Azacitidine-Hesperetin Combination Induces S-phase Cell Cycle Arrest and Apoptosis in Human Leukemia Cells.

BACKGROUND/AIM: Chemotherapy drugs for leukemia, such as 5-azacytidine (Aza), have often various adverse effects. Hesperetin (Hes), a naturally occurring compound, is a potential adjuvant agent for anticancer therapy. This study aimed to investigate the effect of an Aza-Hes combination on acute leukemia cell lines, which elucidates the role of combination treatment in leukemia progression. MATERIALS AND METHODS: HL-60 and U937 cells were treated with Aza and Hes at various concentrations or their combination. Cell proliferation and apoptosis was evaluated using the Cell Counting Kit-8 assay and annexin V/propidium iodide staining, respectively. Cell cycle analysis was conducted using flow cytometry. The expression of apoptosis-related and cell cycle-related proteins in leukemia cells was analyzed through western blotting. The synergistic effect of the Aza and Hes agents was estimated using the Chou-Talalay method. RESULTS: We observed that Aza or Hes monotherapy engendered a dose-dependent reduction in HL-60 and U937 cell viability. However, treatment with the Aza-Hes combination for 24 h synergistically inhibited U937 cell proliferation by inducing both apoptosis and S-phase cell cycle arrest. Furthermore, the Aza-Hes combination down-regulated p-ERK and p-c-Jun N-terminal kinase expression and up-regulated p-p38 expression. CONCLUSION: Overall, our findings indicate that the Aza-Hes combination induces apoptosis and S-phase cell-cycle arrest through the mitogen-activated protein kinase pathway. In conclusion, the Aza-Hes combination is a potential antileukemia treatment.

Automated design of a 3D passive microfluidic particle sorter.

Microfluidic chips that can sort mixtures of cells and other particles have important applications in research and healthcare. However, designing a sorter chip for a given application is a slow and difficult process, especially when we extend the design space from 2D into a 3D scenario. Compared to the 2D scenario, we need to explore more geometries to derive the appropriate design due to the extra dimension. To evaluate sorting performance, the simulation of the particle trajectory is needed. The 3D scenario brings particle trajectory simulation more challenges of runtime and collision handling with irregular obstacle shapes. In this paper, we propose a framework to design a 3D microfluidic particle sorter for a given application with an efficient 3D particle trajectory simulator. The efficient simulator enables us to simulate more samples to ensure the robustness of the sorting performance. Our experimental result shows that the sorter designed by our framework successfully separates the particles with the targeted size.

Elevated Platelet-to-Lymphocyte Ratio and Neutrophil-to-Lymphocyte Ratio after First Cycle of Chemotherapy and Better Survival in Esophageal Cancer Patients Receiving Concurrent Chemoradiotherapy.

Background: Prognostic factors for poor survival have been proposed in esophageal squamous cell carcinoma (SCC) patients receiving concurrent chemoradiotherapy (CCRT). We conducted a retrospective study on hematological profile after first cycle of chemotherapy for esophageal SCC patients receiving CCRT. Methods: From January 2008 to December 2017, a total of 420 patients with esophageal SCC were enrolled. All included patients had undergone CCRT. Complete blood count, differential count, NLR, and PLR before chemotherapy (CHT) and after first cycle of CHT were obtained. Univariate and multivariate Cox regression analyses were used to assess the association between survival and patient, disease, and treatment characteristics. Results: On univariate analysis, significant factors for overall survival (OS) and disease specific survival (DSS) included ECOG performance status, clinical staging, operation, cisplatin dose, prechemotherapy NLR and PLR, and elevated postchemotherapy NLR. On multivariate analysis, ECOG performance status 0-I, Clinical staging I-II, Operation, cisplatin dose >150 mg/m2, prechemotherapy PLR <375, and postchemotherapy platelet count ≥150 × 109/L were independent factors for predicting better OS. Independent factors for predicting better DSS included ECOG performance status 0-I, Clinical staging I-II, Operation, cisplatin dose >150 mg/m2, and prechemotherapy PLR <375. Conclusions: Our study showed that low levels of prechemotherapy PLR and NLR were associated with better OS and DSS. Elevated platelet count and NLR after first cycle of CHT were associated with better OS. Elevated PLR and NLR after first cycle of CHT were associated with better DSS.

Association between serum uric acid level and bone mineral density at multiple skeletal sites in middle-aged and elderly men: a cross-sectional study of a healthy population in Taiwan.

