Apolipoprotein A-I anti-tumor activity targets cancer cell metabolism.

Previously, we reported apolipoprotein A-I (apoA-I), the major protein component of high-density lipoprotein (HDL), has potent anti-melanoma activity. We used DNA microarray and bioinformatics to interrogate gene expression profiles of tumors from apoA-I expressing (A-I Tg) versus apoA-I-null (A-I KO) animals to gain insights into mechanisms of apoA-I tumor protection. Differential expression analyses of 11 distinct tumors per group with > 1.

Aberrant Upregulation of Compensatory Redox Molecular Machines May Contribute to Sperm Dysfunction in Infertile Men with Unilateral Varicocele: A Proteomic Insight.

To understand the molecular pathways involved in oxidative stress (OS)-mediated sperm dysfunction against a hypoxic and hyperthermic microenvironment backdrop of varicocele through a proteomic approach. Protein selection (261) based on their role in redox homeostasis and/or oxidative/hyperthermic/hypoxic stress response from the sperm proteome data set of unilateral varicocele (UV) in comparison with fertile control displayed 85 to be differentially expressed. Upregulation of cellular oxidant detoxification and glutathione and reduced nicotinamide adenine dinucleotide (NADH) metabolism accompanied with downregulation of protein folding, energy metabolism, and heat stress responses were observed in the UV group.

PARP1 Is Up-Regulated in Non-small Cell Lung Cancer Tissues in the Presence of the Cyanobacterial Toxin Microcystin.

Non-small cell lung cancer (NSCLC) is the major form of lung cancer, with adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) being its major subtypes. Smoking alone cannot completely explain the lung cancer etiology. We hypothesize that altered lung microbiome and chronic inflammatory insults in lung tissues contribute to carcinogenesis.

Proteomic Signatures of Sperm Mitochondria in Varicocele: Clinical Use as Biomarkers of Varicocele Associated Infertility.

Purpose: Varicocele may disrupt testicular microcirculation and induce hypoxia-ischemia related degenerative changes in testicular cells and spermatozoa. Superoxide production at low oxygen concentration exacerbates oxidative stress in men with varicocele. Therefore, the current study was designed to study the role of mitochondrial redox regulation and its possible involvement in sperm dysfunction in varicocele associated infertility.

Whole Genome Expression Analysis in a Mouse Model of Tauopathy Identifies MECP2 as a Possible Regulator of Tau Pathology.

Increasing evidence suggests that hyperphosphorylation and aggregation of microtubule-associated protein tau (MAPT or tau) correlates with the development of cognitive impairment in Alzheimer's disease (AD) and related tauopathies. While numerous attempts have been made to model AD-relevant tau pathology in various animal models, there has been very limited success for these models to fully recapitulate the progression of disease as seen in human tauopathies. Here, we performed whole genome gene expression in a genomic mouse model of tauopathy that expressed human gene under the control of endogenous human promoter and also were complete knockout for endogenous mouse tau [referred to as 'hTau ' mice].

Comparative systems pharmacology of HIF stabilization in the prevention of retinopathy of prematurity.

Retinopathy of prematurity (ROP) causes 100,000 new cases of childhood blindness each year. ROP is initiated by oxygen supplementation necessary to prevent neonatal death. We used organ systems pharmacology to define the transcriptomes of mice that were cured of oxygen-induced retinopathy (OIR, ROP model) by hypoxia-inducible factor (HIF) stabilization via HIF prolyl hydroxylase inhibition using the isoquinolone Roxadustat or the 2-oxoglutarate analog dimethyloxalylglycine (DMOG).

Spermatozoa protein alterations in infertile men with bilateral varicocele.

Among infertile men, a diagnosis of unilateral varicocele is made in 90% of varicocele cases and bilateral in the remaining varicocele cases. However, there are reports of under-diagnosis of bilateral varicocele among infertile men and that its prevalence is greater than 10%. In this prospective study, we aimed to examine the differentially expressed proteins (DEP) extracted from spermatozoa cells of patients with bilateral varicocele and fertile donors.

