Comparison of fractional excretion of sodium, uric acid and urea nitrogen in diagnosis of pediatric acute prerenal failure

Background and aim: various factors, in terms of faster diagnosis of acute renal failure have been studied so far, but these studies have been done mostly on adults. Therefore, in this paper we made a comparison of fractional excretion of sodium (FeNa), uric acid (FeUa) and urea nitrogen (FeU) in acute prerenal failure in children to find out which one is more sensitive in diagnosis of acute prerenal failure. Material and Methods: In a cross-sectional study, 5 CC blood was taken from 29 children of 1 month to 15 years old, diagnosed with acute pre-renal failure; the amount of creatinine, sodium, uric acid and urea nitrogen was measured in their plasma. After taking a standard urine specimen, all the mentioned items were measured in patients' urine and put into the formula of FeNa, FeUa and FeU and compared. Results: In this study, 75.8% FeU, 68.9% FeUa and 58.6% FeNa are agreeable to prerenal criteria and the most sensitivity is assigned to FeU. Among the three groups, FeNa is more affected by treatment with diuretic. The difference between FeNa in the receiver group of normal saline and the receiver group of diuretic is more than those groups which did not receive any. Conclusion: Fractional excretion of urea nitrogen in children, especially in the receivers of diuretic is more sensitive in diagnosis of acute prerenal failure. Moreover, this index is more sensitive in diagnosis of acute prerenal failure than the other indexes

Assessment of Adiponectin and Sperm Function Parameters in Obese and Non-Obese: A Comprehensive Study

ObjectiveThe role of adiponectin in sperm function is inconclusive and there is a paucity of evidence. Obesity showsan ambiguous influence on sperm motility, and male subfertility. The aim of this study was to compare the role ofadiponectin and sperm functional parameters among obese and non-obese men.Materials and MethodsIn this comprehensive study, 64 male patients were included, and were classified asnon-obese [body mass index (BMI)25 kg/m2, n=32) groups. Sperm analysis,was conducted using World Health Organization (WHO) 2010 standards. Real-time polymerase chain reaction(PCR) and enzyme-linked immunosorbent assay (ELISA) were used for the analysis of adiponectin gene expressionand protein levels, respectively. Sperm viability was assessed using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT test), Acridine orange (AO) test was utilized to detect DNA denaturation, andsperm chromatin dispersion (SCD) technique was used to investigate the fragmentation of DNA.ResultsIn obese men, adiponectin gene expression (P<0.0001) and protein levels (P<0.001) were significantly lowercompared to the non-obese group. Additionally, sperm motility, was significantly lower in the obese group. The rapidprogressive (RP) motility was less in obese men in comparison to the non-obese group (P<0.001). Sperm countand morphology were not significantly different in the two groups. DNA denaturation and DNA fragmentation weresignificantly more frequent in the obese group than in non-obese men (P<0.05) and (P<0.01), respectively. The obesemen showed significantly lower sperm viability compared to the non-obese group (P<0.05).ConclusionThis study showed no significant correlation between the evaluated variables (sperm parameter, spermviability, DNA fragmentation and integrity), and obesity in men. Based on these results, adiponectin may potentially playpositive role in sperm function for acquiring fertility

Inhibition of MicroRNA miR-222 with LNA Inhibitor Can Reduce Cell Proliferation in B Chronic Lymphoblastic Leukemia

MicroRNAs (miRNAs) are small regulatory molecules that negatively regulate gene expression by base-pairing with their target mRNAs. miRNAs have contribute significantly to cancer biology and recent studies have demonstrated the oncogenic or tumor-suppressing role in cancer cells. In many tumors up-regulation miRNAs has been reported especially miR-222 has been shown to be up-regulated in B chronic lymphocytic leukemia (B-CLL). In this study we assessed the effected inhibition of miR-222 in cell viability of B-CLL. We performed inhibition of mir-222 in B-CLL cell line (183-E95) using locked nucleic acid (LNA) antagomir. At different time points after LNA-anti-mir-222 transfection, miR-222 quantitation and cell viability were assessed by qRT-real time polymerase chain reaction and MTT assays. The data were analyzed by independent t test and one way ANOVA. Down-regulation of miR-222 in B-CLL cell line (183-E95) with LNA antagomir decreased cell viability in B-CLL. Cell viability gradually decreased over time as the viability of LNA-anti-mir transfected cells was <47 % of untreated cells at 72 h post-transfection. The difference in cell viability between LNA-anti-miR and control groups was statistically significant (p < 0.042). Based on our findings, the inhibition of miR-222 speculate represent a potential novel therapeutic approach for treatment of B-CLL

