Protective effect of chitosan treatment against acetaminophen-induced hepatotoxicity

Acetaminophen (APAP) is the most commonly reported toxic ingestion in the world. Severe liver injury resulting from overdose or chronic use of APAP remains a significant clinical problem. In recent years, the mechanisms underlying liver injury caused by APAP have become much better understood. We have studied the protective effect of chitosan supplementation against APAP-induced hepatotoxicity with respect to changes in the levels of total and lipid-bound sialic acid in the serum and in the liver tissue and changes in the activity of diagnostic marker enzymes, lipid peroxidation, and ceruloplasmin oxidase enzyme in normal and experimental groups of rats. During the experimental period, chitosan (200 mg/kg body weight per day) was administered to APAP + chitosan-treated rats by oral gavage. Results showed that treatment with APAP induced a significant increase in the serum alanine aminotransferase and alkaline phosphatase activities, in total and lipid-bound sialic acids levels, and in the liver lipid peroxide content. The administration of chitosan significantly prevented APAP-induced alterations in the levels of diagnostic marker enzymes, total sialic acid, lipid-bound sialic acid, and malondialdehyde in the experimental groups of rats. Furthermore, chitosan administration increased the activity of ceruloplasmin oxidase. In conclusion, our results suggest that chitosan has a protective effect on APAP-induced hepatic injury in rats. The study sheds light on the therapeutic potential of chitosan in an APAP-induced hepatotoxicity model.     

Phenotypic and functional maturation of murine dendritic cells induced by 18 alpha- and beta-glycyrrhetinic acid

Various studies have described glycyrrhizin (GL), an active triterpenoic saponin extract of licorice roots, as an anti-inflammatory, antiviral, antimicrobial, anti-tumor and immunomodulating agent. The activity of GL has been mainly attributed to its metabolites, 18-alpha (GA) and 18-beta-glycyrrhetinic acid (GB), which their mechanism of action on the immune system cells is not clearly known. In this study, we have investigated the effects of GA and GB on the immune system by targeting dendritic cells and analyzing phenotypic and functional maturity of murine dendritic cells (DCs) after treatment with these components. Stimulation of DCs with GA and GB resulted in up-regulation of CD40, CD86 and MHC-II molecules indicating their effects on the maturation of DCs. These components induced the allogenic immunostimulatory capacity of DCs by stimulating the proliferation of T cells and production of the T helper (h)1-promoting cytokine, IL-12. They also increased the production of IFN-γ by T cells in mixed-lymphocyte reaction. In conclusion, these results indicate that GA and GB may insert their immunomodulatory effects by enhancing DC maturation and modulating Th1/Th2 response through an increase in Th1 responses, implying their beneficial in host defense against infectious diseases.     

Tolerogenic dendritic cells produced by lentiviral‐mediated CD40‐ and interleukin‐23p19‐specific shRNA can ameliorate experimental autoimmune encephalomyelitis by suppressing T helper type 17 cells

Down‐regulation of soluble or membrane‐bound co‐stimulatory molecules by RNAi in dendritic cells can prevent the activation of immune responses. Therefore, this study was designed to evaluate the therapeutic efficacy of bone marrow‐derived DCs (BMDCs) transduced with lentiviral vectors to permanently expressed shRNA specific for CD40 (CD40LV‐DCs) and/or p19 subunit of interleukin (IL)‐23 (p19LV‐DCs) mRNAs in experimental autoimmune encephalomyelitis (EAE). In‐vitro studies showed that double‐transduced BMDCs (CD40⁺p19LV‐DCs) resemble tolerogenic DCs due to profound down‐regulation of CD40, lower expression of proinflammatory cytokines (IL‐6 and IL‐12), increased IL‐10 production and stronger stimulation of myelin oligodendrocyte glycoprotein (MOG)_35–55‐specific T cells for production of IL‐10 compared with CD40LV‐DCs, p19LV‐DCs and BMDCs transduced with control lentiviral vector (CoLV‐DCs). Moreover, injection of transduced CD40⁺p19LV‐ BMDCs in EAE mice resulted in more reduction in clinical score, significant reduction in IL‐17 or increased production of IL‐10 by mononuclear cells derived from the lymph nodes or spinal cord compared with CoLV‐DCs‐treated EAE mice. In conclusion, simultaneous knock‐down of CD40 and IL‐23 production by BMDCs may represent a promising therapeutic tool for the treatment of IL‐17‐dependent autoimmune diseases, including multiple sclerosis.     

