Articles in Press

Welcome to Annals of Biomedical Research

Volume 1 Issue 2

Inflammatory vs. Thrombotic States of Platelets: A Mini-review with a Focus on Functional Dichotomy

Seki R, Nishizawa K
Mini Review: ABR-1-107

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Abstract
In addition to roles in hemostasis and thrombosis, the role of platelets in inflammation and immunity have been the focus of recent studies. Both proinflammatory and prothrombotic roles of platelets are considered important in the pathophysiology of sepsis as well as in the protection from severe infections. The facilitation of prothrombotic activity by the proinflammatory activity of platelets has been shown in many studies. Nonetheless, some studies have highlighted the dichotomy of platelet functionality. Within a limited time period and space, only proinflammatory or prothrombotic functionality is often present. In some cases, the activation of the proinflammatory function of platelets is not accompanied by prothrombotic activity. Recent analyses of pattern recognition receptors such as toll-like receptors (TLRs) in platelets motivate us to consider how pathways are activated in innate immunity compared with pathways for thrombogenesis and hemostasis. In this article, we mainly discuss recent studies showing the functional dichotomy of platelets and, in particular, the conditions and possible mechanisms that activate platelets in a biased manner, rather than the concordance between prothrombotic and proinflammatory pathways in platelets.

Acinar Tight Junctions are Altered in an Early Phase of Acute Edematous Pancreatitis in a Rat Pancreatic Duct Ligation Model

Ogata S, Tsuwano S, Tamai S, Nakanishi K
Research Article: ABR-1-108

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Abstract
Background: Although trypsin autoactivation in acinar cells is considered to be an initial event in acute human pancreatitis, mild pancreatitis with/without trypsin autoactivation is common in human acute pancreatitis, and interstitial edema is one of its characteristic features. Methods: To elucidate the mechanism underlying such interstitial edema in acute edematous pancreatitis, we examined the condition of intercellular junction complexes between acinar cells in the initial phase of pancreatitis in a rat pancreatic duct ligation model. For this experiment, serum and pancreatic tissues were obtained at 30, 60, 120, and 180 mins after duct ligation and compared biochemically, morphologically, and immunofluorescently with samples from control or sham-operated rats. Results: In the present experiments, both the tissue water content and the serum amylase values were elevated only in the group 180 min after duct ligation. Tissue trypsin values revealed no significant changes, and histology did not reveal tissue necrosis. In an immunofluorescence study, acinar luminal staining for the tight junction-protein ZO-1 was significantly less distinct in both the groups 120 min and 180 min after duct ligation, although the adherens junction proteins pan-cadherin and β-catenin showed no significant changes throughout the course of the experiment. Ultrastructurally, tight junctions in both groups (120 and 180 mins) appeared leaky (not closed) more frequently than in other groups. Conclusions: Acinar tight junctions were altered in an early phase of pancreatitis in the present acute edematous pancreatitis model, and such alterations may contribute to the interstitial edema formation that is characteristic of mild pancreatitis.

Extracellular Heat Shock Proteins as a Natural Protector of Cells and Organisms: A Review of Recent Studies

Nishizawa K, Nishizawa M
Review Article: ABR-1-109

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Abstract
The heat shock protein (HSP) family consists of molecular chaperones that are evolutionary preserved from prokaryotes and mammals. The extracellular HSPs are now known to be involved in numerous processes including would healing, tissue regeneration, tumor progression and innate and adaptive immunity. In immunity, HSPs exhibit functional dichotomy in both innate and adaptive immunity, triggering or suppressing immune responses, but the majority of studies highlight their cytoprotective and immunoregulatory roles. Especially for several autoimmune diseases including rheumatic arthritis (RA) and systemic lupus erythematosus (SLE), for which specific causative self-antigens remain elusive, the therapeutic expansion of regulatory T cells specific to HSPs is considered a promising approach. In this review, we discuss several articles extracted from diverse biological and medical frontiers of extracellular HSP research.
Keywords: Xenopus; MHC class Ib; Glycosaminoglycans; Dermatan sulphate; BiP (immunoglobulin-binding protein)

