Zhenqing Li

Human papillomavirus (HPV) is a well-known carcinogenic DNA virus, responsible for about 4% of all cancer cases globally. Effective antiviral treatments for those who are already infected with HPV are still in their early stages, despite the fact that prophylactic vaccinations have shown impressive success in preventing new infections. Effective treatments for HPV-related malignancies are also hampered by the fact that current articles address a wide spectrum of pathways but lack thorough systematic studies. In this work, we use bibliometric techniques to examine research trends and innovative approaches in the development of HPV antivirals over the last 40 years. Our results are intended to offer insightful information and direct future research into effective antiviral treatments for HPV-induced cancers.

In a recent study, the PD-1 inhibitor has been widely used in clinical trials and shown to improve various cancers. However, PD-1/PD-L1 inhibitors showed a low response rate and were effective for only a small number of cancer patients. Thus, it is important to figure out the issue about the low response rate of immunotherapy. Here, we performed ssGSEA and unsupervised clustering analysis to identify three clusters (clusters A, B, and C) according to different immune cell infiltration status, prognosis, and biological action. Of them, cluster C showed a better survival rate, higher immune cell infiltration, and immunotherapy effect, with enrichment of a variety of immune active pathways including T and B cell signal receptors. In addition, it showed more significant features associated with immune subtypes C2 and C3. Furthermore, we used WGCNA analysis to confirm the cluster C-associated genes. The immune-activated module highly correlated with 111 genes in cluster C. To pick candidate genes in SD/PD and CR/PR patients, we used the least absolute shrinkage (LASSO) and SVM-RFE algorithms to identify the targets with better prognosis, activated immune-related pathways, and better immunotherapy. Finally, our analysis suggested that there were six genes with KLRC3 as the core which can efficiently improve immunotherapy responses with greater efficacy and better prognosis, and our study provided clues for further investigation about target genes associated with the higher response rate of immunotherapy.

Sour orange (Citrus aurantium L.) is one of the biological sources of polymethoxyflavones (PMFs), which are often used to deal with gastrointestinal diseases. The intestine is highly sensitive to irradiation damage. However, limited certain cures have been released for irradiation-induced gastrointestinal injury, and the potentials of sour orange PMFs as radio-resistance agents have not been fully discussed yet. The present study aims to (1) investigate the PMF components in 12 sour orange cultivars, (2) determine the protective effects of PMFs on irradiation-induced intestinal injury by treating mice that received 12 Gy abdominal irradiation with different doses of PMFs and observing the changes in organ indexes and pathological sections and (3) test cytotoxicity of PMFs by CCK-8 method. The results showed that sour orange PMFs appeared to have high intraspecies similarity. Besides, PMFs protected mice from irradiation-induced injury by alleviating body weight loss, reliving organ index changing and maintaining the intestinal structure. Finally, IC₅₀ concentrations to cell line CCD 841 CoN of PMFs and nobiletin were calculated as 42.23 μg/mL and 51.58 μg/mL, respectively. Our study uncovered PMF contents in 12 sour orange materials and determined the protective effects on irradiation-induced intestinal injuries, providing guidance for the utilization of sour orange resources.

The by-product of citrus juice processing is a huge source of bioactive compounds, especially polymethoxyflavones (PMFs) and fibers. In this study, a method for the separation and purification of PMFs from citrus pomace was established based on citrus nanoporous carbon (CNPC) enrichment. Different biomass porous carbons were synthesized, their adsorption/desorption characteristics were evaluated, and the CNPCs from the peel of Citrus tangerina Tanaka were found to be best for the enrichment of PMFs from the crude extracts of citrus pomace. Using this method, six PMF compounds including low-abundant PMFs in citrus fruits such as 5,6,7,4′-tetramethoxyflavone and 5-hydroxy-6,7,8,3′,4′-pentamethoxyflavone can be simultaneously obtained, and the purities of these compounds were all higher than 95%, with the highest purity of nobiletin reaching 99.96%. Therefore, CNPCs have a great potential for the separation and purification of PMFs in citrus processing wastes, potentially improving the added value of citrus wastes. We also provide a method reference for disposing of citrus pomace in the future.

In this study, a preparative separation method was established to simultaneously isolate the polymethoxylated flavones (PMFs) from the peel of “Dahongpao” tangerine using macroporous adsorptive resins (MARs) combined with prep-HPLC. The total PMFs were enriched using MARs to remove most sugars, water-soluble pigments, and flavanones, and the eluents obtained were analyzed by ultra-performance liquid chromatography (UPLC) to determine the PMF composition. The separation and purification of PMFs were carried out by using a mass spectrometry-guided prep-HPLC with a gradient elution of acetonitrile-water (v/v), simultaneously. The purity of these PMFs was determined by UPLC, and their chemical structures were confirmed by electrospray ionization mass spectrometry (ESI-MS-MS), ultraviolet (UV), and nuclear magnetic resonance (NMR). Using the present method, five PMFs, including 5,6,7,4’-tetramethoxyflavone (1), nobiletin (2), tangeretin (3), sinensetin (4), and 5-hydroxy-6,7,8,3’,4’-pentamethoxyflavone (5), can be purified simultaneously, and the purity of the compounds obtained were 95.3%, 99.7%, 99.5%, 98.9%, and 98.1%, respectively. The method reported here is simple, rapid, and efficient, and it can be used to separate PMFs from citrus fruit peels and, potentially, other plant materials.