Journal of Nature and Science

BACKGROUND: Stroke is one of the leading causes of death and disability worldwide. As a consequence, several excellent rodent models have been developed to gain insight into the pathophysiology of stroke and testing the efficacy of neuroprotective interventions. However, one potential problem is that albeit roughly 80% of strokes occur in awake patients, all existing murine stroke models employ anesthesia. Moreover, epidemiological studies have shown that stroke injury is more severe in the minority of patients that suffer stroke while asleep...

Calpains are a 15-member class of calcium activated nonlysosomal neutral proteases which are involved in a broad range of cellular function. Calpains are usually localized to the cytosol and within mitochondria. Calpastatin is an endogenous protein that specifically binds to and inhibits calpain. Overactivation of calpain has been implicated in a number of disease processes of the brain, eyes, heart, lungs, pancreas, kidneys, vascular system and skeletal muscle. Therefore, calpain may serve as a potential therapeutic target for a wide variety of disease processes...

Chronic Fatigue Syndrome (CFS) is a debilitating disease characterized by physical and mental exhaustion. The underlying pathogenesis is unknown, but impairments in certain mitochondrial functions have been found in some CFS patients. To thoroughly reveal mitochondrial deficiencies in CFS patients, here we examine the key aspects of mitochondrial function in blood cells from a paired CFS patient-control series. Surprisingly, we discover that in patients the ATP levels are higher and mitochondrial cristae are more condensed compared to their paired controls, while the mitochondrial crista length, mitochondrial size, shape, density, membrane potential, and enzymatic activities of the complexes in the electron transport chain remain intact...

Cardiovascular disease is the number one cause of death worldwide. A powerful strategy for cardioprotection would be to identify specific molecules or targets that mimic ischemic preconditioning (IP), where short non-lethal episodes of ischemia and reperfusion prior to myocardial infarction result in dramatic reduction of infarct sizes. Since 1960 researchers believed that adenosine has a strong cardio-protective potential. In fact, with the discovery of cardiac IP in 1986 by Murry et al., adenosine was the first identified molecule that was used in studying the underlying mechanism of IP...

Probing of biomolecular complexes by single-molecule force spectroscopy (SMFS) methods including AFM requires proper and suitable coupling methods for immobilization of biomolecules onto the AFM tip and the surface. The use of flexible tethers for the coupling process has dual advantages. First, they allow the specific immobilization of interacting molecules, and second, their flexibility facilitates the proper orientation of the interacting partners. Recently, we developed an approach termed Flexible Nano Array (FNA) in which interacting partners are located on the same polymeric FNA molecule separated by a flexible segment with a defined length...

OBJECTIVES: Statins partially block the production of coenzyme Q10 (CoQ10), an essential component for mitochondrial function. Reduced skeletal muscle mitochondrial oxidative capacity has been proposed to be a cause of statin myalgia and can be measured using (31)phosphorus magnetic resonance spectroscopy ((31)P-MRS). The purpose of this study is to assess the effect of CoQ10 oral supplementation on mitochondrial function in statin users using (31)P-MRS. DESIGN/SETTING: In this randomized, double-blind, placebo-controlled pilot study, 21 adults aged 47-73 were randomized to statin+placebo (n=9) or statin+CoQ10 (n=12)...

Malnutrition is prevalent in patients undergoing elective total joint arthroplasty (TJA). Malnutrition has been shown to be an independent risk factor for multiple postsurgical complications following TJA in addition to increasing postoperative mortality. In the current healthcare environment, it is important to recognize and correct modifiable risk factors preoperatively to minimize perioperative complications and improve patient outcomes. Recently, multiple studies have been published focusing on the association between malnutrition and perioperative complications following TJA...

The objective of the study was to investigate the pharmacokinetics and efficacy of 5-FU entrapped pH-sensitive liposomal nanoparticles with surface-modified anti-epidermal growth factor receptor (EGFR) antibody (pHLNps-5-FU) delivery system. Cytotoxicity of 5-FU and pHLNps-5-FU was determined in vitro against HCT-116 cells. The biodistribution and pharmacokinetic parameters of the administered 5-FU and pHLNps-5-FU as well as efficacy of 5-FU and pHLNps-5-FU were determined in HCT-116 subcutaneous mouse model...

Prostate cancer is the most common non-skin cancer in men. Those with local or regional disease often have good long-term prognosis, but patients with metastatic disease face high morbidity and mortality. The vast majority of cases with distant spread have some degree of bony involvement. The reason for the disproportionately high percentage of metastasis to bone relative to other metastatic sites remains unclear. A growing body of evidence suggests mitochondrial DNA (mtDNA) is associated with prostate cancer, and the effects of mtDNA on tumor growth may be augmented by the bone microenvironment...

INTRODUCTION: Ventricular tachycardia and ventricular fibrillation are the two most dangerous arrhythmias. Both are related to reentrant electrical activity in the ventricles. Many studies of arrhythmias consider a homogeneous sheet of cardiac tissue. Since normal ventricular myocardium is inhomogeneous and inhomogeneities play an important role in the induction of reentry, we investigate the effect of a localized inhomogeniety developed at the border between normal and ischemic region...

