolic acid， a natural triterpene， as a precursor or precursor， and transforming three modifiable functional groups in the molecule through a series of chemical structure modification. In order to improve its anti-tumor activity， CDDO derivatives are further synthesized. In this paper， the research results of anti-tumor effects and mechanisms of CDDO and its derivatives in recent years are summarized. It is found that CDDO and its derivatives have a wide range of anti-tumor effects， and can show significant anti-tumor effects on breast cancer， pancreatic cancer， lung cancer and ovarian cancer at low concentrations such as micromole or even nanomole， among which CDDO methyl ester compound （CDDO-Me） and CDDO imidazolidinone compound （CDDO-Im） have the most obvious effects. CDDO and its derivatives exert anti-tumor activity mainly by inducing tumor cell apoptosis， and regulating metabolic reprogramming and immune microenvironment. The involved pathways mainly include Janus protein tyrosine kinase （JAK）/ signal transduction and transcription activation protein 3（STAT3） signal pathway， nuclear factor E2-related factor 2 （NRF2） signal pathway， phosphatidylinositol 3 kinase （PI3K）/protein kinase B （also known as Akt）/mammalian rapamycin target protein （mTOR） signal pathway， Wnt/β-catenin signal pathway， nuclear factor κB signal pathway.

Tumor cell lysate with low content of HMGB1 enhances immune response of dendritic cells against lung cancer in mice / 南方医科大学学报

OBJECTIVE@#To assess the effect of tumor cell lysate (TCL) with low high-mobility group B1 (HMGB1) content for enhancing immune responses of dendritic cells (DCs) against lung cancer.@*METHODS@#TCLs with low HMGB1 content (LH-TCL) and normal HMGB1 content (NH-TCL) were prepared using Lewis lung cancer (LLC) cells in which HMGB1 was inhibited with 30 nmol/L glycyrrhizic acid (GA) and using LLC cells without GA treatment, respectively. Cultured mouse DCs were exposed to different doses of NH-TCL and LH-TCL, using PBS as the control. Flow cytometry was used to detect the expressions of CD11b, CD11c and CD86 and apoptosis of the stimulated DCs, and IL-12 levels in the cell cultures were detected by ELISA. Mouse spleen cells were co-cultured with the stimulated DCs, and the activation of the spleen cells was assessed by detecting CD69 expression using flow cytometry; TNF-β production in the spleen cells was detected with ELISA. The spleen cells were then co-cultured with LLC cells at the effector: target ratios of 5:1, 10:1 and 20:1 to observe the tumor cell killing. In the animal experiment, C57/BL6 mouse models bearing subcutaneous LLC xenograft received multiple injections with the stimulated DCs, and the tumor growth was observed.@*RESULTS@#The content of HMGB1 in the TCL prepared using GA-treated LLC cells was significantly reduced (P < 0.01). Compared with NH-TCL, LH-TCL showed a stronger ability to reduce apoptosis (P < 0.001) and promote activation and IL- 12 production in the DCs. Compared with those with NH-TCL stimulation, the DCs stimulated with LH-TCL more effectively induced activation of splenic lymphocytes and enhanced their anti-tumor immunity (P < 0.05). In the cell co-cultures, the spleen lymphocytes activated by LH-TCL-stimulated DCs showed significantly enhanced LLC cell killing activity (P < 0.01). In the tumor-bearing mice, injections of LH-TCL-stimulated DCs effectively activated host anti-tumor immunity and inhibited the growth of the tumor xenografts (P < 0.05).@*CONCLUSION@#Stimulation of the DCs with LH-TCL enhances the anti-tumor immune activity of the DCs and improve the efficacy of DCbased immunotherapy for LLC in mice.

Research progress of sphingosine kinase and sphingosine-1-phosphate (S1P) /S1P receptor signaling in tumor microenvironment / 药学学报

Sphingosine kinase (SphK), sphingosine-1-phosphate (S1P) and S1P receptor (S1PR) are involved in the tumor biological processes such as tumor cell proliferation and migration, and play an important role in the development of cancer. In recent years, researchers have increasingly focused on the interaction between cancer cells and the tumor microenvironment. The tumor microenvironment is genetically stable and can be induced to an antitumor phenotype, which has significant therapeutic advantages. Studies have shown that SphK/S1P/S1PR can regulate multiple aspects of the tumor microenvironment. This review summarizes the effects of SphK and S1P/S1PR signaling on the tumor microenvironment from four perspectives: tumor immune microenvironment, cancer associated fibroblasts, tumor angiogenesis and tumor hypoxic microenvironment, and also outlines potential drug research related to these signal molecules, aiming to elucidate the role of SphK/S1P/S1PR in tumor occurrence and development and provide new ideas for the research of anti-tumor drugs.