Major protein alterations in spermatozoa from infertile men with unilateral varicocele.

Background: The etiology of varicocele, a common cause of male factor infertility, remains unclear. Proteomic changes responsible for the underlying pathology of unilateral varicocele have not been evaluated. The objective of this prospective study was to employ proteomic techniques and bioinformatic tools to identify and analyze proteins of interest in infertile men with unilateral varicocele.

Differential proteomic profiling of spermatozoal proteins of infertile men with unilateral or bilateral varicocele.

Objective: To compare the sperm protein profile between infertile men with unilateral varicocele and infertile men with bilateral varicocele.

Methods: This prospective study investigated 50 infertile patients with clinical varicocele (33 unilateral and 17 bilateral) seeking fertility workup between March 2012 and April 2014. Routine sperm parameters, reactive oxygen species, total antioxidant capacity, and sperm deoxyribonucleic acid fragmentation were assessed in their semen.

Bioengineering silicon quantum dot theranostics using a network analysis of metabolomic and proteomic data in cardiac ischemia.

Metabolomic profiling is ideally suited for the analysis of cardiac metabolism in healthy and diseased states. Here, we show that systematic discovery of biomarkers of ischemic preconditioning using metabolomics can be translated to potential nanotheranostics. Thirty-three patients underwent percutaneous coronary intervention (PCI) after myocardial infarction.

Proteomic analysis of seminal fluid from men exhibiting oxidative stress.

Background: Seminal plasma serves as a natural reservoir of antioxidants. It helps to remove excessive formation of reactive oxygen species (ROS) and consequently, reduce oxidative stress. Proteomic profiling of seminal plasma proteins is important to understand the molecular mechanisms underlying oxidative stress and sperm dysfunction in infertile men.

PRMT5 dimethylates R30 of the p65 subunit to activate NF-κB.

The ubiquitous inducible transcription factor NF-κB plays central roles in immune and inflammatory responses and in tumorigenesis. Complex posttranslational modifications of the p65 subunit (RelA) are a major aspect of the extremely flexible regulation of NF-κB activity. Although phosphorylation, acetylation, ubiquitination, and lysine methylation of NF-κB have been well described, arginine methylation has not yet been found.

Proteomic analysis of human spermatozoa proteins with oxidative stress.

Background: Oxidative stress plays a key role in the etiology of male infertility. Significant alterations in the sperm proteome are associated with poor semen quality. The aim of the present study was to examine if elevated levels of reactive oxygen species cause an alteration in the proteomic profile of spermatozoa.

Functional proteomic analysis of seminal plasma proteins in men with various semen parameters.

Background: Alterations at the molecular level in spermatozoa and seminal plasma can affect male fertility. The objective of this study was to determine if analysis of differential expression of proteins in varying semen parameters can serve as potential biomarkers for male infertility.

Methods: The differential expression of proteins in the seminal plasma of men based on sperm count and morphology were examined utilizing proteomic tools.

Unique DNA methylome profiles in CpG island methylator phenotype colon cancers.

A subset of colorectal cancers was postulated to have the CpG island methylator phenotype (CIMP), a higher propensity for CpG island DNA methylation. The validity of CIMP, its molecular basis, and its prognostic value remain highly controversial. Using MBD-isolated genome sequencing, we mapped and compared genome-wide DNA methylation profiles of normal, non-CIMP, and CIMP colon specimens.

Inflammation-induced endothelial-to-mesenchymal transition: a novel mechanism of intestinal fibrosis.

In addition to mesenchymal cells, endothelial cells may contribute to fibrosis through the process of endothelial-to-mesenchymal transition (EndoMT). We investigated whether human intestinal microvascular endothelial cells (HIMEC) undergo EndoMT and contribute to fibrosis in human and experimental inflammatory bowel disease (IBD). HIMEC were exposed to TGF-β1, IL-1β, and TNF-α or supernatants of lamina propria mononuclear cells (LPMC) and evaluated for morphological, phenotypic, and functional changes compatible with EndoMT.