Comparative In Vitro Evaluation of Human Dental Pulp and Follicle Stem Cell Commitment

Objective: Pulp and periodontal tissues are well-known sources of mesenchymal stem cells (MSCs) that provide a promising place in tissue engineering and regenerative medicine. The molecular mechanisms underlying commitment and differentiation of dental stem cells that originate from different dental tissues are not fully understood. In this study, we have compared the expression levels of pluripotency factors along with immunological and developmentally-related markers in the culture of human dental pulp stem cells (hDPSCs), human dental follicle stem cells (hDFSCs), and human embryonic stem cells (hESCs). Materials and Methods: In this experimental study, isolated human dental stem cells were investigated using quantitative polymerase chain reaction (qPCR), immunostaining, and fluorescence-activated cell sorting (FACS). Additionally, we conducted gene ontology (GO) analysis of differentially expressed genes and compared them between dental stem cells and pluripotent stem cells. Results: The results demonstrated that pluripotency (OCT4 and SOX2) and immunological (IL-6 and TLR4) factors had higher expressions in hDFSCs, with the exception of the JAGGED- 1/NOTCH1 ratio, c-MYC and NESTIN which expressed more in hDPSCs. Immunostaining of OCT4, SOX2 and c-MYC showed cytoplasmic and nucleus localization in both groups at similar passages. GO analysis showed that the majority of hDFSCs and hDPSCs populations were in the synthesis (S) and mitosis (M) phases of the cell cycle, respectively. Conclusion: This study showed different status of heterogeneous hDPSCs and hDFSCs in terms of stemness, differentiation fate, and cell cycle phases. Therefore, the different behaviors of dental stem cells should be considered based on clinical treatment variations

Liposomal Drug Delivery Systems for Cancer Therapy: The Rotterdam Experience

At the Nanomedicine Innovation Center (NICE) at the Erasmus MC in Rotterdam, we have approached the treatment of cancer by starting with a vision of first establishing a platform that enables us to overcome the low levels of drugs delivered to tumors and the issue of dose-limiting toxicity. Showing that a reduction of the volume of distribution, and a lowering of toxicity and side-effects, accompanied by augmented intratumoral drug delivery, could change outcomes in patients, paved the way to target, not only localized disease, but also systemic and metastasized cancers. In particular, the detailed studies with intravital microscopy we performed at NICE provided us with the necessary insights and affected to a large extent our program on liposome-based cancer therapy. Together with our experience with the loco-regional treatment of cancer, this helped us to develop a program that focused on the subsequent aspects discussed here. We recognized that passive accumulation of nanoparticles was not as effective as previously believed and undertook to improve the local accumulation by changing the tumor pathophysiology and, in particular, the vascular permeability. We added the targeting of liposomes using vascular and tumor directed moieties, to improve cellular drug delivery. To improve payload delivery, we studied the modification of liposomes with phospholipids that help passive drug release and augment cellular accumulation. Second, and importantly, modification of liposomes was undertaken, to enable triggered drug release. The capability for modifying liposomes to respond to a trigger, and the ability to now apply an external trigger (e.g., hyperthermia) and specifically reach the tumor volume, resulted in the current smart drug delivery systems. Our experience at NICE, after a few decades of research on lipid-based nanoparticles, shows that, after the first liposomal formulation registered for clinical application in cancer therapy, further developments quickly followed, while further clinical applications lagged behind. Now we need to focus on and make the next steps towards the clinic, to fulfil the promise that is found there

An Updated Review on EPR-Based Solid Tumor Targeting Nanocarriers for Cancer Treatment

The enhanced permeability and retention (EPR) effect in cancer treatment is one of the key mechanisms that enables drug accumulation at the tumor site. However, despite a plethora of virus/inorganic/organic-based nanocarriers designed to rely on the EPR effect to effectively target tumors, most have failed in the clinic. It seems that the non-compliance of research activities with clinical trials, goals unrelated to the EPR effect, and lack of awareness of the impact of solid tumor structure and interactions on the performance of drug nanocarriers have intensified this dissatisfac-tion. As such, the asymmetric growth and structural complexity of solid tumors, physicochemical properties of drug nanocarriers, EPR analytical combination tools, and EPR description goals should be considered to improve EPR-based cancer therapeutics. This review provides valuable insights into the limitations of the EPR effect in therapeutic efficacy and reports crucial perspectives on how the EPR effect can be modulated to improve the therapeutic effects of nanomedicine