Study on the modification and anti-tumor activity of silybin derivatives for CDK4/6 targeted / 药学学报

By using computer-aided drug design, the activities group model which CDK4/6 inhibitors on the market were introduced to silybin C-7, and a series of silybin derivatives were designed and synthesized, and the structure was confirmed by MS, 13C NMR and 1H NMR. The in vitro antitumor activity evaluation of the target compound was carried out by MTT method, and the in vitro anti-tumor activity was carried out in human hepatocellular carcinoma cells (HepG-2). Experimental results show that all compounds are higher than the activity of the parent silybin, of which compound I1 has a certain inhibitory effect on human HepG-2 cells, which is worth further study.

Application research and design strategy on smart responsive mesoporous silica anti-tumor nanodelivery systems / 药学学报

Malignant tumors are major diseases that endanger human health. Due to their complex and variable microenvironment, most anti-tumor drugs cannot precisely reach the focal tissue and be released in a controlled manner. Intelligent responsive nano carriers have become a hot spot in the field of anti-tumor drug delivery systems. As an excellent nano material, mesoporous silica has the advantages of non-toxic, stable, adjustable pore volume and pore diameter, and easy functional modification on the surface. By virtue of its perceptive response to the tumor microenvironment or physiological changes, it can achieve the targeted drug release or controlled drug release of the drug delivery system in the tissue, making it an ideal carrier for intelligent response drug delivery system. In this paper, we review the design strategies and current research status of smart responsive anti-tumor drug delivery systems based on mesoporous silica, in order to provide a reference for the development of anti-tumor drug nanoformulations.

Anti-tumor mechanism study on saffron by network pharmacology and reverse molecular docking / 药学实践杂志

Objective To explore the anti-tumor mechanism of saffron (Crocus sativus L.) by network pharmacology and reverse molecular docking techniques. Methods The main chemical components of saffron were obtained by searching published literature and TCMSP database. The potential targets of these components were predicted using PharmMapper server. The corresponding target genes were identified from UniProt database. The underlying anti-tumor targets of saffron were obtained by mapping the disease genes of cancer or tumor with GeneCards, OMIM and TTD databases. Cytoscape software was used to construct the action target network of saffron active components. The protein-protein interaction analysis was performed by String database, and the GO function and KEGG pathway enrichment analysis were performed by Metascape platform. Finally, molecular docking was performed to evaluate the binding of main components with their potential targets. Results A total of 9 active ingredients in saffron including quercetin, kaempferol, isorhamnetin, picrocrocin and crocin I, were identified, which might act on 37 key targets including AKT1, CCND1, MMP9, EGFR, TP53, involved in P53, TNF and other signaling pathways. Molecular docking indicated modest binding potency through hydrogen bonding, and hydrophobic interactions. Conclusion The anti-tumor effect of saffron was evaluated via the network of components-targets-pathways, which might provide a foundation for further research.

Analysis of ethical review issues of informed consent form for clinical trials of registered anti-tumor drugs in our hospital / 中国药房

OBJECTIVE To promote the standardization and integrity of the informed consent form for clinical trials of registered anti-tumor drugs， and to protect the legitimate rights and interests of the subjects. METHODS The ethical review resolutions of clinical trial projects of registered anti-tumor drugs that were initially reviewed by the Ethics Committee of our hospital from July 1st， 2020 to July 1st， 2022 were summarized to statistically analyze the problematic items according to the “Quality Analysis Form of Informed Consent” prepared by our hospital. RESULTS Of the 316 clinical trials of registered anti- tumor drugs that were initially reviewed， 257 （81.3%） had problems with the contents of informed consent form， mainly domestic multi-center trials and phase Ⅲ trials. The main problems included the vague notification of the test fee bearer （68.5%）， the incomplete notification of the test content （59.1%）， the insufficient notification of rights and interests and risks （58.4%）， the insufficient notification of personal information protection （56.0%）， and the nonstandard expression of the informed consent form （52.5%）. CONCLUSIONS There is still a gap between the informed consent form of the clinical trials of registered anti-tumor drugs in our hospital and the requirements of the new version of Good Clinical Practice for Drugs （GCP）. The parties involved in the test can take a number of measures to improve the standardization and integrity of the informed consent form， and the research team should design the informed consent form in strict accordance with the requirements of the new GCP and pay attention to the comprehensive notification about the test. The Ethics Committee can provide the sponsor and researcher with the template of informed consent form and the key points of writing， continue to strengthen the examination ability， improve the examination quality， and effectively protect the safety and interests of the subjects.

