We explored the differential expression of breast tissue–based panel of microRNAs (miRNAs) and their potential application as prognostic markers of breast cancer (BC). This study was divided into the ...following phases: (1) A panel of 6 BC characteristic miRNAs, which were retrieved based on the microarray signature profiling (released by miRWalk), was explored using SYBR Green–based polymerase chain reaction (PCR) array in 16 cancerous and 16 noncancerous breast tissue; (2) pathway enrichment analysis of the key miRNA target genes; (3) marker choice and validation by real-time PCR in a larger set of 76 patients with BC, 36 benign breast conditions, and 36 healthy volunteers; (4) validation of miRNA (miR)-23a target genes (forkhead box m FOXM1 and histidine-rich glycoprotein HRG ) by conventional reverse transcriptase (RT)-PCR; and (5) the prognostic significance of the investigated parameters in the BC validation group was explored. In PCR array–based miRNA expression analysis, 4 miRNAs were found to be altered more than twice (miR-96, miR-29c, miR-221, and miR-23a). Bioinformatic analysis of the target genes revealed enrichment for special biological process categories, that is, cell cycle, angiogenesis, apoptosis, cell proliferation, and cell adhesion. miR-23a, HRG messenger RNA, and FOX messenger RNA were positive in BC by 82.9%, 72.4%, and 71.1%, respectively. The overall concordance rates between miR-23a with HRG and FOXM1 tissue RNAs were 91% and 79%, respectively. The median follow-up period was 49 months. mi-23a and HRG RNA were significant independent prognostic markers in relapse-free survival. miR-23a may have an oncogenic function and enhance BC progression by directly activating FOXM1 and HRG at RNA level.
Problem-based learning (PBL) remains a valid and effective tool for small-group medical education. Using Virtual patients (VP) case simulation in PBL is a recognizable educational method that has ...successfully prepared students to focus learning on core information that uses realistic patient-based cases relating to everyday clinical scenarios. Using other modalities as the virtual patient in PBL instead of the paper-based methods remains debatable. This study aimed to evaluate the effectiveness of using VP case simulation mannequin in PBL versus the PBL in paper-based cases in improving the cognitive skills by comparing the grades of a multiple-choice question test and assess its ability to reach students' satisfaction using questionnaire with Likert survey instrument.
The study was conducted on 459 fourth-year medical students studying in the pulmonology module of the internal medicine course, Faculty of Medicine, October 6 University. All students were divided into 16 PBL classes and randomly divided into groups A and B by simple manual randomization. The groups were parallel with a controlled cross-over study between paper-based and virtual patient PBL.
The pre-test showed no significant difference between both, while post-test scores were significantly higher in both VP PBL cases 1 discussing COPD (6.25 ± 0.875) and case 2 discussing pneumonia (6.56 ± 1.396) compared to paper-based PBL (5.29 ± 1.166, 5.57 ± SD1.388, respectively) at p < 0.1 When students in Group A experienced PBL using VP in case 2 after paper-based PBL in case 1, their post-test score improved significantly. (from 5.26 to 6.56, p < .01). Meanwhile, there was a significant regression in the post-test score of the students in Group B when they experienced the paper-based PBL session in case 2 after using PBL using VP in case 1, (from 6.26 to 5.57, p < .01). Most of the students recommended using VP in PBL as they found VP was more engaging and inducing concentration in gathering the information needed to characterize the patient's problem than in a classroom- paper-based cases session. They also enjoyed the teaching of the instructor and found it a suitable learning style for them.
Implementing virtual patients in PBL increased knowledge acquisition and understanding in medical students and was more motivating for students than paper based PBL to gather the needed information.
Abstract
Background
NAFLD and NASH are emerging as primary causes of chronic liver disease, indicating a need for an effective treatment. Mutaflor® probiotic, a microbial treatment of interest, was ...effective in sustaining remission in ulcerative colitis patients.
Objective
To construct a genetic-epigenetic network linked to HSC signaling as a modulator of NAFLD/NASH pathogenesis, then assess the effects of Mutaflor
®
on this network.
Methods
First, in silico analysis was used to construct a genetic-epigenetic network linked to HSC signaling. Second, an investigation using rats, including HFHSD induced NASH and Mutaflor
®
treated animals, was designed. Experimental procedures included biochemical and histopathologic analysis of rat blood and liver samples. At the molecular level, the expression of genetic (FOXA2, TEAD2, and LATS2 mRNAs) and epigenetic (miR-650, RPARP AS-1 LncRNA) network was measured by real-time PCR. PCR results were validated with immunohistochemistry (α-SMA and LATS2). Target effector proteins, IL-6 and TGF-β, were estimated by ELISA.
Results
Mutaflor
®
administration minimized biochemical and histopathologic alterations caused by NAFLD/NASH. HSC activation and expression of profibrogenic IL-6 and TGF-β effector proteins were reduced via inhibition of hedgehog and hippo pathways. Pathways may have been inhibited through upregulation of RPARP AS-1 LncRNA which in turn downregulated the expression of miR-650, FOXA2 mRNA and TEAD2 mRNA and upregulated LATS2 mRNA expression.
