Diagnostic efficacy of ischemia modified albumin and its correlation with lipid profile,oxidative stress in acute myocardial infarct patients on admission

ObjectiveTo evaluate the diagnostic efficacy of ischemia modified albumin (IMA) and its correlation with lipid profile, oxidative stress in acute myocardial infarct (AMI) patients attending Cardiology Emergency Department (ED).MethodsAt presentation serum IMA in conjunction with electrocardiogram (ECG) and cardiac troponin T (CTnT) was evaluated in 35 AMI patients attending the ED within 6 hours of chest pain. These patients were subjected to standardized diagnostic procedures and treatment. Thirty five healthy volunteers were enrolled as control.ResultsIMA showed a higher level in ischemic patients than in control with the highest sensitivity (77%) in comparison to CTnT and ECG. With CTnT or ECG, IMA documented a sensitivity of 83% and 88%, respectively. Whereas with both CTnT and ECG, IMA identified 94% of AMI patients with the highest negative predictive value (90%).ConclusionsIMA has evolved as a cost effective, highly sensitive, early diagnostic marker of cardiac ischemia and an earlier rule out test in AMI patients.     

Overexpression of enhancer of zeste homolog 2 (EZH2) and focal adhesion kinase (FAK) in high grade endometrial carcinoma

ObjectiveThe deregulation of E-cadherin is associated with Src/FAK signaling axis and histone deacetylase (HDAC)/EZH2 activity. However, the association between EZH2 and FAK and its clinical significance in endometrial carcinoma has not been reported.Methods202 archived cases of endometrial carcinoma (1996–2000) were reviewed and divided into two subtypes. TMAs were developed as per established procedures. EZH2, FAK, and pFAK immunohistochemical stains were performed and the expression was scored as negative (0), low (1) and high (2). Proper statistical analysis was used to assess the correlation between the expression profiles and the clinicopathological parameters and clinical outcome.ResultsA total of 141 (69.8%) type-1 tumors and 61 (30.2%) type-2 tumors were identified. EZH2 overexpression was identified in 7.6% of type-1 tumors vs. 63% of type-2 tumors (p < 0.001). FAK and pFAK overexpression was only seen in 24.8% and 1.7% of Type-1 tumors as compared to 72% and 58.8% of type-2 tumors, respectively (p < 0.001). A positive correlation between the expression of EZH2, FAK, pFAK and PTEN (p < 0.0001) was found. The overexpression of EZH2, FAK, and pFAK were significantly associated with high histologic grade, angiolymphatic invasion, lymph node metastasis, myometrial invasion and cervical involvement (p < 0.01). Kaplan–Meier analysis demonstrates that the overexpression of EZH2 (p = 0.0024), FAK and pFAK (p = 0.0001) was significantly associated with decreased overall survival.ConclusionThe overexpression of EZH2, FAK and pFAK correlates with well established pathologic risk factors and may predict a more aggressive biologic behavior in endometrial carcinoma, transforming these proteins into potential therapeutic targets for treatment of endometrial cancer.     

Evolutionary conservation of human ketodeoxynonulosonic acid production is independent of sialoglycan biosynthesis

Human metabolic incorporation of nonhuman sialic acid (Sia) N-glycolylneuraminic acid into endogenous glycans generates inflammation via preexisting antibodies, which likely contributes to red meat–induced atherosclerosis acceleration. Exploring whether this mechanism affects atherosclerosis in end-stage renal disease (ESRD), we instead found serum accumulation of 2-keto-3-deoxy-d-glycero-d-galacto-2-nonulosonic acid (Kdn), a Sia prominently expressed in cold-blooded vertebrates. In patients with ESRD, levels of the Kdn precursor mannose also increased, but within a normal range. Mannose ingestion by healthy volunteers raised the levels of urinary mannose and Kdn. Kdn production pathways remained conserved in mammals but were diminished by an M42T substitution in a key biosynthetic enzyme, N-acetylneuraminate synthase. Remarkably, reversion to the ancestral methionine then occurred independently in 2 lineages, including humans. However, mammalian glycan databases contain no Kdn-glycans. We hypothesize that the potential toxicity of excess mannose in mammals is partly buffered by conversion to free Kdn. Thus, mammals probably conserve Kdn biosynthesis and modulate it in a lineage-specific manner, not for glycosylation, but to control physiological mannose intermediates and metabolites. However, human cells can be forced to express Kdn-glycans via genetic mutations enhancing Kdn utilization, or by transfection with fish enzymes producing cytidine monophosphate–Kdn (CMP-Kdn). Antibodies against Kdn-glycans occur in pooled human immunoglobulins. Pathological conditions that elevate Kdn levels could therefore result in antibody-mediated inflammatory pathologies.     