Chemical Components of Phellinus and Antitumor Mechanism： A Review / 中国实验方剂学杂志

Malignant tumor poses a threat to human health and life. The incidence and fatality rate of malignant tumor have been on the rise. The currently available therapies are radiotherapy and chemotherapy， which cause severe adverse reactions and irreversible damage and thus influence the quality of life of patients. Therefore， it is urgent to find new， safe and effective antitumor drugs. Chinese medicinals are safe with little adverse reactions and long-lasting effect in the treatment of tumor， which have attracted the attention of scholars. Amid the advancement of medical research， more and more anti-tumor components have been extracted from Chinese medicinals. Phellinus is a valuable Chinese medicinal material， and the chemical components mainly include polysaccharides， flavonoids， triterpenes， and polyphenols， which have anti-inflammatory， hypoglycemic， liver-protecting， and anti-tumor effect. The chemical components of Phellinus can inhibit various malignant tumors such as lung cancer， gastric cancer， colon cancer， and melanoma. It exerts the anti-tumor effect by inhibiting proliferation and metastasis of tumor cells， inducing apoptosis and autophagy of the cells， suppressing tumor angiogenesis， and regulating the immunity. In addition， it can enhance efficacy， reduce toxicity， and boost the sensitivity in the radiotherapy and chemotherapy. In this paper， articles were retrieved from China National Knowledge Infrastructure （CNKI）， Web of Science， Pubmed， and Google Scholar with keywords such as "Phellinus， chemical components， and anti-tumor"， and then the chemical components of Phellinus and the anti-tumor mechanisms were summarized. The findings are expected to lays a basis for further development and clinical application of this medicinal.

Pharmacological Activities， Pharmacokinetics， and Adverse Reactions of Polyphyllin Ⅱ： A Review / 中国实验方剂学杂志

As a rare Chinese medicinal material， Paridis Rhizoma is mainly distributed in Yunnan， Guangxi， and Guizhou in southwestern China， with the effect of clearing heat and detoxifying， alleviating edema and relieving pain， cooling liver and tranquilizing mind. It is particularly effective for injuries from falls， fractures， contusions and strains， snake bites， cold wind-induced convulsion， and other diseases， which has been used for more than 2 000 years. According to modern research， polyphyllin Ⅱ， one of the main active components of Paridis Rhizoma， belongs to diosgenin in structure. It has the anti-tumor， anti-inflammatory， antiviral， antibacterial， immune-regulating， antioxidant， and multidrug resistance-reversing activities， showing good application prospect. Especially， the anti-tumor effect of polyphyllin Ⅱ has attracted wide attention， and the mechanism is inhibiting proliferation， migration， and invasion of tumor cells， inducing cell cycle arrest， apoptosis， and autophagy， suppressing angiogenesis， and modulating tumor microenvironment. However， the pharmacokinetic results show that polyphyllin Ⅱ has low bioavailability in vivo due to the low solubility， poor absorption， unsatisfactory distribution， and slow metabolism， which limit the clinical application. In recent years， there has been an explosion of research on the adverse reactions of polyphyllin Ⅱ， such as the strong hemolytic activity and obvious cytotoxicity to liver， kidney， myocardium and cardiovascular cells. Thus， papers were retrieved from "CNKI"， "VIP"， "Wanfang Data"， "PubMed"， "Web of Science"， and "Elsevier SD" with "Paris saponin Ⅱ"， "Polyphyllin Ⅱ" as the main keywords， and the pharmacological activities and mechanisms， pharmacokinetics， and adverse reactions were summarized. The findings are expected to serve as a reference for the in-depth research， development， and utilization of polyphyllin Ⅱ.

