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Urinary biomarkers in patients with detrusor underactivity with and without bladder function recovery

Posted by Sheng-Fu C, Yuan-Hong J, Hann-Chorng K. on 2017-08-16 19:31:02

Abstract

Purpose

Detrusor underactivity (DU) is frequently encountered in elderly patients. Part of patients with DU might have bladder function recovery after treatment. This study investigated urinary proteins in these DU patients with and without bladder function recovery.

Methods

A total of 37 patients with chronic urinary retention and urodynamically proven DU were enrolled. After treatment, 24 DU patients had bladder function recovery whereas 13 had not, after 1-year follow-up. Urine collection at baseline was performed, and the urinary protein including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and prostaglandin E2 (PGE2) were measured by ELISA. Twenty urodynamically normal, 34 detrusor overactivity (DO) and 15 detrusor hyperactivity and inadequate contractility (DHIC) patients served as comparative groups.

Results

Urinary NGF levels were significantly higher than normal in patients with DU (9.2 ± 20.3 vs 1.85 ± 2.9 pg/ml, p = 0.037). Urinary BDNF level was only significantly higher in patients with DU than that of the control group (153 ± 199 vs 77.4 ± 47.7 pg/ml, p = 0.033) but not in patients with DHIC or DO. Compared with the control group, the urinary BDNF level was significantly higher in DU patients with bladder function recovery (190 ± 239 pg/ml, p = 0.033) but not in patients without recovery (85.8 ± 43.7 pg/ml, p = 0.612). The PGE2 level was significantly higher than the control group in DU patients with bladder function recovery (1290 ± 836 pg/ml, p < 0.0001) but not in patients without recovery (383 ± 237 pg/ml, p = 0.130).

Conclusion

Patients with DU and higher urinary PGE2 and BDNF levels might have a chance to recover bladder function than those with a lower protein level.

Abstract

Introduction

In the current study, we investigated the effect of low magnitude, low frequency (LMLF) mechanical vibrations on the osteogenic differentiation potential of human adipose derived mesenchymal stem cells (hASC), taken from elderly patients.

Methods

During 21 days in osteogenic culture medium, cells were periodically exposed to three different frequencies (25, 35 and 45 Hz) of continuous sinusoidal oscillation, using a vibration generator. We measured cell proliferation, cell morphology, calcium and phosphorus deposition using Almar Blue assay, fluorescence microscopy, scanning electron microscopy, and a EDX detector, respectively. Osteogenic differentiation was measured by assessing protein and mRNA levels. Osteogenesis was confirmed by detection of specific markers with alkaline phosphatase and enzyme-linked immunosorbent assays for: bone morphogenetic protein 2 (BMP-2), osteocalcin (OCL) and osteopontin (OPN).

Results

We found that 25 Hz vibrations had the greatest impact on hASC morphology, ultrastructure, and proliferation. We observed the formation of osteocyte- and hydroxyapatite-like structures, an increased quantity of calcium and phosphorus deposits, and increased differentiation in the stimulated groups.

Conclusions

Our findings suggest that LMLF vibrations could be used to enhance cell-based therapies for treatment of bone deficits, particularly in elderly patients, where the need is greatest.

Oxidative stress contributes to hepatocyte growth factor-dependent pro-senescence activity of ovarian cancer cells

Posted by Justyna M, Martyna P, Konstantin M, et al. on 2017-08-15 23:14:21

Abstract

The cancer-promoting activity of senescent peritoneal mesothelial cells (HPMCs) has already been well evidenced both in vitro and in vivo. Here we sought to determine if ovarian cancer cells may activate senescence in HPMCs. The study showed that conditioned medium (CM) from ovarian cancer cells (OVCAR-3, SKOV-3, A2780) inhibited growth and promoted the development of senescence phenotype (increased SA-β-Gal, γ-H2A.X, 53BP1, and decreased Cx43) in HPMCs. An analysis of tumors isolated from the peritoneum of patients with ovarian cancer revealed an abundance of senescent HPMCs in proximity to cancerous tissue. The presence of senescent HPMCs was incidental when fragments of peritoneum free from cancer were evaluated. An analysis of the cells secretome followed by intervention studies with exogenous proteins and neutralizing antibodies revealed hepatocyte growth factor (HGF) as the mediator of the pro-senescence impact of the cancer cells. The activity of cancerous CM and HGF was associated with an induction of mitochondrial oxidative stress. Signaling pathways involved in the senescence of HPMCs elicited by the cancer-derived CM and HGF included p38 MAPK, AKT and NF-κB. HPMCs that senesced prematurely in response to the cancer-derived CM promoted adhesion of ovarian cancer cells, however this effect was effectively prevented by the cell protection against oxidative stress. Collectively, our findings indicate that ovarian cancer cells can elicit HGF-dependent senescence in HPMCs, which may contribute to the formation of a metastatic niche for these cells within the peritoneal cavity.