This study revealed that serum uric acid (sUA) levels were not associated with bone mineral density (BMD) at different skeletal sites in middle-aged and elderly men, even adjusting for confounding variables. Nevertheless, a positive association was only found between sUA levels and BMD at all skeletal sites in the normal BMI group. INTRODUCTION: Previous studies have reported an association between serum uric acid (sUA) levels and bone mineral density (BMD). However, their findings are controversial and limited to adult men in the general population. This study was aimed at examining the association between sUA levels and BMD at multiple skeletal sites in middle-aged and elderly men. METHODS: A cross-sectional analysis of BMD at different skeletal sites and sUA levels was conducted on 918 men (age: 50.83 ± 7.95) using data from the Ditmanson Research Database. The participants were categorized into four groups based on quartiles of the sUA level, and BMD were assessed using dual-energy X-ray absorptiometry. Multivariate linear regression models were utilized to investigate the association between sUA levels and BMD. Further, subgroup analyses were performed. RESULTS: After adjusting for potential confounding factors, sUA as a continuous variable was significantly associated with BMD at the femoral neck only (ß, 95% confidence interval: 0.007 [0.001-0.013]). However, in the categorical analysis, no significant differences were detected in terms of BMD at different skeletal sites across the different sUA quartile groups. Moreover, if the body mass index (BMI) was < 24 kg/m2 for each unit increase in sUA level, the spine, femoral neck, and total hip BMD increased by 0.014, 0.013, and 0.015 g/cm2, respectively. CONCLUSION: The sUA level was not associated with BMD at different skeletal sites in middle-aged and elderly men. Nevertheless, a positive association was only found between sUA levels and BMD at all skeletal sites in the normal weight group.

The Application of DTCWT on MRI-Derived Radiomics for Differentiation of Glioblastoma and Solitary Brain Metastases.

BACKGROUND: While magnetic resonance imaging (MRI) is the imaging modality of choice for the evaluation of patients with brain tumors, it may still be challenging to differentiate glioblastoma multiforme (GBM) from solitary brain metastasis (SBM) due to their similar imaging features. This study aimed to evaluate the features extracted of dual-tree complex wavelet transform (DTCWT) from routine MRI protocol for preoperative differentiation of glioblastoma (GBM) and solitary brain metastasis (SBM). METHODS: A total of 51 patients were recruited, including 27 GBM and 24 SBM patients. Their contrast-enhanced T1-weighted images (CET1WIs), T2 fluid-attenuated inversion recovery (T2FLAIR) images, diffusion-weighted images (DWIs), and apparent diffusion coefficient (ADC) images were employed in this study. The statistical features of the pre-transformed images and the decomposed images of the wavelet transform and DTCWT were utilized to distinguish between GBM and SBM. RESULTS: The support vector machine (SVM) showed that DTCWT images have a better accuracy (82.35%), sensitivity (77.78%), specificity (87.50%), and the area under the curve of the receiver operating characteristic curve (AUC) (89.20%) than the pre-transformed and conventional wavelet transform images. By incorporating DTCWT and pre-transformed images, the accuracy (86.27%), sensitivity (81.48%), specificity (91.67%), and AUC (93.06%) were further improved. CONCLUSIONS: Our studies suggest that the features extracted from the DTCWT images can potentially improve the differentiation between GBM and SBM.

Crassolide Induces G2/M Cell Cycle Arrest, Apoptosis, and Autophagy in Human Lung Cancer Cells via ROS-Mediated ER Stress Pathways.

Crassolide, a cembranoid diterpene extracted from the soft coral Lobophytum crissum, has been proven to possess antioxidant and immunomodulatory properties. In the present study, we assessed the anticancer effects of crassolide on human H460 non-small-cell lung cancer (NSCLC) cells. We found that crassolide exerted cytotoxic effects on H460 cancer cells in vitro, inducing G2/M phase arrest and apoptosis. In addition, in H460 cells exposed to crassolide, the expression of the autophagy-related proteins LC3-II and beclin was increased, while the expression of p62 was decreased. Moreover, inhibiting autophagy with chloroquine (CQ) suppressed the crassolide-induced G2/M arrest and apoptosis of H460 cells. Moreover, we also found that crassolide induced endoplasmic reticulum (ER) stress in lung cancer cells by increasing the expression of ER stress marker proteins and that the crassolide-induced G2/M arrest, apoptosis, and autophagy were markedly attenuated by the ER stress inhibitor 4-phenylbutyric acid (4-PBA). Furthermore, we found that crassolide promoted reactive oxygen species (ROS) production by H460 cells and that the ROS inhibitor N-acetylcysteine (NAC) decreased the crassolide-induced ER stress, G2/M arrest, apoptosis, and autophagy. In conclusion, our findings show that crassolide inhibits NSCLC cell malignant biological behaviors for the first time, suggesting that this effect may be mechanistically achieved by inducing G2/M arrest, apoptosis, and autophagy through ROS accumulation, which activates the ER stress pathway. As a result of our findings, we now have a better understanding of the molecular mechanism underlying the anticancer effect of crassolide, and we believe crassolide might be a candidate for targeted cancer therapy.

The impact of ALDH7A1 variants in oral cancer development and prognosis.

