Serum Exosomes-Based Biomarker circ_0008928 Regulates Cisplatin Sensitivity, Tumor Progression, and Glycolysis Metabolism by miR-488/HK2 Axis in Cisplatin-Resistant Nonsmall Cell Lung Carcinoma.

Background: Nonsmall cell lung carcinoma (NSCLC) is a major cause of cancer-related death worldwide. The resistance of NSCLC to chemical drugs, such as cisplatin (CDDP), poses a heavy burden for NSCLC therapy. Herein, the effects of circular_0008928 (circ_0008928) on the CDDP sensitivity and biological behavior of CDDP-resistant NSCLC cells and underlying mechanism are revealed. Materials and Methods: The expression of circ_0008928 and microRNA-488 (miR-488) was detected by quantitative real-time polymerase chain reaction. The expression of hexokinase 2 (HK2) protein and exosome-specific proteins was determined by Western blot. The half-maximal inhibitory concentration (IC50) value of CDDP was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell proliferation and migratory and invasive abilities were illustrated by cell counting kit-8 and transwell assays. Cell glycolysis metabolism was illustrated by extracellular acidification rate assay, glucose kit and lactate kit assays and Western blot analysis. The binding sites between miR-488 and circ_0008928 or HK2 were predicted by starbase or microT-CDS online database, and identified by dual-luciferase reporter and RNA immunoprecipitation assays. Results: Circ_0008928 expression and HK2 protein expression were significantly upregulated, while miR-488 expression was obviously downregulated in NSCLC cells and CDDP-resistant NSCLC cells. Circ_0008928 expression was increased in serum exosomes of CDDP-resistant NSCLC patients compared with CDDP-sensitive NSCLC patients. In addition, circ_0008928 silencing improved CDDP sensitivity and attenuated CDDP-induced cell proliferation, migration, invasion, and glycolysis metabolism. Circ_0008928 was a sponge of miR-488, and miR-488 bound to HK2 in CDDP-resistant NSCLC cells. Furthermore, both miR-488 inhibitor and HK2 overexpression attenuated circ_0008928 absence-mediated impacts on CDDP sensitivity and tumor process in CDDP-resistant NSCLC. Conclusions: Circ_0008928 knockdown improved CDDP sensitivity and hindered cell proliferation, migration, invasion, and glycolysis metabolism by miR-488/HK2 axis in CDDP-resistant NSCLC. This finding provides a new mechanism for studying CDDP-resistant therapy in NSCLC.

Low dose aspirin associated with greater bone mineral density in older adults.

The use of low-dose aspirin in older adults is increasing as is the prevalence of osteoporosis. Aspirin has been shown in numerous studies to affect bone metabolism. However, there is no clear link between low-dose aspirin use and bone mineral density (BMD). This study examined differences in bone mineral density between low-dose aspirin users and non-aspirin users in adults aged 50-80 years. We conducted a cross-sectional study of 15,560 participants who participated in the National Health and Nutrition Examination Survey (NHANES) 2017-March 2020. We used a multivariate logistic regression model to evaluate the relationship between low-dose aspirin and femoral neck BMD, femoral total BMD, intertrochanteric BMD, and the first lumbar vertebra BMD (L1 BMD) in patients aged 50 to 80 years. A total of 1208 (Group 1: femoral neck BMD, total femur BMD, and intertrochanter BMD) and 1228 (Group 2: L1 BMD) adults were included in this study. In both group 1 and group 2, BMD was higher in the low-dose aspirin group than in the non-aspirin group (Total femur BMD ß = 0.019, 95% CI 0.004-0.034; Femoral neck BMD ß = 0.017, 95% CI 0.002-0.032; Intertrochanter BMD ß = 0.025, 95% CI 0.007-0.043; L1 BMD ß = 0.026, 95% CI 0.006-0.046). In subgroup analyses stratified by gender, this positive association existed in both gender after adjusting for confounders. On subgroup analyses stratified by age, this positive association existed in three different age groups after adjusting for confounders. To test whether the effect of low-dose aspirin on BMD was affected by gender and age, the interaction P value was greater than 0.05. These findings from a human study looking into the relationship between low-dose aspirin use and BMD suggest that regular low-dose aspirin may be associated with a higher BMD. The association between low-dose aspirin and BMD did not differ by age group or gender.

