Anti‐inflammatory properties of lemon‐derived extracellular vesicles are achieved through the inhibition of ERK/NF‐κB signalling pathways

Chronic inflammation is associated with the occurrence of several diseases. However, the side effects of anti‐inflammatory drugs prompt the identification of new therapeutic strategies. Plant‐derived extracellular vesicles (PDEVs) are gaining increasing interest in the scientific community for their biological properties. We isolated PDEVs from the juice of Citrus limon L. (LEVs) and characterized their flavonoid, limonoid and lipid contents through reversed‐phase high‐performance liquid chromatography coupled to electrospray ionization quadrupole time‐of‐flight mass spectrometry (RP‐HPLC–ESI‐Q‐TOF‐MS). To investigate whether LEVs have a protective role on the inflammatory process, murine and primary human macrophages were pre‐treated with LEVs for 24 h and then were stimulated with lipopolysaccharide (LPS). We found that pre‐treatment with LEVs decreased gene and protein expression of pro‐inflammatory cytokines, such as IL‐6, IL1‐β and TNF‐α, and reduced the nuclear translocation and phosphorylation of NF‐κB in LPS‐stimulated murine macrophages. The inhibition of NF‐κB activation was associated with the reduction in ERK1‐2 phosphorylation. Furthermore, the ability of LEVs to decrease pro‐inflammatory cytokines and increase anti‐inflammatory molecules was confirmed ex vivo in human primary T lymphocytes. In conclusion, we demonstrated that LEVs exert anti‐inflammatory effects both in vitro and ex vivo by inhibiting the ERK1‐2/NF‐κB signalling pathway.     

Load-Relaxation Properties of the Human Trunk in Response to Prolonged Flexion: Measuring and Modeling the Effect of Flexion Angle

Experimental studies suggest that prolonged trunk flexion reduces passive support of the spine. To understand alterations of the synergy between active and passive tissues following such loadings, several studies have assessed the time-dependent behavior of passive tissues including those within spinal motion segments and muscles. Yet, there remain limitations regarding load-relaxation of the lumbar spine in response to flexion exposures and the influence of different flexion angles. Ten healthy participants were exposed for 16 min to each of five magnitudes of lumbar flexion specified relative to individual flexion-relaxation angles (i.e., 30, 40, 60, 80, and 100%), during which lumbar flexion angle and trunk moment were recorded. Outcome measures were initial trunk moment, moment drop, parameters of four viscoelastic models (i.e., Standard Linear Solid model, the Prony Series, Schapery''s Theory, and the Modified Superposition Method), and changes in neutral zone and viscoelastic state following exposure. There were significant effects of flexion angle on initial moment, moment drop, changes in normalized neutral zone, and some parameters of the Standard Linear Solid model. Initial moment, moment drop, and changes in normalized neutral zone increased exponentially with flexion angle. Kelvin-solid models produced better predictions of temporal behaviors. Observed responses to trunk flexion suggest nonlinearity in viscoelastic properties, and which likely reflected viscoelastic behaviors of spinal (lumbar) motion segments. Flexion-induced changes in viscous properties and neutral zone imply an increase in internal loads and perhaps increased risk of low back disorders. Kelvin-solid models, especially the Prony Series model appeared to be more effective at modeling load-relaxation of the trunk.     

Investigating the inhibition of NMDA glutamate receptors in the basolateral nucleus of the amygdala on the pain and inflammation induced by formalin in male Wistar rats

Background

The role of the amygdala in controlling emotional pain has been emphasized in several studies. In this study, the role of the NMDA glutamate receptors in the basolateral nucleus of the amygdala (BLA) in regulating inflammation and emotional pain, induced by formalin, was studied in male rats.

Methods

Male Wistar rats, weighing 250±20 g, were injected with 20 μL of 2% formalin into the paw of the right hind limb. Memantine, at doses of 1 and 5 mg/rat, was injected bilaterally into the BLA five minutes prior to injecting formalin. Following the injection, the pain and inflammation of the paws were measured using Dubbison-Dennis and mercury immersion methods, respectively. The behavior of the animals, including licking time and foot volume, was assessed.

Results

The results showed that the inactivation of the NMDA receptors in the BLA in the acute phase of pain reduced the licking time (the emotional aspect of pain). However, at a high dose (5 μg/rat), memantine exacerbates the pain induced by formalin in the chronic phase. Additionally, the inhibition of the NMDA receptors in the BLA by memantine enhanced the formalin-induced increase in foot volume (inflammation) in a dose-dependent manner.