Research progress on pharmacological effects of bilirubin nanoparticles / 中国药房

Bilirubin has good anti-inflammatory， antioxidant and immunomodulatory effects， but its poor water solubility and low bioavailability greatly limit its clinical application. Researchers have developed bilirubin into various nanoparticles， which effectively eliminate the limitation of low solubility of bilirubin with the advantage of dosage form， so that they can maximize its pharmacological activities such as anti-inflammatory， anti-oxidation and immune regulation. Bilirubin nanoparticles have great application potential in a variety of gastrointestinal diseases， liver and kidney diseases， skin diseases， autoimmune diseases， islet transplantation and targeted therapy of tumors （both as a direct anti-tumor drug and as a drug delivery system）. The study of bilirubin nanoparticles will promote the clinical application of bilirubin and the development of related new drugs.

Anti-tumor Activity of Chinese Medicine Based on EGFR Signaling Pathway： A Review / 中国实验方剂学杂志

In China， malignant tumors have become the main cause of death. In the past half century， the incidence and mortality of malignant tumors have been on the rise， posing a threat to health of patients， and the burden of cancer has been increasing. At the moment， malignant tumors are mainly treated by surgery， radiotherapy， and cytotoxic drugs， which， however， have limitations and induce great adverse reactions. As biological technology and the research on tumor microenvironment， immunology， cell biology， and molecular biology advance， high-efficiency low-toxicity targeted therapy has attracted wide attention in the treatment of tumors. Epidermal growth factor receptor （EGFR） plays an important role in many cellular processes such as cell proliferation， survival， differentiation， migration， inflammation， and stromal homeostasis. EGFR promotes tumor growth， proliferation， and metastasis in a variety of ways. Chinese medicine has unique efficacy in the comprehensive treatment of malignant tumors. Through multiple components， multiple targets， and multiple pathways， it enhances the efficacy， reduces toxicity， prolongs life， and improves life quality in the treatment of tumors. Many Chinese medicines and their active components exert anti-tumor effect by inhibiting the EGFR signal transduction pathway. Through targeted inhibition of EGFR， Chinese medicine can promote the apoptosis and autophagy of tumor cells， suppress the proliferation and metastasis of tumor cells， and delay the progression of tumors. Thus， EGFR is a potential target for suppressing tumor. This paper summarizes the relationship between EGFR signal transduction pathway and tumor occurrence and development and analyzes the anti-tumor action mode and possible mechanisms of Chinese medicine and the active components by regulating EGFR signaling pathway， which is expected to provide a reference for clinical practice.

Effect and Mechanism of Cinobufotalin Against Gastrointestinal Malignant Tumors： A Review / 中国实验方剂学杂志

Digestive tract diseases， especially digestive tract tumors， including liver cancer， pancreatic cancer， and colorectal cancer， have high incidence in China. Digestive tract tumor is one of the top 10 cancers in terms of the number of new cases and deaths in the world， and the incidence and mortality of tumor diseases have been increasing year by year. Therefore， the prevention and treatment of tumors is particularly important. With the application and promotion of traditional Chinese medicine in the medical field and the rapid development of molecular biology and pharmacology， more and more potential active components of Chinese medicinal materials have been extracted and studied. These active components can inhibit tumor cells in a multi-target and multi-pathway manner. Cinobufotalin is an effective component extracted from the skin of Bufo bufo gargarizans. It has been prepared into a variety of agents with anti-tumor， immunomodulatory， cardiac boosting， pain-easing， anti-inflammatory， and swelling-relieving activities. In clinical practice， cinobufotalin is mainly used to assist the treatment of liver cancer， lung cancer， colorectal cancer， gastric cancer and other malignant tumors， which can reduce the adverse reactions of patients in the middle and late stages and improve the quality of life and five-year survival rate of patients. The available studies of molecular mechanism have demonstrated that cinobufotalin can play a therapeutic role by inducing cell apoptosis， regulating cell cycle， inhibiting cell proliferation and angiogenesis， modulating immune response， reversing multidrug resistance， enhancing radiochemotherapy sensitivity， inhibiting tumor inflammation， invasion， and metastasis， etc. This review focuses on the clinical application and mechanism of cinobufotalin against digestive tract tumors in recent years， aiming to provide a theoretical basis for the anti-tumor research of cinobufotalin， promote the application of cinobufotalin in tumor treatment， and facilitate the further research and development of this compound.