Multiple preconditioning paradigms converge on interferon regulatory factor-dependent signaling to promote tolerance to ischemic brain injury.

Ischemic tolerance can be induced by numerous preconditioning stimuli, including various Toll-like receptor (TLR) ligands. We have shown previously that systemic administration of the TLR4 ligand LPS or the TLR9 ligand unmethylated CpG oligodeoxynucleotide before transient brain ischemia in mice confers substantial protection against ischemic damage. To elucidate the molecular mechanisms of preconditioning, we compared brain genomic profiles in response to preconditioning with these TLR ligands and with preconditioning via exposure to brief ischemia.

Using the gene ontology to enrich biological pathways.

Most current approaches to automatic pathway generation are based on a reverse engineering approach in which pathway plausibility is solely derived from gene expression data and not independently validated. Alternative approaches use prior biological knowledge to validate automatically inferred pathways, but the prior knowledge is usually not sufficiently tuned to the pathology of focus. We present a novel pathway generation approach that combines insights from the reverse engineering and knowledge-based approaches to increase the biological plausibility of automatically generated regulatory networks and describe an application of this approach to transcriptional data from a mouse model of neuroprotection during stroke.

Gene expression changes in an animal model of in utero irradiation-induced Cortical Dysplasia.

Purpose: Cortical Dysplasia (CD) is the histopathological substrate in almost half of all drug-resistant focal epilepsies. Little is known about the gene expression profile of CD. As such information may help target therapeutics more effectively, our aim was to perform a gene expression analysis of an animal model of cortical dysplasia induced by in utero irradiation.

Systemic lipopolysaccharide protects the brain from ischemic injury by reprogramming the response of the brain to stroke: a critical role for IRF3.

Lipopolysaccharide (LPS) preconditioning provides neuroprotection against subsequent cerebral ischemic injury through activation of its receptor, Toll-like receptor 4 (TLR4). Paradoxically, TLR activation by endogenous ligands after ischemia worsens stroke damage. Here, we define a novel, protective role for TLRs after ischemia in the context of LPS preconditioning.

Gene expression profiles in rainbow trout, Onchorynchus mykiss, exposed to a simple chemical mixture.

Among proposed uses for microarrays in environmental toxiciology is the identification of key contributors to toxicity within a mixture. However, it remains uncertain whether the transcriptomic profiles resulting from exposure to a mixture have patterns of altered gene expression that contain identifiable contributions from each toxicant component. We exposed isogenic rainbow trout Onchorynchus mykiss, to sublethal levels of ethynylestradiol, 2,2,4,4-tetrabromodiphenyl ether, and chromium VI or to a mixture of all three toxicants Fluorescently labeled complementary DNA (cDNA) were generated and hybridized against a commercially available Salmonid array spotted with 16,000 cDNAs.

Mechanical stress induces biotic and abiotic stress responses via a novel cis-element.

Plants are continuously exposed to a myriad of abiotic and biotic stresses. However, the molecular mechanisms by which these stress signals are perceived and transduced are poorly understood. To begin to identify primary stress signal transduction components, we have focused on genes that respond rapidly (within 5 min) to stress signals.

Combining hierarchical and associative gene ontology relations with textual evidence in estimating gene and gene product similarity.

Two approaches have recently emerged where the similarity between two genes or gene products is obtained by comparing Gene Ontology (GO) annotations associated with the genes or gene products. One approach captures GO-based similarity in terms of hierarchical relations within each gene subontology, while the other relies on associative relations across the three gene subontologies. We propose a novel methodology where the two approaches can be merged and enriched by textual evidence extracted from biomedical literature with ensuing benefits in coverage and stronger correlation with sequence-based similarity.

Bioinformatic insights from metagenomics through visualization.

Cutting-edge biological and bioinformatics research seeks a systems perspective through the analysis of multiple types of high-throughput and other experimental data for the same sample. Systems-level analysis requires the integration and fusion of such data, typically through advanced statistics and mathematics. Visualization is a complementary computational approach that supports integration and analysis of complex data or its derivatives.