Oxide and hybrid nanostructures for therapeutic applications

The research on biomedical applications of nanoparticles has seen an upsurge in recent years due to their unique capabilities in treatment of ailments. Though there are ample reviews on the advances of nanoparticles right from their fabrication to applications, comparatively fewer reviews are available for the nanostructured materials particularly on oxides and hybrids. These materials possess unique physicochemical properties with an ability to get functionalized at molecular and cellular level for biochemical interactions. Keeping the enormosity of the nanostructures in mind, we intend to cover only the recent and most noteworthy developments in this area. We, particularly emphasize on iron oxide and its derivatives, zinc oxides, layered double hydroxides, silica and binary/ternary metal oxides and their applications in the area of therapeutics. This review also focuses on the designing of biodegradable and biocompatible nanocarriers and critical issues related to their therapeutic applications. Several representative examples discuss targeting strategies and stimuli responsive nanocarriers and their therapeutics.     

Cisplatin and TRAIL enhance breast cancer stem cell death

Triple negative breast cancer (TNBC) has increased recurrence and poor survival, despite a high response rate to neoadjuvant chemotherapy. The aim of this study was to determine whether current drug treatment(s) eliminates bulk of tumor cells, but it has a minimal effect on cancer stem cells (CSCs) leading to tumor recurrence. We studied the effects of PARP inhibitors (AZD2281 and BSI-201), paclitaxel, docetaxel, cisplatin and cisplatin plus TRAIL on CSCs derived from CRL-2335 and MDA-MB-468 TNBC cells in?vitro. The in?vitro data indicate that cisplatin plus TRIAL treatment was most effective in eliminating CSCs compared to PARP inhibitors, cisplatin, paclitaxel and docetaxel. Treatment with cisplatin plus TRAIL also inhibits Wnt-1 signaling and its downstream target, β-catenin, phospho β-catenin, cyclin D1, increased apoptosis, reduced proliferation and mammosphere formation. Inhibition of Wnt-1 by siRNA significantly reduced the ability of CSCs to form mammospheres compared to control. However, maximum effect was seen in cisplatin plus TRAIL-treated cells. Taken together the data suggest that cisplatin plus TRAIL treatment has the potential of providing a new strategy for improving the therapeutic outcome in TNBC patients.     

Serum paraoxonase activity and protein thiols in patients with hyperlipidemia

Objective： In the present study we evaluated the paraoxonase activity and protein thiols level in south Indian population with newly diagnosed hyperlipidemia. Methods： The study was conducted on 55 newly diagnosed hyplerlipidemic patients and 57 healthy controls. Serum paraoxonase activity and protein thiols were estimated by spectrophotometeric method and lipid profile by enzymatic kinetic assay method. Results： Serum paraoxonase activity, protein thiols and high density liPopretein levels were low and total cholesterol, triglycerides and low density lipoprotein levels were high in patients with hyperlipidemia compared to healthy controls （P〈 0.01 ）. Serum paraoxonase activity correlated positively with protein thiols and high density lipoprotein （P〈0.01）. Conclusion： Decreased paraoxonase activity and protein thiols were found in patients with hyperlipi- demia. This may indicate the susceptibility of this population to accelerated atherogenesis and protein oxidation.