table1_Application Potential of Plant-Derived Medicines in Prevention and Treatment of Platinum-Induced Peripheral Neurotoxicity.docx

As observed with other chemotherapeutic agents, the clinical application of platinum agents is a double-edged sword. Platinum-induced peripheral neuropathy (PIPN) is a common adverse event that negatively affects clinical outcomes and patients’ quality of life. Considering the unavailability of effective established agents for preventing or treating PIPN and the increasing population of cancer survivors, the identification and development of novel, effective interventions are the need of the hour. Plant-derived medicines, recognized as ideal agents, can not only help improve PIPN without affecting chemotherapy efficacy, but may also produce synergy. In this review, we present a brief summary of the mechanisms of platinum agents and PIPN and then focus on exploring the preventive or curative effects and underlying mechanisms of plant-derived medicines, which have been evaluated under platinum-induced neurotoxicity conditions. We identified 11 plant extracts as well as 17 plant secondary metabolites, and four polyherbal preparations. Their effects against PIPN are focused on oxidative stress and mitochondrial dysfunction, glial activation and inflammation response, and ion channel dysfunction. Also, ten clinical trials have assessed the effect of herbal products in patients with PIPN. The understanding of the molecular mechanism is still limited, the quality of clinical trials need to be further improved, and in terms of their efficacy, safety, and cost effectiveness studies have not provided sufficient evidence to establish a standard practice. But plant-derived medicines have been found to be invaluable sources for the development of natural agents with beneficial effects in the prevention and treatment of PIPN.</p

Through-Process Analytical Modeling of Photoconductance Spectrum for Porous ZnO Nanocrystalline Film

In the past decades, many models have been developed to describe the photoconductance and the related photoresponse phenomena in wide-band gap metal oxides, but the related mechanisms and kinetics are still confused. Here, based on the persistent photoconductance observed in the porous ZnO nanocrystalline film, a donor photoionization model (DPM) is proposed to decipher the photoelectric kinetics both upon the sub-band gap and the above-band gap illuminations. In the DPM, the reaction rate equations and the related analytical functions are employed to numerically model the through processes of photoconductance spectra in a time-domain by comprehensively considering the photoelectric processes in ZnO such as the band-to-band transition, the donor photoionization, the surface oxygen adsorption/desorption, and the photogenerated electron recapture by donors. In the DPM simulation processes, some essential parameters, such as the electron yield from donor photoionization, the electron capture rates by donors, and the oxygen adsorption reaction rates on ZnO surface, are extracted quantitatively from the photoconductance spectra. The DPM analytical process herein reveals the photoresponse kinetics in detail and proposes a new insight into the basic theory of metal oxide photoresponse that might be helpful for further understanding the photoexcited carrier kinetics and the related photochemical processes

High Photoconductive Response of Gas-Sensitized Porous Nanocrystalline TiO₂ Film in Formaldehyde Ambience and Carrier Transport Kinetics

We propose a gas-sensitized porous nanocrystalline TiO₂ film with a potential application in photovoltaic devices and report about the systematic photoconductivity study of it. The quantitative results show that the gas-sensitized TiO₂ film in formaldehyde atmosphere exhibits much higher photoconductivity (3–4 orders of magnitude) and longer carrier lifetime than usual. The intriguing performance of the gas-sensitized TiO₂ film indicates the distinct charge carrier transport kinetic courses, whose contributions to the photoconductivity are shown in a designed flowchart. From the flowchart, it is clearly found that two electron loss processes, recombination and electron scavenging, are suppressed for the gas-sensitized TiO₂ film in formaldehyde gas, leading to large improvements of photoconductivity and carrier lifetime. The results provide the potential of improving efficiency of photovoltaic devices, and measuring photoconductivity under target gas appears to be a useful tool for research on photocatalytic and photoelectrical processes

Supplementary Tables. Analysis of the expression patterns and clinical relevance of m6A regulators in 33 cancer types

