Influence of Surface States on the Optical and Cellular Property of Thermally Stable Red Emissive Graphitic Carbon Dots.

Red emissive carbon dots from sucrose (SCD) were synthesized using a facile, isolation-free, one-pot method via microwave pyrolysis. Various passivation agents were used along with sucrose, and a relative change in the chemical and optical properties of the carbon dots was investigated. A detailed systematic study of the effect of various passivations, different solvents, pHs, and temperatures on optical properties was carried out. The influence of excitation wavelength and passivation on photoluminescence (PL) is discussed considering the functional groups associated with the passivating agents. The effect of different solvents on dispersibility and PL behavior has been understood in terms of the dielectric properties of the solvents. The decrease in PL intensity of SCD from pH 3 to 11 facilitates pH sensing. The PL of SCD was found to be essentially stable between the temperature range of 20 and 80 °C. Additionally, the effects of physicochemical properties with respect to passivation, such as charge and surface chemistry in determining the cellular uptake and cytotoxicity, are also addressed. Aside from sensors, the potential of SCDs as bioimaging agents has also been studied for mammalian cells. Moreover, SCD exhibits excellent PL stability investigated under different storage conditions for 15 days.

A Protein Microarray-Based Investigation of Cerebrospinal Fluid Reveals Distinct Autoantibody Signature in Low and High-Grade Gliomas.

Gliomas are one of the most aggressive primary brain tumors arising from neural progenitor cells. Delayed diagnosis, invasive biopsy, and diagnostic challenges stems the need for specific, minimally-invasive, and early diagnostic biomarkers. Tumor-associated (TA) autoantibodies are measurable in the biofluids long before the onset of the symptoms, suggesting their role in early diagnosis and clinical management of the patients. In the current study, cerebrospinal fluid (CSF) samples from patients with low-grade glioma (LGG) and the Glioblastoma multiforme (GBM) that characterizes advanced disease were compared with healthy control samples to identify putative TA autoantibodies, using protein microarrays. The CSF samples from LGGs (n = 10), GBM (n = 7) were compared with the control CSF samples (n = 6). Proteins showing significant antigenic response were cross-verified. Proteins NOL4 (a cancer-testis antigen) and KALRN showed an antigenic response in the CSF of GBM patients, whereas, UTP4 and CCDC28A showed an antigenic response in low grade gliomas when compared with the control samples. TA autoantibodies identified in this study from the CSF of the patients could supplement current screening modalities. Further validation of these TA autoantibodies on a larger clinical cohort could provide cues towards relevance of these proteins in early diagnosis of the disease.

Multi-pronged proteomic analysis to study the glioma pathobiology using cerebrospinal fluid samples.

PURPOSE: Gliomas are one of the most aggressive and lethal brain tumors arising from neoplastic transformation of astrocytes and oligodendrocytes. A comprehensive quantitative analysis of proteome level differences in cerebrospinal fluid (CSF) across different grades of gliomas for a better understanding of glioma pathobiology is carried out. EXPERIMENTAL DESIGN: Glioma patients are diagnosed by radiology and histochemistry-based analyses. Differential proteomic analysis of high (n = 12) and low (n = 5) grade gliomas, and control (n = 3) samples is performed by using two complementary quantitative proteomic approaches; 2D-DIGE and iTRAQ. Further, comparative analysis of three IDH wild-type and five IDH mutants is performed to identify the proteome level differences between these two sub-classes. RESULTS: Level of several proteins including haptoglobin, transthyretin, osteopontin, vitronectin, complement factor H and different classes of immunoglobulins are found to be considerably increased in CSF of higher grades of gliomas. Subsequent bioinformatics analysis indicated that many of the dysregulated CSF proteins are associated with metabolism of lipids and lipoproteins, complement and coagulation cascades and extracellular matrix remodeling in gliomas. Intriguingly, CSF of glioma patients with IDH mutations exhibite increased levels of multiple proteins involved in response to oxidative stress. CONCLUSION AND CLINICAL RELEVANCE: To the best of our knowledge, this is the foremost proteome level investigation describing comprehensive proteome profiles of different grades of gliomas using proximal fluid (CSF); and thereby providing insights into disease pathobiology, which aided in identification of grade and sub-type specific alterations. Moreover, if validated in larger clinical cohorts, a panel of differentially abundant CSF proteins may serve as potential disease monitoring and prognostic markers for gliomas.