The gene encoding aldehyde dehydrogenase 7 family member A1 (ALDH7A1) has been associated with the development and prognosis in multiple cancers; however, the role of ALDH7A1 polymorphisms in oral cancer remains unknown. For this purpose, the influences of ALDH7A1 rs13182402 and rs12659017 on oral cancer development and prognosis were analyzed. Our resulted showed that ALDH7A1 rs13182402 genotype had less pathologic nodal metastasis among betel quid chewer. ALDH7A1 rs13182402 also corresponded to higher expressions in upper aerodigestive mucosa, whole blood, the musculoskeletal system and oral cancer tissues than did the ALDH7A1 wild type. Furthermore, ALDH7A1 overexpression in oral cancer cells increased in vitro migration, whereas its silencing reduced cell migration. Conversely, ALDH7A1 expression in tumor tissues and in patients with advanced disease was lower than that in normal tissues and in patients with early-stage disease. When the patients were classified into ALDH7A1-high and -low-expression groups, the high-ALDH7A1 group had superior outcomes in progression-free survival than the low-ALDH7A1 group (5-year survival of 58.7% vs. 48.0%, P = 0.048) did. In conclusion, patients with high ALDH7A1 expression might, however, have more favorable prognoses than those with low ALDH7A1 expression have.

Influence of Risk of Drug⁻Drug Interactions and Time Availability on Patient Trust, Satisfaction, and Cooperation with Clinical Pharmacists.

Patients with multiple diseases requiring several medications often face the risk of drug-drug interactions (DDIs). Such patients need more care and services from clinical pharmacists. Given the importance of this issue in clinical medicine, the present study aims to investigate how DDIs and time availability affect patient trust in clinical pharmacists and how patient trust influences patient satisfaction and cooperation between patients and clinical pharmacists. Sample data of 741 patients in central Taiwan hospitals were analyzed, and the results of structural equation modeling showed that DDIs and time availability positively affect patient trust, which, in turn, positively influenced patient satisfaction and cooperation between patients and clinical pharmacists. Overall, the results indicated that patient satisfaction is an important predictor of cooperation between patients and clinical pharmacists.

Is definitive concurrent chemoradiotherapy effective for locally advanced head and neck cancer in the elderly aged ≥ 75 years: A single-institute, retrospective, cohort study.

BACKGROUND: Definitive chemoradiotherapy (CRT) is the standard treatment for locally advanced head and neck cancer (HNC). However, for very elderly patients, the comparison of benefit/risk between definitive radiotherapy (RT) with and without systemic chemotherapy was equivocal. PATIENTS AND METHODS: The study was a single-institute, retrospective, cohort study. Seventy patients aged ≥75 years who had a locally advanced HNC were enrolled. The patients were divided into those with CRT and those with RT alone. Survival, compliance/adverse events and independent prognostic factors were analyzed. RESULTS: For baseline characteristics, the patients who received RT alone had worse performance status, comorbidity score and neutrophil-to-lymphocyte ratio. However, during definitive therapy, the CRT group had more adverse events such as neutropenia, febrile neutropenia and thrombocytopenia. There were no significant differences in disease-specific survival (DSS) and overall survival (OS) (P = 0.864 and 0.788, respectively). As to OS, several independent prognostic factors were identified. Performance status (hazard ratio [HR], 2.312; confidence interval [CI], 1.176-4.546; P = 0.015), clinical T staging (HR, 2.240; 95% CI, 1.021-4.913; P = 0.004) and total RT dose (HR, 2.555; 95% CI, 1.246-5.238; P = 0.010) were independent prognostic factors of OS. CONCLUSIONS: Definitive RT with or without systemic chemotherapy did not significantly influence DSS and OS for very elderly patients. Therefore, for elderly patients aged ≥ 75 years who have HNC, conservative RT might be sufficient for treatment purposes.

Integrated LC-MS/MS Analytical Systems and Physical Inspection for the Analysis of a Botanical Herbal Preparation.

The herbal decoction process is generally inconvenient and unpleasant. To avoid using herbal medicine decoctions, various high-quality industrial and pharmaceutical herbal decoction products have been used in clinical applications for more than ten years in Taiwan. However, the consistency and standardization of the quality of these herbal medicines are goals that remain to be achieved. The aim of study was to develop a validated liquid chromatography-tandem electrospray ionization mass spectrometry (LC-MS/MS) method to determine the biomarkers astragaloside I, astragaloside IV, formononetin, cinnamic acid, paeoniflorin and gingerol in the herbal preparation known as Huangqi-Guizhi-Wuwu (HGW). To investigate the physical quality of HGW, methods such as scanning electron microscopy, light microscopy with Congo red and potassium iodine staining, solubility measurements, swelling power tests, and crude fiber analysis were used to identify additives in commercial pharmaceutical products. The optimal LC-MS/MS multiple reaction-monitoring system included a gradient program using 5 mM ammonium acetate buffer with 0.05% formic acid/methanol. The results demonstrate deviations in biomarker content across different brands. In addition to the herbal extract, starch and excipients in the pharmaceutical granule, and crushed crude herb powder was added to the pharmaceutical products to increase their herbal ingredient content. In conclusion, a rigorous examination should be performed to certify the quality of the herbal products.