Research progress on chemical structures and pharmacological effects of natural cytisine and its derivatives / 中国中药杂志

Cytisine derivatives are a group of alkaloids containing the structural core of cytisine, which are mainly distributed in Fabaceae plants with a wide range of pharmacological activities, such as resisting inflammation, tumors, and viruses, and affecting the central nervous system. At present, a total of 193 natural cytisine and its derivatives have been reported, all of which are derived from L-lysine. In this study, natural cytisine derivatives were classified into eight types, namely cytisine type, sparteine type, albine type, angustifoline type, camoensidine type, cytisine-like type, tsukushinamine type, and lupanacosmine type. This study reviewed the research progress on the structures, plant sources, biosynthesis, and pharmacological activities of alkaloids of various types.

Antitumor activity of aumolertinib, a third-generation EGFR tyrosine kinase inhibitor, in non-small-cell lung cancer harboring uncommon EGFR mutations

Uncommon epidermal growth factor receptor (EGFR) mutations account for 10%-20% of all EGFR mutations in non-small-cell lung cancer (NSCLC). The uncommon EGFR-mutated NSCLC is associated with poor clinical outcomes and generally achieved unsatisfactory effects to the current therapies using standard EGFR-tyrosine kinase inhibitors (TKIs), including afatinib and osimertinib. Therefore, it is necessary to develop more novel EGFR-TKIs to treat uncommon EGFR-mutated NSCLC. Aumolertinib is a third-generation EGFR-TKI approved in China for treating advanced NSCLC with common EGFR mutations. However, it remains unclear whether aumolertinib is effective in uncommon EGFR-mutated NSCLC. In this work, the in vitro anticancer activity of aumolertinib was investigated in engineered Ba/F3 cells and patient-derived cells bearing diverse uncommon EGFR mutations. Aumolertinib was shown to be more potent in inhibiting the viability of various uncommon EGFR-mutated cell lines than those with wild-type EGFR. And in vivo, aumolertinib could also significantly inhibit tumor growth in two mouse allograft models (V769-D770insASV and L861Q mutations) and a patient-derived xenografts model (H773-V774insNPH mutation). Importantly, aumolertinib exerts responses against tumors in advanced NSCLC patients with uncommon EGFR mutations. These results suggest that aumolertinib has the potential as a promising therapeutic candidate for the treatment of uncommon EGFR-mutated NSCLC.

Pancreatic melatonin enhances anti-tumor immunity in pancreatic adenocarcinoma through regulating tumor-associated neutrophils infiltration and NETosis

Tumor microenvironment contributes to poor prognosis of pancreatic adenocarcinoma (PAAD) patients. Proper regulation could improve survival. Melatonin is an endogenous hormone that delivers multiple bioactivities. Here we showed that pancreatic melatonin level is associated with patients' survival. In PAAD mice models, melatonin supplementation suppressed tumor growth, while blockade of melatonin pathway exacerbated tumor progression. This anti-tumor effect was independent of cytotoxicity but associated with tumor-associated neutrophils (TANs), and TANs depletion reversed effects of melatonin. Melatonin induced TANs infiltration and activation, therefore induced cell apoptosis of PAAD cells. Cytokine arrays revealed that melatonin had minimal impact on neutrophils but induced secretion of Cxcl2 from tumor cells. Knockdown of Cxcl2 in tumor cells abolished neutrophil migration and activation. Melatonin-induced neutrophils presented an N1-like anti-tumor phenotype, with increased neutrophil extracellular traps (NETs) causing tumor cell apoptosis through cell-to-cell contact. Proteomics analysis revealed that this reactive oxygen species (ROS)-mediated inhibition was fueled by fatty acid oxidation (FAO) in neutrophils, while FAO inhibitor abolished the anti-tumor effect. Analysis of PAAD patient specimens revealed that CXCL2 expression was associated with neutrophil infiltration. CXCL2, or TANs, combined with NET marker, can better predict patients' prognosis. Collectively, we discovered an anti-tumor mechanism of melatonin through recruiting N1-neutrophils and beneficial NET formation.