Conclusion
Mutaflor
®
may slow the progression of NAFLD/NASH by modulating a genetic-epigenetic network linked to HSC signaling. The probiotic may be a useful modality for the prevention and treatment of NAFLD/NASH.
We developed a specific hybridization assay for direct detection of long non-coding RNA urothelial carcinoma associated-1 (lncRNA-UCA1). Total RNA was extracted from urine pellet samples (bladder ...carcinoma patients and controls). Then, we compared the developed nanoassay with quantitative real time polymerase chain reaction (qRT-PCR) results in detection of urine UCA1 in bladder cancer and control samples. The sensitivity and the specificity of UCA1 nanoassay were 92.1% and 93.3%, respectively. The concordance of the two methods was 98%. Interestingly, all bilharzial benign cases showed negative lncRNA-UCA1 using both methods. UCA1-nanoassay is a valid test for direct detection of urine UCA1 for bladder cancer detection.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Advances in the field of breast cancer (BC) biomarkers discovery facilitate diagnosis and treatment of BC in its pre-invasive state. While the genetic tissue markers are making significant advances ...in understanding the molecular basis of BC, serum has long been considered a rich source for biomarkers. So, integrated genomic and proteomic strategies play a huge role in the analytical validation of BC biomarkers and represent a true milestone in the areas of diagnostics and personalized medicine. This study included 60 cases (BC), 30 patients with fibroadenoma and 30 healthy women. Histidine-rich glycoprotein RNA (HRG) tissue expression was analyzed through gene expression-based outcome for breast cancer online algorithm (GOBO) bioinformatic analysis. To confirm our informatics analysis, HRG RNA was detected in breast tissue samples by RT-PCR, and HRG serum protein was estimated by ELISA. GOBO analysis revealed increased HRG RNA expression in all subtypes of BC with relative higher expression in basal subtype and grade 2. We confirmed these findings by HRG tissue RNA with 71.7 % sensitivity and 93.3 % specificity. HRG serum protein was 86.7 % sensitivity and 80 % specificity. HRG tissue RNA and serum protein could be considered as promising novel markers for prediction of BC prognosis.
OBJECTIVE
To assess the contemporary inter‐institutional accuracy of urinary cytology in predicting the recurrence of transitional cell carcinoma (TCC) of the bladder, in a large multi‐institutional ...cohort from four continents, as cystoscopy and urinary cytology represent the ‘gold standards’ for surveillance of TCC recurrences, but the ability of cytology to predict recurrence varies.
PATIENTS AND METHODS
Ten institutions contributed 2542 patients with a history of superficial TCC, of whom 898 had TCC recurrence. Age‐ and gender‐adjusted logistic regression models were used to evaluate the association between urine cytology and TCC recurrence. The predictive accuracy derived from the logistic regression model was tested using the area under the receiver operating characteristic curve. The resulting predictive accuracy estimates were internally validated with 200 bootstrap re‐samples.
RESULTS
The mean (range across institutions) age of the patients was 65 (48–69) years and 75 (67–87)% were men. Cytology was positive in 19 (10–38)% of patients; recurrence was identified in 35 (27–54)% of patients. The sensitivity was 38–65% across institutions. Urinary cytology varied significantly in its ability to predict recurrence of bladder cancer. Institution‐specific predictive accuracy adjusted for gender and age was 0.627–0.893. Stratifying by grade and stage only partly attenuated the discrepancies between centres.
CONCLUSIONS
The variability of urinary cytology results was very appreciable among the 10 centres and ranged from poor (63%) to excellent (89%).
Abstract Background A potential approach adopted in the current study is to design a panel based on in silico retrieval of novel miRNAs related to diabetic kidney disease and to evaluate its ...usefulness in disease diagnosis. Patient and Methods In the current study, we measured the differential expression of a 6 miRNA panel in urine pellet and exosome in an initial screening group using syber green-based PCR array. Also, we performed pathway enrichment analysis of the key target genes of these miRNAs. Finally, we selected the most significantly up-regulated miRNAs in DKD, exosomal miR-15b, miR-34a and miR-636, that were measured by real-time PCR in a larger independent set of 180 participants to evaluate their usefulness as novel urine biomarkers for diagnosis diabetic kidney disease. Results PCR array analysis showed that miR-15b, miR-34a, and miR-636 were upregulated in both urine pellet and exosome of type 2DKD patients. qRT-PCR validation in the larger independent set of participants confirmed the significant up-regulation of these urinary exosomal miRs ( P < 0.001). Notably, a positive correlation was found between these miRs, serum creatinine and urinary protein creatinine ratio. The sensitivity of this miRs based panel in urine exosomes reached 100% in diagnosis of DKD. Conclusion We identified urinary exosomal miR-15b, miR-34a, and miR-636 as a novel diagnostic panel and a major contributor in the pathogenesis of diabetic kidney disease.
