Nephrotoxicity assessment of podophyllotoxin-induced rats by regulating PI3K/Akt/mTOR-Nrf2/HO1 pathway in view of toxicological evidence chain (TEC) concept.

Adverse reactions to traditional Chinese medicine have hindered the healthy development and internationalization process of the traditional Chinese medicine industry. The critical issue that needs to be solved urgently is to evaluate the safety of traditional Chinese medicine systematically and effectively. Podophyllotoxin (PPT) is a highly active compound extracted from plants of the genus Podophyllum such as Dysosma versipellis (DV). However, its high toxicity and toxicity to multiple target organs affect the clinical application, such as the liver and kidney. Based on the concurrent effects of PPT's medicinal activity and toxicity, it would be a good example to conduct a systematic review of its safety. Therefore, this study revolves around the Toxicological Evidence Chain (TEC) concept. Based on PPT as the main toxic constituent in DV, observe the objective toxicity impairment phenotype of animals. Evaluate the serum biochemical indicators and pathological tissue sections for substantial toxic damage results. Using metabolomics, lipidomics, and network toxicology to evaluate the nephrotoxicity of PPT from multiple perspectives systematically. The results showed that PPT-induced nephrotoxicity manifested as renal tubular damage, mainly affecting metabolic pathways such as glycerophospholipid metabolism and sphingolipid metabolism. PPT inhibits the autophagy process of kidney cells through the PI3K/Akt/mTOR and Nrf2/HO1 pathways and induces the activation of oxidative stress in the body, thereby causing nephrotoxic injury. This study fully verified the feasibility of the TEC concept for the safety and toxicity evaluation of traditional Chinese medicine. Provide a research template for systematically evaluating the safety of traditional Chinese medicine.

The role of metabolic reprogramming in cancer metastasis and potential mechanism of traditional Chinese medicine intervention.

Metabolic reprogramming is one of the most prominent features underlying cancer cells progression and metastasis.Traditional Chinese medicine (TCM) has been widely used in the clinical treatment of cancer, with the advantages of multi-pathway, multi-target, multi-component anti-tumor pharmacological effects and low risk of adverse effects. However, the mechanisms underlying the anti-tumor effects of TCM are not fully understood, especially on cellular metabolic reprogramming. In this review, we summarize the role of glucose, lipid and amino acid metabolism in cancer metastasis, which is key in cancer cells and tumor micro-environment (TME) cell metabolism. Furthermore, we reviewed the potential mechanisms by which, most bioactive TCM compounds suppress cancer metastasis by regulating metabolic reprogramming and the possibility of sensitizing other anti-tumor drugs. TCM and its bioactive compounds have huge prospects for clinical application in the treatment of cancer metastasis. Unfortunately, little is currently known about the regulatory effects of Chinese herbal medicines and their bioactive compounds on the metabolic reprogramming of cancer cells and the combination therapy for cancers. This review provides novel insights into the regulation of metabolic reprogramming by TCM in combination with other anti-tumor drugs against cancer metastasis and the possibility of becoming sensitizers for other anti-tumor drugs.

Combination of UPLC-Q-TOF/MS and Network Pharmacology to Reveal the Mechanism of Qizhen Decoction in the Treatment of Colon Cancer.

Traditional Chinese medicine (TCM) has been utilized for the treatment of colon cancer. Qizhen decoction (QZD), a potential compound prescription of TCM, possesses multiple biological activities. It has been proven clinically effective in the treatment of colon cancer. However, the molecular mechanism of anticolon cancer activity is still not clear. This study aimed to identify the chemical composition of QZD. Furthermore, a collaborative analysis strategy of network pharmacology and cell biology was used to further explore the critical signaling pathway of QZD anticancer activity. First, ultraperformance liquid chromatography-quadrupole time-of-flight/mass spectrometry (UPLC-Q-TOF/MS) was performed to identify the chemical composition of QZD. Then, the chemical composition database of QZD was constructed based on a systematic literature search and review of chemical constituents. Moreover, the common and indirect targets of chemical components of QZD and colon cancer were searched by multiple databases. A protein-protein interaction (PPI) network was constructed using the String database (https://www.string-db.org/). All of the targets were analyzed by Gene Oncology (GO) bioanalysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and the visual network topology diagram of "Prescription-TCM-Chemical composition-Direct target-Indirect target-Pathway" was constructed by Cytoscape software (v3.7.1). The top molecular pathway ranked by statistical significance was further verified by molecular biology methods. The results of UPLC-Q-TOF/MS showed that QZD had 111 kinds of chemical components, of which 103 were unique components and 8 were common components. Ten pivotal targets of QZD in the treatment of colon cancer were screened by the PPI network. Targets of QZD involve many biological processes, such as the signaling pathway, immune system, gene expression, and so on. QZD may interfere with biological pathways such as cell replication, oxygen-containing compounds, or organic matter by protein binding, regulation of signal receptors or enzyme binding, and affect cytoplasm and membrane-bound organelles. The main antitumor core pathways were the apoptosis metabolic pathway, the PI3K-Akt signal pathway, and so on. Expression of the PI3K-Akt signal pathway was significantly downregulated after the intervention of QZD, which was closely related to the inhibition of proliferation and migration of colon cancer cells by cell biology methods. The present work may facilitate a better understanding of the effective components, therapeutic targets, biological processes, and signaling pathways of QZD in the treatment of colon cancer and provide useful information about the utilization of QZD.