 

Cromolyn chitosan nanoparticles as a novel protective approach for colorectal cancer

Posted by Tare K. M, Shohda A. E, Aliaa Nabil E, et al. on 2017-08-15 22:45:19

Abstract

Colorectal cancer is the third most common cancer in the world. Cromolyn is a mast cell stabilizer and was proposed as an anticancer agent; however its high polarity limits its bioavailability by rapid washing from the body. We formulated 10 cromolyn chitosan nanoparticles (CCSNPs)1 following ionic gelation technique to improve its bioavailability and investigated the protective anticancer effect of the optimum formula against colorectal cancer in dimethylhydrazine-induced model in rats. Rats were divided into seven groups, group-1: normal control, group-2: cromolyn control, group-3: CCSNPs control, groups-4 to 7 received dimethylhydrazine for 16 weeks to induce colorectal cancer. Groups-5 to 7 received cromolyn solution, non-medicated chitosan nanoparticles and CCSNPs, respectively as protective treatments. Optimum CCSNPs (size 112.4 nm, charge +39.9 mV, enclosed 93.6% cromolyn and showed a sustained drug release pattern over 48 h) significantly reduced tumor-signaling molecules and the number of aberrant crypt foci compared to dimethylhydrazine. Histopathological examination of colon samples revealed that CCSNPs exerted an augmented protective anticancer effect by ameliorating tumor pathology compared to cromolyn solution. In conclusion, CCSNPs ameliorated tumor pathology and malignant oncogenic signaling molecules in colorectal cancer tissue. Thus, CCSNPs may provide a novel protective approach in colorectal cancer treatment. Moreover, encapsulating cromolyn in chitosan nanoparticles augmented the protective anticancer effect of the drug.

Abstract

MicroRNAs (miRNAs) are of interest because they are dysregulated in different diseases, including liver diseases. MicroRNA-122 is an organ specific miRNA representing 70% of total miRNA in hepatocytes. The aim of this study was to investigate serum miRNA-122 expression in Egyptian patients with non-alcoholic fatty liver disease (NAFLD) and to determine its relationship with insertion/deletion polymorphism within the 3′ UTRs regions of interleukin-1A (IL-1A) gene which represents the binding site of miRNA-122. The study included 75 healthy subjects and 75 patients with NAFLD. Patients were recruited from the internal medicine outpatient clinic at Suez Canal University Hospital, Ismailia, Egypt. Serum miRNA-122 expression was determined using quantitative real-time PCR and normalization was done against RNU6B as an internal control. Our results reveled that about 76% of patients exhibited up-regulation of miRNA-122. The median miRNA-122 expression level in patients increased significantly (6.68 fold) compared to control (p = 0.001). Serum miRNA-122 expression level in NAFLD patients showed positive correlation with both serum triglycerides (TG) and very low density lipoprotein-cholesterol (VLDL-C) level (p = 0.048), and with serum IL-1A (p = 0.03). Regarding the relation between serum miRNA-122 expression and different genotypes of IL-1A insertion/deletion gene polymorphism (DD, ID, and II genotypes), patients carrying the major high risk DD genotype had a significant increase in miRNA-122 expression than those with heterozygous ID and the homozygous II genotypes (p = 0.002). In conclusion, serum miRNA-122 expression showed positive association with increased susceptibility to NAFLD in the study population. Insertion/deletion IL-1A gene polymorphism may be a marker for genetic susceptibility to NAFLD in Egyptian population, likely through miRNA-122 mediated regulation.

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