Pinellia ternata-containing traditional Chinese medicine combined with 5-HT3RAs for chemotherapy-induced nausea and vomiting: A PRISMA-compliant systematic review and meta-analysis of 22 RCTs.

BACKGROUND: Pinellia ternata (P. ternata, Banxia)-containing traditional Chinese medicine (TCM) is widely used in China as an adjuvant treatment for chemotherapy-induced nausea and vomiting (CINV). However, evidence of its efficacy and safety remains limited. PURPOSE: To investigate the efficacy and safety of P. ternata-containing TCM combined with 5-hydroxytryptamine-3 receptor antagonists (5-HT3RAs) in the treatment of CINV. STUDY DESIGN: Systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: All relevant RCTs were systematically retrieved from seven internet databases (up to February 10, 2023). P. ternata-containing TCM combined with 5-HT3RAs to treat CINV was included in all RCTs. The clinical effective rate (CER) was defined as the primary outcome, while appetite, quality of life (QOL), and side effects were secondary outcomes. RESULTS: The meta-analysis included 22 RCTs with 1,787 patients. Our results indicated that P. ternata-containing TCM combined with 5-HT3RAs significantly improved the CER of CINV (RR = 1.46, 95% CI = 1.37-1.57, p < 0.00001), appetite (RR = 1.77, 95% CI = 1.42-2.20, p < 0.00001), QOL (RR = 7.67, 95% CI = 1.56-13.78, p = 0.01), the CER of several 5-HT3RA medications (RR = 1.47, 95% CI = 1.37-1.57, p < 0.00001), and acute and delayed vomiting (RR = 1.23, 95% CI = 1.12-1.36, p < 0.0001) compared with the 5-HT3RAs alone, while the combination therapy decreased the incidence of side effects induced by 5-HT3RAs for CINV (RR = 0.50, 95% CI = 0.42-0.59, p < 0.00001). CONCLUSION: According to the findings of this systematic review and meta-analysis, P. ternata-containing TCM combined with 5-HT3RAs was safer and more effective than 5-HT3RAs alone for CINV patients. However, due to the limitations of the included studies, more high-quality clinical trials are required to further validate our findings.

Identification of genes modified by N6-methyladenosine in patients with colorectal cancer recurrence.

Background: Recent studies demonstrate that N6-methyladenosine (m6A) methylation plays a crucial role in colorectal cancer (CRC). Therefore, we conducted a comprehensive analysis to assess the m6A modification patterns and identify m6A-modified genes in patients with CRC recurrence. Methods: The m6A modification patterns were comprehensively evaluated by the NMF algorithm based on the levels of 27 m6A regulators, and tumor microenvironment (TME) cell-infiltrating characteristics of these modification patterns were systematically assessed by ssGSEA and CIBERSORT algorithms. The principal component analysis algorithm based on the m6A scoring scheme was used to explore the m6A modification patterns of individual tumors with immune responses. The weighted correlation network analysis and univariable and multivariable Cox regression analyses were applied to identify m6A-modified gene signatures. The single-cell expression dataset of CRC samples was used to explore the tumor microenvironment affected by these signatures. Results: Three distinct m6A modification patterns with significant recurrence-free survival (RFS) were identified in 804 CRC patients. The TME characterization revealed that the m6A modification pattern with longer RFS exhibited robust immune responses. CRC patients were divided into high- and low-score subgroups according to the m6A score individually, which was obtained from the m6A-related signature genes. The patients with low m6A scores had both longer RFS and overall survival (OS) with altered immune cell infiltration. Notably, m6A-modified genes showed significant differences related to the prognosis of CRC patients in the meta-GEO cohort and TCGA cohort. Single-cell expression indicated that ALVRL1 was centrally distributed in endothelial tip cells and stromal cells. Conclusion: The m6A modification plays an indispensable role in the formation of TME diversity and complexity. Importantly, the signatures (TOP2A, LRRC58, HAUS6, SMC4, ACVRL1, and KPNB1) were identified as m6A-modified genes associated with CRC recurrence, thereby serving as a promising predictive biomarker or therapeutic target for patients with CRC recurrence.

The Synergism of Natural Compounds and Conventional Therapeutics against Colorectal Cancer Progression and Metastasis.

Cancer progression and metastases are the leading causes of poor outcomes in patients with colon cancer. Colon cancer metastasis is a multigene, multistep, multistage complex process in which target genes, microRNAs, epithelial-stromal transformation, tumour stem cells, the tumour microenvironment, and various cell signalling pathways are implicated in the progression and metastasis of colon cancer. Although conventional therapies have made significant advances in treating the progression and metastasis of colorectal cancer, they have failed to improve survival outcomes. Natural compounds may have more significant potential in preventing and treating colon cancer. Active natural compounds exert their antitumor effects by inducing tumour cell differentiation, promoting tumour cell apoptosis, inhibiting tumour vascular growth, and regulating immunity. Natural compounds, combined with conventional therapies, can target mutant genes and various cellular signalling pathways, inhibit epithelial-stromal transformation, and improve the tumour microenvironment to inhibit tumour progression and metastasis. The synergism of natural compounds and conventional therapeutics has the potential to become a promising therapy for treating colorectal cancer progression and metastases.

The Pharmacological Mechanism of Curcumin against Drug Resistance in Non-Small Cell Lung Cancer: Findings of Network Pharmacology and Bioinformatics Analysis.