We previously identified a human monoclonal antibody, termed HIgM12 that stimulates spontaneous locomotor activity in a chronically demyelinating mouse model of multiple sclerosis. When tested as a molecular substrate, HIgM12 stimulated neurite outgrowth in vitro. We recently reported that polysialic acid (PSA) attached to the neural cell adhesion molecule (NCAM) is one of the cellular antigens for HIgM12. Fluorescent double-labeling of astrocytes using HIgM12 and commercially available anti-PSA antibody showed dramatic co-localization...

OBJECTIVES: Abdominal aortic aneurysms (AAA) that rupture have a high mortality rate. Rupture occurs when local mechanical stress exceeds the local mechanical strength of an AAA, so stress profiles such as those from finite element analysis (FEA) are useful. The role and effect of surrounding tissues, like the vertebral column, which have not been extensively studied, are examined in this paper. METHODS: Longitudinal CT scans from ten patients with AAAs were studied to see the effect of surrounding tissues on AAAs...

OBJECTIVE: Elevated systemic stress is a predictor of adverse health outcomes, and stress can be objectively quantified by cortisol concentration. Despite its utility, such testing is rarely performed in otolaryngology. This manuscript provides details on the principles, methodology, and feasibility of performing laboratory assessments of hair and salivary cortisol to inform researchers wishing to incorporate these novel tests in future otolaryngologic studies. METHODS: Participants were older adults with hearing impairment...

OBJECTIVE: Minimal definitive literature identifies patients with radicular pain who would benefit most from epidural steroid injection (ESI). This study investigated if electromyographic (EMG) confirmation of radiculopathy with active or chronic denervation predicts a positive treatment outcome following ESI. DESIGN: Longitudinal cohort study of adults who underwent EMG and subsequent transforaminal ESI within 6 months. The proportion of individuals who experienced >50% pain relief and mean change in daily morphine equivalents (DME) were calculated...

According to the 'amyloid cascade hypothesis of Alzheimer's disease' first proposed about 16 years ago, the accumulation of Aβ peptides in the human central nervous system (CNS) is the primary influence driving Alzheimer's disease (AD) pathogenesis, and Aβ peptide accretion is the result of an imbalance between Aβ peptide production and clearance. In the last 18 months multiple laboratories have reported two particularly important observations: (i) that because the microbes of the human microbiome naturally secrete large amounts of amyloid, lipopolysaccharides (LPS) and other related pro-inflammatory pathogenic signals, these may contribute to both the systemic and CNS amyloid burden in aging humans; and (ii) that the clearance of Aβ peptides appears to be intrinsically impaired by deficits in the microglial plasma-membrane enriched triggering receptor expressed in microglial/myeloid-2 cells (TREM2)...

The death of immune cells in response to pathogens often dictates the outcome of an infection. In some contexts, pathogens specifically kill immune cells by producing highly potent toxins or by triggering host cell death pathways, thus ensuring successful infections. But for intracellular pathogens and viruses, the death of host cells normally is disastrous for their intracellular life cycle. Our recent experiments with the pathogen Legionella pneumophila revealed that the bacterial ribosomal protein RpsL is able to trigger lysosomal membrane permeabilization (LMP) and the subsequent macrophage cell death...

The two-component regulatory system, WalR/WalK is necessary for growth of different gram-positive bacteria, including Staphylococcus aureus. In present study, we confirmed the essentiality of both the histidine kinase protein WalK and the response regulator WalR for growth using S. aureus RN4220 strain and demonstrated that the histidine kinase protein WalK and the response regulator WalR function differently in regulation of staphylococcal autolysis. The down-regulation of walR expression effectively inhibited Triton X-100-induced lysis and had a weak impact on bacterial tolerance to penicillin induced cell lysis...

OBJECTIVES: This study evaluated the effect of incorporating increasing concentrations of sodium fluoride in incubation media, on the loss of dry mass and solubilization of collagen from demineralized dentin beams incubated for up to 7 days. The effect of fluoride on the inhibition of matrix-bound metalloproteinases (MMPs) was also measured. METHODS: Dentin beams were completely demineralized in 10% phosphoric acid. After baseline measurements of dry mass, the beams were divided into six groups (n=10) and incubated at 37°C either in buffered media containing sodium fluoride (NaF) at 75, 150, 300, 450, 600 ppm or in fluoride-free media (control) for seven days...

OBJECTIVE: Progressive myopia in humans and lid-sutured myopia in primates have been considered to be different processes. This report seeks to establish the connection between progressive myopia in humans and lid suture myopia in macaque monkeys. METHODS: We followed the axial length of 4 lid-sutured macaque monkeys over an 18 month period. Their axial length is directly related to myopia. We also studied the myopia progression in corrected human subjects. Macaques and humans exhibit a linear time course of myopia progression when lid-sutured or corrected with lenses, respectively...

In this short review, Puyang and her colleagues compared the results from three laboratories on the dendritic and functional degeneration of retinal ganglion cells (RGCs) in mouse models of experimental glaucoma [1-4]. Acute or chronic ocular hypertension was induced in mice, and different techniques were applied to identify RGC types. The dendritic alternations of RGCs were examined following the induction of ocular hypertension, and their light response properties were characterized by the multi-electrode array (MEA) recording...