Clinical antitumor application and pharmacological mechanisms of Dahuang Zhechong Pill / 中草药·英文版

Cancer still has elevated morbidity and mortality, which undoubtedly impacts the life quality of affected individuals. Remarkable advances have been made in cancer therapy, although the toxicities of traditional therapies remain an obvious challenge. Dahuang Zhechong Pill (DHZCP), developed by Zhongjing Zhang in the Synopsis of the Golden Chamber, represents an effective anticancer traditional Chinese medicine (TCM). In this review, it was found that DHZCP is therapeutically utilized in liver, lung, gastric, pancreatic and other cancers in clinic. Pharmacological evidence showed that its anti-tumor mechanisms mainly involve induced cell cycle arrest, apoptosis and autophagy, as well as suppressed tumor cell proliferation, obstructed angiogenesis and metastasis, enhanced immunity, and reversal of multidrug resistance. The present review provides a solid basis for the clinical application of DHZCP and may promote the wide use of TCM in clinical antitumor application.

Progress on pharmacological activities and hepatotoxicity of bavachinin / 药学实践杂志

Bavachinin is a dihydroflavone isolated from dried ripe fruits of Psoralea corylifolia L.，which has various pharmacological activities, such as anti-tumor, anti-virus, anti-diabetes, anti-inflammatory and neuroprotective, and good potential in clinical applications. With the increasing concern about the safety of P. corylifolia applications in clinical, the bavachinin has been found to be one of the main components causing liver injury. In this paper, the pharmacological activities and hepatotoxicity of bavachinin in the recent 20 years were reviewed, in order to provide reference for the further study and clinical application.

Preclinical study of LMP1-RNAi-based anti-tumor therapy in EBV-positive nasopharyngeal carcinoma

RNA interference (RNAi) treatment has been proven to be an important therapeutic approach in cancer based on downregulation of target-oncogenes, but its clinical efficacy still needs further investigation. LMP1 is usually presented by Epstein-Barr virus (EBV)-positive tumor cells like EBV-associated nasopharyngeal carcinoma (NPC) and acts as an oncogene in tumorigenesis. However, the mechanism of LMP1 as a proto-oncogene in nasopharyngeal carcinoma is still unclear. Two sequence-specific shRNAs 1 and 2 were designed to target the different nucleotide loci of EBV latent antigen LMP1 gene and a series of in vivo and in vitro experiments were performed to investigate the therapeutic effect of sequence-specific shRNAs targeting LMP1 and its related molecular mechanisms in EBV-positive NPC. LMP1-shRNA2 generated a truncated LMP1 mRNA and protein, whereas LMP1-shRNA1 completely blocked LMP1 mRNA and protein expression. Both LMP1-shRNAs inhibited the proliferation and migration of NPC cells overexpressing LMP1 (NPC-LMP1) as well as the NPC-associated myeloid-derived suppressor cell (MDSC) expansion in vitro. However, LMP1-shRNA2 maintained the immunogenicity of NPC-LMP1 cells, which provoked MHC-class I-dependent T cell recognition. LMP1-shRNAs inhibited tumor growth in nude mice but did not reach statistical significance compared to control groups, while the LDH nanoparticle loaded LMP1-shRNAs and the antigen-specific T cells induced by NPC-LMP1 cells treated with LMP1-shRNA2 significantly reduced tumor growth in vivo. LMP1-RNAi-based anti-tumor therapy could be a new hope for the clinical efficacy of RNAi treatment of tumors like NPC.

Research progress on the pharmacological effects and mechanisms of sanggenon C / 中国药房

Sanggenon C is a kind of flavonoid compound mainly extracted from the traditional Chinese medicine Morus alba. The pharmacological effects and mechanisms of sanggenon C are systematically reviewed and summarized， and it is found that this component can improve pulmonary fibrosis by regulating transforming growth factor-β1 and nuclear factor-κB； it can exert anti- tumor effects by inhibiting the proliferation of tumor cells and inducing the apoptosis of tumor cells； it can exert cardioprotective， neuroprotective and hepatoprotective effects by regulating multiple signaling pathways， such as calcineurin/nuclear factor of activated T cells 2， peroxisome proliferators-activated receptor α， and Ras homolog gene family member A/Rho-associated coiled- coil containing protein kinase， enhancing autophagy， reducing inflammatory response and reducing the level of oxidative stress； it can treat osteoporosis by inhibiting osteoclast uptake and promoting osteoblast formation； it has certain inhibitory effect on many enzymes； it can exert anti-inflammatory effects by regulating nuclear factor-κB signaling pathway； it can exert antioxidant effects by scavenging free radicals. However， researches on the pharmacological effects of sanggenon C mostly focus on the cellular and animal field， and the specific mechanism of action is not yet clear. In the future， basic research and clinical trials are still needed to explore and verify.