Immune dysregulation is a hallmark of patients infected by SARS-CoV2 and the balance between immune reactivity and tolerance is a key determinant of all stages of infection, including the excessive inflammatory state causing the acute respiratory distress syndrome. The kynurenine pathway (KP) of tryptophan (Trp) metabolism is activated by pro-inflammatory cytokines and drives mechanisms of immune tolerance. We examined the state of activation of the KP by measuring the Kyn:Trp ratio in the serum of healthy subjects (n = 239), and SARS-CoV2-negative (n = 305) and -positive patients (n = 89). Patients were recruited at the Emergency Room of St. Andrea Hospital (Rome, Italy). Kyn and Trp serum levels were assessed by HPLC/MS-MS. Compared to healthy controls, both SARS-CoV2-negative and -positive patients showed an increase in the Kyn:Trp ratio. The increase was larger in SARS-CoV2-positive patients, with a significant difference between SARS-CoV2-positive and -negative patients. In addition, the increase was more prominent in males, and positively correlated with age and severity of SARS-CoV2 infection, categorized as follows: 1 = no need for intensive care unit (ICU); 2 ≤ 3 weeks spent in ICU; 3 ≥ 3 weeks spent in ICU; and 4 = death. The highest Kyn:Trp values were found in SARS-CoV2-positive patients with severe lymphopenia. These findings suggest that the Kyn:Trp ratio reflects the level of inflammation associated with SARS-CoV2 infection, and, therefore, might represent a valuable biomarker for therapeutic intervention. 相似文献
The Andean tree Schinus areira L. has multiple traditional uses, from the treatment of bronchitis and rheumatic diseases to menstrual cycle regulation and wound healing. With reported hypotensive, analgesic, antitumoral and anti-inflammatory properties, it acts predominantly against diseases related to oxidative stress. This study focuses on the antioxidant activity and phytochemical profile of the extracts of Schinus areira L.Serial extraction of the fruits was performed both by maceration and by Soxhlet. Total phenols and flavonoids were measured using the Folin-Ciocalteu method and AlCl3, respectively. In vitro antioxidant activity was determined by FRAP and DPPH.Results were similar for both extraction methods. Primary metabolites detected included carbohydrates, proteins and amino acids; secondary metabolites included tannins, flavonoids, saponins, steroids and triterpenes. Antioxidant activity was confirmed for ethyl acetate, methanolic and aqueous extracts. The methanolic extract had both the highest polyphenol content (>195 mg GAE/ g dry weight) and the highest antioxidant activity [EC50 > 476 μg/mL; >273 mg AA/g dry weight (DPPH); >301 mg AA/ g dry weight (FRAP)]. The extract does not produce macrophage cytotoxicity in RAW 264.7, which is indicated by an average cytotoxicity of 2% over 24 h.Our study serves as a starting point for future research on the pharmacological properties of Schinus areira L. 相似文献
The influence of climate change on the ecological impacts of invasive alien species (IAS) remains understudied, with deoxygenation of aquatic environments often-overlooked as a consequence of climate change. Here, we therefore assessed how oxygen saturation affects the ecological impact of a predatory invasive fish, the Ponto-Caspian round goby (Neogobius melanostomus), relative to a co-occurring endangered European native analogue, the bullhead (Cottus gobio) experiencing decline in the presence of the IAS. In individual trials and mesocosms, we assessed the effect of high, medium and low (90%, 60% and 30%) oxygen saturation on: (1) functional responses (FRs) of the IAS and native, i.e. per capita feeding rates; (2) the impact on prey populations exerted; and (3) how combined impacts of both fishes change over invasion stages (Pre-invasion, Arrival, Replacement, Proliferation). Both species showed Type II potentially destabilising FRs, but at low oxygen saturation, the invader had a significantly higher feeding rate than the native. Relative Impact Potential, combining fish per capita effects and population abundances, revealed that low oxygen saturation exacerbates the high relative impact of the invader. The Relative Total Impact Potential (RTIP), modelling both consumer species’ impacts on prey populations in a system, was consistently higher at low oxygen saturation and especially high during invader Proliferation. In the mesocosm experiment, low oxygen lowered RTIP where both species were present, but again the IAS retained high relative impact during Replacement and Proliferation stages at low oxygen. We also found evidence of multiple predator effects, principally antagonism. We highlight the threat posed to native communities by IAS alongside climate-related stressors, but note that solutions may be available to remedy hypoxia and potentially mitigate impacts across invasion stages.
