Effects of the degree of deacetylation on the physicochemical properties and Schwann cell affinity of chitosan films

Chitosan is a potential material for the preparation of nerve repair conduits. In order to find a better chitosan for the application in peripheral nerve regeneration, the effects of the degree of deacetylation (DD) on the physicochemical properties and Schwann cell affinity of chitosan films have been evaluated. Six kinds of chitosan samples with similar molecular weight, but various DD in a range from 70.1 to 95.6% were prepared from one stock chitosan material and fabricated into films. X-ray diffraction analysis showed that there were more crystalline regions in the higher DD chitosan films. Swelling and mechanical property measurements revealed that the swelling index of chitosan films decreased and their elastic modulus and tensile strength increased with the increase in DD. The adsorption amount of fibronectin and laminin on chitosan films was measured by means of enzyme-linked immunosorbent assay (ELISA). Culture of adult rat Schwann cells on the films showed that the chitosan films with higher DD provided better substrata for Schwann cell spreading and proliferation. In conclusion, DD of chitosan plays an important role in their physicochemical properties and affinity with Schwann cells. The results suggest that chitosan with a DD higher than 90% is considered as a promising material for application in peripheral nerve regeneration.     

γ型干扰素、CD4+CD25+调节性T细胞与自身免疫病

γ型干扰素在适应性免疫应答中起重要作用.在MHC-Ⅱ类分子限制性自身免疫病中,T细胞反应主要以1型辅助性T细胞(Th1)为主,并伴有IFN-γ水平增高,而剔除小鼠胸腺来源的CD4 CD25 调节性T细胞则导致自身免疫病的发生,有研究认为调节性T细胞在诱导免疫耐受产生的过程中起关键性作用.IFN-γ及其受体缺陷小鼠的CD4 CD25 调节性T细胞的免疫抑制能力明显受损,这表明IFN-γ及其受体在CD4 CD25 调节性T细胞免疫调节作用中以及在自身免疫病发生中可能发挥重要而复杂的免疫调节作用.本文仅就IFN-γ与调节性T细胞及自身免疫病发病三者之间关系的研究进展进行简要综述.     

The antibody response to Epstein–Barr virions is altered in multiple sclerosis

Infection with Epstein–Barr virus (EBV) is associated with multiple sclerosis (MS), and patients with MS have an increased antibody response to some EBV antigens. The major antigens of EBV are only partly defined. Our hypothesis is that the antibody response to EBV is altered in MS. With ELISA, we found that antibodies to EB virions were increased in both serum and CSF of MS patients. Western blots demonstrated that there are multiple different antigens recognized. The antibody response was generally higher in MS to all EBV antigens, with particularly significant increases for certain antigens. We conclude that the antibody response to EBV in MS is generally increased with altered specificity.     

Reactive oxygen at the heart of metabolism

During heart development, the progression from a pluripotent, undifferentiated embryonic stem cell to a functional cardiomyocyte in the adult mammalian heart is characterised by profound changes in gene expression, cell structure, proliferative capacity and metabolism. Whilst the precise causal relationships between these processes are not fully understood, it is clear that the availability and cellular ability to utilise oxygen are critical effectors of cardiomyocyte differentiation and function during development. In particular, cardiomyocytes switch from a largely glycolytic-based production of ATP to predominantly β-oxidation of long-chain fatty acids to generate the cellular energy requirements. Whilst this transition occurs progressively during embryonic and foetal development, it is particularly abrupt over the period of birth. In the adult heart, many cardiopathologies are accompanied by a reversal to a more foetal-like metabolic profile. Understanding the mechanistic causes and consequences of the normal metabolic changes that occur during heart development and those in the pathological heart setting is crucial to inform future potential therapeutic interventions. It is becoming clear that reactive oxygen species (ROS) play critical roles in the regulation of redox-mediated molecular mechanisms that control cellular homoeostasis and function. ROS are generated as a consequence of metabolic processes in aerobic organisms. An overproduction of ROS, when not balanced by the cell's antioxidant defence mechanisms (termed “oxidative stress”), results in non-specific oxidation of proteins, lipids and DNA and is cytotoxic. However, the tightly regulated temporal and spatial production of ROS such as H₂O₂ acts to control the activity of proteins through specific post-translational oxidative modifications and is crucial to cellular function. We describe here the metabolic changes that occur in the developing heart and how they can revert in cardiopathologies. They are discussed in the light of what is currently known about the regulation of these processes by changes in the cellular redox state and levels of ROS production.     

Regulatory CD4+CD25+ T-cells are Controlled by Multiple Pathways at Multiple Levels

CD4⁺CD25⁺ regulatory T-cells (Treg cells) are an important subset of T-cells that functions to negatively control immune responses to self or non-self antigens. Depletion of CD4⁺CD25⁺ Treg cells leads to the occurrence of lymphoproliferative autoimmune diseases in animals and humans. Therefore, CD4⁺CD25⁺ Treg cells must be tightly regulated in the physiologic situation. In this article, we try to summarize the regulating pathways of the development, survival, and function of CD4⁺CD25⁺ Treg cells at multiple levels and multiple pathways, including the dendritic cells, costimulatory signals, cytokines, as well as intracellular signals.     

