No abstract

Background-Collectrin is an orphan member of the renin-angiotensin system and is a homolog of angiotensin-converting enzyme 2, sharing ≈50% sequence identity. Unlike angiotensin-converting enzyme 2, collectrin lacks any catalytic domain. Collectrin has been shown to function as a chaperone of amino acid transporters. In rodents, the renal expression of collectrin is increased after subtotal nephrectomy and during high-salt feeding, raising the question of whether collectrin has any direct role in blood pressure regulation. Methods and Results-Using a susceptible genetic background, we demonstrate that deletion of collectrin results in hypertension, exaggerated salt sensitivity, and impaired pressure natriuresis. Collectrin knockout mice display impaired endothelium-dependent vasorelaxation that is associated with vascular remodeling, endothelial nitric oxide synthase uncoupling, decreased nitric oxide production, and increased superoxide generation. Treatment with Tempol, a superoxide scavenger, attenuates the augmented sodium sensitivity in collectrin knockout mice. We report for the first time that collectrin is expressed in endothelial cells. Furthermore, collectrin directly regulates l-arginine uptake and plasma membrane levels of CAT1 and y

The function of the NAD(P)H oxidases (NOXs) family member NOX4 is to generate reactive oxygen species (ROS), however, the molecular function of NOX4 has not been fully studied and waiting to be clarified. To elucidate the function of endogenous Nox4 in human thyroid carcinomas, papillomatosis thyroid cancer cells were used to study the cell growth by knocking down the expression of NOX4 and knocking out its functional partner p22phox/CYBA. As a result, the increasement of mitochondrial ROS(mROS) was abolished due to both knockdown of NOX4 and p22phox knockout in hypoxia, which destabilized HIF1α decreasing glycolysis and retarded cell growth. These data suggests that Nox4 is potent oncotarget due to its role in regulating glycolysis through mROS-HIF1α pathway, thereby mediating proliferation in thyroid carcinomas.

In the present study, a new type of DSPE-PEG2000 polymeric liposome for the brain-targeted delivery of poorly water-soluble anticancer drugs was successfully prepared and characterized. The nanoparticles were formed by the self-assembly of an amphiphilic polymer consisting of hydrophilic 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000). These nanoliposomes served as a safe delivery platform for the simultaneous delivery of quercetin (QUE) and temozolomide (TMZ) to rat brains. The 2-in-1 PEG2000-DSPE nanoliposomes containing QUE and TMZ (QUE/TMZ-NLs) were rapidly taken up by the U87 glioma cells in vitro, whereas at the same concentrations, the amounts of the free drugs taken up were minimal. The QUE/TMZ-NLs showed an enhanced potency in the U87 cells and the TMZ-resistant U87 cells (U87/TR cells), possibly due to the high intracellular drug concentration and the subsequent drug release. In vivo biodistribution experiments revealed a significant accumulation of QUE/TMZ-NLs in the brain, with significantly increased plasma concentrations of QUE and TMZ, as well as delayed clearance in our rat model of glioma. The results were not so significant for the QUE-loaded nanoliposomes (QUE-NLs) and free TMZ. The findings of our study establish the DSPE-PEG2000 polymeric liposome as a novel and effective nanocarrier for enhancing drug delivery to brain tumors.

Although the incidence of OM was higher in early-stage ADC than SCC according to ovarian pathology, it might be relatively safe to perform ovarian preservation with early-stage ADC because of low ovarian recurrence rate in short-term follow-ups.

BackgroundOsteosarcoma is the most common primary bone cancer in growing adolescents and young adults. The prognostic role of C-reactive protein (CRP) in patients with osteosarcoma is not fully investigated. The purpose of this study is to perform a meta-analysis and literature review on the role of CRP in osteosarcoma and to assess the potential role of serum CRP as a prognostic factor for patients with osteosarcoma.MethodsA detailed literature search was made in Medline for related research publications written in English. Methodological quality of the studies was also evaluated. The data were extracted and assessed by two reviewers independently. Analysis of pooled data were performed, risk ratio (RR) and corresponding confidence intervals (CIs) were calculated and summarized respectively.ResultsFinal analysis of 397 patients from 2 eligible studies was performed. Combined RR of CRP expression suggested that the raised serum CRP level had an adverse prognostic effect on overall survival of patients with osteosarcoma (n = 397 in 2 studies; RR = 0.35; 95% CI: 0.18–0.68; p = 0.002). In the uni- and multivariate survival analysis, response rate and CRP levels were the only independent prognostic variables.ConclusionsThe results of this meta-analysis suggest that CRP expression confers a worse prognosis in patients with osteosarcoma. Large prospective studies are necessary to provide solid data to confirm the prognostic significance of CRP.

Background: The melastatin-related transient receptor potential 7 channel (TRPM7) is a nonselective cation channel that has been shown to promote tumor metastasis and progression. In this study, we determined the expression of TRPM7 in ovarian carcinomas and investigated its possible prognostic value. Materials and Methods: Samples were collected from 138 patients with ovarian cancer. Expression of TRPM7 was assessed by real-time PCR and immunohistochemistry, expressed with reference to an established scoring system and related to clinical pathological factors. Kaplan-Meier survival analysis was applied to estimate disease-free survival (DFS) and overall survival (OS). Univariate and multivariate cox regression analyses were performed to correlate TRPM7 expression levels with DFS and OS. Results: TRPM7 was highly expressed in ovarian carcinoma and significantly associated with decreased disease-free survival (DFS: median 20 months vs. 42 months, P=0.0002) and overall survival (OS: median 27 months vs. 46 months, P<0.001). Conclusion: Overexpression of TRPM7 expression is significantly associated with poor prognosis in patients with ovarian cancer.

Posterior reversible encephalopathy syndrome (PRES) is a rare neurological disease. Recently, an increase in the number of transplantations has led to more cases being associated with PRES than what was previously reported. Calcineurin inhibitors (CNIs) are major risk factors for PRES in posttransplantation patients. The mechanisms of the development of PRES remain to be unclear. The typical clinical symptoms of PRES include seizures, acute encephalopathy syndrome, and visual symptoms. The hyperintense signal on fluid-attenuated inversion recovery image is the characteristic of the imaging appearance in these patients. In addition, other abnormal signals distributed in multiple locations are also reported in some atypical cases. Unfortunately, PRES is often not recognized or diagnosed too late due to complicated differential diagnoses, such as ischemic stroke, progressive multifocal leukoencephalopathy, and neurodegenerative diseases. Thus, this review emphasizes the importance of considering the possibility of PRES when neurological disturbances appear after solid organ transplantation or hematopoietic cell transplantation. Moreover, this review demonstrates the molecular mechanisms of PRES associated with CNIs after transplantation, which aims to help clinicians further understand PRES in the transplantation era.