To test whether the influence of manual activity should be considered when interpreting the results of nerve conduction study (NCS) of the upper limbs performed during work shifts, we evaluated the short-term effect of 90-min repetitive manual work on NCS parameters. Twenty-eight healthy volunteers underwent NCS of the dominant limb at the end of an interview (T0), after a 30-min rest in sitting position (T1) and after performing a standardized 90-min manual task (T2). The task was designed to simulate typical assembly and packing activities. No significant differences were observed for skin temperature (Ts) and NCS parameters between T0 and T1. Significantly (p < 0.001) higher Ts mean values were found at T2 as compared to the previous tests for both females and males. The regression analysis showed an association between temperature variation and nerve conduction velocity values for the median and ulnar nerve at T2 as compared to T1. In females, a reduction of the mean sensory nerve action potential (SNAP) amplitude at T2 was recorded, whereas an opposite trend was observed among males. Manual work is able to influence hand Ts and to modify NCS parameters. SNAP amplitudes changes suggest gender differences in peripheral nerve characteristics that deserve further investigation. 相似文献
The excessive production of reactive oxygen species (ROS) associated with inflammation leads to oxidative stress, which is involved with the high mortality from several diseases such as endotoxic shock and can be controlled to a certain degree by antioxidants. The immune cells use ROS in order to support their functions and, therefore, need adequate levels of antioxidant defenses in order to avoid the harmful effect of an excessive ROS production. In the present work, the effect of the administration of the antioxidant N-acetylcysteine (NAC) on the redox state of peritoneal macrophages and lymphocytes from mice with lethal endotoxic shock (100 mg/kg i.p. of lipopolysaccharide, LPS), was studied. In both types of immune cells at 0, 2, 4, 12 and 24 h after LPS injection, an increase of ROS, of the proinflammatory cytokine tumor necrosis factor alpha (TNFα), the lipid peroxidation (malonaldehyde levels, MDA), inducible nitric oxide synthase (iNOS) expression and the oxidized/reduced glutathione (GSSG/GSH) ratio, as well as a decrease of enzymatic antioxidant defenses, such as superoxide dismutase (SOD) and catalase (CAT) activity, was observed. The injection of NAC (150 mg/kg i.p. at 30 min after LPS injection) decreased the ROS, the TNFα the MDA levels, iNOS expression and the GSSG/GSH ratio, and increased the antioxidant defenses in both macrophages and lymphocytes. Moreover, the NAC treatment prevented the activation of nuclear translocation of the nuclear factor κB (NF-κB), which regulates ROS, inflammatory cytokines and antioxidant levels. Our present results provide evidence that both cell types have a relevant role in the pathogenesis of endotoxic shock, and that NAC, by improving the redox state of these immune cells, could increase mouse survival. Thus, antioxidants could offer an alternative treatment of human endotoxic shock. 相似文献
From the aerial parts of Salsola oppositofolia, S. soda and S. tragus an alkaloid extract was obtained and tested to evaluate antioxidant and anti-cholinesterase activities. The in vitro study of the antioxidant activity by the DPPH method revealed a significant activity of Salsola alkaloid extracts with IC50 values ranging from 16.30 μg/mL for S. oppositifolia to 26.17 μg/mL for S. tragus. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities were evaluated. S. tragus alkaloid extract exerted the highest inhibitory activity against AChE (IC50 of 30.2 μg/mL) and BChE (IC50 of 26.5 μg/mL). Interestingly, S. soda and S. oppositifolia exhibited a selective inhibitory activity against BChE with IC50 values of 34.3 μg/mL and 32.7 μg/mL, respectively. Tetrahydroisoquinoline alkaloids were identified and quantified by GC/MS analysis. 相似文献
Recent genome‐wide association studies have linked type‐2 diabetes mellitus to a genomic region in chromosome 9p21 near the Ink4/Arf locus, which encodes tumor suppressors that are up‐regulated in a variety of mammalian organs during aging. However, it is unclear whether the susceptibility to type‐2 diabetes is associated with altered expression of the Ink4/Arf locus. In the present study, we investigated the role of Ink4/Arf in age‐dependent alterations of insulin and glucose homeostasis using Super‐Ink4/Arf mice which bear an extra copy of the entire Ink4/Arf locus. We find that, in contrast to age‐matched wild‐type controls, Super‐Ink4/Arf mice do not develop glucose intolerance with aging. Insulin tolerance tests demonstrated increased insulin sensitivity in Super‐Ink4/Arf compared with wild‐type mice, which was accompanied by higher activation of the insulin receptor substrate (IRS)‐PI3K‐AKT pathway in liver, skeletal muscle and heart. Glucose uptake studies in Super‐Ink4/Arf mice showed a tendency toward increased 18F‐fluorodeoxyglucose uptake in skeletal muscle compared with wild‐type mice (P =0.079). Furthermore, a positive correlation between glucose uptake and baseline glucose levels was observed in Super‐Ink4/Arf mice (P < 0.008) but not in wild‐type mice. Our studies reveal a protective role of the Ink4/Arf locus against the development of age‐dependent insulin resistance and glucose intolerance. 相似文献