Efficacy and safety of autologous hematopoietic stem cell transplantation in the treatment of malignant lymphoma after chemotherapy: a systematic review and meta-analysis.

Background: Autologous hematopoietic stem cell transplantation (AHSCT) is a common method for the clinical treatment of malignant lymphomas that recur after conventional chemotherapy. It has been reported that its efficacy is better than conventional chemotherapy, but the efficacy of its first-line treatment is controversial, and the existing clinical randomized controlled trials have not yet reached a unified conclusion. This work intended to use meta-analysis to systematically evaluate the efficacy and safety of AHSCT in the treatment of malignant lymphoma after high-dose chemotherapy, and draw reliable conclusions to provide reference and basis for clinical application. Methods: The inclusion and exclusion criteria were formulated based on the PICOIS principle. Relevant articles were retrieved from Medline, Excerpta Medica Database (EMBASE), Elton B. Stephens. Company (EBSCO), Ovid Technologies (OVID), China Biomedical Database, and Wanfang. The search period was limited the study published between January 1, 1980 and November 2021. The search terms included malignant lymphoma, autologous hematopoietic stem cell transplantation, AHSCT, high-dose chemotherapy, etc. The study subjects were diagnosed as malignant lymphoma patients. The experimental group was defined as AHSCT after high-dose chemotherapy, and the control group was defined as conventional chemotherapy (the chemotherapy regimen was not limited). The outcome indicators were overall survival (OS), complete remission rate [complete response (CR) + partial response (PR)], and event-free survival (EFS). RevMan5.3 software provided by the Cochrane Collaboration was used for meta-analysis. Results: A total of 6 pieces of literature were included, with 264 cases in the experimental group and 389 cases in the control group. There was no risk of bias in the included literature. The intervention method in the control group was conventional chemotherapy (chemotherapy regimen was not limited). The differences in the rates of overall survival and progression-free survival between the groups were compared, and it was found that the overall survival between groups was [odds ratio (OR) =2.88; 95% confidence interval (CI): 1.78-4.66; Z=4.31; P<0.0001] and progression-free survival rate was (OR =2.70; 95% CI: 1.86-3.92, Z=5.21; P<0.00001). Discussion: AHSCT treatment can significantly prolong the overall survival and progression-free survival rates of patients with malignant lymphoma after chemotherapy.

Elevated pretreatment platelet distribution width and platelet count predict poor prognosis in nasopharyngeal carcinoma.

BACKGROUND: Previous studies have demonstrated that platelets play a multifaceted role in cancer progression and metastasis. However, the value of platelet indices for predicting survival in nasopharyngeal carcinoma (NPC) patients remains unknown. The aim of this study was to evaluate the predictive significance of platelet indices in NPC cases. MATERIALS AND METHODS: A total of 168 patients who were diagnosed with NPC between January 2011 and June 2012 were recruited. The optimal cut-off values for the platelet indices were determined using a receiver operating characteristic curve. The Kaplan-Meier method and Cox regression were used to evaluate the prognostic impact of the potential predictors. RESULTS: Of the 168 patients, high platelet distribution width (PDW) and platelet count (PLT) levels were observed in 81 (48.21%) and 68 (40.48%) of the patients, respectively. An increased PDW was associated with the depth of invasion (T stage, P = 0.019), lymph node metastasis (N stage, P = 0.026), and clinical stage (P < 0.001). Moreover, the survival analysis showed that the overall survival of the patients with a PDW > 16.3 fL or platelet count > 266 × 109/L was associated with a poorer prognosis (both P < 0.001). In the multivariate Cox regression model, the PDW (P < 0.001), PLT (P = 0.001), T stage (P < 0.001), N stage (P = 0.006), clinical stage (P = 0.005), and Epstein-Barr virus DNA (P = 0.039) were independent prognostic factors for the overall survival. CONCLUSIONS: The PDW and PLT are easily available via a routine blood test, and our study showed that the PDW and PLT could be prognostic predictors in NPC patients. However, further studies are required to confirm this conclusion.