Lentinan combined with cisplatin for the treatment of non-small cell lung cancer.

BACKGROUND: A growing number of studies suggest that lentinan combined with cisplatin thoracic injection for the treatment of lung cancer is an effective combination of traditional Chinese and Western medicine, which has a continuous and beneficial effect on eliminating clinical symptoms and improving cachexia in lung cancer patients. However, whether this treatment is effective and safe for lung cancer patients or not, evidence supporting the effectiveness and safety of this treatment is still incomplete. Besides, there is lack of systematic review to assess the detailed situation (including risk of bias and methodology) of current related clinical studies. OBJECTIVE: This study aimed to evaluate the effectiveness and safety of lentinan combined with cisplatin thoracic injection in the treatment of lung cancer. METHODS: The major databases (Embase, PubMed, the Cochrane Library, China National Knowledge Infrastructure, Chinese Scientific Journals Database [VIP] Database, Chinese Biomedical Literature Service System [SinoMed], and Wanfang Database) were searched from inception to March 1, 2020. Randomized controlled trials (RCTs) of lentinan combined with cisplatin chest injection on patients with non-small cell lung cancer (NSCLC) were identified. Two assessors reviewed each trial independently. The methodological quality of the eligible studies was evaluated according to the Cochrane Collaboration's tool for assessing risk of bias. Both the data extraction and the literature quality screening evaluation were conducted independently by 2 researchers. RESULTS: Totally 17 clinical RCTs were included in this study, involving 1390 patients. Meta-analysis results showed that the clinical efficacy (risk ratio [RR] = 1.34, 95% confidence interval [CI] 1.21-1.48), effective subgroup analysis (RR = 1.51, 95% CI 1.3-1.77), and quality of life (RR = 1.48, 95% CI 1.27-1.72), the differences are statistically significant. In terms of adverse reactions, mainly related to gastrointestinal reactions and bone marrow suppression, the incidence and degree of adverse reactions of lentinan combined with cisplatin thoracic injection group were lower than those of cisplatin thoracic injection group alone. CONCLUSIONS: The current evidence prompted that Lentinan combined with cisplatin in thoracic injection might benefit patients with NSCLC on a certain extent; this systematic review revealed some definite conclusions about the application of Lentinan combined with cisplatin in thoracic injection for NSCLC. Due to the low methodological quality, high risk of bias, and inadequate reporting on clinical data, these results still require verification by a large number of well designed, heterogeneous RCT studies. More rigorous, multicenter, sufficient-sample, and double-blind RCTs are warranted.

A combination of PD­1/PD­L1 inhibitors: The prospect of overcoming the weakness of tumor immunotherapy (Review).

Programmed cell death protein­1 (PD­1)/programmed death protein ligand­1 (PD­L1) inhibitors for treatment of a various types of cancers have revolutionized cancer immunotherapy. However, PD­1/PD­L1 inhibitors are associated with a low response rate and are only effective on a small number of patients with cancer. Development of an anti­PD­1/PD­L1 sensitizer for improving response rate and effectiveness of immunotherapy is a challenge. The present study reviews the synergistic effects of PD­1/PD­L1 inhibitor with oncolytic virus, tumor vaccine, molecular targeted drugs, immunotherapy, chemotherapy, radiotherapy, intestinal flora and traditional Chinese medicine, to provide information for development of effective combination therapies.