BBA Clinical

BACKGROUND: Lung cancer is the leading cause of cancer-related mortality in both men and women throughout the world. The need to detect lung cancer at an early, potentially curable stage, is essential and may reduce mortality by 20%. The aim of this study was to identify distinct proteomic profiles in bronchoalveolar fluid (BALF) and plasma that are able to discriminate individuals with benign disease from those with non-small cell lung cancer (NSCLC). METHODS: Using label-free mass spectrometry analysis of BALF during discovery-phase analysis, a significant number of proteins were found to have different abundance levels when comparing control to adenocarcinoma (AD) or squamous cell lung carcinoma (SqCC)...

A series of studies were carried out in Farber disease (OMIM #228000) cells and mice to evaluate the feasibility of enzyme replacement therapy (ERT) for this disorder. Media from Chinese hamster ovary (CHO) cells overexpressing human recombinant acid ceramidase (rhAC) was used to treat fibroblasts from a Farber disease patient, leading to significantly reduced ceramide. We also found that chondrocytes from Farber disease mice had a markedly abnormal chondrogenic phenotype, and this was corrected by rhAC as well...

The L-type calcium channel (LTCC) is one of the major ion channels that are known to be associated with the electrical remodeling of atrial fibrillation (AF). In AF, there is significant downregulation of the LTCC, but the underlying mechanism for such downregulation is not clear. We have previously reported that microRNA-499 (miR-499) is significantly upregulated in patients with permanent AF and that KCNN3, the gene that encodes the small-conductance calcium-activated potassium channel 3 (SK3), is a target of miR-499...

BACKGROUND: Despite a remarkable increase in the depth of our understanding and management of breast cancer in the past 50 years, the disease is still a major public health problem worldwide and poses significant challenges. The palpability of breast tumors has facilitated diagnosis and documentation since ancient times. The earliest descriptions of breast cancer date back to around 3500 BCE. For centuries to follow, theories by Hippocrates (460 BCE) and Galen (200 CE), attributing the cause of breast cancer to an "excess of black bile" and treatment options including the use of opium and castor oil, prevailed...

BACKGROUND: Patients with end-stage renal disease (ESRD) undergoing haemodialysis (HD) experience enhanced oxidative stress and systemic inflammation, which are risk factors for cardiovascular disease, the most common cause of excess morbidity and mortality for these patients. Different pathways producing different types of oxidative stress occur in ESRD. The purpose of our study was to determine the effect of HD on plasma levels of protein-bound dityrosine (di-Tyr), a biomarker of protein oxidation...

BACKGROUND: Association of Alzheimer's Disease (AD) with Type 2 Diabetes (T2D) has been well established. Cyclo(His-Pro) plus zinc (Cyclo-Z) treatment ameliorated diabetes in rats and similar improvements have been seen in human patients. Treatment of amyloid precursor protein (APP) transgenic mice with Cyclo-Z exhibited memory improvements and significantly reduced Aβ-40 and Aβ-42 protein levels in the brain tissues of the mice. SCOPE OF REVIEW: Metabolic relationship between AD and T2D will be described with particular attention to insulin sensitivity and Aβ degradation in brain and plasma tissues...

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of severe immune activation with macrophage and T-cell infiltration resulting in, multi organ damage. HLH may be primary or secondary in etiology. A high index of suspicion is essential for early diagnosis and treatment. Diagnostic criteria need to be refined and newer treatment options to be explored in order to improve survival especially in adult HLH and malignancy-associated HLH (M-HLH). We report a case of malignancy associated HLH (M-HLH) in adult treated on one of the only FDA-approved protocols for adult HLH to highlight the diagnostic and therapeutic challenges of this disease entity...

BACKGROUND: Stress has demonstrated effects on inflammation though underlying cell-cell communication mechanisms remain unclear. We hypothesize that circulating RNAs and extracellular vesicles (EVs) in patients with chronic stress contain signals with functional roles in cell repair. METHODS: Blood transcriptome from patients with Irritable Bowel Syndrome versus controls were compared to identify signaling pathways and effectors. Plasma EVs were isolated (size-exclusion chromatography) and characterized for effectors' presence (immunogold labelling-electron microscopy)...

OBJECTIVE: Microparticles (MPs) are membrane-bound vesicles derived from vascular and intravascular cells such as endothelial cells (EMPs) and platelets (PMPs). We investigated EMP and PMP numbers across a spectrum of autoimmune rheumatic diseases (AIRDs) with the aim of comparing the levels of, and relationship between, EMPs and PMPs. METHODS: Patients with Systemic Lupus Erythematosus (SLE) ( n  = 24), Systemic Sclerosis (SSc) ( n  = 24), Primary Raynauds Phenomenon (RP) ( n  = 17) and "other CTD" ( n  = 15) (Primary Sjogrens Syndrome, UCTD or MCTD) as well as 15 healthy controls were recruited...

BACKGROUND: Metabolomics represents a promising approach for discovering novel targets and biomarkers in head and neck squamous cell carcinoma (HNSCC). Here we used metabolomics to identify oral metabolites associated with HNSCC. METHODS: Tumor and adjacent normal tissue from surgical resections and presurgical oral washes as well as oral washes were collected from healthy participants. Metabolites extractions of these samples were analyzed by liquid chromatography-mass spectroscopy (LC/MS), LC/MS/MS and gas chromatography-MS (GC/MS)...