Diabetes mellitus, myocardial reperfusion, and outcome in patients with acute ST-elevation myocardial infarction treated with primary angioplasty (from HORIZONS AMI)

Diabetes mellitus (DM) increases mortality in acute ST-segment elevation myocardial infarction (STEMI) but the responsible mechanism is not fully elucidated. We compared the rate of successful myocardial reperfusion measured by tissue myocardial perfusion grade (TMPG) and outcomes in patients with and without DM undergoing primary percutaneous coronary intervention (PCI) for STEMI. Patients enrolled in the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS AMI) trial were analyzed according to presence of DM with respect to TMPG after PCI and outcomes at 30 days and 3 years. Multivariable logistic regression was performed to identify the independent contribution to mortality of DM and TMPG and the interaction between the 2 was assessed. Complete data were available for 3,265 patients, of whom 533 (16.3%) had DM. Diabetic patients were significantly older and heavier and had more risk factors for coronary disease and more previous MI, revascularization, and heart failure. There were no differences in rates of Thrombolysis In Myocardial Infarction grade 3 flow after PCI in the infarct artery or TMPG 2/3 between patients with and without DM. Compared to nondiabetics, mortality was significantly higher at 30 days and at 3 years in the DM group (1.8% vs 4.5%, p = 0.0002 and 5.4% vs 11.0%, p <0.0001, respectively). DM and TMPG were significantly associated with 3-year mortality, but there was no statistical interaction between DM and TMPG (p = 0.70). In conclusion, DM is associated with a significantly higher risk of death but this association is not mediated by impaired epicardial or myocardial reperfusion.     

Brain Inconspicuous Effect by Local Sinusoidal Extremely Low Frequency Magnetic Exposure Based on Wavelet Packet Analysis: Innovation in Online Passive Neurofeedback Therapy by the Neuro-LSELF System

Neurofeedback (NF) is a training approach that aims to reinforce brain activity by using the information of human electroencephalogram (EEG) rhythms as a feedback. In addition, some studies have reported Extremely Low Frequency (0–300 Hz, intensity < 500 µT) Magnetic Field (ELF MF) effects upon the EEG and its rhythms. The purpose of this study is to determine if an approach that combines the effects of Local Sinusoidal Extremely Low Frequency Magnetic Fields (LSELF MF) with NF yields higher performance on desired NF goals. The NF protocol used in this study consisted of enhancement of the beta rhythm and inhibition of theta and high beta rhythms in exposed and sham groups for the purpose of improving attention. Twenty-four healthy subjects of at least average intelligence attended 10 sessions of NF training. Sixteen of them were exposed to 45 Hz sinusoidal ELF (360 µT) at F3 to lead to the desired LSELF MF effects on Cz. Wavelet packet analysis was used for the detection of changes in EEG rhythms. Results suggest that, compared to sham exposure, LSELF magnetic waves can significantly affect and modulate brainwaves according to this new neurofeedback approach. In comparison to sham exposure, improved ability to attend (as measured by a decrease in the theta-to-beta ratio) was observed when LSELF MF was combined with NF (p < .05). The hypothesis that LSELF MF can affect the theta-to-beta ratio was confirmed. These effects occurred after approximately 10 min of each NF procedure. This study aimed to pilot a new NF system known as the Neuro-ELF system, a method that may allow for more effective control of brainwave activity. However, we suggest that the effects of LSELF-NF require further research.