Supplementary Table 1. Analysis of the expression patterns and clinical relevance of m6A regulators in 33 cancer types Correspondence between 20 M6A RNA methylation regulatory factors and 18 cancers in differential expression-related (A) P value and (B) Log FC (fold change) Supplementary Table 2. Analysis of the expression patterns and clinical relevance of m6A regulators in 33 cancer types COX analysis between the expression levels of 20 M6A RNA methylation regulatory factors and the prognosis of different cancers Supplementary Table 3. Analysis of the expression patterns and clinical relevance of m6A regulators in 33 cancer types Differences of 20 M6A RNA methylation regulatory factors among different immune subtypes of pan-cancer Supplementary Table 4. Analysis of the expression patterns and clinical relevance of m6A regulators in 33 cancer types The difference between 20 M6A RNA methylation regulatory factors in different immune subtypes and different stages of breast cancer Supplementary Table 5. Analysis of the expression patterns and clinical relevance of m6A regulators in 33 cancer types The correlation between 20 regulatory factors and the prognosis of different cancers. </div

MOESM5 of Exploration of methylation-driven genes for monitoring and prognosis of patients with lung adenocarcinoma

Additional file 5. All relevant methylated sites of the five methylation-driven genes obtained from the TCGA database. (1–16) methylated sites of the gene CCDC181; (17–33) methylated sites of the gene ELF3; (34–47) methylated sites of the gene KLHDC9; (48) methylated site of the gene PLAU; (49–57) methylated sites of the gene S1PR1

Table1_Identifying the Effect of Ursolic Acid Against Triple-Negative Breast Cancer: Coupling Network Pharmacology With Experiments Verification.XLSX

Triple negative breast cancer (TNBC) is a subtype of breast cancer with complex heterogeneity, high invasiveness, and long-term poor prognosis. With the development of molecular pathology and molecular genetics, the gene map of TNBC with distinctive biological characteristics has been outlined more clearly. Natural plant extracts such as paclitaxel, vinblastine, colchicine etc., have occupied an important position in the treatment of hormone-independent breast cancer. Ursolic acid (UA), a triterpenoid acid compound derived from apple, pear, loquat leaves, etc., has been reported to be effective in a variety of cancer treatments, but there are few reports on the treatment of TNBC. This study performed comprehensive bioinformatics analysis and in vitro experiments to identify the effect of UA on TNBC treatment and its potential molecular mechanism. Our results showed that UA could not only reduce the proliferation, migration, and invasion in MDA-MB-231 and MDA-MB-468 cell lines with a dose-dependent manner but also induce cell cycle arrest and apoptosis. Meanwhile, we collected the gene expression data GSE45827 and GSE65194 from GEO for comparison between TNBC and normal cell type and obtained 724 DEGs. Subsequently, PLK1 and CCNB1 related to TNBC were screened as the key targets via topological analysis and molecular docking, and gene set enrichment analysis identified the key pathway as the p53 signaling pathway. In addition, quantitative real-time PCR and western blot verified the key genes were PLK1 and CCNB1. In vivo and in vitro experiments showed that UA could inhibit the growth of TNBC cells, and down-regulate the protein expression levels of PLK1 and CCNB1 by mediating p53 signaling pathway. These findings provide strong evidence for UA intervention in TNBC via multi-target therapy.</p

DataSheet1_Identifying the Effect of Ursolic Acid Against Triple-Negative Breast Cancer: Coupling Network Pharmacology With Experiments Verification.PDF

Triple negative breast cancer (TNBC) is a subtype of breast cancer with complex heterogeneity, high invasiveness, and long-term poor prognosis. With the development of molecular pathology and molecular genetics, the gene map of TNBC with distinctive biological characteristics has been outlined more clearly. Natural plant extracts such as paclitaxel, vinblastine, colchicine etc., have occupied an important position in the treatment of hormone-independent breast cancer. Ursolic acid (UA), a triterpenoid acid compound derived from apple, pear, loquat leaves, etc., has been reported to be effective in a variety of cancer treatments, but there are few reports on the treatment of TNBC. This study performed comprehensive bioinformatics analysis and in vitro experiments to identify the effect of UA on TNBC treatment and its potential molecular mechanism. Our results showed that UA could not only reduce the proliferation, migration, and invasion in MDA-MB-231 and MDA-MB-468 cell lines with a dose-dependent manner but also induce cell cycle arrest and apoptosis. Meanwhile, we collected the gene expression data GSE45827 and GSE65194 from GEO for comparison between TNBC and normal cell type and obtained 724 DEGs. Subsequently, PLK1 and CCNB1 related to TNBC were screened as the key targets via topological analysis and molecular docking, and gene set enrichment analysis identified the key pathway as the p53 signaling pathway. In addition, quantitative real-time PCR and western blot verified the key genes were PLK1 and CCNB1. In vivo and in vitro experiments showed that UA could inhibit the growth of TNBC cells, and down-regulate the protein expression levels of PLK1 and CCNB1 by mediating p53 signaling pathway. These findings provide strong evidence for UA intervention in TNBC via multi-target therapy.</p

