Quantification of complanatoside A in rat plasma using LC-MS/MS and its application to a pharmacokinetic study.

Complanatoside A is a flavonol glycoside isolated from Astragalus complanatus, and currently it is used as a quality control index for A. complanatus in the 2010 edition of the Chinese Pharmacopoeia. For the first time, a simple and sensitive LC-MS/MS method was developed for the determination of complanatoside A in rat plasma over the range of 2.3-575 ng/mL. Complanatoside A was extracted from plasma by a protein precipitation procedure, separated by LC and detected by MS/MS in positive electrospray ionization mode. The method was validated for selectivity, carryover, sensitivity, linearity, extraction recovery, matrix effect, accuracy, precision and stability studies. The lower limit of quantification was established at 2.3 ng/mL. Intra- and inter-day precisions (LLOQ, low-QC, med-QC and high-QC) were <7.9%, and accuracies were between 94.0 and 105.1%. Matrix effect was acceptable (97.9-103.0%) and extraction recovery was reproducible (88.5-94.4%). Complanatoside A was stable in the investigated conditions. The method was applied to the pharmacokinetics of complanatoside A in rats. Copyright © 2015 John Wiley & Sons, Ltd.

Up-regulation of MIC19 promotes growth and metastasis of hepatocellular carcinoma by activating ROS/NF-κB signaling.

BACKGROUND: Mitochondrial malfunction has been well-recognized as a critical step in the pathogenesis of many types of diseases, including cancer. MIC19 is a core a subunit of the MICOS complex that plays a critical role in maintaining the normal function of mitochondria. However, the biological functions of MIC19 in human hepatocellular carcinoma (HCC) remain unclear. METHODS: The expression level of MIC19 in HCC was evaluated by bioinformatics analysis, quantitative real-time PCR and immunohistochemistry staining assays. Cell growth and metastasis experiments were used to assess the biological functions of MIC19 in HCC cells. FINDINGS: MIC19 expression was frequently upregulated in both human HCC specimens and cell lines, and its upregulation is closely associated with patients' survival. Results from loss-of-function and gain-of-function experiments demonstrated that knockdown of MIC19 significantly attenuated, while overexpression of MIC19 enhanced, the proliferation, colony formation, migration and invasion abilities of HCC cells. Mechanistically, we found that MIC19 has no effect on mitochondrial energy production, while activated ROS/NF-κB signaling, which was required for MIC19-promoted HCC growth and metastasis. INTERPRETATION: Our findings suggest that MIC19 play a critical oncogenic role in HCC, implying that MIC19 may serve as a potential therapeutic target in the treatment of HCC.

Corrigendum: Atherogenic index of plasma and coronary artery disease in the adult population: A meta-analysis.

[This corrects the article DOI: 10.3389/fcvm.2021.817441.].

Precision-based tertiary care improves nutritional status and quality of life in patients undergoing adjuvant chemotherapy after radical gastrectomy for gastric cancer.

OBJECTIVE: To assess the impact of a precision-based tertiary care protocol, including participatory dietary care, on the nutritional status, immune function, and quality of life in gastric cancer patients after radical gastrectomy. METHODS: The clinical and laboratory data of 124 patients diagnosed with gastric cancer at the Second People's Hospital of Lanzhou City from June 2020 to May 2022 were collected and retrospectively analyzed. The patients were grouped into a control group of 54 patients who received standard care and a study group of 70 patients who additionally received detailed tertiary care and bundled nutritional interventions. The clinical data (age, gender, surgical method, clinical staging, chemotherapy regimen, histories of diabetes, hypertension, smoking, alcohol consumption, time to first flatus and bowel movement, time to first liquid intake, length of hospital stay, complications at discharge, PG-SGA score, and QLQ-C30 score) and lab indices (serum albumin (ALB), prealbumin (PA), transferrin (TRF), hemoglobin (Hb), immunoglobulin A (IgA), M (IgM), and G (IgG)) were compared between the two groups. RESULTS: Study group had significantly higher levels of ALB, PA, TRF, Hb, IgA, IgM, and IgG compared to the control group after intervention (all P<0.001). QLQ-C30 score was higher while PG-SGA score was lower in the study group (both P<0.01). Postoperative digestive system recovery was faster in the study group, as evidenced by a shorter time to first anal defecation, bowel movement, liquid food intake, and hospital stay (P<0.001). Complication rate was significantly lower in the study group (P<0.05). Cox regression analysis showed age (P=0.021) and clinical stage (P=0.039) as independent prognostic factors, while treatment regimen was not (P>0.05). CONCLUSION: Precision-based tertiary care protocol can improve nutritional status, enhance immune function, and facilitate faster postoperative recovery for gastric cancer patients following gastrectomy, thus greatly improving the quality of life of the patient. However, age and clinical staging, rather than the care protocol, are independent prognostic factors for patients' 1-year survival.

