A systematic study to evaluate the safety of ticagrelor combined with aspirin in the treatment of PCI patients in Chinese population: A single nucleotide polymorphisms study.

The aim of this study was to identify genes and their associated loci related to ticagrelor pharmacokinetics and pharmacodynamics in Chinese patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). The study included 1115 patients with ACS who received a drug-eluting stent implantation between October 2019 and January 2021. Among them, 98 cases of adverse reactions were observed; thus, 97 cases without adverse reactions were selected as the comparison group. The steady-state serum drug concentration was determined via high-performance liquid chromatography-mass spectrometry, and 15 single nucleotide polymorphism (SNP) loci were genotyped using the SNaPshot SNP Multiplex System. Our results showed that age and sex may affect ticagrelor serum concentration in patients with ACS. In particular, the SNPs CYP3A4∗1 (rs2242480 C > T), IGT2B (rs5911 A > C), P2Y12 (rs6787801) and CYP3A5 (rs776746 C > T) may affect the steady-state blood concentration of ticagrelor after PCI in ACS patients, and CYP3A4∗1 may also be related to adverse events. In addition, we found that the SNPs PEAR1 (rs4661012 T > G) and P2Y12 (rs6787801 A > G) may be associated with dyspnea. These findings can provide a useful reference to establish guidelines for future clinical individualized dosage regimens of ticagrelor after PCI.

Radioimmunotherapy Targeting B7-H3 in situ glioma models enhanced antitumor efficacy by Reconstructing the tumor microenvironment.

Radionuclide drug conjugates (RDCs) with antibodies serve as a novel approach for the treatment of malignant tumors including glioblastoma. However, RDCs require optimal antibodies to work efficiently. Hu4G4, a novel B7-H3-targeting humanized monoclonal IgG1 antibody, is highly specific for the human B7-H3 protein (a marker of tumor cells, including glioblastoma cells). Herein, we established 131I-labeled hu4G4 (131I-hu4G4) and showed that it specifically bound to B7-H3 with high affinity (Kd = 0.99 ± 0.07 nM) and inhibited the growth of U87 cells in vitro. 131I-hu4G4 displayed potent in situ antitumor activity in a mouse model of glioma based on GL261 Red-Fluc-B7-H3 cells. More importantly, 131I-hu4G4 remodeled the tumor microenvironment and promoted the transformation of glioma from "cold" to "hot" tumors by promoting CD4+ and CD8+ T cell infiltration and the polarization of M2 to M1. Therefore, the antitumor activity observed with 131I-hu4G4, together with its ability to enhance antitumor immune responses, makes it a novel candidate for radioimmunotherapy of glioblastoma.

Prognostic value of myosteatosis in patients with lung cancer: a systematic review and meta-analysis.

The prognostic value of myosteatosis has been widely investigated in lung cancer, yet conclusions remain controversial. The purpose of this meta-analysis was to illuminate this issue. Medline, Embase, Cochrane Library and Web of Science Core Collection online databases were systematically searched from inception to 24 September 2021. Newcastle-Ottawa Scale tool was applied to evaluate the quality of included studies. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS) were used to examine prognostic value of myosteatosis. Subgroup analysis and sensitivity analysis were conducted to assess heterogeneity and stability of results. A total of 484 articles were screened from which 9 eligible studies involving 1667 patients were enrolled in this meta-analysis. Lung cancer patients with myosteatosis had significantly worse OS than patients without myosteatosis (HR 1.10, 95% CI 1.05-1.16, P < 0.001), both in six multivariate analysis (HR 1.46, 95% CI 1.16-1.85, P = 0.001) and in three univariate analysis (HR 1.08, 95% CI 1.03-1.14, P = 0.003). Pooled data from five studies using multivariate survival analysis also showed that patients with myosteatosis had a statistically significant unfavorable PFS (HR = 1.27, 95% CI 1.00-1.62, P = 0.049). Sensitivity analysis showed the result for OS was stable. But for PFS, the result was not robust. Myosteatosis might serve as an independent indicator of unfavorable survival outcomes for OS and PFS in lung cancer patients. Further studies are needed to confirm our results.

Identification of Biomarkers Associated with Hepatocellular Carcinoma Stem Cell Characteristics Based on Co-Expression Network Analysis of Transcriptome Data and Stemness Index.

Mounting evidence has revealed the key role of cancer stem cells in hepatocellular carcinoma (HCC) metastasis and therapy resistance, yet the genes maintaining HCC stem cell features remain to be explored. This study aimed to identify and validate the key biomarkers associated with HCC stemness. mRNA expression-based stemness index (mRNAsi) was calculating using one-class logistic regression algorithm. RNA-sequencing data and clinical information of HCC samples were downloaded from the cancer genome atlas (TCGA) and merged with the corresponding mRNAsi. We investigated the correlation between mRNAsi and HCC clinical characteristics, including tumor grades, pathologic stages, vascular invasion, and survival outcomes. Significant genes associated HCC stemness features were screened through weighted gene co-expression network analysis (WGCNA) and were functionally annotated using enrichment analysis. Protein-protein interaction network was constructed among significant genes and the key biomarkers were finally identified based on the maximal clique centrality (MCC) method. The expression of key biomarkers and its correlation with HCC clinical outcomes were validated using oncomine and gene expression omnibus (GEO) database. mR-NAsi was significantly higher in HCC tissues and gradually increased according to tumor grades and pathologic stages. Patients with vascular invasion or poor survival exhibited higher mRNAsi. Forty-four highly-correlated significant gens were screened through WGCNA and functionally related to cell cycle, cellular senescence, p53 signaling pathway, DNA replication, and mismatch repair. Four different GEO datasets confirmed that the expression levels of these 44 genes were notably higher in HCC tissues. We finally identified 15 key biomarkers (KIF4A, TTK, CCNB1, CDC20, NCAPG, CCNB2, CDC45, UBE2C, CENPA, AURKB, RRM2, CDCA8, BIRC5, TPX2, and KIF2C) through MCC method. The expression of these biomarkers was up-regulated in multiple types of cancers and showed a gradually increasing trend with HCC tumor grades. Furthermore, high expression levels of these biomarkers were also correlated with HCC metastasis, recurrence, sorafenib resistance, and poor overall survival. We identified 15 key biomarkers associated with HCC stemness features and these genes might serve as promising therapeutic targets for HCC.