Screening of APP interaction proteins by DUALmembrane yeast two-hybrid system

Alzheimer’s disease (AD) is one of the most common forms of neurodegenerative disease. There is a growing interest in the amyloid precursor protein (APP) over the years due to its involvement in AD. Besides its role in pathological mechanisms of AD, APP participates in many signaling pathways as well. APP functions through protein-protein interactions, and in this report staufen 1 (STAU1) is demonstrated to have interaction with APP, using yeast two-hybrid screening and co-immunoprecipitation in mammalian system. STAU1 belongs to the double-stranded RNA binding protein family and can mediate mRNA degradation in mammalian system, implicating that APP may be involved in the regulation of mRNA as well.     

Microgravity inhibition of lipopolysaccharide-induced tumor necrosis factor-α expression in macrophage cells

Objective and design

Microgravity environments in space can cause major abnormalities in human physiology, including decreased immunity. The underlying mechanisms of microgravity-induced inflammatory defects in macrophages are unclear.

Material or subjects

RAW264.7 cells and primary mouse macrophages were used in the present study. Lipopolysaccharide (LPS)-induced cytokine expression in mouse macrophages was detected under either simulated microgravity or 1g control.

Methods

Freshly isolated primary mouse macrophages and RAW264.7 cells were cultured in a standard simulated microgravity situation using a rotary cell culture system (RCCS-1) and 1g control conditions. The cytokine expression was determined by real-time PCR and ELISA assays. Western blots were used to investigate the related intracellular signals.

Results

LPS-induced tumor necrosis factor-α (TNF-α) expression, but not interleukin-1β expression, in mouse macrophages was significantly suppressed under simulated microgravity. The molecular mechanism studies showed that LPS-induced intracellular signal transduction including phosphorylation of IKK and JNK and nuclear translocation of NF-κB in macrophages was identical under normal gravity and simulated microgravity. Furthermore, TNF-α mRNA stability did not decrease under simulated microgravity. Finally, we found that heat shock factor-1 (HSF1), a known repressor of TNF-α promoter, was markedly activated under simulated microgravity.

Conclusions

Short-term treatment with microgravity caused significantly decreased TNF-α production. Microgravity-activated HSF1 may contribute to the decreased TNF-α expression in macrophages directly caused by microgravity, while the LPS-induced NF-κB pathway is resistant to microgravity.     

Superoxide flashes: elemental events of mitochondrial ROS signaling in the heart

The role of mitochondrial reactive oxygen species (mitoROS) in cellular function remains obscure. By synthesizing recent data, we propose here that local dynamic mitoROS in the form of "superoxide flashes" serve as "signaling ROS" rather than "homeostatic ROS", distinguishable from basal mitoROS due to constitutive leakage of the electron transfer chain (ETC). Individual superoxide flashes are 10-s mitoROS bursts that are compartmentalized to a single mitochondrion or local mitochondrial networks. As a highly-conserved universal mitochondrial activity, it occurs in intact cells, in ex vivo beating hearts, and even in living animals. Unlike basal mitoROS, superoxide flashes are ignited by transient openings of a type of mitochondrial permeability transition pore (mPTP), and their incidence is richly regulated by an array of factors that converge on either the mPTP or ETC. Emerging evidence has shown that superoxide flashes decode dietary and metabolic status or exercise, gauge oxidative stress (e.g., during reoxygenation after hypoxia or anoxia), and constitute early mitochondrial signals that initiate oxidative stress-related apoptosis in a context-dependent manner. That they make only a miniscule contribution to global ROS attests to the high efficiency of local ROS signaling. However, the exact mechanisms underlying superoxide flash formation, regulation and function remain uncertain. Future investigation is warranted to uncover the cellular logic and molecular pathways of local dynamic mitoROS signaling in heart muscle cells and many other cell types.     

Null genotype of glutathione S-transferase Tl contributes to colorectal cancer risk in the Asian population: a meta-analysis

Background and Aim: Previous studies investigating the association between the glutathione S‐transferase Tl (GSTT1) null genotype and colorectal cancer (CRC) risk in the Asian population have reported controversial results. Thus, a meta‐analysis was performed to clarify the effect of the GSTT1 null genotype on CRC risk in the Asian population. Methods: A comprehensive study was conducted, and 12 case‐control studies were finally included, involving a total of 4517 CRC cases and 6607 controls. Subgroup analyses were performed by the sample size. Results: A meta‐analysis of all 12 studies showed that the GSTT1 null genotype was significantly associated with an increased CRC risk in the Asian population (odds ratio [OR] = 1.10, 95% confidence interval [CI] = 1.02–1.19, the P‐value of the OR [P_OR] = 0.02, the value of the heterogeneity analysis [I²] = 42%). A more obvious association was observed after the heterogeneity was eliminated by excluding one study (OR = 1.15, 95% CI: 1.06–1.25, P_OR = 0.001, I² = 0%). This association was further identified by both subgroup analyses and a sensitivity analysis. Conclusions: This meta‐analysis suggests that the GSTT1 null genotype contributes to an increased colorectal cancer risk in the Asian population.