Platelet-Derived Procoagulant Microparticles as Blood-based Biomarker of Breast Cancer

Objective: Breast cancer is the main cause of cancer death in women worldwide. Elevated plasma levels of circulating cell-derived microparticles (MPs) have been reported in various types of cancer, including breast cancer, with the ability to mediate inflammation and thrombosis. Microparticles are bioactive agents, and it has been suggested that MPs can be used as a diagnostic, prognostic, or therapeutic biomarker in various diseases. The aim of this study was to investigate the levels of platelet-derived MPs (PMPs) in breast cancer patients. Materials and Methods: In this case-control study, 30 patients with breast cancer and 20 normal subjects were sampled after obtaining written consent. MPs were isolated from blood samples by centrifugation technique. CD42b and annexin V markers were used respectively for counting PMPs and procoagulant MPs with flow cytometry. Results: Flow cytometry results showed that the number of PMPs and procoagulant annexin V positive MPs was significantly higher in the breast cancer patients than normal subjects (p <0.001). The number of the annexin V MPs differed significantly in patients with high tumor size (T2) compared to the patients with low tumor size (T1) and controls (p <0.001). Significant and positive correlations were found between PMP levels and tissue-based biomarkers, tumor grading, and distant metastasis (p <0.05). Tumor histological type did not correlate with the numbers of PMPs (p=0.065). Conclusion: Increased levels of PMPs and activity in terms of hemostasis and having a positive and significant relationship with tumor grading and metastasis may indicate the effective role of PMPs in the pathogenesis and prognosis of breast cancer.     

Quercetin ameliorates cytotoxic effects of zinc oxide nanoparticles on sertoli cells by enhancing autophagy and suppressing oxidative stress

Previous studies have demonstrated the toxic impacts of zinc oxide nanoparticles (ZO-NPs) on male reproductive cells. The effect of quercetin (QCT) on ZO-NPs-induced mouse Sertoli cell (TM4 cell line) toxicity and its underlying mechanisms were investigated in this study. The TM4 cells were exposed to ZO-NPs or QCT in different groups for 24 hr. The TM4 cells pre-treated with 3MA (3-Methyladenine, an autophagy inhibitor) to evaluate the autophagy role of QCT and ZO-NPs in the TM4 cells. ZO-NPs significantly reduced the viability percentage of the TM4 cells. The apoptosis percentage and Bax/Bcl-2 ratio of the ZO-NPs group were significantly increased, while the expression of autophagy-related genes was considerably downregulated. ZO-NPs also induced oxidative stress in the TM4 cells through increasing malondialdehyde contents and reactive oxygen species levels (ROS) and reducing antioxidant factors including superoxide dismutase, catalase, glutathione and glutathione peroxidase. In QCT + ZO-NPs group, these events were considerably reversed. 3MA could significantly decrease the cell viability of TM4 cells exposed to the QCT and ZO-NPs in comparison with the untreated 3MA groups. According to these results, the protective effects of QCT on ZO-NPs-exposed TM4 cells are related to inducing autophagy, prevention apoptosis and suppressing oxidative stress.     

Evaluating naloxegol for the treatment of opioid-induced constipation

ABSTRACT

Introduction

Due to the increased use of opioids for pain and their abuse globally, the rate of restrictive side effects is elevating. Opioid-induced constipation (OIC) is probably the most widespread, underdiagnosed, and yet common adverse effect. Naloxegol, as an opioid antagonist, is associated with beneficial impacts in OIC. Indeed, blocking mu (μ)-opioid receptors in the gastrointestinal tract (GI) may lead to neutralization of the GI adverse events of opioids.     

A case of adult onset Sandhoff disease that mimics Brown-Vialetto-Van Laere syndrome

Sandhoff disease is a rare fatal infantile neurologic disorder. Adult onset Sandhoff is even rarer. Variability of clinical features in adult onset Sandhoff patients and overlaps between these and features of other neurologic diseases have sometimes led to mis-diagnosis. We describe an adult onset Sandhoff disease affected individual whose clinical presentation were also consistent with the Brown-Vialetto-Van Laere syndrome (BVVL) diagnosis. Screening of BVVL-causing genes, SLC52A3 and SLC52A2, did not identify candidate disease-causing mutations, but exome sequencing revealed compound heterozygous mutations in the known Sandhoff disease-causing gene, HEXB. Decreased blood hexosaminidase activity and evidence of cerebellar atrophy confirmed Sandhoff disease diagnosis. To the best of our knowledge, this is the first report of a Sandhoff disease case that mimics BVVL and that presents with prominent cranial nerve involvement. For differential diagnosis, measurement of hexosaminidase activity and MRI should quickly be performed. Genetic analysis can be done for confirmation of diagnosis.     

Global trends in colorectal cancer mortality: projections to the year 2035

Colorectal cancer (CRC) is the third most common cancer worldwide and the fourth most common cause of cancer death. Predictions of the future burden of the disease inform health planners and raise awareness of the need for cancer control action. Data from the World Health Organization (WHO) mortality database for 1989–2016 were used to project colon and rectal cancer mortality rates and number of deaths in 42 countries up to the year 2035, using age-period-cohort (APC) modelling. Mortality rates for colon cancer are predicted to continue decreasing in the majority of included countries from Asia, Europe, North America and Oceania, except Latin America and Caribbean countries. Mortality rates from rectal cancer in general followed those of colon cancer, however rates are predicted to increase substantially in Costa Rica (+73.6%), Australia (+59.2%), United States (+27.8%), Ireland (+24.2%) and Canada (+24.1%). Despite heterogeneous trends in rates, the number of deaths is expected to rise in all countries for both colon and rectal cancer by 60.0% and 71.5% until 2035, respectively, due to population growth and ageing. Reductions in colon and rectal cancer mortality rates are probably due to better accessibility to early detection services and improved specialized care. The expected increase in rectal cancer mortality rates in some countries is worrisome and warrants further investigations.