Causal influences of neuropsychiatric disorders on Alzheimer's disease.

Previous studies have observed a significant comorbidity between Alzheimer's disease (AD) and some other neuropsychiatric disorders. However, the mechanistic connections between neuropsychiatric disorders and AD are not well understood. We conducted a Mendelian randomization analysis to appraise the potential influences of 18 neurodegenerative and neuropsychiatric disorders on AD.

Shared genetics and bidirectional causal relationships between type 2 diabetes and attention-deficit/hyperactivity disorder.

Background: Type 2 diabetes (T2D) is a chronic metabolic disorder with high comorbidity with mental disorders. The genetic links between attention-deficit/hyperactivity disorder (ADHD) and T2D have yet to be elucidated.

Aims: We aim to assess shared genetics and potential associations between ADHD and T2D.

In a search of a protective titer: Do we or do we not need to know?

The level of postvaccine protection depends on two factors: antibodies and T-cell responses. While the first one is relatively easily measured, the measuring of the second one is a difficult problem. The recent studies indicate that the first one may be a good proxy for the protection, at least for SARS-CoV-2.

An exploratory study examining how nano-liquid chromatography-mass spectrometry and phosphoproteomics can differentiate patients with advanced fibrosis and higher percentage collagen in non-alcoholic fatty liver disease.

Background: Non-alcoholic steatohepatitis (NASH) is among the leading causes of liver disease worldwide. It is increasingly recognized that the phenotype of NASH may involve a number of different pathways, of which each could become important therapeutic targets. The aim of this study is to use high resolution mass spectrometry (MS) and phosphoproteomics techniques to assess the serum proteome and hepatic phosphoproteome in subjects with NASH-related fibrosis.

Optogenetic regulation of transcription.

Optogenetics has become widely recognized for its success in real-time control of brain neurons by utilizing non-mammalian photosensitive proteins to open or close membrane channels. Here we review a less well known type of optogenetic constructs that employs photosensitive proteins to transduce the signal to regulate gene transcription, and its possible use in medicine. One of the problems with existing gene therapies is that they could remain active indefinitely while not allowing regulated transgene production on demand.

Expression of energy metabolism related genes in the gastric tissue of obese individuals with non-alcoholic fatty liver disease.

Background: Stomach is an integral part of the energy balance regulating circuit. Studies exploring the effects of cross-system changes in the energy homeostasis in stomach tissue are scarce. The proximity of the stomach to liver--the most common secondary target affected by obesity--suggests that these two organs are exposed to each other's local secretion.

Molecular signature of adipose tissue in patients with both non-alcoholic fatty liver disease (NAFLD) and polycystic ovarian syndrome (PCOS).

Background: Polycystic ovarian syndrome (PCOS) is one of the most common reproductive disorders with strong association with both insulin resistance and non-alcoholic fatty liver disease (NAFLD). To untangle the complex relationship between PCOS and NAFLD, we analyzed serum biomarkers of apoptosis, some adipokines and mRNA profiles in the visceral adipose tissue of obese patients with NAFLD who were also diagnosed with PCOS and compared to a group with NAFLD only.

Methods: We included patients with biopsy-proven NAFLD and PCOS (N = 12) and BMI-matched biopsy-proven NAFLD patients without PCOS (N = 12).

Expression of genes for microRNA-processing enzymes is altered in advanced non-alcoholic fatty liver disease.

Background And Aim: Recently, microRNAs (miRNA) have been linked to the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and its progression to non-alcoholic steatohepatitis (NASH). First transcribed as pri-miRNA, these molecules are further processed by a complex of endonuclear and cytosolic RNA binding molecules to form mature miRNAs. The aim of this study is to investigate mechanisms of miRNA regulation in the visceral adipose of obese NAFLD patients via measuring expression of miRNA processing enzymes and pri-miRNA.

Expression of inflammation-related genes is altered in gastric tissue of patients with advanced stages of NAFLD.

Obesity is associated with chronic low-grade inflammation perpetuated by visceral adipose. Other organs, particularly stomach and intestine, may also overproduce proinflammatory molecules. We examined the gene expression patterns in gastric tissue of morbidly obese patients with nonalcoholic fatty liver disease (NAFLD) and compared the changes in gene expression in different histological forms of NAFLD.