Additional file 1: of Deciphering the mechanism of Indirubin and its derivatives in the inhibition of Imatinib resistance using a “drug target prediction-gene microarray analysis-protein network construction” strategy

Figure S1. Heat maps of differentially expressed genes associated with imatinib resistance (we selected 100 genes with the most significant differential expression) (P < 0.05). The color from blue to red shows a trend from low to high expression. (JPG 298 kb

Image_1_7-lncRNA Assessment Model for Monitoring and Prognosis of Breast Cancer Patients: Based on Cox Regression and Co-expression Analysis.TIF

Background: Breast cancer is one of the deadliest malignant tumors worldwide. Due to its complex molecular and cellular heterogeneity, the efficacy of existing breast cancer risk prediction models is unsatisfactory. In this study, we developed a new lncRNA model to predict the prognosis of patients with BRCA.Methods: BRCA-related differentially-expressed long non-coding RNA were screened from the Cancer Genome Atlas database. A novel lncRNA model was developed by univariate and multivariate analyses to predict the prognosis of patients with BRCA. The efficacy of the model was verified by TCGA-based breast cancer samples. Identified lncRNA-related mRNA based on the co-expression method.Results: We constructed a 7-lncRNA breast cancer prediction model including LINC00377, LINC00536, LINC01224, LINC00668, LINC01234, LINC02037, and LINC01456. The breast cancer samples were divided into high-risk and low-risk groups based on the model, which verified the specificity and sensitivity of the model. The Area Under Curve (AUC) of the 3- and 5-year Receiver Operating Characteristic curve were 0.711 and 0.734, respectively, indicating that the model has good performance.Conclusion: We constructed a 7-lncRNA model to predict the prognosis of patients with BRCA, and suggest that these lncRNAs may play a specific role in the carcinogenesis of BRCA.</p

Table_7_From tumor mutational burden to characteristic targets analysis: Identifying the predictive biomarkers and natural product interventions in cancer management.DOCX

High-throughput next-generation sequencing (NGS) provides insights into genome-wide mutations and can be used to identify biomarkers for the prediction of immune and targeted responses. A deeper understanding of the molecular biological significance of genetic variation and effective interventions is required and ultimately needs to be associated with clinical benefits. We conducted a retrospective observational study of patients in two cancer cohorts who underwent NGS in a “real-world” setting. The association between differences in tumor mutational burden (TMB) and clinical presentation was evaluated. We aimed to identify several key mutation targets and describe their biological characteristics and potential clinical value. A pan-cancer dataset was downloaded as a verification set for further analysis and summary. Natural product screening for the targeted intervention of key markers was also achieved. The majority of tumor patients were younger adult males with advanced cancer. The gene identified with the highest mutation rate was TP53, followed by PIK3CA, EGFR, and LRP1B. The association of TMB (0–103.7 muts/Mb) with various clinical subgroups was determined. More frequent mutations, such as in LRP1B, as well as higher levels of ferritin and neuron-specific enolase, led to higher TMB levels. Further analysis of the key targets, LRP1B and APC, was performed, and mutations in LRP1B led to better immune benefits compared to APC. APC, one of the most frequently mutated genes in gastrointestinal tumors, was further investigated, and the potential interventions by cochinchinone B and rottlerin were clarified. In summary, based on the analysis of the characteristics of gene mutations in the “real world,” we obtained the potential association indicators of TMB, found the key signatures LRP1B and APC, and further described their biological significance and potential interventions.</p