High SIRPA Expression Predicts Poor Prognosis and Correlates with Immune Infiltrates in Patients with Esophageal Carcinoma.

BACKGROUND: Signal regulatory protein alpha (SIRPA) is an inhibitory receptor expressed in macrophages and a potential therapeutic target in cancers. This study aims to investigate the functional role of SIRPA in esophageal carcinoma (ESCA). METHODS: Based on the Oncomine and The Cancer Genome Atlas (TCGA) database, SIRPA expression and clinical value were determined. Gene set enrichment analysis (GSEA) was performed to predict the mechanism underlying the oncogene role of SIRPA. Spearman's correlation analysis was used to analyze the effects of SIRPA on the molecular relationship and immune landscape. RESULTS: SIRPA was highly expressed across Oncomine and TCGA databases and correlated with poor overall survival and disease-specific survival. There was an expression difference among clinical characteristics. Functional annotation showed that cancer-related biological function and pathways were enriched in the high SIRPA expression group. Besides, SIRPA strongly and extensively affected the immune infiltrates. CONCLUSION: SIRPA might be an oncogene and a target of immunotherapy in ESCA.

Atherogenic Index of Plasma and Coronary Artery Disease in the Adult Population: A Meta-Analysis.

Background: The atherogenic index of plasma (AIP), which is the logarithm of the ratio between the triglyceride and high-density lipoprotein cholesterol (TG/HDL-C) concentrations in molar units, is correlated with the burden of atherosclerosis. This study aimed to evaluate the association between the AIP and coronary artery disease (CAD) in the adult population by performing a meta-analysis. Methods: Observational studies relevant for this meta-analysis were identified by searching the PubMed, Embase, and Web of Science databases. Only studies using multivariate analysis were considered. A random-effects model, which incorporates potential intra-study heterogeneity, was applied to combine the results. Results: Ten observational studies were included. In studies with the AIP analyzed as a continuous variable, a higher AIP was associated with a higher odds of CAD (adjusted risk ratio [RR] per 1-standard deviation [SD] increment of AIP: 2.10, 95% confidence interval [CI]: 1.51-2.93, P < 0.001, I2 = 90%). Further analysis of studies with the AIP analyzed as a categorical variable showed a higher odds of CAD (adjusted RR: 2.35, 95% CI: 1.88-2.93, P < 0.001, I2 = 37%) in the participants with the highest versus the lowest AIP value. Subgroup analyses demonstrated consistent results in asymptomatic and symptomatic populations as well as in male and female participants (all between-group P values > 0.05). Discussion: Current evidence, mostly from cross-sectional studies, suggests that a higher AIP value may be independently associated with CAD in the adult population.

Efficacy of carboplatin plus S-1 for the treatment of non-small cell lung cancer: A protocol for a systematic review of randomized controlled trial.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common lung cancer. Numerous clinical studies have reported that the combination of carboplatin and S-1 (CS) can be used to treat NSCLC effectively. However, no systematic review has been conducted to assess its efficacy and safety for NSCLC. This systematic review aims to evaluate the efficacy and safety of CS for treatment of patients with NSCLC. METHODS: This study will retrieve the following electronic databases from inception to the February 1, 2019: Cochrane Library, EMBASE, MEDILINE, CINAHL, AMED, and 4 Chinese databases without any language limitations. This systematic review will include randomized controlled trials (RCTs) and case-control studies for assessing the efficacy and safety of CS for the treatment of NSCLC. Cochrane risk of bias will be used as methodological quality assessment for each qualified study. The RevMan V.5.3 software will be utilized to synthesize the data and conduct the meta-analysis if it is allowed. The data will be pooled by using the random-effects model or fixed-effects model. RESULTS: The primary outcome is overall response rate. The secondary outcomes are overall survival, progression-free survival, the disease control rate, and any adverse events. CONCLUSION: It will provide latest evidence to determine the efficacy and safety of CS for treatment of patients with NSCLC. ETHICS AND DISSEMINATION: No research ethic approval is needed in this study because this study will not analyze individual patient data. The results are expected to disseminate through peer-reviewed journals. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019124860.