Real-time iTRAQ-based proteome profiling revealed the central metabolism involved in nitrogen starvation induced lipid accumulation in microalgae.

To understand the post-transcriptional molecular mechanisms attributing to oleaginousness in microalgae challenged with nitrogen starvation (N-starvation), the longitudinal proteome dynamics of Chlorella sp. FC2 IITG was investigated using multipronged quantitative proteomics and multiple reaction monitoring assays. Physiological data suggested a remarkably enhanced lipid accumulation with concomitant reduction in carbon flux towards carbohydrate, protein and chlorophyll biosynthesis. The proteomics-based investigations identified the down-regulation of enzymes involved in chlorophyll biosynthesis (porphobilinogen deaminase) and photosynthetic carbon fixation (sedoheptulose-1,7 bisphosphate and phosphoribulokinase). Profound up-regulation of hydroxyacyl-ACP dehydrogenase and enoyl-ACP reductase ascertained lipid accumulation. The carbon skeletons to be integrated into lipid precursors were regenerated by glycolysis, ß-oxidation and TCA cycle. The enhanced expression of glycolysis and pentose phosphate pathway enzymes indicates heightened energy needs of FC2 cells for the sustenance of N-starvation. FC2 cells strategically reserved nitrogen by incorporating it into the TCA-cycle intermediates to form amino acids; particularly the enzymes involved in the biosynthesis of glutamate, aspartate and arginine were up-regulated. Regulation of arginine, superoxide dismutase, thioredoxin-peroxiredoxin, lipocalin, serine-hydroxymethyltransferase, cysteine synthase, and octanoyltransferase play a critical role in maintaining cellular homeostasis during N-starvation. These findings may provide a rationale for genetic engineering of microalgae, which may enable synchronized biomass and lipid synthesis.

Clinicopathological Analysis and Multipronged Quantitative Proteomics Reveal Oxidative Stress and Cytoskeletal Proteins as Possible Markers for Severe Vivax Malaria.

In Plasmodium vivax malaria, mechanisms that trigger transition from uncomplicated to fatal severe infections are obscure. In this multi-disciplinary study we have performed a comprehensive analysis of clinicopathological parameters and serum proteome profiles of vivax malaria patients with different severity levels of infection to investigate pathogenesis of severe malaria and identify surrogate markers of severity. Clinicopathological analysis and proteomics profiling has provided evidences for the modulation of diverse physiological pathways including oxidative stress, cytoskeletal regulation, lipid metabolism and complement cascades in severe malaria. Strikingly, unlike severe falciparum malaria the blood coagulation cascade was not found to be affected adversely in acute P. vivax infection. To the best of our knowledge, this is the first comprehensive proteomics study, which identified some possible cues for severe P. vivax infection. Our results suggest that Superoxide dismutase, Vitronectin, Titin, Apolipoprotein E, Serum amyloid A, and Haptoglobin are potential predictive markers for malaria severity.

Surface defect rich ZnO quantum dots as antioxidants inhibiting α-amylase and α-glucosidase: a potential anti-diabetic nanomedicine.

Preventing chronic hyperglycaemia and associated oxidative stress is utmost important for the treatment and management of Type 2 Diabetes Mellitus (T2DM). Here we report the role of different size surface defect rich ZnO quantum dots (D-QDs) for inhibiting metabolic enzymes and scavenging free radicals, which plays a key role in reducing hyperglycaemia and oxidative stress. Quantitative analysis of radical scavenging and metabolic enzyme inhibition activity of D-QDs demonstrates a size dependent behaviour, where D-QDs with a smaller diameter shows superior activity compared to larger size D-QDs. Considering the size dependence in surface defect formation, the increased surface defect density in smaller size D-QDs can be considered as the reason behind this enhancement. Detailed studies establishing the underlying mechanism behind potent free radical scavenging and enzyme inhibition provides an intense scientific rationale for considering D-QDs to design safe and effective nanomedicine for T2DM.

Enhanced visible photoluminescence in ZnO quantum dots by promotion of oxygen vacancy formation.

We report on the synthesis of ZnO quantum dots (QDs) rich in oxygen vacancies by inducing an oxygen deficient environment. The precise tunability of particle size is achieved by counter ion capping of the precursor used for synthesis. The prepared QDs show size tunable visible emission with high quantum yield.