Abstract

It is still an open question as to whether or not aseptic injuries affect the generation of fever due to exogenous pyrogens including bacterial products. Therefore, in the present paper we have investigated the course of endotoxin fever in rats induced with lipopolysaccharide (LPS; given intraperitoneally in a dose of 50?μg/kg) 48?h after subcutaneous administration of turpentine oil (TRP; 0.1?mL per rat) that causes aseptic necrosis of tissues. We found that febrile response was significantly augmented in the animals pre-treated with turpentine compared to control rats (pre-treated with saline), and that observed excessive elevation of body temperature (Tb) was accompanied by enhanced release of fever mediators: interleukin-6 (IL-6) and prostaglandin E2 (PGE2) into plasma. Moreover, we found that sensitization to pyrogenic effects of lipopolysaccharide was associated with the increase in plasma level of high mobility group box 1 protein (HMGB1), one of the best-known damage-associated molecular patterns (DAMP), which was recently discovered as inflammatory mediator. Since the injection of anti-HMGB1 antibodies weakened observed hyperpyrexia in the animals pre-treated with turpentine, we conclude that HMGB1 is a plasma-derived factor released in the course of aseptic injury that enhances pyrogenic effects of LPS.

Abstract

Type 1 diabetes (T1D) is a chronic metabolic disease of unknown etiology that results from β-cell destruction. The onset of the disease, which arises after a long asymptomatic period of autoimmune attack, may be followed by a relapsing and remitting progression, a phenomenon that is most evident during the partial remission phase (PR). This stage lasts for a few months, shows minor requirements of exogenous insulin and could be explained by a recovery of immunological tolerance. This study aims to identify new biomarkers at early stages of pediatric T1D that reflect immunoregulatory changes. To that end, pediatric patients with T1D (n?=?52) and age-related control subjects (n?=?30) were recruited. Immune response-related molecules and lymphocyte subsets were determined starting at T1D onset and until the second year of progression. Results showed that circulating TGF-β levels decreased during PR, and that betatrophin concentration was increased in all the considered stages without differing among studied checkpoints. Moreover, an increase of regulatory T, B and NK subsets was found during T1D progression, probably reflecting an attempt to restore self-tolerance. By contrast, a reduction in monocyte levels was observed at the early stages of diabetes. The results reveal significant changes in immunological parameters during the different early stages of T1D in children, which could ultimately serve as potential biomarkers to characterize the progression of T1D.

Abstract

N-acetylcysteine (NAC) has largely been used as an effective chemo- protective agent owing to their beneficial effect in restoring several physiological parameters and relieving oxidative stress. Interestingly, it has been suggested that NAC mechanisms of action extend beyond being a precursor to the antioxidant glutathione and that they may involve several neurotropic and inflammatory pathways. Exposure to fenitrothion, an organophosphorus insecticide, promotes oxidative stress and induces several deleterious changes in the immune response and various tissues including cerebrum and spleen. The main objective of our study was to investigate ameliorative efficacy of N-acetylcysteine for immunological and neurological alterations and oxidative DNA damage induced by fenitrothion toxicity in cerebrum and spleen tissues of male rats. Our results revealed that oral exposure to fenitrothion for 30?days caused a reduction in the erythrocyte count in addition to leukocytosis, lymphocytosis, and neutrophilia. Also, this route of administration increased the serum levels of LDH, TNF-α, and IL-2 with reduction in serum immunoglobulins (IgG & IgM) concentrations. Furthermore, a significant downregulation in the antioxidant markers (GSH & SOD) with an elevation of free radical (MDA) levels were noticed. Regarding the brain, fenitrothion administration inhibited AchE activity and increased brain GABA, serotonin and dopamine levels. Moreover, it induced an elevation in oxidative DNA damage indicated by 8-hydroxy 2-deoxyguanosine (8OH2dG) and mRNA expression of pro-apoptotic genes, including Bax, and p53, but Bcl-2 expression was reduced. N-acetylcysteine co-treatment restored the normal physiological tone in most of these parameters. Immunostaining for GFAP and Caspase-3 markers in the brain and spleen tissues were increased respectively. In conclusion, N-acetylcysteine supplementation has an ameliorative effect against immunotoxic, neurotoxic and oxidative DNA damage induced by fenitrothion exposure.

Abstract
Chronic obstructive pulmonary disease (COPD) is associated with abnormal inflammation and high oxidative stress. Studies suggest that reactive oxygen species modulator 1 (Romo1) involve in diseases associated with oxidative stress and inflammation. However, the relationship between COPD and Romo1 is still not clear. In this study, we compared serum Romo1 in 49 COPD patients and 34 health controls, and their correlation with lung function, systematic inflammation, and oxidative stress. In addition, serum levels of Romo1, C-reactive protein (CRP), and oxidative stress (measured by reactive oxygen species, ROS) were analyzed using commercial kits. Serum Romo1 was significantly higher in COPD patients than that of control (132.24 ± 10.34 vs. 93.26 ± 7.75 pg/ml, P < 0.05). Serum CRP and ROS were also significantly higher in COPD patients. Serum Romo1 was correlated inversely with FEV1% predicted in COPD patients (? = − 0.347, ? = 0.016), while it was correlated positively with CRP and ROS levels, respectively. These results suggest that serum Romo1 increase in COPD patients and that these levels are associated with lung function, inflammation, and oxidative stress in COPD.

Abstract
Introduction
Matrix metalloproteinases (MMP’s) and tribbles 3 human homolog (Trb3) are implicated in atherosclerosis. Changes in the concentration of these biomolecules signal the risk of atherosclerosis in type 2 subjects (T2DM), with or without hypertension (HT), at an early stage.

Aim
Our aim was to assess the relation between noninvasive arterial stiffness indices and circulating levels of MMP2, MMP9 and Trb3.

Methodology
The study included 144 participants divided into 4 groups: T2DM > 5 years + HT, DM + HT (n = 55), T2DM < 2 years, DM (n = 28), HT (n = 31), and healthy controls (HC) (n = 30). Anthropometric measurements and blood biochemistry profiles were established using standard protocols. MMP2, MMP9 and Trb3 were estimated using ELISA. Pulse wave velocities (PWV) and arterial stiffness indices (ASI) were measured using PeriScopeTM. Results were analysed using SPSS 21.

Results
MMP2, average Brachial Stiffness Index (ba ASI) (Pearson’s r = 0.235, p = 0.005) and Ankle-Brachial Index (ABI) (Pearson’s r = 0.225, p = 0.007) were positively correlated. Average Ankle ASI (Ank ASI) was positively correlated to Trb3 (Pearson’s r = 0.184, p = 0.028), but negatively to MMP9 (Pearson’s r = − 0.184, p = 0.027). In multiple linear regression, MMP2 influenced ba ASI [adjusted R2 = 0.038; F (3) = 2.862, p = 0.039] and ABI [adjusted R2 = 0.033; F (3) = 2.642, p = 0.052]. MMP9 influenced Ank ASI [adjusted R2 = 0.058; F (3) = 3.912, p = 0.01].

Conclusion
Arterial stiffness indices and matrix metalloproteinases conform early risk of atherosclerosis in diabetic subjects.