All Articles

Bioinformatic Resources for Diabetic Nephropathy

Abstract:

The number of individuals with diabetes is increasing worldwide and a large subset of those affected will develop diabetic nephropathy. Diabetic nephropathy is the leading cause of end-stage renal disease, has serious health consequences for affected individuals, and represents a major monetary cost to healthcare providers.

Technological and analytical developments have enabled large-scale, collaborative studies that are revealing risk factors associated with diabetic nephropathy. However, much of the inherited predisposition and biological mechanisms underpinning risk of this disease remain to be identified. Meta-analyses and integrated pathway studies are becoming an increasingly important part of research for diabetic nephropathy including, genetic, epigenetic, transcriptomic, proteomic research, clinical observations and the development of animal models.

This report highlights current bioinformatic resources and standards of rep...

Kynurenines and Vitamin B6: Link Between Diabetes and Depression.

Abstract:

The increased association between depression and diabetes mellitus is generally acknowledged. Recent studies suggest that depression leads to diabetes.However, the underlying molecular mechanisms for this association remain unclear.Literature and our data indicate that inflammatory and/or stress factors in depression up-regulate tryptophan (TRP) conversion into kynurenine (KYN), a substrate for nicotinamide adenine dinucleotide (NAD) biosynthesis. Deficiency of vitamin B6, a co-factor of the key enzymes of KYN – NAD pathway, shunts KYN metabolism from formation of NAD towards production of xanthurenic (XA) and kynurenic (KYNA) acids. Human and experimental studies reveal that XA, KYNA and their metabolites interfere with production, release and biological activity of insulin. We propose that inflammation- and/or stress-induced up-regulation of TRP – KYN metabolism in combination with vitamin B6 deficiency is one of the mechanisms mediating increased risk of di...

Determination of the Proteomic Response to Lapatinib Treatment using a Comprehensive and Reproducible Ion-Current-Based Proteomics Strategy

Abstract:

Lapatinib, a small molecule tyrosine kinase inhibitor is currently used in the treatment of HER2-positive breast cancer. The aim of this study was to further understanding of lapatinib response for the development of novel treatment lapatinib-focussed treatment strategies.

HER2-overexpressing SKBR3 breast cancer cells were treated with lapatinib for 12 hours and the resultant proteome analyzed by a comprehensive ion-current-based LC-MS strategy.

Among the 1224 unique protein identified from SKBR3 cell lysates, 67 showed a significant change in protein abundance in response to lapatinib. Of these, CENPE a centromeric protein with increased abundance, was chosen for further validation. Knockdown and inhibition of CENPE demonstrated that CENPE enhances SKBR3 cell survival in the presence of lapatinib.

Based on this study, CENPE inhibitors may warrant further investigation for use in combination with lapatinib.

Testing Maternal-Fetal Genotype Incompatibility with Mother-Offspring Pair Data

Abstract:

Maternal-fetal genotype (MFG) incompatibility has been shown to be strongly associated with a number of genetic diseases. Most current methods for the MFG test rely on parents-offspring trio genotype data and do not apply to mother-offspring pair data where paternal genotype is unavailable. In this paper, we developed a two-stage method for testing the allelic effect of given SNP through subgroup analysis of compatible MFG pairs and further tested the MFG incompatibility effect according to different scenarios determined by the allelic effect. Simulation studies demonstrated that this novel two-stage model is powerful in detecting the MFG incompatibility effect. This method can be implemented through publicly available statistical software, such as SAS, R, etc. We demonstrate with a case-control study of small for gestational age neonates that the method identified a SNP in the IGF2R gene with a significant allelic effect (p = 0.037), and a SNP in the IGF1 gene wi...

Quantitative Proteomics Using 15N SILAC Mouse

Abstract:

In biomedical research the use of mammalian tissues is crucial to increase our understanding of complex human diseases. Mass spectrometry-based proteomic approach has become the most powerful tool of studying large-scale protein expression profiles in mammalian tissues. To perform global proteome analysis quantification of mammalian tissues, we generated ¹⁵N SILAC mice to obtain tissue-matched labeled peptide libraries for mass spectrometry-based quantitative proteomic analysis. We developed a new labeling protocol to circumvent adverse effects of introducing ¹⁵N labeled diet to mice, and showed that the new labeling scheme has no significant effect on the fertility and reproduction of C57/BL6 mice. Using labeled tissues from these mice, we compared the reproducibility of mass spectrometry-based quantification with or without ¹⁵N labeled internal standards among biological replicates of young and old brains. We found that labeled-...

Differences in the Alveolar Macrophage Proteome in Transgenic Mice Expressing Human SP-A1 and SP-A2

Abstract:

Surfactant protein A (SP-A) plays a number of roles in lung host defense and innate immunity. There are two human genes, SFTPA1 and SFTPA2, and evidence indicates that the function of SP-A1 and SP-A2 proteins differ in several respects. To investigate the impact of SP-A1 and SP-A2 on the alveolar macrophage (AM) phenotype, we generated humanized transgenic (hTG) mice on the SP-A knockout (KO) background, each expressing human SP-A1 or SP-A2. Using two-dimensional difference gel electrophoresis (2D-DIGE) we studied the AM cellular proteome. We compared mouse lines expressing high levels of SP-A1, high levels of SP-A2, low levels of SP-A1, and low levels of SP-A2, with wild type (WT) and SP-A KO mice. AM from mice expressing high levels of SP-A2 were the most similar to WT mice, particularly for proteins related to actin and the cytoskeleton, as well as proteins regulated by Nrf2. The expression patterns from mouse lines expressing ...

Editorial for Journal of Proteomics and Genomics Research: Second Issue

Abstract:

An editorial for the second issue highlights notable contributions and reaffirms peer review and openness as pillars for the field.

Correlation of Cryptococcal Antigen Assay with C-reactive Protein as Serum and Urine Biomarker in Cryptococcal Meningitis: Experience in a Tertiary Hospital

Abstract:

The incidence of cryptococcal meningitis caused by Cryptococcus neoformans has risen markedly over the past 20 years as a result of theHIV epidemic and increasing use of immunosuppressive therapies. The objectives of this study were to isolate and identify Cryptococcus neoformans from clinically suspected cases of fungal meningitis by conventional techniques and evaluate the role of C-reactive protein (CRP) as a serum or urine biomarker for the diagnosis and monitoring of patients with cryptococcal meningitis.

Pattern of Use of Highly Active Antiretroviral Therapy Regimens and Pattern of Occurrence of Adverse Drug Reactions in an Indian Human Immunodeficiency Virus Positive Patients

Abstract:

In India, Human immunodeficiency (HIV) infected patients with highly active antiretroviral therapy (HAART) are at higher risk of developing adverse drug reactions (ADRs).

When and How Should we be Measuring Adherence to Antiretroviral Therapy in Resource-Limited Settings?

Abstract:

This perspective reviews practical approaches to measuring ART adherence in resource‑limited settings. It weighs self‑report, pill counts, pharmacy refill data, and biologic measures, emphasizing feasibility, bias, and programmatic integration to support sustainable HIV care.