ஜர்னல் ஆஃப் மாலிகுலர் பயோமார்க்ஸ் & நோயறிதல்

Aluminum (Al) is a potent environmental neurotoxin, which is involved in the progression of neurodegenerative processes. Remarkable biological and medicinal properties of Centella asiatica (CA) are well known in last few decades. Therefore, the present study has been designed to explore the neuroprotective effect of CA on chronic aluminium chloride (AlCl3) exposure induced neurotoxicity in rat brain regions (cerebral cortex, striatum, hypothalamus and hippocampus). Wistar albino rats were segregated into four groups: group 1-control rats, group 2- rats received AlCl3 (300 mg/kg body weight, every day orally) for 60 days, rats in group 3-received CA (500 mg/kg body weight, orally) and group 4 rats were initiated with both AlCl3 and CA treatment. Administration of AlCl3 developed behavioral deficits, triggered lipid peroxidation (LPO), compromised acetylcholine esterase (AChE) activity, and reduced the levels of superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and glutathione-S-transferase (GST) and caused histologic aberrations. AlCl3–induced alterations in the activities of SOD, CAT, GSH and GST, levels of LPO, activity of AChE, behavioral deficits and histologic aberrations were attenuated on treatment with CA. Results of the study demonstrate neuroprotective potential of CA against AlCl3- induced oxidative damage and cognitive dysfunction.

Introduction: To ensure the appropriate assignment of vemurafenib to patients with unresectable or metastatic melanoma, accurate detection of activating BRAF mutations is now a clinical imperative. However, the performance of commercially available test kits on challenging samples is unknown.

Methods: 126 formalin-fixed, paraffin-embedded melanoma samples were selected for challenging attributes, such as small sample size, that might affect test kit performance. The Qiagen BRAF RGQ PCR version 2 (RGQv2) test kit, intended for research use only, and the FDA-approved companion diagnostic cobas 4800 BRAF V600 Mutation Test were compared for their ability to detect the V600E mutation in challenging samples, using a single 5 μm unstained slide.

Results: of the 126 specimens, three samples were invalid by the RGQv2 test, three other samples were invalid by the cobas test, and an additional two samples were found invalid by both tests. For the 118 samples that yielded valid results with both tests, concordant results were observed for 105 (89.0% [95% CI, 82.1%-93.5%]) samples. Of the 12 discordant samples with sufficient material for further testing, next generation sequencing confirmed the cobas test result for 6 (50.0%) and confirmed the RGQv2 test result for the other 6 (50.0%) samples. Five (4.0%) of the RGQv2 test results yielded multiple positive mutation calls and two results had a sample control assay PCR cycle threshold (CT) >33, indicating insufficient amounts of DNA template, but gave accurate mutation calls. Workflow analysis showed that the total time to result was 5.65 hours for the cobas test to process 24 samples and 7.84 hours for RGQv2 assay to process 7 samples.

Conclusions: The two commercially available, PCR-based methods demonstrated similar abilities to detect BRAF V600 mutations in challenging melanoma samples. However, the total time-to-result, assay hands-on time, and diagnostic interpretation were more efficient and rapid with the cobas test.

We present a useful approach towards for biomarkers identification in an innovative self-assembling protein microarray based on “Nucleic Acid Programmable Protein Array” (NAPPA) and SNAP tag coupled to E.coli cell free expression system. This approach prove capable to resolve the “background” problem associated to the above label free detection system for the identification of proteins and of protein-protein interaction in humans that could become used in clinical practice.