The pharmacological mechanism of curcumin against drug resistance in non-small cell lung cancer (NSCLC) remains unclear. This study aims to summarize the genes and pathways associated with curcumin action as an adjuvant therapy in NSCLC using network pharmacology, drug-likeness, pharmacokinetics, functional enrichment, protein-protein interaction (PPI) analysis, and molecular docking. Prognostic genes were identified from the curcumin-NSCLC intersection gene set for the following drug sensitivity analysis. Immunotherapy, chemotherapy, and targeted therapy sensitivity analyses were performed using external cohorts (GSE126044 and IMvigor210) and the CellMiner database. 94 curcumin-lung adenocarcinoma (LUAD) hub targets and 41 curcumin-lung squamous cell carcinoma (LUSC) hub targets were identified as prognostic genes. The anticancer effect of curcumin was observed in KEGG pathways involved with lung cancer, cancer therapy, and other cancers. Among the prognostic curcumin-NSCLC intersection genes, 20 LUAD and 8 LUSC genes were correlated with immunotherapy sensitivity in the GSE126044 NSCLC cohort; 30 LUAD and 13 LUSC genes were associated with immunotherapy sensitivity in the IMvigor210 cohort; and 12 LUAD and 13 LUSC genes were related to chemosensitivity in the CellMiner database. Moreover, 3 LUAD and 5 LUSC genes were involved in the response to targeted therapy in the CellMiner database. Curcumin regulates drug sensitivity in NSCLC by interacting with cell cycle, NF-kappa B, MAPK, Th17 cell differentiation signaling pathways, etc. Curcumin in combination with immunotherapy, chemotherapy, or targeted drugs has the potential to be effective for drug-resistant NSCLC. The findings of our study reveal the relevant key signaling pathways and targets of curcumin as an adjuvant therapy in the treatment of NSCLC, thus providing pharmacological evidence for further experimental research.

A Novel Diagnostic and Therapeutic Strategy for Cancer Patients by Integrating Chinese Medicine Syndrome Differentiation and Precision Medicine.

Applying Chinese medicine (CM) is an important strategy for malignant tumor treatment in China. One of the significant characteristics of CM is to treat diseases based on syndrome differentiation. For Western medicine, it is of important clinical significance to formulate guidelines for the diagnosis and treatment of cancer patients based on the characteristics of disease differentiation. In Chinese clinical practice, the combination of disease differentiation and syndrome differentiation is an important feature for cancer treatment in the past. Currently, molecular profiling and genomic analysis-based precision medicine optimizes the anticancer drug design and holds the greatest success in treating cancer patients. Therefore, we want to know which populations of cancer patients can benefit more from CM treatment if the theory of precision medicine is applied to CM clinical practice. So, we developed a novel diagnostic and therapeutic strategy "disease-syndrome differentiation-genomic profiling-prescriptions" for cancer patients by CM syndrome differentiation and precision medicine. As a result, this strategy has greatly enhanced the anti-tumor efficacy of CM and improved clinical outcomes for cancer patients with some gene mutations. Our idea will hopefully establish a novel approach for the inheritance and innovation of CM.

Curcumenol triggered ferroptosis in lung cancer cells via lncRNA H19/miR-19b-3p/FTH1 axis.

Curcumenol, an effective ingredient of Wenyujin, has been reported that exerted its antitumor potential in a few cancer types. However, the effect and molecular mechanism of curcumenol in lung cancer are largely unknown. Here, we found that curcumenol induced cell death and suppressed cell proliferation in lung cancer cells. Next, we demonstrated that ferroptosis was the predominant method that contributed to curcumenol-induced cell death of lung cancer in vitro and vivo for the first time. Subsequently, using RNA sequencing, we found that the long non-coding RNA H19 (lncRNA H19) was significantly downregulated in lung cancer cells treated with curcumenol, when compared to untreated controls. Overexpression of lncRNA H19 eliminated the anticancer effect of curcumenol, while lncRNA H19 knockdown promoted ferroptosis induced by curcumenol treatment. Mechanistically, we showed that lncRNA H19 functioned as a competing endogenous RNA to bind to miR-19b-3p, thereby enhanced the transcription activity of its endogenous target, ferritin heavy chain 1 (FTH1), a marker of ferroptosis. In conclusion, our data show that the natural product curcumenol exerted its antitumor effects on lung cancer by triggering ferroptosis, and the lncRNA H19/miR-19b-3p/FTH1 axis plays an essential role in curcumenol-induced ferroptotic cell death. Therefore, our findings will hopefully provide a valuable drug for treating lung cancer patients.

NPCDR: natural product-based drug combination and its disease-specific molecular regulation.

Natural product (NP) has a long history in promoting modern drug discovery, which has derived or inspired a large number of currently prescribed drugs. Recently, the NPs have emerged as the ideal candidates to combine with other therapeutic strategies to deal with the persistent challenge of conventional therapy, and the molecular regulation mechanism underlying these combinations is crucial for the related communities. Thus, it is urgently demanded to comprehensively provide the disease-specific molecular regulation data for various NP-based drug combinations. However, no database has been developed yet to describe such valuable information. In this study, a newly developed database entitled 'Natural Product-based Drug Combination and Its Disease-specific Molecular Regulation (NPCDR)' was thus introduced. This database was unique in (a) providing the comprehensive information of NP-based drug combinations & describing their clinically or experimentally validated therapeutic effect, (b) giving the disease-specific molecular regulation data for a number of NP-based drug combinations, (c) fully referencing all NPs, drugs, regulated molecules/pathways by cross-linking them to the available databases describing their biological or pharmaceutical characteristics. Therefore, NPCDR is expected to have great implications for the future practice of network pharmacology, medical biochemistry, drug design, and medicinal chemistry. This database is now freely accessible without any login requirement at both official (https://idrblab.org/npcdr/) and mirror (http://npcdr.idrblab.net/) sites.