Abstract Non-alcoholic steatohepatitis (NASH) is the clinically aggressive variant of non-alcoholic fatty liver disease. Hippo pathway dysregulation can contribute to NASH development and ...progression. The use of probiotics is effective in NASH management. Our aim is to investigate the efficacy of kefir Milk in NASH management via modulation of hepatic mRNA-miRNA based panel linked to NAFLD/NASH Hippo signaling and gut microbita regulated genes which was identified using bioinformatics tools. Firstly, we analyzed mRNAs (SOX11, SMAD4 and AMOTL2), and their epigenetic regulator (miR-6807) followed by validation of target effector proteins (TGFB1, IL6 and HepPar1). Molecular, biochemical, and histopathological, analyses were used to evaluate the effects of kefir on high sucrose high fat (HSHF) diet -induced NASH in rats. We found that administration of Kefir proved to prevent steatosis and development of the inflammatory component of NASH. Moreover, Kefir improved liver function and lipid panel. At the molecular level, kefir down-regulated the expression of miR 6807-5p with subsequent increase in the expression of SOX 11, AMOTL2 associated with downregulated SMAD4, resulting in reduction in the expression of the inflammatory and fibrotic markers, IL6 and TGF-β1 in the treated and prophylactic groups compared to the untreated rats. In conclusion, Kefir suppressed NASH progression and improved both fibrosis and hepatic inflammation. The produced effect was correlated with modulation of SOX11, SMAD4 and AMOTL2 mRNAs) – (miR-6807-5p) – (TGFB, IL6 and, HepPar1) expression.
Breast cancer (BC) is the most notorious cancer between females with high rates of morbidity and mortality. The aim of this study was to determine the differential expression of breast tissues ...microRNA-221 (miR-221) and assess its prognostic and biological significance in breast cancer (BC).
A quantitative reverse transcription PCR (qPCR) assay was performed to detect the expression of breast tissue miR-221 in different subtypes of BC (n=76) and controls (n=36) and its correlations with clinicopathological factors of patients. Univariate and multivariate analyses using the Cox proportional hazards model were performed to analyze the prognostic significance of miR-221 expression.
Our data indicated that the relative level of miR-221 expression in BC tissues was significantly higher than that in noncancerous breast tissues (p<0.01). Of 76 BC patients, 62 (81.6%) were positive cases. By statistical analyses, high miR-221 expression was observed to be closely correlated with advanced clinical stage (p<0.01). Moreover, patients with high miR-221 expression had worse 5-year relapse free survival (p=0.0124). Univariate and multivariate analyses indicated that high miR-221 expression was an independent poor prognostic factor for BC patients.
miR-221 is a potential biomarker for predicting the survival of BC patients and may be a molecular therapeutic target for BC.
•miRNA-221 plays a role in breast cancer development and progression.•miRNA-221 was detected by Syber green based QPCR.•miRNA-221 is overexpressed in breast cancer tissue compared to none cancerous tissue.•miR-221 expression is an independent poor prognostic factor for BC patients.•High miR-221 expression was observed to be closely correlated with advanced clinical stage of BC.
The art of mural formation has been associated with human civilization since the Stone Age, as it is the focus and painter of its cultures, and it is the result of civilized communication, and the ...porcelain and glass materials have also been associated with the civilization development of man over the ages, and the research has dealt with the historical development of the mural through different ages and the most important characteristic of mural photography in each era of In terms of formation, subjects, materials and techniques, it also dealt with environmental, technical and aesthetic considerations of mural design and its relationship to formation and its design determinants and their differences according to the previous criteria, then the research moved to an applied study that provided design solutions for the design of the mural based on the research methodology in classifying murals into wall photography murals according to the determinants of direct printing techniques on porcelain and glass And the technique of water jetting using glazed porcelain tiles and mosaic technology, then moved to dynamic murals, which depended on waterjet techniques for glass and glazed slices, ending with interactive murals, as it relied on the use of modules, whose arrangement or rotation results in a variety of formation, levels, surfaces or colors. Research problem:1- How to employ murals in the design of architectural cladding in airports and public places such as train and metro stations ... in a way that reflects the plastic richness in design, and is compatible with the possibilities of the porcelain and glass materials in expression and wall design?2- Are there technical and environmental limitations that make the role of ceramics/glass as murals limited and ineffective?4- Reducing the use of glass mural techniques in mosaic techniques despite the great diversity in glass technologies.. research aims:1- Emphasis on the visual richness in the design of murals in porcelain and glass materials for public places such as airports and public parks.2- Determine the most important design considerations that the designer must take into account in the wall formation of glass and ceramic materials.research importance:1- Providing an analytical study specializing in the design of porcelain and glass murals and their aesthetic and cultural value to support architects and designers interested in the relationship of mural design to the technology, materials used, and the proposed context for implementation
PDF