Today we are facing a large problem of overtreatment in men with prostate cancer (PCa) due to the current lack of reliable prognostic biomarkers. Aberrations including ETS family gene rearrangements, phosphatase and tensin homolog (PTEN) deletions, enhancer of zeste homolog 2 (EZH2) overexpression and changes in the androgen receptor (AR) are commonly described in PCa and are believed to have an important role in progression of the disease. The aim of this study is to analyze if the protein expression of ERG, AR, PTEN and EZH2, and the deletion status of the PTEN, either alone or in combination can predict clinical outcome. Our cohort consists of 214 men that have undergone radical prostatectomy at the University Hospital of Örebro, Sweden between 1989-2005. Immunohistochemistry was used to detect AR, ERG, PTEN and EZH2 antigen and PTEN deletion was assessed using chromogenic in situ hybridization. The overall frequency showed AR-, ERG- and EZH2 expression in 99.5%, 52.9%, and 92.3% respectively. PTEN deletion was seen in 37.4% of the cases, where homozygous and heterozygous deletion was present in 18.1% and 19.2%, respectively. Our results show that there was a significant association between the combined ERG- and EZH2 expression and PTEN deletion with PCa specific death (p=0.035). This significant association was also seen in the group of cases that harbored both ERG expression and PTEN deletion (p=0.036). Cases expressing ERG, exhibiting PTEN loss (either hetero- or homozygous loss) and a Gleason score ≥8 showed a significantly higher rate of developing castration-resistant PCa (CRPC) and dying of PCa. The current lack of a reliable prognostic tool available for PCa is a large problem, the results from this study and others shows the great potential in using multiple biomarkers to predict PCa outcome.

Background: Primary hypothyroidism is one of the most frequent endocrine complications observed in patients suffering from thalassemia where iodine deficiency is a major contributing factor. We aim at assessing the iodine status in multitransfused pediatrics with thalassemia major, compliant to iron chelation, to evaluate its contributing role to the occurring hypothyroidism for the potential future replacement therapy.

Procedure: Sixty young thalassemia patients (31 males, 29 females; aged 14.4 ± 3.83 years) were randomly selected from the hematology clinic of the Children’s Hospital, Cairo University, added to 36 age and sex matched control subjects.

Results: The study revealed a highly significant difference in urinary iodine, FT3, FT4 and TSH between the thalassemic group and their controls (P<0.001). Twenty seven patients (45%) had overt hypothyroidism (low T4 and elevated TSH >10 uIU/ml), and 34/36 had normal urinary iodine level. Severe iodine deficiency was manifested in 9/60 patients (15%), moderate deficiency in 27/60 patients (45%) and mild deficiency in 24/60 patients (40%). A negative correlation was found between urinary iodine and both serum ferritin and TSH (r=-0.413 at P<0.001, r=-0.881 at P<0.001; respectively).

Conclusion: To this end, iodine deficiency is at least partially responsible for the high prevalence of thalassemia–induced hypothyroidism among Egyptian young patients.

Background: Apolipoprotein E (apoE) is carried by all major lipoprotein classes in plasma and is likely to contribute to the development of atherosclerosis. We set out to determine the extent to which plasma apoE is related to various VLDL, LDL and HDL subfractions in subjects with and without metabolic syndrome (MetS).

Methods: Plasma lipids, lipoprotein subfractions (nuclear magnetic resonance spectroscopy) and plasma apoE were determined in 60 subjects with and 62 subjects without MetS (APOE ε2/ε2 carriers excluded).

Results: Plasma apoE was higher in MetS, coinciding with increased total and large VLDL particles, as well as total LDL particles (p<0.01 for each after age, sex and diabetes status adjustment). Age- and sex-adjusted multivariable linear regression analysis revealed that plasma apoE was related positively to the VLDL particle concentration (p=0.003), in particular large VLDL (p<0.001) and to the LDL particle concentration (p=0.013), independent of MetS and diabetes status (p>0.30). Plasma apoE was unrelated to HDL particle concentration (p=0.88).

Conclusions: Plasma apoE is elevated in MetS in conjunction with increased concentrations of (large) VLDL and LDL particles. These novel findings provide a rationale to explore whether preferential association of apoE with (large) VLDL and LDL could modify its influence on atherosclerosis development.

Biphenotypic AL (BAL) is characterised by presence of blasts which coexpress myeloid and T or B lineage antigens. In this study we describe the biological, clinical characteristic and outcome of 24 adult BAL patients treated in our center. We have analyzed a group of 480 patients with AL. To define BAL we used European Group for the Immunological Characterisation of Leukemias (EGIL) scoring system. Among whole group, 24 (5%) patients fulfilled the EGIL criteria of BAL. 22 patients were treated with conventional chemotherapy and in two cases allogeneic bone marrow transplantation from matched unrelated donors (MUD alloBMT) was performed. 50% of patients achieved complete remission. Ten patients died due to disease progression (no response after conventional therapy). In one case an extramedullary relapse after MUD alloBMT was a cause of death. Overall survival (OS) was 40%. Patients with BAL had poor outcome: induction of remission was difficult and overall survival was low.