Protein partners of KCTD proteins provide insights about their functional roles in cell differentiation and vertebrate development.

The KCTD family includes tetramerization (T1) domain containing proteins with diverse biological effects. We identified a novel member of the KCTD family, BTBD10. A comprehensive analysis of protein-protein interactions (PPIs) allowed us to put forth a number of testable hypotheses concerning the biological functions for individual KCTD proteins.

Knowledge-based identification of soluble biomarkers: hepatic fibrosis in NAFLD as an example.

The discovery of biomarkers is often performed using high-throughput proteomics-based platforms and is limited to the molecules recognized by a given set of purified and validated antigens or antibodies. Knowledge-based, or systems biology, approaches that involve the analysis of integrated data, predominantly molecular pathways and networks may infer quantitative changes in the levels of biomolecules not included by the given assay from the levels of the analytes profiled. In this study we attempted to use a knowledge-based approach to predict biomarkers reflecting the changes in underlying protein phosphorylation events using Nonalcoholic Fatty Liver Disease (NAFLD) as a model.

Association of obestatin, ghrelin, and inflammatory cytokines in obese patients with non-alcoholic fatty liver disease.

Background: Three protein products of ghrelin gene (acylated ghrelin, des-acylated ghrelin, and obestatin) are involved in appetite stimulation and suppression. Additionally, there is some evidence suggesting their involvement in metabolic and inflammatory pathways which may be implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). The aim of this study was to examine the relationships of ghrelin gene products in patients with NAFLD.

Inhibition of potassium currents as a pharmacologic target for investigation in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) represents 22-30% of all leukemia cases, thus being the most commonly diagnosed form of adult leukemia in the Western world. On a cellular level, the disease progresses due to the prolonged survival of B-cell CLL cells arrested in the G₀ stage of the cell cycle. The current standard treatment for CLL is a combination regimen containing purine analogues and monoclonal antibodies.

Association of serum adipocytokines with hepatic steatosis and fibrosis in patients with chronic hepatitis C.

Background: The pathogenic mechanisms of hepatic steatosis in hepatitis C (HCV) remain unclear.

Aim: To assess the potential role of cytokines and adipokines in HCV-related steatosis and fibrosis.

Methods: We profiled several adipokines, cytokines, and related soluble molecules in 99 HCV patients and analyzed their potential associations with hepatic steatosis and fibrosis.

Validation of endogenous reference genes for qRT-PCR analysis of human visceral adipose samples.

Background: Given the epidemic proportions of obesity worldwide and the concurrent prevalence of metabolic syndrome, there is an urgent need for better understanding the underlying mechanisms of metabolic syndrome, in particular, the gene expression differences which may participate in obesity, insulin resistance and the associated series of chronic liver conditions. Real-time PCR (qRT-PCR) is the standard method for studying changes in relative gene expression in different tissues and experimental conditions. However, variations in amount of starting material, enzymatic efficiency and presence of inhibitors can lead to quantification errors.

Phosphoproteomic biomarkers predicting histologic nonalcoholic steatohepatitis and fibrosis.

The progression of nonalcoholic fatty liver disease (NAFLD) has been linked to deregulated exchange of the endocrine signaling between adipose and liver tissue. Proteomic assays for the phosphorylation events that characterize the activated or deactivated state of the kinase-driven signaling cascades in visceral adipose tissue (VAT) could shed light on the pathogenesis of nonalcoholic steatohepatitis (NASH) and related fibrosis. Reverse-phase protein microarrays (RPMA) were used to develop biomarkers for NASH and fibrosis using VAT collected from 167 NAFLD patients (training cohort, N = 117; testing cohort, N = 50).

Pro-apoptotic and antiproliferative activity of human KCNRG, a putative tumor suppressor in 13q14 region.

Deletion of 13q14.3 and a candidate gene KCNRG (potassium channel regulating gene) is the most frequent chromosomal abnormality in B-cell chronic lymphocytic leukemia and is a common finding in multiple myeloma (MM). KCNRG protein may interfere with the normal assembly of the K+ channel proteins causing the suppression of Kv currents.