Myofibrillar myopathy (MFM) is a group of inherited muscular disorders characterized by myofibrils dissolution and abnormal accumulation of degradation products. So far causative mutations have been identified in nine genes encoding Z-disk proteins, including αB-crystallin (CRYAB), a small heat shock protein (also called HSPB5). Here, we report a case study of a 63-year-old Polish female with a progressive lower limb weakness and muscle biopsy suggesting a myofibrillar myopathy, and extra-muscular multisystemic involvement, including cataract and cardiomiopathy...

Normal extension and skull expansion is a synchronized process that prevails along the osteogenic intersections of the cranial sutures. Cranial sutures operate as bone growth sites allowing swift bone generation at the edges of the bone fronts while they remain patent. Premature fusion of one or more cranial sutures can trigger craniosynostosis, a birth defect characterized by dramatic manifestations in appearance and functional impairment. Up until today, surgical correction is the only restorative measure for craniosynostosis associated with considerable mortality...

BACKGROUND: Diabetes and cancer are public health issues worldwide; studies have shown that diabetes is related to increased breast cancer mortality. The purpose of this study was to examine associations between HbA1C and obesity with tumor stage and mortality among breast cancer patients. METHODS: Data for 82 patients with breast cancer (36-89 years of age, diagnosed /treated 1999-2009) were provided by the University of Arkansas for Medical Sciences (UAMS) Data Trust Warehouse...

BACKGROUND: MicroRNAs (miRNAs or miRs) are post-transcriptional regulators of eukaryotic cells and knowledge of differences in miR levels may provide new approaches to diagnosis and therapy. METHODS: The present study measured the levels of nine miRs in head and neck squamous cell carcinomas (HNSCC) and determined whether clinical pathological features are associated with differences in miR levels. SET (I2PP2A) and PTEN protein levels were also measured, since their levels can be regulated by miR-199b and miR-21, respectively...

BACKGROUND: Pathophysiology of attention-deficit hyperactivity disorder (ADHD) is not known, and therefore the present study investigated mitochondrial defects, if any in cybrids created from patients and control population. METHODS: To investigate mitochondrial pathology in ADHD, cybrids cell lines were created from ADHD probands and controls by fusing their platelets with ρ(0)-cells prepared from SH-SY5Y neuroblastoma cell line. Cellular respiration, oxidative stress, mitochondrial membrane potential and morphology were evaluated employing oxygraph, mitochondria-specific fluorescence staining and evaluation by FACS, and immunocytochemistry...

Endometriosis, the hormone-dependent extrauterine dissemination of endometrial tissue outside the uterus, affects 5-15% of women of reproductive age. Pathogenesis remains poorly understood as well as the estrogen production by endometriotic tissue yielding autocrine growth. Estrogens (E2) are normally produced by the ovaries. We investigated whether aberrant "ovarian-like" differentiation occurred in endometriosis. 69 women, with (n = 38) and without (n = 31) histologically proven endometriosis were recruited...

BACKGROUND: Omentin is related with metabolic syndrome and obesity. Pancreatic adenocarcinoma (PA) is a lethal and obesity-linked malignancy. This study was conducted to investigate the serum levels of omentin in patients with PA and the relationship with tumor progression and known prognostic parameters. MATERIAL AND METHODS: Serum samples were obtained from thirty-three patients on first admission before any treatment. Age, sex and body mass index (BMI) matched 30 healthy controls were included in the analysis...

Glatiramer acetate (GA; Copaxone) is a random copolymer of glutamic acid, lysine, alanine, and tyrosine used for the treatment of patients with multiple sclerosis (MS). Its mechanism of action has not been already fully elucidated, but it seems that GA has an immune-modulatory effect and neuro-protective properties. Lymphocyte mitochondrial dysfunction underlines the onset of several autoimmune disorders. In MS first diagnosis patients, CD4(+), the main T cell subset involved in the pathogenesis of MS, undergo a metabolic reprogramming that consist in the up-regulation of glycolysis and in the down-regulation of oxidative phosphorylation...

Symptoms of early hepatocellular carcinoma (HCC) often go unnoticed, so more than half of patients with primary HCC are diagnosed after their disease has already reached an intermediate or advanced stage, or after portal hypertension has appeared. While hepatic resection is widely recognized as a first-line therapy to treat very early or early HCC, its use in treating intermediate or advanced HCC or HCC involving portal hypertension remains controversial. Here we review PubMed-indexed literature covering the use of hepatic resection for such patients...

Photobiomodulation (PBM) describes the use of red or near-infrared light to stimulate, heal, regenerate, and protect tissue that has either been injured, is degenerating, or else is at risk of dying. One of the organ systems of the human body that is most necessary to life, and whose optimum functioning is most worried about by humankind in general, is the brain. The brain suffers from many different disorders that can be classified into three broad groupings: traumatic events (stroke, traumatic brain injury, and global ischemia), degenerative diseases (dementia, Alzheimer's and Parkinson's), and psychiatric disorders (depression, anxiety, post traumatic stress disorder)...