A bioinspired 3D shape olibanum-collagen-gelatin scaffolds with tunable porous microstructure for efficient neural tissue regeneration

There are a number of procedures for regeneration of injured nerves; however, tissue engineering scaffolds seems to be a promising approach for recovery of the functionality of the injured nerves. Consequently, in this study, olibanum-collagen-gelatin scaffolds were fabricated by freeze-cast technology. For this purpose, the olibanum and collagen were extracted from natural sources. The effect of solidification gradient on microstructure and properties of scaffolds was investigated. Scanning electron microscopy micrographs showed the formation of lamellar-type microstructure in which the average pore size reduced with an increase in freezing rate. According to the results, the prepared scaffolds at lower freezing rate showed a slight reduction in mechanical strength while the swelling and biodegradation ratio were increased due to the presence of larger pores and unidirectional channels. The composition of scaffolds and oriented microstructure improved cellular interaction. In addition, scaffolds with lower freezing rate exhibited promising results in terms of adhesion, spreading, and proliferation. In brief, the synthesized scaffolds at lower solidification rate have the potential for more in vitro and in vivo analyses to regeneration of neural defects.     

HER-2-based design of pertuzumab mimetic peptides

An in silico peptide design strategy is conducted in order to introduce a novel series of pertuzumab mimetic peptides, aimed to target the extracellular domain of HER-2 and prevent its signal transduction. A combination of alanine scanning and contact surface analysis is employed to assess the pertuzumab paratope, HER-2 epitope and their hot spots. Furthermore, the recognised residues are utilised to construct nine 10-mer peptides. Some of the peptides are modified pertuzumab paratope sequences, whereas the others are designed and modified as strongly binding complementary peptides for HER-2 epitope. Evaluation of the peptides is carried out through homology modelling, molecular dynamics simulation (MDS) and docking. It was revealed that all peptides mimic pertuzumab performance since they exhibit noticeable binding interaction energies, inhibitory efficiencies and number of hot spots. However, YNDSTHGERL with five hot spots and considerable interaction energy has the highest ability in interfering with HER-2-specific epitope. Inhibiting potency of this peptide is verified through MDSs.     

The influence of drinking-water pollution with heavy metal on the expression of IL-4 and IFN-γ in mice by real-time polymerase chain reaction

In recent years, water pollution has been converted to a challenging discussion in health area of human being. Heavy elements are one of the most important water pollutants and their negative adverse effects on body systems have been confirmed. In this study, investigation of effects of two heavy elements including lead (Pb) and copper (Cu) on expression of interlukin-4 (IL-4) and interferon-gamma (IFN-γ) as humoral and cellular immunity biomarkers, respectively, was aimed and PCR, real-time PCR and electrophoresis techniques were used. In this study, BALB/c mice were studied that had free access to drinking water which contained Cu or Pb salts. After 2 weeks, spleens of mice were removed, RNA extracted, and cDNA was prepared for RT-PCR. Then the expression of IL-4 and IFN-γ genes were assessed by real-time PCR. The expression of IFN-γ was up-regulated in both treated groups and the expression of IL-4 was only up-regulated in the group treated with Cu and down-regulated in the group treated with Pb. This study shows that the presence of heavy elements as drinking-water pollutants results in a disproportion of natural cytokines balances, and thus may result in a negative effect on immune system.     

Stimulation of neurotrophic factors and inhibition of proinflammatory cytokines by exogenous application of triiodothyronine in the rat model of ischemic stroke

There is a positive relation between decreases of triiodothyronine (T3) amounts and severity of stroke. The aim of this study was to evaluate the effect of exogenous T3 application on levels of neurogenesis markers in the subventricular zone. Cerebral ischemia was induced by middle cerebral artery occlusion in male Wistar rats. There were 4 experimental groups: sham, ischemic, vehicle, and treatment. Rats were injected with T3 (25 μg/kg, IV injection) at 24 hours after ischemia. Animals were sacrificed at day 7 after ischemia. There were high levels of brain‐derived neurotrophic factor, nestin, and Sox2 expressions in gene and protein levels in the T3 treatment group (P ≤ .05 vs ischemic group). Treatment group showed high levels of sera T3 and thyroxine (T4) but low levels of thyrotropin (TSH), tumor necrosis factor‐α, and interleukin‐6 (P ≤ .05 vs ischemic group) at day 4 after ischemia induction. Findings of this study revealed the effectiveness of exogenous T3 application in the improvement of neurogenesis possibly via regulation of proinflammatory cytokines.     