Hepatic stellate cell and myofibroblast-like cell gene expression in the explanted cirrhotic livers of patients undergoing liver transplantation.

Background: Hepatic stellate cells (HSC) are involved in hepatic fibrogenesis. Cell signaling associated with an insult to the liver affects an HSC transdifferentiation to fibrogenic myofibroblast-like cells.

Aims: To investigate the transcriptional expression distinguishing HSC and myofibroblast-like cells between livers with and without cirrhosis.

Expression of cytokine signaling genes in morbidly obese patients with non-alcoholic steatohepatitis and hepatic fibrosis.

Background: White adipose tissue (WAT) from visceral adiposity plays an important role in the pathogenesis of non-alcoholic steatohepatitis (NASH). Development of NASH and its progression to fibrosis is partially due to cytokines and adipokines produced by WAT. The aim of this study was to assess the association of hepatic fibrosis and NASH by evaluating the intrinsic differences in the inflammatory cytokine signaling in the visceral adipose tissue obtained from morbidly obese patients.

Evidence for the ectopic synthesis of melanin in human adipose tissue.

Melanin is a common pigment in animals. In humans, melanin is produced in melanocytes, in retinal pigment epithelium (RPE) cells, in the inner ear, and in the central nervous system. Previously, we noted that human adipose tissue expresses several melanogenesis-related genes.

Laser capture microdissection and protein microarray analysis of human non-small cell lung cancer: differential epidermal growth factor receptor (EGPR) phosphorylation events associated with mutated EGFR compared with wild type.

Little is known about lung carcinoma epidermal growth factor (EGF) kinase pathway signaling within the context of the tissue microenvironment. We quantitatively profiled the phosphorylation and abundance of signal pathway proteins relevant to the EGF receptor within laser capture microdissected untreated, human non-small cell lung cancer (NSCLC) (n = 25) of known epidermal growth factor receptor (EGFR) tyrosine kinase domain mutation status. We measured six phosphorylation sites on EGFR to evaluate whether EGFR mutation status in vivo was associated with the coordinated phosphorylation of specific multiple phosphorylation sites on the EGFR and downstream proteins.

A novel diagnostic biomarker panel for obesity-related nonalcoholic steatohepatitis (NASH).

Background: Within the spectrum of nonalcoholic fatty liver disease (NAFLD), only patients with nonalcoholic steatohepatitis (NASH) show convincing evidence for progression. To date, liver biopsy remains the gold standard for the diagnosis of NASH; however, liver biopsy is expensive and associated with a small risk, emphasizing the urgent need for noninvasive diagnostic biomarkers. Recent findings suggest a role for apoptosis and adipocytokines in the pathogenesis of NASH.

Degradation of circulating von Willebrand factor and its regulator ADAMTS13 implicates secreted Bacillus anthracis metalloproteases in anthrax consumptive coagulopathy.

Pathology data from the anthrax animal models show evidence of significant increases in vascular permeability coincident with hemostatic imbalances manifested by thrombocytopenia, transient leucopenia, and aggressive disseminated intravascular coagulation. In this study we hypothesized that anthrax infection modulates the activity of von Willebrand factor (VWF) and its endogenous regulator ADAMTS13, which play important roles in hemostasis and thrombosis, including interaction of endothelial cells with platelets. We previously demonstrated that purified anthrax neutral metalloproteases Npr599 and InhA are capable of cleaving a variety of host structural and regulatory proteins.

Gene expression patterns in hepatic tissue and visceral adipose tissue of patients with non-alcoholic fatty liver disease.

Background: Non-alcoholic fatty liver disease (NAFLD) and its progressive form, non-alcoholic steatohepatitis (NASH), are among the least understood metabolic consequences of obesity. Increasingly, omental adipose tissue is recognized as a biologically active organ in the pathogenesis of NAFLD. Differences in transcriptional regulation in omental adipose tissue and liver tissue may provide important insights into the pathogenesis of NAFLD and its progression.