RESUMEN
Background: Cancer is concerning owing to its high mortality rate. Consequently, methods of prolonging the life of patients with cancer have become the primary focus of attention research. In recent years, immune checkpoint inhibitors (ICIs) have achieved good clinical efficacy as antitumor drugs; however, their severe adverse effects have made their use challenging. In order to clarify the predictors of adverse effects, scientists have conducted a series of studies. Blood counts can potentially monitor risk factors associated with the occurrence of immune-related adverse events (irAEs). Herein, a meta-analysis was performed to clarify further the guiding significance of blood counts in the clinical setting. Methods: Studies that satisfied the inclusion criteria were obtained by searching the database. Included studies were those in which irAEs had been observed, and evidence of an association between blood counts and irAEs was reported. The included ones were evaluated for quality. In addition to sensitivity analysis and subgroup analysis, a meta-analysis was performed using the odds ratio (OR) and 95% confidence interval (CI) for each study. Results: A total of 18 articles were included in our study. The analyses were performed separately according to different blood cell count indicators. The blood cell count metrics associated with irAEs were: absolute eosinophil count, neutrophil: lymphocyte ratio, and platelet: lymphocyte ratio. Conclusion: Our review and meta-analysis of studies suggest that absolute eosinophil count, neutrophil: lymphocyte ratio, and platelet: lymphocyte ratio may serve as predictors of the emergence of irAEs. Given the small number of studies focusing on the relationship between patient blood cell counts and the risk of irAEs, future studies need to further explore the mechanisms of occurrence and potential associations.
Asunto(s)
Antineoplásicos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Enfermedades del Sistema Inmune , Neoplasias , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Neoplasias/tratamiento farmacológico , Neoplasias/inducido químicamente , Antineoplásicos/uso terapéutico , Factores de Riesgo , Recuento de Leucocitos , Enfermedades del Sistema Inmune/inducido químicamenteRESUMEN
BACKGROUND: Acute pneumonia (AP) has a high seasonal prevalence every year, which seriously threatens the lives and health of patients. Six traditional Chinese medicines in Ruhao Dashi formula (RDF) have excellent antiinflammatory, antibacterial, and antiviral effects. RDF is commonly used in the clinical treatment of AP. However, the mechanism and target of RDF are unclear. Therefore, this study aimed to use network pharmacology and molecular docking to evaluate the target and mechanism of RDF in the treatment of AP. METHODS: The Herbs and Disease Gene databases were searched to identify common targets of AP and RDF. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and Protein-Protein Interaction (PPI) network analyses were performed to identify the potential molecular mechanisms behind RDF. Molecular docking was performed to compare the binding activities of the active molecules with that of the target protein. RESULTS: The "drug-component-common target" network contained 64 active compounds and 134 targets. GO and KEGG analyses indicated that RDF could act by regulating cell death, cell proliferation, apoptosis, and hypoxic response. The PPI network and "pathway-target" network identified 31 core targets. Molecular docking revealed that the 14 active ingredients of RDF bind vigorously to the core targets. CONCLUSION: Through network pharmacology and molecular docking, we found that RDF contains 14 active components and 31 core AP targets. These targets were linked to the development of an antiinflammatory response and could be used to develop new drugs to treat AP.
Asunto(s)
Medicamentos Herbarios Chinos , Neumonía , Humanos , Simulación del Acoplamiento Molecular , Farmacología en Red , Mapas de Interacción de Proteínas , Antibacterianos , Medicina Tradicional China , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéuticoRESUMEN
SChLAP1 is recently reported as a key oncogenic long non-coding RNA in human cancer. However, whether SChLAP1 functions in non-small cell lung cancer (NSCLC) and its specific potential regulatory mechanism remain unexplored. In this study, we found that depletion of SChLAP1 significantly inhibited NSCLC cell proliferation, migration and invasion in vitro, and retarded tumour growth and lung metastasis in vivo. SChLAP1 facilitated NSCLC cell immune evasion against CD8+ T cells through PD-1/PD-L1 immune checkpoint. In detail, SChLAP1 was able to directly interact with AUF1, antagonizing the binding between AUF1 and PDL1 mRNA 3'-UTR, resulting in increasing PDL1 mRNA stability and expression, thereby repressing CD8+ T cell function. Consistently, anti-PD-1/PD-L1 treatment evidently blocked the enhanced cell proliferation and invasion caused by SChLAP1 overexpression. Importantly, SChLAP1 was significantly upregulated in NSCLC cell lines, serum and tissues, which was identified as an excellent indicator for the diagnosis and prognosis of NSCLC. In conclusion, our data for the first time uncover that SChLAP1 functions an oncogene in NSCLC by promoting cancer cell immune evasion via regulating the AUF1/PDL1 axis, targeting of SChLAP1 may be a potential approach to improve the efficacy of immunotherapy in NSCLC patients.