Emerging Mechanisms and Disease Implications of Ferroptosis: Potential Applications of Natural Products.

Ferroptosis, a newly discovered form of regulatory cell death (RCD), has been demonstrated to be distinct from other types of RCD, such as apoptosis, necroptosis, and autophagy. Ferroptosis is characterized by iron-dependent lipid peroxidation and oxidative perturbation, and is inhibited by iron chelators and lipophilic antioxidants. This process is regulated by specific pathways and is implicated in diverse biological contexts, mainly including iron homeostasis, lipid metabolism, and glutathione metabolism. A large body of evidence suggests that ferroptosis is interrelated with various physiological and pathological processes, including tumor progression (neuro)degenerative diseases, and hepatic and renal failure. There is an urgent need for the discovery of novel effective ferroptosis-modulating compounds, even though some experimental reagents and approved clinical drugs have been well documented to have anti- or pro-ferroptotic properties. This review outlines recent advances in molecular mechanisms of the ferroptotic death process and discusses its multiple roles in diverse pathophysiological contexts. Furthermore, we summarize chemical compounds and natural products, that act as inducers or inhibitors of ferroptosis in the prevention and treatment of various diseases. Herein, it is particularly highlighted that natural products show promising prospects in ferroptosis-associated (adjuvant) therapy with unique advantages of having multiple components, multiple biotargets and slight side effects.

The Potential Clinical Value of Curcumin and its Derivatives in Colorectal Cancer.

BACKGROUND: Curcumin, a naturally occurring polyphenol, possesses pleiotropic pharmacologic properties, including anti-inflammatory and anti-oxidant activities. Epidemiological evidence suggests that curcumin intake is associated with a reduced risk of Colorectal Cancer (CRC), highlighting the enormous potential of this botanical agent in the prevention and treatment of CRC. OBJECTIVE: We summarize the anticancer activity of curcumin and its derivatives in CRC. METHODS: We conducted a literature review on the therapeutic effects of curcumin and its derivatives in CRC. RESULTS: In this review, a summary of the activities of curcumin in the treatment of CRC regarding its bioavailability, anticancer activity, modes of action, curcumin delivery systems have been provided based on the researches from preclinical experiments. Also, we discuss the therapeutic effects of curcumin derivatives in CRC. The human clinical trials that used curcumin or curcumin derivatives for the treatment of CRC are also highlighted here. CONCLUSION: Curcumin possesses great potential as a chemopreventive agent in CRC. Moreover, emerging evidence reveals that it can be an effective adjuvant to CRC therapy. To date, few studies have explored the anticolon cancer activity of curcumin formulation and curcumin derivatives in vivo; therefore, more works are needed to confirm their effectiveness. In clinical trials, curcumin treatment protocols (formulation, dose, and duration) vary among studies. However, these trials consistently point out that the compound is well-tolerated and safe, albeit with little consensus on its therapeutic efficacy.

The diagnostic and prognostic value of exosome-derived long non-coding RNAs in cancer patients: a meta-analysis.

PURPOSE: Exosome-derived long non-coding RNAs (lncRNAs) as novel biomarkers are widely investigated in various cancers, yet results remain controversial. The aim of this meta-analysis was to clarify the diagnostic and prognostic value of exosome-derived lncRNAs in cancer. METHODS: PubMed, Web of Science, EMBASE, CNKI, and WanFang online databases were comprehensively searched for eligible studies up to January, 2020. To evaluate the diagnostic effect, sensitivity, specificity, and area under the curve (AUC) were pooled. Threshold effect, subgroup analysis, and meta-regression were applied to explore heterogeneity. Deeks' funnel plot and sensitivity analysis were used to examine publication bias and stability of meta-analysis, respectively. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) and recurrence free survival (RFS) were calculated to assess the prognostic value. RESULTS: A total of 29 eligible studies involving 3882 patients were enrolled in the meta-analysis, which included 26 on diagnosis and 11 on prognosis. For diagnosis analysis, the pooled sensitivity, specificity, and AUC were 0.83 (95% CI 0.78-0.87), 0.80 (95% CI 0.75-0.84), and 0.88 (95% CI 0.85-0.91), respectively. Meta-regression revealed that the cancer type acted as the potential source of heterogeneity. Sensitivity analysis and Deeks' funnel plot indicated that results were relatively robust and had no publication bias. For the prognosis analysis, results suggested that overexpression of exosome-derived lncRNAs which upregulated in cancer showed a significant association with poor OS (HR 2.21, 95% CI 1.79-2.71, p < 0.001). Conversely, overexpression of exosome-derived lncRNAs which downregulated in cancer was markedly related to better OS (HR 0.28, 95% CI 0.14-0.55, p < 0.001). CONCLUSION: This meta-analysis reveals that exosome-derived lncRNAs might serve as promising diagnostic and prognostic biomarkers for cancer. However, the clinical value of exosome-derived lncRNAs needs to be further confirmed.