C-reactive Protein Associates with Metabolic Syndrome: An Improved Conventional Assay may Fit for Purpose in Population-based Analyses

Seki R, Inoue K, Akimoto K
Research Article: ABR-1-110

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Abstract
Background and Aim: The plasma C-reactive protein (CRP) is a well-studied biomarker of infection and systemic inflammation. In large prospective studies, high-sensitivity CRP (hs-CRP) has been shown to be a useful predictor of metabolic syndrome (MetS) in healthy subjects. However, the hs-CRP-based studies of the associations between CRP and MetS-relevant metrics in East Asian populations have analyzed a limited number of subjects. Several authors have also pointed out between-institution and between-reagent kit differences of hs-CRP assays. In this study, we aim to examine associations of CRP with other MetS-related metrics in the dataset of over 34,000 Japanese adults using an improved conventional CRP assay. Methods: A cross-sectional study was conducted using the dataset of apparently healthy individuals drawn from the general Japanese population (16,040 men; 16,439 women; mean age 51 years). We divided subjects into four groups based on CRP levels: <1, 1 to <2, 2 to <3, and 3 to <9 mg/L. We used the multivariate logistic regression analysis to examine the age/sex-adjusted odds ratio of each group for the MetS-associated conditions. Results: After adjustment for age and sex, the odds ratio of MetS were significantly greater in the higher CRP groups compared to the low CRP group (<1 mg/L). Conclusions: Consistent with recent studies using hs-CRP assay, the subjects with 1 to 2 mg/L CRP showed an increased risk for MetS, reinforcing the view that CRP is an efficient independent predictor for MetS. In the light of the financial and operational merits, our data also suggests the usefulness of improved conventional CRP assays for the percentile-based studies on the risk assessment of CRP values.

Renal Dysfunction is a Common Phenotypic Feature of Kearns-Sayre Syndrome

Finsterer J, Zarrouk-Mahjoub S
Letter to the Editor: ABR-1-111

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Keywords: mtDNA deletion; Renal dysfunction; Mutation; Gene; Bartter-like syndrome

Force-field Dependency of Leu-rich Helical Peptides Dimerization Energy in Lipid Bilayers. I. United-atom Simulations Show Discrepancy from Experiments and All-atom Simulations

Nishizawa M and Nishizawa K
Research Article: ABR-1-112

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Abstract
United-atom (UA) description of aliphatic carbon-hydrogen atoms with single particles have been used in simulation analyses of protein/lipid systems. However, UA force fields (FFs) simulations have shown inaccuracy in transmembrane (TM) helical peptides dimerization dynamics within lipid membranes. For example, the self-dimerized state of a TM helical peptide (AALALAA)3 in a phospholipid bilayer is unrealistically unstable in simulations under two FFs, namely, the OPLS-all atom (AA) protein/Berger UA lipids and GROMOS 53A6 (Gr53a6) FFs, whereas AA Charmm36 (Ch36AA) FF showed a dimerization energy comparable with the experiment. Here we show that the dimer stability of a Lys-flanked poly-Leu peptide (KL22) exhibits no or little dimerization propensity with Gr53a6, but shows dimerization propensity of the free energy of −7.5 kJ/mol with Ch36AA comparable to the experiment (−8.3 kJ/mol). A peptide comprised solely of Leu (L21) showed similar FF-dependency. Although the dimer stability was fairly similar between Ch36AA and Gr53a6 for both poly-Ile and poly-Val helices, a Ch36AA>Gr53a6 stability difference was also seen for poly-Ala helices. While the UA parameters have normally been adjusted guided by the experiments with simple systems using the amino acid side chain analogues, the findings presented here highlight limited transferability of UA parameters to the settings of peptides/lipid membranes.