Metabolic flexibility determines human NK cell functional fate in the tumor microenvironment

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Characterisation of extracellular vesicles isolated from hydatid cyst fluid and evaluation of immunomodulatory effects on human monocytes

Hydatidosis is a disease caused by the larval stage of Echinococcus granulosus, which involves several organs of intermediate hosts. Evidence suggests a communication between hydatid cyst (HC) and hosts via extracellular vesicles. However, a little is known about the communication between EVs derived from HC fluid (HCF) and host cells. In the current study, EVs were isolated using differential centrifugation from sheep HCF and characterized by western blot, electron microscope and size distribution analysis. The uptake of EVs by human monocyte cell line (THP-1) was evaluated. The effects of EVs on the expression levels of pro- and anti-inflammatory cytokines were investigated using quantitative real-time PCR (RT-PCR), 3 and 24 h after incubation. Moreover, the cytokine level of IL-10 was evaluated in supernatant of THP-1 cell line at 3 and 24 h. EVs were successfully isolated and showed spherical shape with size distribution at 130.6 nm. After 3 h, the expression levels of pro-inflammatory cytokine genes (IL1Β, IL15 and IL8) were upregulated, while after 24 h, the expression levels of pro-inflammatory cytokines were decreased and IL13 gene expression showed upregulation. A statistically significant increase was seen in the levels of IL-10 after 24 h. The main mechanism of the communication between EVs derived from HCF and their host remains unclear; however, time-dependent anti-inflammatory effects in our study suggest that HC may modulate the immune responses via EVs.     

Effect of Resistance Training and <i>Spirulina platensis</i> on Expression of IL-6, Gp130 Cytokines,JAK-STAT Signaling in Male Rats Skeletal Muscle

The effect of resistance training and a herbal supplement on muscular signaling pathways are limited. We investigated the expression of IL-6, Gp130, JAK and STAT after resistance training, and Spirulina platensis supplementation in animal muscle. Thirty-two male Sprague Dawley rats (weight: 290 ± 20 g, and 9 weeks of age) were divided into four groups: control (CO; n = 8), Spirulina platensis supplementation (SP; n = 8), resistance exercise (RE; n = 8), and Spirulina platensis + resistance exercise (SP + RE; n = 8). The resistance exercise group trained five sessions each week for eight weeks. Spirulina 200 mg kg⁻¹ d⁻¹ was used in the SP and SP + RE groups. Gene expression was measured by real-time PCR following the last training session. One-way ANOVA test with Tukey’s post-hoc test were used for analysis of data (SPSS, version, 21). Data analysis revealed that the expression of IL-6 (P = 0.001), Gp130 (P = 0.001), JAK (P = 0.0001) and STAT (P = 0.004) increased significantly in the RE group. The expression of IL-6 (P = 0.018), JAK (P = 0.001) and STAT (P = 0.001) in SP + RE group also increased significantly (P ≤ 0.05). SP showed a significant increase in Gp130 (P = 0.001) and STAT (P = 0.001). Supplementation by Spirulina platensis may enhance muscle accretion during resistance training.     

Thymoquinone protects against 5-Fluorouracil-induced mucositis by NF-κβ and HIF-1 mechanisms in mice

Mucositis is among the most common side effects of 5-Fluorouracil (5-FU) and other cancer therapeutic drugs. Thymoquinone (TQ), a bioactive constituent extracted from Nigella sativa, has antioxidant and anti-inflammatory properties and can modify acute gastrointestinal injury. To investigate the effects of TQ on mucositis induced by 5-FU, studied animals were divided into four groups: control, 5-FU unit dose (300 mg/kg) to cause oral and intestinal mucositis (OM and IM), TQ (2.5 mg/kg) and TQ (2.5 mg/kg) plus 5-FU. Due to The molecular mechanisms, it was confirmed that the expression of NF-κβ and HIF-1 increases in OM. The serum levels of malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD), as well as pathological parameters, were assessed. Based on our results, the nuclear factor-kappa β gene expression in the tongue was downregulated significantly in the 5-FU + TQ compared to the 5-FU. TQ treatment can diminish MDA, and a reduction in oxidative stress was shown. TQ could also reduce the severity of tissue destruction and damaging effects induced by 5-FU on the tongue and intestine. We also observed lower villus length and width in the intestine of the 5-FU group compared to the control group. According to our research's pathological, biochemical, and molecular results, treatment with TQ as an anti-inflammatory and antioxidant compound may be the potential to improve and treat 5-FU-induced OM and IM, and TQ could be used against cancer treatment drugs and exhibit fewer adverse effects.