Using network pharmacological analysis and molecular docking to investigate the mechanism of action of quercetin's suppression of oral cancer.

OBJECTIVE: This investigation seeks to explore the mechanism of quercetin in oral cancer by incorporating network pharmacology analysis and molecular docking. METHODS: First, we use the network pharmacology analysis to discover possible core targets for quercetin and oral cancer. We subsequently utilized the docking of molecules techniques to calculate the affinities of critical targets and quercetin for verification. RESULTS: TCMSP and the Swiss Target Prediction database found 190 quercetin action targets, while GeneCards, OMIM, PharmGkb, and the Therapeutic Target Database found 8971 oral cancer-related targets. Venny 2.1.0 online software conducted an intersection analysis of quercetin-related target information with information about oral cancer, and 172 putative quercetin-anti-oral cancer targets were examined. Six prospective core targets for quercetin treatment of oral cancer were identified from the PPI network topology analysis of 172 putative therapeutic targets. These targets include AKT1, PIK3R1, MYC, HIF1A, SRC, and HSP90AA1. GO enrichment function analysis showed that 2372 biological processes, 98 cell components, and 201 molecular functions were involved. Through enrichment analysis of the KEGG pathway, 172 signal pathways were obtained. A few examples are PI3K-AKT, HIF-1, IL-17, and other signaling pathways. The molecular docking scores of quercetin and the primary therapeutic targets AKT1, HIF1A, HSP90AA1, MYC, PIK3R1, and SRC are all less than -0.7 points, demonstrating good compatibility between the medicine and small molecules and suggesting that quercetin may affect oral cancer through the primary target. CONCLUSION: This study explores quercetin's mechanism and possible targets for oral cancer treatment, offering novel approaches. Quercetin may be a multitarget medication against oral cancer in the future.

Combination therapy with oncolytic viruses and immune checkpoint inhibitors in head and neck squamous cell carcinomas: an approach of complementary advantages.

Squamous cell carcinomas are the most common head and neck malignancies. Significant progress has been made in standard therapeutic methods combining surgery, radiation, and chemotherapy. Nevertheless, the 5-year survival rate remains at 40-50%. Immune checkpoint inhibitors (ICIs) are a new strategy for treating head and neck squamous cell carcinomas (HNSCCs). Still, the overall response and effective rates are poor, as HNSCCs are 'cold' tumors with an immunosuppressive tumor microenvironment (TME), limiting ICI's beneficial effects. In this case, transforming the tumor suppression microenvironment before using ICIs could be helpful. Oncolytic viruses (OVs) can transform cold tumors into hot tumors, improving the situation. Talimogene laherparepvec (T-VEC), oncolytic immunotherapy authorized for advanced melanoma, also showed good safety and antitumor activity in treating head and neck cancer and pancreatic cancer. In combination with pembrolizumab, T-Vec may have more anticancer efficacy than either drug alone. Therefore, understanding the mechanisms underpinning OVs and their potential synergism with ICIs could benefit patients with HNSCC.

Membrane Derived Vesicles as Biomimetic Carriers for Targeted Drug Delivery System.

Extracellular vesicles (EVs) are membrane vesicles (MVs) playing important roles in various cellular and molecular functions in cell-to-cell signaling and transmitting molecular signals to adjacent as well as distant cells. The preserved cell membrane characteristics in MVs derived from live cells, give them great potential in biological applications. EVs are nanoscale particulates secreted from living cells and play crucial roles in several important cellular functions both in physiological and pathological states. EVs are the main elements in intercellular communication in which they serve as carriers for various endogenous cargo molecules, such as RNAs, proteins, carbohydrates, and lipids. High tissue tropism capacity that can be conveniently mediated by surface molecules, such as integrins and glycans, is a unique feature of EVs that makes them interesting candidates for targeted drug delivery systems. The cell-derived giant MVs have been exploited as vehicles for delivery of various anticancer agents and imaging probes and for implementing combinational phototherapy for targeted cancer treatment. Giant MVs can efficiently encapsulate therapeutic drugs and deliver them to target cells through the membrane fusion process to synergize photodynamic/photothermal treatment under light exposure. EVs can load diagnostic or therapeutic agents using different encapsulation or conjugation methods. Moreover, to prolong the blood circulation and enhance the targeting of the loaded agents, a variety of modification strategies can be exploited. This paper reviews the EVs-based drug delivery strategies in cancer therapy. Biological, pharmacokinetics and physicochemical characteristics, isolation techniques, engineering, and drug loading strategies of EVs are discussed. The recent preclinical and clinical progresses in applications of EVs and oncolytic virus therapy based on EVs, the clinical challenges and perspectives are discussed.

The limiting factors of oncolytic virus immunotherapy and the approaches to overcome them.

Oncolytic virus (OV) immunotherapy is characterized by viruses which specifically target cancer cells and cause their cytolysis. They provide a unique and promising new tool for the eradication of cancer as they interact with and affect the tumor microenvironment (TME), vasculature, and immune system. Advancements of genetic engineering have allowed for these viruses to be armed in such a way to have enhanced targeting, strong immunomodulation properties, and an ability to modify the TME. However, there are still major limitations in their use, mostly due to difficulties in delivering the viral particles to the tumors and in ensuring that the immunomodulatory properties are able to stimulate the host immune response to mount a complete response. Using novel delivery systems and using OVs as a complementary therapy in a combinatorial treatment have shown some significant successes. In this review, we discuss the major issues and difficulties in using OVs as anti-tumor agents and some of the strategies put in place so far to overcome these limitations. KEY POINTS: • Oncolytic viruses (OVs) infect cancer cells and cause their cytolysis. • The major limitations in using OVs as anti-tumor therapy were discussed. • The potential strategies to overcome these limitations were summarized.

Mutation of mitochondrial DNA G13513A presenting with Leigh syndrome, Wolff-Parkinson-White syndrome and cardiomyopathy.

Mutation of mitochondrial DNA (mtDNA) G13513A, encoding the ND5 subunit of respiratory chain complex I, can cause mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) and Leigh syndrome. Wolff-Parkinson-White (WPW) syndrome and optic atrophy were reported in a high proportion of patients with this mutation. We report an 18-month-old girl, with an 11-month history of psychomotor regression who was diagnosed with WPW syndrome and hypertrophic cardiomyopathy, in association with Leigh syndrome. Supplementation with coenzyme Q10, thiamine and carnitine prevented further regression in gross motor function but the patient's heart function deteriorated and dilated cardiomyopathy developed 11 months later. She was found to have a mutation of mtDNA G13513A. We suggest that mtDNA G13513A mutation is an important factor in patients with Leigh syndrome associated with WPW syndrome and/or optic atrophy, and serial heart function monitoring by echocardiography is recommended in this group of patients.