Conclusion

The study showed that the NMDA glutamate receptors in the BLA are crucial for the emotional pain and inflammation in both chronic and acute phases of formalin-induced pain. However, their roles are more pronounced in the chronic phase than in the acute phase of pain.

     

Acetyl-<Emphasis Type="SmallCaps">l</Emphasis>-Carnitine Attenuates Arsenic-Induced Oxidative Stress and Hippocampal Mitochondrial Dysfunction

Augmentation of mitochondrial oxidative stress through activating a series of deadly events has implicated as the main culprit of arsenic toxicity and therapeutic approaches based on improving mitochondrial function hold a great promise for attenuating the arsenic-induced toxicity. Acetyl-l-carnitine (ALC) through balancing the coenzyme A (CoA)/acyl-CoA ratio plays an important role in mitochondrial metabolism and thereby can help protect hippocampal neurons from oxidative damage. In the present study, we aimed to explore the effect of arsenic interactions on the mitochondrial function in the hippocampus of rats. Rats were randomly divided into five groups of control (distilled water), sodium arsenite (NaAsO₂, 20 mg/kg), and co-treatment of NaAsO₂ with various doses of ALC in three groups (100, 200, 300 mg/kg) and were treated orally for 21 consecutive days. Our results point out that arsenic exposure caused oxidative stress in rats’ hippocampus, which led to the reactive oxygen species (ROS) generation, mitochondrial swelling, the collapse of the mitochondrial membrane potential, and release of cytochrome c. It also altered Bcl-2/Bax expression ratio and increased caspase-3 and caspase-9 activities. Furthermore, arsenic exposure via activation of NF-κB and microglia increased inflammation. ALC could concentration-dependently counteract the arsenic-induced oxidative stress, modulate the antioxidant defense capacity, and improve mitochondrial functions. In addition, ALC decreased the expression of both death-associated proteins and of inflammatory markers. These findings indicate that ALC improved the arsenic-induced hippocampal mitochondrial dysfunction which underlines the importance of ALC in providing a possible therapeutic strategy for the prevention of arsenic-induced neurodegeneration.     

西藏珞巴族的肤纹参数和聚类分析

本文报道了珞巴族正常人群的１２项肤纹参数．样本包括了１４２名男性和１９０名女性．参数与汉族及其他少数民族作了比较,用聚类分析法算出各民族间的距离,并绘制了聚类图．结果提示民族间的肤纹参数均有显著差异．     

Tissue composition effect on dose distribution in neutron brachytherapy/neutron capture therapy

Aim

The aim of this study is to assess the effect of the compositions of various soft tissues and tissue-equivalent materials on dose distribution in neutron brachytherapy/neutron capture therapy.

Background

Neutron brachytherapy and neutron capture therapy are two common radiotherapy modalities.

Materials and methods

Dose distributions were calculated around a low dose rate ²⁵²Cf source located in a spherical phantom with radius of 20.0 cm using the MCNPX code for seven soft tissues and three tissue-equivalent materials. Relative total dose rate, relative neutron dose rate, total dose rate, and neutron dose rate were calculated for each material. These values were determined at various radial distances ranging from 0.3 to 15.0 cm from the source.

Results

Among the soft tissues and tissue-equivalent materials studied, adipose tissue and plexiglass demonstrated the greatest differences for total dose rate compared to 9-component soft tissue. The difference in dose rate with respect to 9-component soft tissue varied with compositions of the materials and the radial distance from the source. Furthermore, the total dose rate in water was different from that in 9-component soft tissue.

Conclusion

Taking the same composition for various soft tissues and tissue-equivalent media can lead to error in treatment planning in neutron brachytherapy/neutron capture therapy. Since the International Commission on Radiation Units and Measurements (ICRU) recommends that the total dosimetric uncertainty in dose delivery in radiotherapy should be within ±5%, the compositions of various soft tissues and tissue-equivalent materials should be considered in dose calculation and treatment planning in neutron brachytherapy/neutron capture therapy.     

Join queries optimization in the distributed databases using a hybrid multi-objective algorithm

Cluster Computing - In the distributed database systems, the relations needed by a query can be kept in several locations. This process significantly increases potential corresponding Query...